annual report 2011 scientific supplement

Delivering hope through life-changing research

infectious disease researcher dr deborah lehmann with riley principal partner

Telethon Institute for Child Health Research

Contents

Aboriginal Health Research...... 2 Biostatistics, Bioinformatics and Data Services...... 8 Cell Biology...... 13 Children’s Leukaemia and Cancer Research...... 20 Diabetes and Obesity...... 30 Drug Discovery...... 41 Inflammation...... 45 Lung Growth and Respiratory Environmental Health...... 48 Molecular Biotechnology...... 52 Paediatric Respiratory Physiology...... 54 Population Sciences...... 57 Vaccine Trials Group...... 105 Publications...... 116 Delivering hope through life-changing research

How does a research organisation deliver hope? It is through medical research that one day there will be a cure for children’s cancers and asthma. It is how better treatments are developed for children with cerebral palsy and how it was discovered that a vitamin – folate – could prevent many cases of spina bifida. We know that when a child is born with or develops a serious disease or disability, their families look to medical research to give them hope for the future. It’s a responsibility we take very seriously. At the Telethon Institute for Child Health Research, our community not only actively participates in our research projects but informs and shapes what we do through our Consumer and Community Advisory Council and Community Conversations. Our Annual Report is part of our commitment to share more about the research that we are currently doing. We also have a new, easy to navigate website with an index of every project currently underway – just use the search button and type in your key words. In this Scientific Supplement you will find complete scientific research reports from 2011. For our general annual report, please visit our website. Find our more at www.childhealthresearch.org.au

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 1 aboriginal health research

The Centre for Research the disconnection between researchers, Looking Forward: Improving the lead researcher. service providers and the community in mental health service outcomes for

Excellence in Aboriginal Health a practical and empowering way. History Aboriginal people living in the south- and Wellbeing (CREAHW) has seen significant issues, such as racism, east metropolitan corridor Implementing the AEDI in the Western perpetuated and become embedded in the Desert Overview Aboriginal community with a significant Michael Wright, Fiona Stanley negative impact on health and wellbeing. Roz Walker The Centre for Research Excellence in This project is a partnership between The CREAHW investigators are seeking to The key objective of this research project is Aboriginal Health and Wellbeing (CREAHW) is a Aboriginal families[1], government and non- change this cycle by listening and working in to improve the maternal and child health strategic program of intervention research that government mental health service providers, partnership with the community and investing and wellbeing of Martu communities living is focused on achieving radical and sustainable primary health-care providers (GP’s) Aboriginal energy and attention to get the best result in the Western Desert communities of change for the Aboriginal community and Medical Service, and the Telethon Institute for for the community. This will require system Jigalong, Punmu, Parngurr and Kunawarritji improving the lives of Aboriginal people. The Child Health Research. change and involve investing time with and Newman in the Pilbara. The project program is a unique validation of Aboriginal The goal of this project is to increase the decision makers in order to inform policy and is undertaken in partnership with funding knowledge and demonstration of Aboriginal effectiveness of the public mental health practice. through BHP Billiton Iron Ore, Indigenous methodology involving a multi-disciplinary services for Aboriginal families whose lives are Community Investment Program 2010-2014. team of Aboriginal and non-Aboriginal Funders of the project: In 2010, the National affected by serious mental illness living in the Using Community-based Participatory Action researchers, who will contribute to the body Health and Medical Research Council south-east metropolitan corridor. The project Research methods the project provides the of knowledge, work transparently with the awarded the Centre for Research Excellence will engage service users, Aboriginal and non- evidence base and conceptual underpinnings Aboriginal community and embrace Aboriginal in Aboriginal Health and Wellbeing (CREAHW) Aboriginal service providers, policy makers and to inform and evaluate the new maternal and culture and ways of thinking. grant to a group of 10 Chief Investigators managers. (CI) headed by Professor Fiona Stanley AC child health initiatives being developed by The CREAHW brings the research strengths (Director, Telethon Institute for Child Health The project aims to develop in consultation World Vision Australia and other stakeholders of each of the Chief Investigators together Research). The CREAHW is a collaborative with service users (Aboriginal families) and to improve the social, educational and in a cohesive program of community-based research venture between seven research service providers a culturally safe mental maternal and child health and wellbeing intervention research, well known both institutions, and is funded with a grant of health framework that will assist in the outcomes of the Western Desert communities. nationally and internationally, but with local delivery of mental health services to Aboriginal $2.5m over five years. Specifically the project involves implementing, relevance to Western Australia. It will be families living in the south-east metropolitan communicating and disseminating the AEDI supported by the outstanding track record region. results to relevant stakeholders in health of the Telethon Institute for Child Health Sub projects within the CREAHW: The methodology for the project includes and education Aboriginal across the Western Research in working with government and conducting a series of community forums Desert communities over the five years 2010- informing policy and practice and build on The CREAHW has several Chief Investigators across the region. The forums commenced in 2014. It also involves trialling appropriate past achievements by developing the next and their individual and collaborative research March 2011 and will extend for a period of 18 tools and communication strategies to share generation of Aboriginal health researchers projects aim to answer specific research and months, finishing in July 2012. A report will the information with Aboriginal families to and leadership among the Chief Investigator policy relevant questions within Aboriginal be published and released at the end of 2012. build of their knowledge and strengthen team. Health and Wellbeing. Projects being undertaken by researchers at the Telethon The project is expected to be completed at the community capacity. There is strong research The CREAHW team program of research will Institute are as follows: end of 2013. evidence which confirms the benefits of using build capacity in the community and bridge the Early Development Index to bring about Funders of the project: NHMRC are funding

2 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 community level change in Australia and in culturally appropriate health care services; guide The project is being done in collaboration with It is hoped that this project with provide Canada. health professionals’ practice; and guide health Kimberley Aboriginal Medical Services Council evidence that changes can be culturally secure policy for the provision of culturally appropriate (KAMSC) Social Emotional Wellbeing Unit. This and sustainable. This project will also take into health services. project stems from the high rates of Suicide in consideration the existing Department of Health Connection, belonging and health of the Kimberley in 2010. The aims of this project Cultural Respect Implementation Framework Australian Aboriginal people and their are to strengthen the capacity of community and other documentation/policies in regard communities in the City of Swan and the Strengthening social and emotional members to empower themselves and others to this issue. An arm of the Cultural Security Pilbara region of Western Australia. wellbeing of Australian Aboriginal to change their lives, their communities and project in the North Metropolitan region has people: How does racial identity and the systems that are barriers to good social also been established through the PindiPindi Rhonda Marriott, Fiona Stanley, Nick de Klerk, related self-esteem mediate the mental and emotional wellbeing. The findings will Centre as part of improving culturally secure Cheryl Kickett-Tucker, Roz Walker & Denise wellbeing of Aboriginal people? be used to develop an accredited innovative health service delivery to Aboriginal people in Groves program that is culturally appropriate to the the North Metropolitan Health Service Area. Cheryl Kickett-Tucker This holistic, 4 year qualitative study will empowerment of Aboriginal people in different This will ensure great research translation across explore the relationship between connection This is an extension of Cheryl Kickett-Tucker’s geographical locations. The project consists rural, remote and urban settings of the proposed and belonging for Aboriginal people living in research on the development of racial identity of the following two stages - community and methodology and model. The Framework the City of Swan and the Pilbara with health and related self-esteem of Aboriginal children, stakeholder consultation; program development. strategies and actions will be developed by the Cultural Security Aboriginal Leadership Group; outcomes to develop a conceptual framework. youth and adults (using her IRISE measures This important and original work will add to across the life span). This research will describe this group will provide practical implementation the paucity of knowledge in this area. The the mediating factors of racial identity and Cultural Security for Yamaji (Aboriginal guidance and cultural advice to the program. researcher will apply a community participatory related self-esteem in relation to Aboriginal people) within health services in the action research approach and thus, engage people’s mental wellbeing and identify effective Midwest Murchison region of Western with the community at all steps in the research ways to strengthen the social, cultural and Australia. Western Australian Aboriginal project. A conceptual framework will evolve emotional wellbeing and identity of Aboriginal Intergenerational Fetal growth Study Juli Coffin from the research data and this will be applied children, youth and young adults onwards. (WAAIFS ) to selected health priorities: for example, This research will encompass development This project aims to create a culturally secure Sandra Eades, Bridgette McNamara, Glenn the relationship of Aboriginal spirituality and of new instrumentation, complemented by in health service for Yamaji (Aboriginal people) Pearson, Amanda Langridge, Carrington birthing on country. The work will also test depth personal interviews using Community in the Midwest/Murchison region of Western Shepherd, Nicholas de Klerk & Fiona Stanley the phenomenological variant of ecological Participatory Action Research (CPAR) methods. Australia. This will be achieved through the systems theory (PVEST) (Spencer, Dupree and mapping of current policies and practices This project will investigate determinants of Hartman, 1997; Spencer, Fegley and Dupree, when treating and engaging Aboriginal fetal growth across generations, in all Aboriginal 2006) in understanding cultural resilience and Consulting with the Community to health consumers across all health sectors, mothers and children born in Western Australia its relationship with connection, belonging and develop an innovative and culturally implementation of the ‘Cultural Security between 1980 and 2009, using a novel measure health. This important and original work will responsive Empowerment, Healing and Framework’ (Coffin 2007) within each health of fetal growth; the percentage of optimal add to the paucity of knowledge on resilience Leadership program sector to show the strengths and weaknesses for birth weight (POBW). POBW measures the and health outcomes. Recommendations will priority, and working within each health sector appropriateness of fetal growth for a given drive health policy; build community resilience Pat Dudgeon, Roz Walker, Clair Scrine, Cheryl to create strategies/policies and practice to gestational age, fetal gender, maternal height and capacity; inform non-Aboriginal health care Dunkley, Divinna D’Anna, & Kathleen Cox improve areas of weakness. and parity, and allows the prevalence and professionals’ understanding of the need for severity of both growth restriction and excessive

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 3 growth to be assessed. use while they are at the centre. The centre’s Kulunga Research Network metropolitan communities. The research outreach program informally works with the sought to explore people’s motivations and Using unique data from linked administrative family of the attending person to help them Overview experiences as a non-smoker and successful health datasets spanning over 30 years to understand what the centre is offering and quitter. It sought to document the personal and multilevel models, the study will map The aims of the Kulunga Research Network to provide support while their member is circumstances of individuals as well as the differing contributions of fetal growth are to (1) facilitate high quality research receiving treatment. The outreach program examining the role of more common issues to chronic diseases in individuals, the links that is community based and culturally safe, also assists both the family and the client including family and social, economic, and between maternal fetal growth and that (2) to develop the capacity of Aboriginal with their transition back into the family and cultural influences that exist around tobacco of her offspring, and how the occurrence and non-Aboriginal people to conduct high community on completion of the program. use among Aboriginal adults in contemporary of medical conditions and pregnancy quality research with Aboriginal communities, Western Australia. complications influences that relationship. We When looking at the health and social and (3) to facilitate the translation of research will explore the causal pathways involved in mental well-being of their clients MR now into policy and practice and (4) to act as an A qualitative research process was utilised the perpetuation of sub-optimal fetal growth want to integrate the support service that advocate for Aboriginal families in public in order to facilitate an understanding of across generations, as well as those that are they offer to the families of their clients policy development. In addition to progressing the complexity of people’s experiences and protective. and develop a family assessment tool that its research projects, the focus of the team circumstances and allow participants to tell can more effectively help their workers in in 2011 has been on building relationships their story. The research found that people These investigations will be to inform whether developing a specific case plan that engages with communities and community-based chose not to smoke and to quit for a number the most important pathways to chronic with the family during the rehabilitation organisations, and assisting government of reasons. Many factors including family, disease began in grand-maternal environments process of their member. The current project and non-government organisations to work social norms, group dynamics and peer or in the next generation. The results are is to work with the management, clinical and effectively with Aboriginal people and pressure act as both supports and barriers to likely to provide evidence for when maternal outreach team, clients, families, community ensure their messages are appropriate and people’s quitting and in influencing whether and child health interventions are likely to be members and service stakeholders to develop effective. In addition, staff have been working people chose to smoke or not. The research most effective for the prevention of lifelong a family assessment tool. This tool will collaboratively across TICHR with a number of found an observable strong sense of self adult diseases including those influencing become an integral part of the MR’s service projects. among the participants which seemingly reproductive risks. and will be used by clinical and outreach team underpinned their actions and their ability to workers to assess the needs of the client’s remain strong as a non-smoker or effective family at the time of intake. The project will Examining the Critical Factors in quitter. Both non-smokers and successful Family Assessment Tool, Milliya utilize the community based participatory Aboriginal non-smoking quitters spoke with pride of their achievement Rumurra, Broome research approach. The aim of the assessment at not smoking knowing that they were Clair Scrine, Rose Murray Dawn Bessarab tool is to improve the health and quality of improving their personal and extended family the Aboriginal client and their family during The Kulunga Research Network was engaged health through their actions. The sense of Milliya Rumurra (MR) is a residential centre their journey through AOD treatment. The by the Cancer Council (WA) to ascertain achievement was especially notable among providing treatment and rehabilitation to final outcome of the project will be the reasons why some Aboriginal people have the quitters, despite the pressures some Indigenous community members wishing to development of a family assessment tool never taken up smoking and how other experienced from friends and family in their address their misuse of alcohol and other which will be trialled by MR’s clinical and Aboriginal people have successfully quit. attempts to quit and in their stance against drugs (AOD). Currently as part of their formal outreach team and evaluated for its usefulness Results were sought to better inform future smoking. program MR assess all individuals attending and effectiveness. health promotion campaigns and projects the centre to develop a specific treatment plan Funders of the project: The Cancer Council WA targeting Aboriginal families in regional and to assist each person in addressing their AOD

4 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Addressing Aboriginal Rates of Organ Awareness Grant’. the program on students’ self-esteem and raised by genetic research with Indigenous Donation aspirations is particularly significant given the communities, and promote informed debate evidence on the importance of positive self- on these issues. It has five overlapping phases: Clair Scrine, Rose Murray Evaluation of the Michael Leslie Pilbara esteem to children and young people’s healthy literature review, community consultation, This project sought to have a greater Performing Arts Program lives and futures. A series of recommendations participant-observation, interviews, and analysis understanding of the cultural barriers and were also made concerning ways to enhance and feedback. There will be three groups of Clair Scrine, Rose Murray perceptions regarding organ and tissue donation the program’s effectiveness and increase the participants: genetic researchers, Indigenous among Aboriginal people, and identify the The evaluation assessed the Michael Leslie number of students accessing its benefits. community leaders, and Indigenous people who are participating in genetic research projects. barriers some Aboriginal people experience Pilbara Performing Arts Program against its core Funders of the project: This project was funded or perceive with the current organ donor objectives of enabling improved educational by a Healthway ‘Health Promotion Research This project commenced as a post-doctoral registration process. It also sought to work attainment, self-esteem and aspiration in its Starter Grant’ research project (has subsequently received to increase Aboriginal people’s understanding Aboriginal and non-Aboriginal students. It found an NHMRC grant) and is being led by Dr Emma of the critical need for donation and raise that the impact of the program is consistent with Kowal from the University of Melbourne awareness and understanding among Aboriginal much of the literature on the positive impact of Treading Carefully: Socio political people about the need and processes involved young people’s involvement in the performing Implications of Genetic Research in for organ and tissue donation. Finally the arts on their self-esteem, confidence, learning, Aboriginal and Torres Strait Islander Working Together: Aboriginal and project sought to provide accurate information and motivation. Through a qualitative research Communities Torres Strait Islander Mental Health to enable Aboriginal people to promote family process, the project found that participation in and Wellbeing Principles and Practice discussions and to develop messages about the program can be a transformative experience Emma Kowal, Glenn Pearson donation for use in their local community. Key that brings about significant changes in students’ Roz Walker (Project Leader), Glenn Pearson Human genetic research promises to deliver findings included differing ideas and cultural lives. The program provides students with (Manager, Kulunga), Jacqueline Ann Bradley a range of health benefits to the population. beliefs about donation; a notable lack of skills and experience that can assist them to (Communications Project Officer), Pat Dudgeon, Where this research involves Indigenous understanding and limited knowledge about the collaborate, be disciplined both physically and (Expert Consultant), and Clinton Shultz, communities, many sensitive issues are raised. process of donation and registering to donate mentally, be expressive, listen and respond, (Indigenous Consultant). Indigenous peoples around the world have among Aboriginal people consulted; a real lack and take personal risks, complete a complex expressed concern about a lack of benefit to Working Together was produced as an important of awareness of the emphasis on discussing task and then perform it in front of peers - all their communities; a diversion of attention resource to improve the capacity of Aboriginal the issue with family and current campaigns highly valuable and transferable skills that are from non-genetic causes of health disparities; a and non‐Aboriginal health workers, mental regarding donation; a high level of mistrust important in a range of contexts including a reinforcement of ‘victim-blaming’; and possible health workers and relevant practitioners and fear of medical professions, institutions learning environment. The program’s focus misuse of tissue samples. These issues have not to identify and address mental illness and and procedures among Aboriginal people on youth engagement and youth participation been studied in an Australian context. As there associated issues of substance misuse and which are impacting on people’s views about provides a range of students with skills is an imminent expansion of genetic research suicide in Aboriginal and Torres Strait Islander donation; the need for appropriate educational necessary for fostering qualities of leadership with Indigenous people in Western Australia, communities, to recognise the early signs of aids and resources to facilitate discussion and and different styles of communication amongst both non-Indigenous genetic researchers and mental illness and make referrals for treatment understanding about donation among Aboriginal their peers and communities. Similarly, the Indigenous researchers have expressed the need where appropriate. It is also intended for people. program increases cultural pride and self- to rectify this. staff working in Healing Centres and Link‐up determination which, in turn, encourages Funders of the project: This research was funded agencies to address issues of grief, loss and students to take leadership of their life, their This project aims to identify the ethical, by an Organ and Tissue Authority ‘Community trans-generational trauma associated with family, and their community. The impact of socio-political and philosophical issues

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 5 the impact of forced removal from families The Council comprises a group of professional, Nina Boydell, BA, Dip Ed and /or country. The book is also intended passionate people committed to ensuring Rose Murray, Dip. Teaching (Primary), for students working in courses in nursing, Aboriginal people and the wider Aboriginal Graduate Cert. Indigenous Health Promotion External Committees medical schools, social work, psychiatry, community benefit from the research psychology and primary health care. conducted through the Telethon Institute. Dr Claire Scrine, PhD International 2011 saw a continuation and extension of The goal and over-arching principles for Fred Stacey, BA Roz Walker, Invited Valued Friend; Indigenous the initial promotion, dissemination and the work of the Council is to ensure the Research Network, Canada & USA (2011-) evaluation of the book. Since commencing facilitation, translation and application of National distribution of Working Together in August research findings into policy and practice to The Aboriginal Collaborative Council 2010 over 35,000 hard copies of the book improve health and wellbeing outcomes for Advising on Research and Evaluation Roz Walker, Australian Research Association have been widely distributed to a broad range Aboriginal families. (ACCARE) for Children and Youth (ARACY) (2006-); of target audiences. The on-going feedback Research Staff Roz Walker, Association of Qualitative Research and evaluation from both the survey monkey (AQR), Australia (2011-) feedback, and student, practitioner and Staff and Students 2011 Patricia Walsh stakeholder evaluations confirms that the Roz Walker, National Advisory Committee for book is an important and effective resource for the Kimberley Empowerment Project (2011-) a range of health, allied health practitioners OTHER Research Staff Local and educators and other professionals Centre for Research Excellence in Aboriginal Health and Wellbeing and agencies supporting and working with Jacqueline-Anne Bradley Rose Murray, COAG Aboriginal Child Health Aboriginal and Torres Strait peoples in mental (CREAHW) Jaxon Reibel Project Steering Group, (2010-) health and wellbeing. Research Staff Rose Murray, Aboriginal Health Action and Funders of the project: Office of Aboriginal and Dr Tamika Heiden, BSc, PhD Advisory Committee, (2010-) Torres Strait Islander Health Awards Tanya Jones, BA Psychology Glenn Pearson, Health Consumer Council of Western Australia Dawn Bessarab, Richmond Fellowship Associate Professor Roz Walker, PhD, BA (Hons) The Aboriginal Collaborative Council Aboriginal & Torres Strait Islander Award, WA Politics and Philosophy Glenn Pearson, Curtin University Human Advising on Research and Evaluation Social Worker of the Year Awards, 2011 Research Ethics Committee (ACCARE) Dr Michael Wright, PhD Rhonda Marriott, Patron of the Nursing and Glenn Pearson, Telethon Institute for Child The Aboriginal Collaborative Council Advising Midwifery office WA – NAIDOC award, 2011 Health Research Consumer and Community on Research and Evaluation (ACCARE) was Advisory Council Kulunga Research Network Sandra Eades, Centenary of International formed in 2008 to provide support and Women’s Day – listed as one of 100 Aboriginal Glenn Pearson, Key Aboriginal Advisory direction to Aboriginal research conducted Manager and Torres Strait Islander women who have Group, Strong Spirit Strong Future - Promoting through the Telethon Institute for Child Health achieved change in their communities, Healthy Women and Pregnancies 2011 Research (the Telethon Institute). ACCARE is a Glenn Pearson, BA (Education), PhD candidate National Aboriginal and Torres Strait Islander committee of the Institute Board advising on Roz Walker, Public Health Association (PHA) Research Staff Women’s Alliance, 2011 Aboriginal research. WA (2006-)

6 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Roz Walker, Primary Health Care Research and maternal and child health outcomes in the Western Australian, Environmental Health Campus, September 2011 Evaluation Network, WA (2006-) Western Desert, AIATSIS National Indigenous Australia (WA) State Conference Environmental Roz Walker, Guest Lecture, Research with Studies Conference 2011 - ‘Young and Old: Health: Imagine Life Without Us. South Perth Roz Walker, WA Australian Early Development Aboriginal Families, Indigenous Studies, Kulbardi Connecting Generations’ 19-22 September 2011, 28th- 30th March 2012 Index Steering Committee (2010-) Murdoch University, October 2011 Canberra Clair Scrine, Developing an empowerment, Roz Walker, Steering Committee for the Roz Walker, Developing a community-led healing and leadership program in the Kimberly. research project “Indigenous Meaning Making empowerment leadership and healing program Suicide Prevention in Aboriginal Communities. Through Narrative: Cultural Interpretations Active collaborations in the Kimberley, AIATSIS National Indigenous Perth, 14 September, 2011 of Preventable Deaths in Children and Young Studies Conference 2011 - ‘Young and Old: People” (2009-) Roz Walker, Aboriginal women’s health and Leslie L. Randall, RN, MPH Nez Perce Tribal Connecting Generations’ 19-22 September 2011, wellbeing, School of Nursing and Midwifery, member, Native American Health Research Roz Walker, Pilbara Child and Youth Project Canberra Murdoch, University Peel Campus, Mandurah, Network, to explore future collaborations (2009-) Roz Walker, Consulting with the Community to WA October 2011 between the CRE in Aboriginal Health and Roz Walker, Pilbara Early Learning Alliance develop an innovative and culturally responsive Wellbeing and the Indigenous Research Network Roz Walker, Aboriginal young people health and (2008-) Empowerment, Healing and Leadership (2011-); David Hendrix, Belgium Collaboration wellbeing, School of Nursing and Midwifery, program; Community Feedback Forum, Broome on Aboriginal traditional medicines to prevent Murdoch, University Peel Campus, Mandurah, 24 October, 2011 scabies among Aboriginal families in remote WA October 2011 communities – Scabies is a preventative but Invited Presentations Roz Walker, Research with Aboriginal Families, neglected tropical disease with a raft of adverse, long term outcomes (2011-) International Local Indigenous Studies, Kulbardi, Murdoch University, Murdoch, WA, August 2011 Roz Walker, From Marginalised to Empowered: Juli Coffin, Solid Kids and Cultural Security – Roz Walker, Lectures and workshops on cultural Transformative Methods for Aboriginal Health Lecture Geraldton November 2011 safety and cultural competence. Graduate Social and Wellbeing, 23rd Annual Native Health Juli Coffin, Creating a Culturally SecureU niversity Work Program, University of Western Australia, Research Conference, Niagara Falls, USA, July - Notre Dame Fremantle, WA August 2011 July 2011 2011 Juli Coffin, Introduction to Cultural Security Roz Walker, Lectures and workshops, Working National Notre Dame Fremantle, WA May 2011 towards cultural safety and cultural competence Juli Coffin, We All Solid Port Augusta Youth Rally Juli Coffin, Cultural Security for the Midwest – principles and practice. State-wide Mental on bullying to kids and parents (Over 1000), Port Murchison Health Sector Yamaji Forum, Office of Health Graduate Registered Nurse Program, Augusta, SA, November 2011 Education & Research Centre – Nursing North Health Department, Geraldton, WA May 2011 Metropolitan Area Service - Mental Health Shaw Roz Walker, Exploring Cultural Competence, Rose Murray, Kicked to the Curb: Examining the House, Graylands Hospital, May & September, Royal Australian and New Zealand Council of critical factors in Aboriginal non-smoking, WA 2011 Obstetricians and Gynaecologists (RANZCOG) State Cancer Conference, Perth, 24 March, 2011 Indigenous Women’s Health Meeting - Cairns - 3 Roz Walker, Guest Lecture, Aboriginal young - 5 June 2011 Glenn Pearson, Do You See What I See? people and Aboriginal women’s health. School of Environmental Health Australia 66th Annual Nursing and Midwifery, Murdoch University Peel Roz Walker, Starting on Track: Addressing

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 7 biostatistics, bioinformatics and data services

Overview research statisticians and analysts, a common leukaemias and solid tumours) are be published. FusionFinder is made freely enthusiasm to share common problems as well chromosomal translocations that may lead to available for non-commercial use and can be Gone are the days when conducting one as expertise, ensures that all biostatisticians the occurrence of gene fusions, whereby two downloaded from the project website. experiment meant obtaining one result. at TICHR regularly meet to share and normally separated genes are brought into The study was funded by the WA State Modern science often involves single exchange ideas and problems, for mutual close proximity and activated as a single gene. Government Centres of Excellence Program experiments generating millions of results, encouragement and stimulation. This activation often results in an abnormal and the Children’s Leukaemia and Cancer which need to be analysed alongside the protein product, which can have oncogenic The Data Services group provides specialised Research Foundation, Perth. wealth of data held in public databases. We (cancer causing) properties. The importance research support services to researchers have reached the point where the majority of detecting gene fusions in cancer lies in the and research groups at TICHR, in the areas of scientific research projects simply cannot fact that as only cancerous cells contain these of: data management, databases, and iCARE Virtual Dataset Infrastructure succeed without the intervention of advanced abnormal products they make ideal drug computer programming. A large proportion computing and statistical analysis. With the targets. of the group’s work involves developing Kim Carter, Richard Francis, and the iCARE number of our researchers growing and an ‘database applications’ (computer software) Recently, there has been a significant Consortium ever increasing reliance on the computational in 2 key areas. One is the collection of data advancement in our ability to identify all Research studies exploring the determinants analysis of rapidly increasing research data for TICHR studies using questionnaires or products that are being activated within a of disease often require increased power sizes, both Bioinformatics and Biostatistics data entry applications. The other area is cell at a single point in time. This collection of to detect small effects. Obtaining sufficient are becoming ever more important to the research project management software for products is known as a cell’s transcriptome. sample sizes can be achieved through the Institute. This Division encompasses both keeping track of study participants and their Using Next Generation Sequencing techniques pooling of datasets, although these are these closely linked disciplines. interactions with a research study. at the transcriptome level (called RNA-Seq) invariably in disparate locations. Coupled Bioinformatics is a cutting edge research field we can now verify known and discover novel During 2011, with strong encouragement with this, ethico-legal and data-ownership that uses computing technology, mathematics activated gene fusions. Trawling through from our chief research partners, all areas of issues may prevent the pooling of datasets or and statistics to answer biological research the hundreds of millions of data points this the Division moved towards providing active permanent data transfer across international questions. This year there has been a primary technology produces to discover the 10-100 or collaboration and research support to the borders. Methods that facilitate the sharing of focus on the analysis of Next Generation so that point to the existence of a gene fusion whole child health ‘campus’, TICHR, SPACH, research data that are both sympathetic with Sequencing both at the transcriptome (RNA- is a considerable task, which is essential in and PMH research. ethico-legal issues and enable more flexible Seq) and genome (Genome-Seq) levels. In order to direct the focus of downstream lab and detailed statistical analyses are required to addition we have created a platform for the work. overcome this problem. simultaneous analysis of epidemiological data We have written FusionFinder which is We have created a computational housed at multiple sites. Details of both these Bioinformatics designed to automate the discovery of infrastructure that implements database highlights are below. FusionFinder candidate gene fusion partners from RNA-Seq federation techniques to provide researchers The requirement for Biostatistics expertise data. To date FusionFinder has been applied with simultaneous analytical access to cuts across all areas of research at TICHR and Richard Francis (TICHR), Katherine Thompson- to a number of datasets both from within datasets housed in disparate locations elsewhere. The aim of statistical analysis Wicking (TICHR), Kim Carter (TICHR), Denise the institute and obtained elsewhere. These without the need for permanent pooling. is to aid in the interpretation of complex Anderson (TICHR), Ursula Kees (TICHR), Alex analyses have confirmed known gene fusions The application is currently in use by the numerical data which abounds in medical, Beesley (TICHR) and detected additional previously unreported International Collaboration for Autism Registry health, and biological research. While many The hallmarks of many cancers (including novel fusion genes, which have been Epidemiology (iCARE) who are analysing research groups at TICHR employ their own confirmed experimentally and will shortly datasets from across Europe and Australia to

8 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 determine Autism risk factors and trends. Our Klerk (TICHR), Grant Smith (TICHR), Steve Ball vascular disease. Atherosclerosis is a chronic stem cells (NSCs) using qRT-PCR in a low- platform is accessed and controlled via a secure (TICHR) inflammatory process, with subclinical density array format, and have integrated these project management and analysis web-interface inflammation leading to vascular damage. There data with gene expression microarrays. We Asthma is the most common chronic illness in we have created to facilitate querying of the is mounting evidence that childhood infection anticipate that ongoing research based on these Australian children, and over half of all asthma- federated research datasets. We are currently may play a role in the initiation, progression data will rationalise our understanding of the related hospitalisations are for children under preparing a manuscript for publication, as well or acute presentation of atherosclerosis which fundamental molecular mechanisms that initiate 15. Research suggests that environmental as preparing a generic version of the software becomes clinically apparent in later life. We are and maintain the brain tumour phenotype and lifestyle factors play an important part for public release to the research community. investigating the relationship between severe in increasing the risk of developing asthma. This work was supported by the Raine Medical infection in childhood and atherosclerosis in This work was funded by Autism Speaks (US). Western Australia (WA) has internationally Research Foundation and John Lillie Fellowship. later life using the internationally unique linkable unique capacity to link population-based health population-level health databases available in data on individuals who have lived in the state Western Australia. Toxicity Evidence Integration over the past 4 decades. By combining existing Biostatistics health survey data and state health data with This study is supported by a University of Alison Anderson (TICHR & UWA), Kim Carter geographical and environmental data, we have Western Australia, Research Development Members of the Division collaborated closely (TICHR), Denise Anderson, Michael Wise (UWA) a powerful resource for investigating factors Award. with most research groups at TICHR, in Over the past decade evidence has accumulated influencing the development of childhood particular: that environmental contaminants are causing asthma and its epidemiology, without the Denise Anderson: a range of adverse health outcomes. The aim need for conducting new surveys or expensive microRNA regulation in Brain tumours of this PhD and research project is to explore cohort studies. We are examining factors that Major study involvement in(i) was involved in a Laura Genovesi (TICHR), Peter Dallas (TICHR), how in silico bioinformatics approaches can help contribute to childhood asthma risk in terms number of Genome Wide Association Studies Kim Carter (TICHR), Keith Giles (WAIMR and to reveal new relationships in toxicogenomics of psychosocial life stress, perinatal and family (GWAS) which aim to detect associations UWA), Nick Gottardo (TICHR and PMH). data by intelligently integrating toxicology, gene characteristics, sociodemographics and spatio- between genetic variants and human diseases expression, and epigenetic and other ‘omics temporal influences using state of the art Medulloblastoma (MB) is the most common or traits of interest. Some of the examples of the platforms. biostatistical and geospatial methods. malignant brain tumours of childhood. Many diseases and traits studied include asthma, type children with these tumours remain incurable 2 diabetes, body mass index (BMI) and immune This work was supported by a William and and survivors are often left with devastating response. GWAS are a powerful tool to help Marlene Schrader Postgraduate Scholarship Hospitalisation, infection, and heart long-term side effects. unravel the multiple genes involved in a complex awarded by the William and Marlene Schrader disease disease such as asthma. Trust (through UWA). MicroRNAs (miRNAs) are a large class of short Kim Carter (TICHR), David Burgner (MCRI), non-coding RNAs that regulate growth and (ii) was also involved in microarray gene Matthew Cooper (TICHR), Nick de Klerk (TICHR), development in eukaryotic cells. It is now clear expression studies which is a technology that Developing risk models for predicting Peter Thompson (UWA), Fiona Stanley (TICHR), that deregulated miRNA expression plays an enables measurement of genome wide gene childhood asthma using linked health Hannah Moore (TICHR). important role in the pathogenesis of many expression. Gene expression can then be data different types of cancer, including adult brain compared between groups of interest (e.g. Cardiovascular disease is a major worldwide tumours. normal patients versus cancer patients) to health and economic burden. Atherosclerosis Kim Carter (TICHR), Max Bulsara (Notre Dame), identify genes with altered expression that may (hardening and narrowing of the arteries) We have analysed the expression levels of a Peter Franklin (UWA), Monique Robinson play a role in the disease process. Groups of causes heart attacks, strokes, and peripheral panel of miRNAs in MB specimens and neural (TICHR), Steve Stick (TICHR & PMH), Nick de genes with altered expression are also analysed

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 9 to determine if they act together in a biological different misclassification rates and sample (vii) Statistical support for a variety of studies of environmental and occupational exposure pathway which further helps to elucidate the sizes. conducted by Helen Leonard’s team involving to asbestos at Wittenoom and in Aboriginal disease process. health and social outcomes for children with communities (with James Cook University); Peter Jacoby: Rett syndrome and Down syndrome. GWAS for malignant mesothelioma; Matt Cooper: Major study involvement in: respiratory effects of silica exposure; studies of Nick de Klerk: Major study involveement in: respiratory disease in the aluminium industry (i) Continuing analysis of data from infectious Major study involvement in: (with WAIMR and Monash University). (i) Epidemiology of Epilepsy: Intrauterine disease studies including the Kalgoorlie Otitis growth historically been measured using crude Media research project and the Papua New (i) The Western Australian Twin Register methods of child weight distribution based Guinea neonatal pneumococcal conjugate as Director continuing with ongoing data on gestational age. Using the Proportion of vaccine trial. collection and joining in data collection with Data Services Optimal Birth Weight (POBW), as calculated the Australian Twin Register and joining the (ii) Analysis of data from the WA influenza by a method derived at TICHR in 2005, we worldwide twin register consortium, Intrepid. Highlights and significant achievements for the vaccine effectiveness study. were able to investigate the association of group in 2011 include -: (ii) Continuing in a supervisory role for the intrauterine growth on the incidence of (iii) Methodological research involving Developmental Pathways Project. Developing a database management system to epilepsy in children. Results from this study simulations to evaluate the relative be used by the ‘WA Autism Register’ to store show that children with both low and high performance of different vaccine effectiveness (iii) Continuing in a supervisory role for the and manage data in that register. POBW are at a higher risk of developing observational study designs. Raine Study, on the Executive Committee, epilepsy during childhood compared to those Management Committee, and on the paper Creation of online surveys for collection of (iv) Collaboration with spatial epidemiologist who showed appropriate intrauterine growth. submission oversight and statistical advisory data relating to flu vaccinations as part of (Steve Ball) to develop techniques for This finding is of interest to neurologists groups. Continued work with the mental a project called the WA Influenza Vaccine investigating geographical variation of disease investigating the pathways that lead to the health, diet and cardiovascular groups. Effectiveness Study (WAIVE). incidence in WA. These techniques have development of epilepsy by suggesting areas been applied to an analysis of the role of (iv) Continued collaboration with the Development of a project management system of the brain affecting during intrauterine socioeconomic disadvantage in explaining Childhood Cancer Epidemiology Group in for the study: ‘Pregnancy Investigation of growth may be involved. spatial variation in the prevalence of fetal studies of ALL, CBT, and DNA damage. Siblings and Mothers (PRISM)’. A longitudinal (ii) Genotype Misclassification: When applying growth-restricted births within metropolitan study aimed at identifying biomarkers for (v) Continued collaboration with the cystic Whole Genome Amplification (WGA) there Perth. autism in-utero and in the early post-natal fibrosis group, in particular on the AREST-CF are a number of factors that can affect the period. (v) Investigation of the relationship between and COMBAT-CF studies. quality of a sample, leading to incorrectly prenatal androgens measured in cord blood The development of an online data collection called genotypes (misclassification). A (vi) working as part of the Epidemiology and subsequent mental health indicators using questionnaire used to collect data for the statistical method, applied in R, was created NHMRC Program Grant in particular on Raine study data. ‘Breathing for Life’ study. This study is to correct for this misclassification when intellectual disability and autism, as well as investigating breathing and airway problems in the misclassification rates can be quantified (vi) Statistical support for other studies input into the TICHR part of the CRC on Spatial children and adults with Cerebral Palsy. through comparison, using say a subset of involving mental health outcomes in Raine Information, coordinated by Steve Ball. study children including the association with Re-development of a legacy ‘Diabetes Patient data, between WGA genotypes and another (vii) Continued collaboration with the prenatal stress (with Monique Robinson), Management System’ used by the PMH method no misclassification. This correction Occupational Respiratory Epidemiology group maternal overweight (also with Monique) and Diabetes group to store clinical information method showed good performance in at UWA School of Population Health in: studies correcting model estimates over a range of parental work patterns (with Sarah Johnson). on children with diabetes who are enrolled in

10 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 diabetes clinics. Data from this system is used (funded from separate research grants but developing Radiation Protection Standard for Autism Research (IMFAR), San Diego, CA, USA, for a variety of research collaborations of which contributing to campus-wide biostatistics and Exposure to ELF May 2011. TICHR is a research partner. bioinformatics collaboration and support) Local Kim Carter. “A bioinformatics infrastructure Peter Jacoby, MSc. for creating virtual pooled research datasets: Kim Carter, Western Australian Data Linkage Application to autism research”. Asia Pacific Matt Cooper, BSc. Staff and Students Network (2011-) Autism Conference, September 2011, Perth Patrick FitzGerald, PhD. Kim Carter, Australian Society for Medical Head of Division Kim Carter & Richard Francis “Sophisticated Amanda Langridge, PhD. Research, WA Committee (2006 -) techniques for sharing and analysing research First Name followed by surname followed by data”. Invited Speaker, Australian Research Guicheng Zhang, PhD. Kim Carter, WA Deep Sequencer Users Group abbreviated qualifications followed by current (2011-) Alliance for Children and Youth (ARACY) positions. See example below. Data Sharing and Harmonisation Workshop, Kim Carter, WA Next-Generation Sequencing Melbourne, October 2011 Nicholas de Klerk, PhD. Postgraduate Students User Group (2011-) Nick de Klerk. Childhood leukaemia and Head of Bioinformatics and Biostatistics Nick de Klerk co-supervised the following PhD Amanda Langridge: Scientific Advisory Sub- exposure to ELF-EM fields: using epidemiological students at UWA: Winthrop Research Professor, University of Committee, PMH Ethics Committee studies in guiding standard setting. Australian Western Australia M-A Measey: “The epidemiology of unexplained Nick de Klerk: Clinical Drug Trial Committee, Sir Radiation Protection Society, Annual Conference, fetal death in Western Australia” (submitted Charles Gairdner Hospital Melbourne, 2011. 2011); K Ayonrinde; L Mott; R Francis; M Jokic; Nick de Klerk: Mesothelioma Committee of Nick de Klerk. Association of lung tissue content Research Staff S Fehr. Western Australia - co-ordinating the Western of different mineral fibre types with occurrence Richard Francis, MSc. Australian Mesothelioma Register of malignant mesothelioma. 8th Perth Mesothelioma Group Symposium, Perth, 2011. Kim Carter, PhD. Awards Nick de Klerk: Busselton Population Medical Research Institute Inc, Board & Research Nick de Klerk. Association of lung tissue content Denise Anderson, BSc. R Francis, Highly Commended for Excellence and Committee. of different mineral fibre types with occurrence Marty Firth, BSc(Hons). of malignant mesothelioma. EPICOH , Oxford, Commitment to Research Nick de Klerk: Western Australian Medical 2011. Phyllis Alessandri. K Carter, Highly Commended for Excellence and Radiation and Cancer Working Party Nick de Klerk. Some non-technical aspects of Michelle de Klerk. Commitment to Research data integration – consumer and community Peter Cosgrove. BSc. support and engagement. SHIP , St Andrews, Invited Presentations 2011. Girard Good. External Committees First name, surname followed by presentation Peter Jacoby. “Modelling the effect of crowding Hoan Nguyen. National title, conference/meeting name, city and date. on carriage of otitis media bacteria”. Australian See example below. Epidemiological Association Conference, Perth, Nick de Klerk: NHMRC Academy Affiliated staff Richard Francis. “Building the iCARE Web-based September 2011 Nick de Klerk: Australian Working Group Analysis Portal”, The International Meeting for

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 11 ACTIVE collaborations

Professor Paul Burton, University of Leicester, United Kingdom Associate Professor David Burgner, Murdoch Children’s Research Institute, Victoria, Australia Dr Diana Schendel, Centres for Disease Control (US) & head of the International Collaboration for Autism Registry Epidemiology (collaboration of leading Autism researchers located at Karolinska Institute (Sweden), Aarhus University (Denmark), Turku University (Finland), Kings College London, the Norwegian Institute of Public Health, Columbia University (US), CDC (US) and TICHR)

12 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 cell biology

Overview responsible for triggering T-lymphocyte studies has involved parallel analysis of IgE involved in this case was the more abundant activation in the airway mucosa during the and IgG antibody subclass responses to major IgG1 subclass, in contrast to the IgG4 which The central research theme of this Division is “late phase response” in asthma. The main aeroallergens, comparing results obtained on is active in the context of immunotherapy. the basis for resistance versus susceptibility to focus of this aspect of our research is on large birth cohorts from Manchester and Perth. Followup studies are in progress with asthma, in particular we are seeking to elucidate interactions between T-regulatory cells and In our case this involved 1100 and 1400 serum colleagues in London to further investigate the the mechanisms that drive this disease are the network of airway mucosal Dendritic Cells samples respectively from subjects assessed mechanism(s) of this “blocking” effect, and to operative during its very early stages. Our long- that are responsible for immune surveillance in the 5yr and 14 year followups of the RAINE test the possibility that deliberate stimulation

term goal is to utilize this information to guide in the respiratory tract. We are additionally cohort, and these were compared with ~500 of allergen-specific IgG1 production may be a the development of preventative treatments for expanding this experimental area to encompass samples from the Manchester cohort. The study valid target for development of new asthma asthma for use in early childhood, before the viral infections and how these interact with focused on responses to cat allergen, which is treatments. disease consolidates into its persistent form. In and exploit allergic inflammatory mechanisms. recognized as a strong trigger for respiratory This work is funded by the National Health and addition, we have developed a specific focus In addition, we have developed a network of allergies and asthma-like symptoms in both Medical Research Council of Australia. on the mechanisms responsible for triggering national and international collaborators to Australia and UK. As expected, univariate acute severe asthma attacks in children with translate some of the key findings from this regression analysis demonstrated that risk for established asthma, in particular how virus research, into clinical settings. wheezing symptoms increased with serum Early respiratory infections and infections harness allergic responses to aid IgE titres against the major cat allergen FelD1, development of persistent asthma: them in escaping antimicrobial defences. We in both populations. However, recent studies Aetiology and pathogenesis of fever as a marker of risk are also continuing our research in areas atopy and asthma in other areas of allergy suggested to us that related to pediatric vaccines and immune additional elements of the allergic response M.M.H. Kusel, P.G. Holt, in collaboration with enhancers, particularly those which increase Modulation of IgE-associated risk for to cat may also be involved. In particular, P.D. Sly1 and S.L. Johnston2 resistance to respiratory infections. A unifying wheeze via allergen-specific IgG studies from a number of centres on the use 1Queensland Children’s Medical Research theme in this research stems from our earlier of immunotherapy to suppress IgE-associated 1 2 3 Institute, University of Queensland; findings that risk for development of allergy, P.G. Holt, A. Custovic , S. Ahlstedt , P.D. Sly allergy symptoms have suggested that the 2 respiratory infections and asthma is determined 1The University of Manchester Academic Health success of this treatment may be due in part to Imperial College, London primarily by factors that control the functional stimulation of production of allergen-specific Science Centre, UK; During 2011 we completed the 10 year followup maturation of the immune system during IgG antibody from the IgG4 subclass, which 2 on the CAS birth cohort, encompassing a group early childhood. In particular we have shown Centre for Allergy Research, Karolinska Institute, binds circulating allergen and prevents it from of 147 children selected on the basis of high risk that a variety of the cellular immune effector Stockholm, Sweden; reacting with IgE. We already had evidence for asthma and allergy as defined by positive mechanisms which are suppressed in utero in 3 that the immune response of allergic (and non Queensland Children’s Medical Research family history. The main aim of this prospective order to protect the placenta from inflammatory allergic) children to natural (environmental) Institute, University of Queensland birth cohort study has been to collect detailed damage are vital for protection against both cat exposure also involved production of some information concerning the respiratory infection infections and allergy during infancy, and the As part of a long term collaboration with IgG4 antibodies, and so we tested the theory history of these children throughout their first speed of their functional maturation during the colleagues in UK and Sweden, we have been that as per the situation in immunotherapy, 5 years of life, and determine how this relates preschool years is retarded in children from studying the relationships between antibody naturally produced cat-specific IgG4 may reduce to their risk for development of asthma initially families with a history of allergic diseases. An responses to aeroallergens and risk for asthma- the allergy-promoting effects of IgE. We indeed at age 5yrs, and in turn for asthma that persists important complementary stream of research like wheezing symptoms amongst children of demonstrated significant attenuation of cat- into later childhood. As part of this study, in our Division involves animal model studies different ages and from different geographic specific IgE-related wheeze by cat-specific IgG, collaborators initially in London and now in the on immunoregulation of the cell populations locations. A major component of these but unexpectedly found that the type of IgG

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 13 US and in Melbourne are using genomics- in a new NHMRC-funded project (commencing showing association (combined P < 5 × 10−8) airways with specific bacteria predisposes based techniques to identify the viral and 2012), focusing on cryobanked clinical material with pulmonary function in or near MFAP2, children towards development of asthma. bacterial microflora that was present in the from the CAS children. TGFB2, HDAC4, RARB, MECOM (also known We are testing this premise in the Childhood airways of these children at the time of each as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, Asthma Study (CAS) birth cohort, which This work is funded by the National Health and infection, and we will factor this information CDC123, C10orf11, LRP1, CCDC38, MMP15, comprises children at high-risk for asthma Medical Research Council of Australia. into our ongoing analyses during 2012. CFDP1 and KCNE2. Identification of these and allergy due to parental history of allergy. An important breakpoint in this study was 16 new loci may provide insight into the Post-nasal aspirate samples were collected reassessment of the relationship between molecular mechanisms regulating pulmonary and cryobanked from CAS participants both at Genome-wide association and large- the frequency and (most importantly) the function and into molecular targets for future regular follow-up appointments and at times scale follow up for identification intensity of infant lower respiratory infections therapy to alleviate reduced lung function. of respiratory infection up to age 5 years. A of new genetic loci influencing lung (LRIs) and risk for asthma, focusing on We are proceeding with this collaboration pilot study was initiated in collaboration with function outcomes beyond age 5yrs. In particular we on a number of fronts related to respiratory Drs Kathryn Holt and Michael Inouye, to assess wanted to reassess the relative impact of P.G. Holt in collaboration with C.E.Pennell1, functions and susceptibility to asthma and the use of nasopharyngeal aspirate samples to early LRIs that were associated with wheezing P.D.Sly2 and the consortium detailed in Nature related diseases. identify whole bacterial communities within symptoms, which have traditionally been an individual’s upper respiratory tract, using Genetics2011:43(11):1082-90. This work is funded by the National Health and assumed to carry maximal risk for later asthma cutting-edge metagenomics techniques. We 1School of Women’s and Infants’ Health, The Medical Research Council of Australia. development, and to compare these with have utilized post-nasal aspirates obtained University of Western Australia; infections associated with febrile responses. from a panel of 3-6 month old infants, Both wheeze and fever in association with 2 collected at a routine follow-up without Queensland Children’s Medical Research Characterisation of nasopharyngeal infant LRI were equivalently strong markers respiratory infection (“controls”). Sequencing Institute, University of Queensland. microbial populations in children at of risk for asthma at age 5yrs. However, it is by the Roche 454 GS FLX Titanium genome Pulmonary function measures reflect high risk of asthma and allergy using now recognized that a significant proportion sequencer detected ~200 bacterial genera. respiratory health and are used in the bacterial metagenomics of children carrying a physician diagnosis of Significantly, the abundance of S. pneumoniae diagnosis of a variety of pulmonary diseases. A asthma at the end of the preschool years in D. Mok, K. Holt1, M. Inouye2, E.M. Hollams, B.J. positively associated with wheeze at 5 years large international consortium of researchers, reality have a relatively benign form of wheeze Holt, M.M.H. Kusel, P.D. Sly3, P.G. Holt of age. Abundance of S. pneumoniae also which has included our group contributing due mainly to low airway caliber, which associated with colonisation by genera data from the 14yr respiratory followup of the 1Microbiology Department, University of spontaneously resolves over the ensuing Moraxella, Haemophilus, Porphorymonas, RAINE birth cohort, have pooled resources Melbourne few years, revealing the truly “persistent” Prevotella, Gemella, Lactobacillus, Veillonella, in order to mount a large scale genome wide asthmatics. Of major interest in this context: 2Department of Pathology, University of Fusobacterium, Neisseria and lower odds for association study to identify genetic variants we have now shown via the 10year outcome Melbourne Acinetobacter or Methylobacterium. A small which influence lung function. The group has data in the CAS cohort that the impact of subset of these samples was re-sequenced tested genome-wide association with forced 3Queensland Children’s Medical Research wheezy infections wanes over time and by Ion Torrent, for validation of the bacterial expiratory volume in 1 second and the ratio Institute, University of Queensland. maximal risk for asthma that persists to age 10 reads as determined by 454 sequencing. of forced expiratory volume in 1 second to is associated with infections that trigger febrile Accumulating evidence suggests a potential Analysis of these reads is currently ongoing, forced vital capacity in 48,201 individuals of responses. This is suggestive of underlying role of bacterial infections in the pathogenesis before proceeding to the next phase of the European ancestry with follow up of the top hyperactivity of the inflammasome component of childhood asthma. This is particularly project, which is to examine samples in the associations in up to an additional 46,411 of the host response to infection in affected relevant within the first year of life, where cohort collected at the time of a respiratory individuals. New regions were identified children, and we are exploring this hypothesis we hypothesise that early colonisation of the infection, for bacterial profiling by 454

14 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 sequencing. Changes in bacterial colonisation to amplified presentation to and ensuing models of the gene networks that cause asthma of the inherent complexity of the immune will then be tracked back to the controls to activation of pro-inflammatory Th2 effector cells; symptoms in humans in vivo. A major focus of responses involved. A number of groups have determine the relationships between the if this occurs at tissue sites already inflamed this work is to characterize the role of IRF7 in recently sought to develop unbiased systems composition of upper airways bacterial flora and as a result of viral infection and associated regulation of the gene networks that underpin biology approaches to investigate these issues. risk for asthma development in childhood. immune responses, the result may be a self- viral asthma exacerbations in children. In We have recently published the results of one sustaining inflammatory cascade. The results parallel we are also developing novel humanized such study from our group involving attempts This work is funded by the National Health and of epidemiological studies from a number of mouse models of asthma to determine how to elucidate superficially similar Th2-associated Medical Research Council of Australia. groups on patterns of expression of severe inflammatory gene networks damage the responses to paediatric vaccines and allergens, asthma exacerbations during the “common airways and impact on lung function. and to differentiate between them via gene cold season” in atopic children are consistent coexpression network analysis. We have Prevention of virus-associated asthma This work is funded by the University of Western with such a mechanism. If this is explanation is demonstrated that in immune responses to exacerbations in atopic children Australia. correct, it follows that “blocking out” IgE during the DTaP and pneumococcal polysaccharide P.G. Holt, A. Bosco, D.H. Strickland in the virus season may prevent the triggering of conjugate vaccines, potentially antagonistic collaboration with P.D. Sly1, P.N. Lesouef2, and this amplification loop, and help to maintain Th1-/IFN-associated and Th2-associated gene M. Tang3. levels of airways inflammation ensuing from Pediatric Vaccine Studies networks coexist in an apparent state of viral infection below the threshold required for dynamic equilibrium, whereas in Th2-dominant 1Queensland Children’s Medical Research severe asthma exacerbation. The collaborators Development of genomics-based allergen-specific responses of atopics the Th1 Institute, University of Queensland; in this project have secured NHMRC funding to approaches to assessing the safety of and IFN networks are respectively disrupted pediatric vaccines 2Dept of Pediatrics, University of WA; test this hypothesis via treatment of high risk and downregulated. Capacity to detect and atopic children with anti-IgE (Xolair) over the interpret these covert differences between 3Murdoch Childrens Research Institute, P.G. Holt, A. Bosco, K.L. McKenna, O. White, winters of 2012/13. responses to vaccines and allergens relies on the University of Melbourne. A.H.J. van den Biggelar, E.M. Hollams in 1 use of sophisticated algorithms that underpin This work is funded by the National Health and collaboration with P. Richmond Ongoing studies in the Division point to an coexpression network analysis, which identify Medical Research Council of Australia with drug 1 important role for atopy, acting in concert School of Pediatrics and Child Health, UWA genes that function co-ordinately in complex support from Novartis (Switzerland). with viral infection, in triggering acute severe Immune responses to vaccines in infants and pathways. This methodology has significant asthma exacerbations in children. In particular, young children are typically Th2-biased, giving potential to identify covert interactions between we have demonstrated that upregulation of inflammatory pathways triggered by vaccination, Identification of the gene networks rise to concerns regarding potential atopy- high affinity IgE receptors (FcER1a) on the bone and as such may be developed further into a that underpin inflammatory processes like side effects exemplified by the injection- marrow derived precursors of airway mucosal useful tool to aid in prediction of vaccine safety/ in asthma site reactions observed in a subset of atopic dendritic cells (DC), triggered by stimuli released children immunized with the diptheria/acellular efficacy. during the host response to respiratory viral A. Jones, P.G. Holt, A. Bosco pertussis/tetanus (DTaP) vaccine under the This work is funded by the National Health infection, provides a potential mechanism It is well known that viral infections and original infant vaccination schedule. Associated and Medical Research Council of Australia and for the recruitment of atopic inflammatory exposure to allergens can cause asthma, but our theoretical concerns also exist regarding Wellcome Trust (UK). pathways into the overall antiviral response in knowledge of the molecular processes involved potential antagonism or deviation of Th1- airway tissues. In particular, arming airway DC is incomplete. We are currently utilizing mediated sterilising immunity. Conventional with FcER1a may lead to IgE binding to the DC molecular profiling technologies and data immunological methodology has limited capacity Pneumococcal conjugate vaccination surface which can be used to enhance their analysis algorithms to generate computational to effectively address these problems because at birth in a third world setting: no efficiency in allergen sampling, in turn leading

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 15 evidence for neonatal T-cell tolerance balanced and stable Th1-polarised memory investigating the functions of neonatal antigen Animal Model Studies responses accompanied by antibody titres that presenting cells (APC) in children born in PNG 1 A.H.J. van den Biggelaar, W. Pomat , A. Bosco, were equivalent to subjects vaccinated later compared to those born in Australia (AUS). Determining the factors that govern S. Phuanukoonnon1, C.J. Devitt, M.A. Nadal- in infancy. PCV vaccination at birth is safe and These studies involve collecting cord blood resolution of allergic airways 2 Sims, P.M. Siba1, P.C. Richmond , D. Lehmann, not associated with immunological tolerance. mononuclear cells (CBMC) from PNG and AUS inflammation P.G. Holt Neonatal immunisation schedules should newborns and comparing both APC and T cell D.H. Strickland, J.A. Thomas, A.N. Larcombe, 1Papua New Guinea Institute of Medical therefore be considered in high-risk areas phenotype and function. UA S cord naïve T + - + P.G. Holt. Research where this may result in improved vaccine cells (CD4 CD25 CD127 ) showed an enhanced coverage and the earliest possible protection and more rapid proliferative response in an This study aims to map the central 2School of Paediatrics and Child Health, against pneumococcal disease and death. autologous APC-dependent culture system, mechanisms that underpin expression of University of Western Australia, Princess a result of differences in neonatal APC rather atopic asthma at the target tissue level, Margaret Hospital for Children than T-cell function. This included an increased and hence regulation of the maintenance Concerns about the risk of inducing immune Neonatal antigen presenting cell capacity to process antigen and to up-regulate of “normal” function in the airways. In deviation-associated “neonatal tolerance” function in children from 1st versus activation markers following stimulation. In humans, sensitization to aeroallergen(s) is as described in mice have restricted the 3rd world environments contrast, resting PNG APC exhibited higher one of the major risk factors predictive of widespread adoption of neonatal vaccination. baseline levels of activation and inhibitory development of chronic asthma. We have J.G. Lisciandro1, S.L. Prescott1, M. Nadal-Sims, The aim of this study was to demonstrate markers, and were less or non-responsive to developed a unique rat model featuring C.J. Devitt, P.C. Richmond1, W. Pomat2, P.M. the immunological feasibility of neonatal stimulation in vitro. This study supports the two inbred rat strains closely approximating Siba2, P.G. Holt, D.H. Strickland, A.H.J. van den pneumococcal conjugate vaccination (PCV) hypothesis that prenatal environments can human “high risk for allergy - HR” and Biggelaar^ which could potentially protect the most influence the developing immune system “low risk for allergy LR” phenotypes. We vulnerable age group in high-risk human 1School of Paediatrics and Child Health, in utero, in particular children born under have established that in sensitized LR rats, populations in 3rd world settings against University of Western Australia, Perth, modern environmental conditions exhibit continued aeroallergen challenge involves the severe pneumococcal disease and mortality. Australia increased APC reactivity at birth compared to induction of a regulatory network (involving In Papua New Guinea, 313 newborns were children born under 3rd world environmental interactions between specific cell types 2Papua New Guinea Institute of Medical randomised to be vaccinated with the 7-valent conditions. We speculate that the functionally within the airway microenvironment) that Research, Goroka, Papua New Guinea PCV (7vPCV) at birth, 1 and 2 months (neonatal more quiescent nature of PNG neonatal APC operates to efficiently control the intensity group, , n = 104), at 1, 2 and 3 months of ^ Current affiliation: Crucell, Innovation & may represent an adaptation to the more and duration of allergic airways responses. age (infant group, n = 105), or not to receive Discovery Lab, Archimedesweg 4-6, 2333 CN, robust 3rd world microbial environment In contrast, sensitized HR animals mount 7vPCV (control group, n = 109). T-cell and The Netherlands in which relatively high-level exposure of exaggerated uncontrolled airway responses pneumococcal serotype specific IgG antibody newborns to proinflammatory microbial There is increasing interest in the possibility to repeated aerosol challenge, resulting titers were assessed at 3 and 9 months of stimuli represents the norm; the significance that there may be developmental differences in a more persistent and severe form of age and children were monitored for disease of these findings in relation to vaccine in immune functions between infants born in inflammatory disease with continuing airways to age 18 months. Despite transient Th2 responsiveness in early life remains to be 1st and 3rd world environments, which in turn inflammation and hyperresponsiveness polarisation of memory responses to the established. influence their responses to early vaccination. (both hallmarks of the human chronic atopic PCV-carrier protein at 3 months, neonatal With this in mind, as part of our studies asthmatic response). Our studies have vaccinees manifested protective levels of on responses to the PCV vaccine in Papua demonstrated that in the airway mucosa of pneumococcal serotype-specific IgG antibody New Guinea (PNG) infants, we have been HR rats there is an association between the at this age, and by 9 months displayed development of persistent AHR and reduced

16 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 number and function of cells capable of viral infection models in our rats strains. We minor numbers of T cells in peripheral blood. cell retention in DLN may play a role. Work is regulating the inflammatory airways response. are using a Rhinovirus (RV) adapted to infect CD103 expression has been characterized in continuing on characterising this response, with Moreover, we have also demonstrated a series rats (mengovirus) to best compliment the mice in great detail, and similarly to human the focus on further characterising the inflammatory of abnormalities in the functions of other findings in humans that have shown strong majority of intraepithelial T cells in the gut are response in CD103 KO mice in terms of cytokine major cellular players associated with both the associations between RV infection and acute CD103+. In mice, it has been reported that a production and other potential regulatory T cell development and expression of disease, namely asthma exacerbation in children. We have large proportion of mucosal T cells are CD103+, responses. Additionally as CD103 is associated airway mucosal dendritic cells (AMDC) and T documented the response to viral infection compared to a small proportion of splenic or with binding to epithelial cells, we are in the helper cells. Furthermore, these abnormalities following a time course post infection day in blood T cells. CD103 is also expressed on some process of identifying the precise location of DC are restricted to respiratory tissues. Our findings the HR and LR rat strains, including viral titres dendritic cell (DC) subpopulations and these subsets within the lung and airways of CD103KO suggest that “site specific” factor(s) related in bronchoalveolar lavage (BAL) fluid and lung have been associated with T cell immunity at mice. As location may be central to antigen to the airway mucosa microenvironment homogenates, airways inflammatory response barrier sites such as the intestine and skin. In capture this may potentially play a role in the may ultimately determine whether allergic and cytokine response in BAL fluid. We are the respiratory mucosa, it is known that CD103 ensuing immune response. individuals mount a chronic asthmatic response currently finalising the assessment of T cell and CD11b (reciprocally) expressing AMDC This work was funded by the Asthma Foundation to aerosol allergen exposure. Most importantly, and DC population responses following the subsets exist, however we currently have little of W.A. we have shown that “correcting” for the same time course as above post infection in knowledge of their specific role in the cycle of deficiency that we have identified in HR animals the rat strains. Once baseline infection data inhaled antigen capture, processing and delivery can reverse ongoing disease. The concept of is completed work will progress to overlaying to airway draining lymph nodes (DLN) for Pulmonary immune response and lung “site specific failure of regulation” underpinning viral infection on sensitized/ challenged rats to presentation to T cells and induction of immune function alteration in the developing these experimental model studies, if it can be enhance our current understanding of how viral responses. To explore the role of CD103 on lung system after exposure to validated and elucidated mechanistically, offers infection markedly amplifies local Th2 responses DC we are using CD103 knock-out (CD103KO) nanoparticles exciting new possibilities for drug development to aeroallergen challenge in the airway mucosa animals and our well-characterised model of for asthma treatment, and this represents the of sensitised rats, increasing the intensity of experimental allergic airways inflammation. K.G. Schuepp, J.A. Thomas, G. Zosky, P.G. Holt, long-term aim of our research program. acute inflammation and the duration of ensuing Our initial studies have demonstrated D.H. Strickland. airways hyperresponsiveness (AHR). significant differences in the development of This research was funded by the National Health Nanoparticles offer promising new possibilities airways hyperresponsiveness (AHR) in CD103 and Medical Research Council of Australia. This research is funded by the National Health for diverse biomedical applications due to the KO compared to normal mice. Interestingly, and Medical Research Council of Australia. unique physico-chemical properties that they whilst AHR responses were reduced, CD103 possess. Currently, much attention is being KO mice still developed airways inflammation Respiratory viral infections as triggers focused internationally on providing rationale characterised by eosinophil infiltration of acute severe asthma exacerbations The role of the integrin CD103 for use of nanotechnology in biomedical indicating that the mice had been sensitised in atopics: mechanistic studies in an in development of airways applications. One of the potential uses of to the allergen. These findings are novel and experimental model. hyperresponsiveness nanoparticles is as delivery vehicles for lung- raise the question of how this response is based vaccines for children. In this context it D.H. Strickland, V. Fear, J.A. Thomas. P.G. Holt. V. Fear, K. Wiqvist, M.E. Wikstrom, S. Lai, G. being mediated. Initial studies suggest that T is known that exposure of children to larger Zosky, P.D. Sly, P.G. Holt, D.H. Strickland and P. cell recruitment into airways is unchanged in We are expanding our asthma research to particles, such as traffic-related pollutants, can Stumbles CD103KO mice, thus not the limiting factor in encompass how viral infections interact with have adverse effects on health. It is recognised AHR development in this model. However, naïve and exploit allergic inflammatory mechanisms. In humans, CD103 is expressed on the majority that ambient air can contain significant levels T cell numbers in draining lymph nodes were Our initial phase has been to establish the of CD4+ and CD8+ T cells in gut, compared to of nanoparticles from many sources. However, increased in CD103 KO mice suggesting that T

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 17 the potential effect of nanoparticle exposure, Staff and Students Dr D.H. Strickland, PhD - Senior Research Deborah Strickland. Netherlands Asthma particularly in children, on later health Fellow Foundation. outcome remains unclear. We hypothesize Head of Division †Dr P.A. Stumbles, PhD - Senior Lecturer, National that following exposure to nanoparticles the Patrick G Holt PhD FRCPath DSc FRCPI Murdoch University responses of the developing respiratory tract Patrick Holt. National Health & Medical MD(Hon) FAA will significantly differ from adult responses Mrs J.A. Thomas, BSc - Research Officer Research Council of Australia Career and have initiated a research program to Deputy Director, Telethon Institute for Child Mrs J. Tizard - Research Assistant Development Award Committee. investigate this. Our initial studies have been Health Research to determine baseline developmental data Professor, Centre for Child Health Research, †Honorary Fellow at TICHR; all research Deborah Strickland. Murdoch Vet and on the pulmonary immune system of mice, UWA activities remain based within this Division. Biomedical School Grant Review Panel focusing on different cell populations that Senior Principal Research Fellow, National are known to play central roles in immunity, Health & Medical Research Council of Australia Presentations 2011 and comparing neonates to adults. This has Visiting Research Fellows been done for various tissues, including lung, Dr Karen Schuepp MD, University Children’s Patrick G. Holt airway mucosa, draining lymph nodes and Research Staff Hospital, Bern, Switzerland. bronchoalveolar washouts. Additionally we Plenary Speaker: Regulation of immunological Ms M. Amarasekara – Graduate Student have also mapped lung function at various homeostasis in the respiratory tract – ERS Lung developmental ages from neonate to adult. Mr Scott Bazeley – Graduate Student Science Conference, Estoril, 2011. Using bioengineered fluorochrome-labelled Dr A. Bosco , PhD - Research Fellow External Committees Symposium Speaker: Preventing development particles we have exposed neonatal and adult of allergic diseases via oral mucosal Mr L. Cheung – Graduate Student International mice via the respiratory route to nanoparticles immunotherapy – AAAAI Congress, San and are currently assessing the inflammatory Dr V. Fear – Research Fellow Patrick Holt. NIH Expert Committee on Francisco, 2011. changes induced in various respiratory Immunotherapy. tissues. To complement this data we are Dr E.M. Hollams, PhD - Research Fellow Symposium Speaker: Innate immunity, allergy, and asthma exacerbations – AAAAI Congress, also determining the effect of nanoparticle Mrs B.J. Holt, BSc - Research Officer Patrick Holt. NIH Expert Committee: exposure of various aged mice on lung Development of strategies for asthma San Francisco, 2011. Ms A. Jones – Research Officer function. prevention Keynote Plenary Speaker: Bridging the gap This work was funded by the Asthma Mr A. Jones – Garduate Student Patrick Holt. NIH Program Grant advisory panel between innate and adaptive immunity in the lung – Keystone Symposium, Vancouver, 2011. Foundation of WA, and supported by the Ms J. Lisciandro BSc (Hons) – Graduate Student - URECA study, University of Wisconsin. Friends of the Institute. Symposium Speaker: Altered immune Dr K.L. McKenna, PhD - Research Fellow Patrick Holt. International Scientific Advisory Board, Centre for Translational Medicine, responses and asthma development – ATS Dr D. Mok, PhD – Research Fellow James Connolly Memorial Hospital, Dublin. Congress, Denver, 2011. Mr R. Ng – Graduate student Patrick Holt. NIH Project Grant advisory panel Symposium Speaker: Interactions between atopic and antimicrobial pathways in asthma Mr S. Ramanayake – Research Assistant – Precursors of Food Allergy in Newborns, Children’s Memorial Hospital, Chicago. pathogenesis – EAACI Congress, Istanbul, 2011. Mr M. Serralha, BSc (Hons) - Research Symposium Speaker: The role of airways Assistant Deborah Strickland. Asthma UK

18 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 inflammation in development of persistent Australian Society Immunology, Annual Meeting, Christophe von Garnier, Bern University Hospital, asthma during childhood: emerging targets for Mucosal Special Interest group Bern Switzerland asthma prevention – 10th World Congress on Inflammation, Paris, 2011. Symposium Speaker: Food and inhalant Active collaborations allergy - 2nd Saudi Allergy, Asthma and Clinical Immunology Symposium, Riyadh, 2011. Fernando Martinez, Respiratory Sciences Center, University of Arizona, USA Symposium Speaker: The role of infections in asthma pathogenesis - 2nd Saudi Allergy, James Gern, Clinical Science Centre, University Asthma and Clinical Immunology Symposium, Of Wisconsin Medical School, USA Riyadh, 2011. Robert Lemanske, Division of Pediatric Allergy, Symposium Speaker: Primary and secondary Immunology and Rheumatology, Wisconsin prevention of allergy - 2nd Saudi Allergy, Asthma University, USA and Clinical Immunology Symposium, Riyadh, Adnan Custovic, University Hospital of South 2011. Manchester, UK Plenary Speaker: New perspectives on asthma – Peter Sly, Queensland Children’s Medical WAO Regional Congress, Dubai, 2011. Research Institute, Australia Workshop Presenter: Development of asthma – Mimi Tang, Royal Children’s Hospital, preventative strategies for use in children - NIH Melbourne, Australia Workshop, Washington, 2011. Claus Bachert, Gabi Holtappels, UZG, Upper Plenary Speaker: Immune-infection interactions Airway Research Laboratory, Belgium in the early development of allergy – PAAM Congress of EAACI, Barcelona, 2011. Hugh Sampson, Department of Pediatrics, Division of Allergy & Immunology, Mount Sanai Deborah H. Strickland School of Medicine, USA World Immune Regulation meeting, Davos, Steve Durham, Dept Allergy & Clinical Switzerland; Speaker and session Chair and Immunology, National Heart & Lung Institute, UK judge Sebastian Johnston, Imperial College, School of Bern University Hospital, Davos, Switzerland Medicine at St. Mary’s, National Heart and Lung National Institute, UK Steffan Ahlstedt, Karolinska Institute, Sweden ASMR; Session chair and judge Charles Hardy, Monash University, Melbourne, Child and Adolescent Health Research Australia Symposium; Judge

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 19 children’s leukaemia and cancer research

Overview Acute lymphoblastic leukaemia cytosine arabinoside. Compounds designed to overexpressed in 75% of pre-B ALL specimens block the identified cellular interactions within and showed a 19-fold up-regulation by qRT- Cancers in children comprise many different Interactions between acute the bone marrow microenvironment are PCR versus normal CD34+ cells. Incubation of diseases. More than half of them affect cells lymphoblastic leukaemia and bone expected to mobilise the leukaemic cells and recombinant human CTGF with either a pre-B of the immune system and the central nervous marrow stromal cells influence make them more accessible to contemporary ALL cell line or a human bone marrow cell line system, while only a minority are carcinomas, response to therapy antileukaemic agents. The data provide novel (HS5) was examined to monitor effects on contrasting with cancer diagnoses in adults. insight into the pathobiology of ALL and proliferation and adhesion. CTGF increased Hence, the most common malignancy in Y Tesfai, J Ford, NG Gottardo and UR Kees, in indicate new therapeutic targets for patients proliferation of bone marrow stromal cells children is leukaemia, followed by brain collaboration with MJ Firth, RA O’Leary and with ALL. yet did not alter the proliferation of pre-B ALL tumours. Despite marked improvements in the KW Carter, Division of Biostatistics and Genetic cells. Furthermore, CTGF acted on stromal This work was supported by the Cancer cure rates for paediatric cancers, leukaemias Epidemiology, and C Cole, Department of cells to increase adhesion of pre-B ALL cells Council of WA and the Children’s Leukaemia and brain tumours account for half of the Haematology-Oncology, Princess Margaret to the stroma. Microarray gene expression and Cancer Research Foundation, WA. deaths. In order to find better therapies Hospital. analysis of HS5 cells incubated with CTGF for children with cancer, our Division at the The cure rate for paediatric patients with B affected genes involved in cholesterol and Institute and the Oncology Total Care Unit at fatty acid metabolism, extracellular matrix precursor acute lymphoblastic leukaemia Role of microenvironment Princess Margaret Hospital (PMH) are both production, cell motility and cell cycle. This (pre-B ALL) is steadily improving, however interactions in childhood leukaemia members of the largest study group into these relapses do occur despite initial response clear link between CTGF and interactions diseases, the US-based Children’s Oncology to therapy. To identify links between drug JE Wells, M Howlett, J Ford, AL Samuels, J between pre-B ALL and microenvironment Group (COG). The major goal is to improve resistance and gene deregulation we used Heng and UR Kees in collaboration with C Cole, will be validated and further characterised in our understanding of paediatric cancers and oligonucleotide microarray technology and Haematology-Oncology, Princess Margaret vitro through overexpression of CTGF in pre-B leukaemia, and work towards curative therapy determined in 184 pre-B ALL specimens genes Hospital and DR Brigstock, Paediatric Surgery ALL cells using stable retroviral transfection. for patients. differentially expressed compared to normal Research Laboratory, Children’s Research We hypothesise that secretion of CTGF + initiates a cascade of events, contributing to The Division focuses on research into CD34 specimens. We identified 20 signature Institute, Columbus, Ohio, USA. genes including CTGF, BMP-2, CXCR4 and IL7R, leukaemogenesis and adhesion-mediated childhood leukaemia, brain tumours and a In children with acute lymphoblastic leukaemia documented to regulate interactions in the drug resistance. Delineating these events will very rare disease in children, undifferentiated (ALL) the bone marrow microenvironment bone marrow. We recorded remarkably similar lead to a better understanding of therapy carcinoma. The main aims are the is the site of leukaemic cell proliferation. levels of expression in three independent resistance in children with ALL and strategies identification of genetic alterations that lead Recently, the surrounding bone marrow patient cohorts, and found distinct patterns for overcoming resistance. to childhood cancers and the application of stromal cells have been shown to play a in cytogenetically defined subgroups of this knowledge to the prognosis and improved critical role in clinical outcome by affecting This work was supported by NHMRC, Cancer pre-B ALL. The canonical pathways that were therapeutic approaches for patients. In order leukaemic cell survival and drug resistance. Council of WA and the Children’s Leukaemia affected are involved in inter- and intra-cellular to examine the genetic lesions present in The mechanism by which this stromal and Cancer Research Foundation, WA. communication, regulating signaling within the the various types of cancer, we make use of protection takes place is unclear. To identify microenvironment. We tested experimentally microarray and sequencing technologies. Our genes and pathways linked to the disease and whether interaction with stromal cells experimental model systems, including a panel drug resistance we performed transcriptional CpG island methylation correlates conferred protection to four drugs used of established leukaemia and cancer cell lines, profiling of B precursor (pre-B) ALL compared with CTGF gene expression in paediatric in current ALL therapy, and demonstrated are ideal tools for testing potential new drugs to normal CD34+ cells. We found that pre-B acute lymphoblastic leukaemia that bone marrow stromal cells significantly for the treatment of patients. connective tissue growth factor (CTGF) was influenced resistance to vincristine and M Welch and UR Kees in collaboration with

20 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 WK Greene, Division of Health Science, Murdoch across the CTGF CpG island was a feature of Hence, we hypothesize that CTGF plays a role in O’Leary, Division of Biostatistics and Genetic University, Perth. CTGF positive cell lines, while those lacking CTGF haematopoiesis. We studied mice with targeted Epidemiology and DL Baker, Department of expression were hypermethylated at this locus. disruption of the Ctgf gene. Ctgf -/- mice die Haematology-Oncology, Princess Margaret Acute lymphoblastic leukaemia (ALL) is the The study has now been extended to included perinatally, owing to respiratory failure. Flow Hospital, Perth. most common form of childhood cancer, with primary patient specimens. Future experiments cytometry was used to enumerate the B, T and precursor B-cell (pre-B ALL) comprising around Continuous complete clinical remission in T-cell aim to examine the effect of pharmacological myeloid populations. Ctgf -/- neonatal livers were 80 percent of ALL cases. Using microarray acute lymphoblastic leukaemia (T-ALL) is now modulation of CpG methylation upon CTGF examined, and Ctgf +/- mice were studied and technology we compared the gene expression approaching 80% due to the implementation of expression in vitro. compared to wild type (WT) at 4 weeks and 8 profile of pre-B ALL to normal CD34+ and CD19+/ aggressive chemotherapy protocols, but patients weeks of age. IgMneg cells. Many of the top ranked genes This work was supported by the Cancer Council that relapse continue to have a poor prognosis. identified in this study are known to mediate of WA and the Children’s Leukaemia and Cancer Initially we measured the content of B, T and Such patients could benefit from augmented cell-cell interactions. One of them, connective Research Foundation, WA. myeloid populations in blood, bone marrow therapy if their clinical outcome could be more tissue growth factor (CTGF) has been implicated (BM), spleen, thymus and lymph nodes, accurately predicted at the time of diagnosis. in the biology of several solid tumours. Four comparing WT with Ctgf +/- mice. No significant Gene expression profiling offers the potential independent studies on B-lineage ALL in Identifying the role of connective tissue differences were recorded. Interestingly, the to identify additional prognostic markers, but paediatric and adult patients showed that 75 growth factor (CTGF) in haematopoiesis neonatal liver cells of Ctgf -/- mice showed has had limited success in generating robust percent of patients expressed CTGF at very high increased proportions of B cells and a decrease signatures that predict outcome across multiple levels, and in our paediatric patient specimens CTL Cheung and UR Kees in collaboration with of myeloid cells compared to Ctgf +/- and WT patient cohorts. This study aimed to identify CTGF was expressed over a wide range DH Strickland, Division of Cell Biology, and AK liver cells. Taken together, we demonstrated robust gene classifiers that could be used for the from 2.3 to 380-fold by array measurement. Charles, Princess Margaret Hospital, Perth and that deletion of Ctgf influences the balance of accurate prediction of relapse in independent Immunoblotting confirmed secretion of WS Alexander, Walter and Eliza Hall Institute of B lymphopoiesis and myelopoiesis in mutant cohorts and across different experimental CTGF in our panel of pre-B ALL cell lines and Medical Research, Melbourne, and KM Lyons, neonatal livers. To further examine the role of platforms. Using HG-U133Plus2 microarrays interestingly, novel variants of CTGF mRNA were UCLA, Los Angeles, USA. CTGF in HSCs and microenvironment, a series of we modelled a five-gene classifier (5-GC) that identified in severalCTGF -positive cell lines by Connective tissue growth factor (CTGF) is transplantation experiments are under way;Ctgf accurately predicted clinical outcome in a cohort RNA blotting and sequencing of RACE products. a member of the CCN gene family, whose -/- or Ctgf +/- HSCs are being transplanted into WT of 50 T-ALL patients. The 5-GC was further tested CTGF is not normally expressed in B cells or their protein products have critical roles in bone mice, to determine the repopulation capacity of against three independent cohorts of T-ALL progenitors and secretion of CTGF proteins may formation, and in fibroblasts, chondrocytes and cells. patients, using either qRT-PCR or microarray play a prominent role in ALL, leading to modified CTGF gene expression, and could predict patients with endothelial cells. Our studies showed that This work was supported by the Children’s interactions with the microenvironment. significantly adverse clinical outcome in each. was highly upregulated in acute lymphoblastic Leukaemia and Cancer Research Foundation, CTGF The 5-GC featured the interleukin-7 receptor (IL- The present study focused on investigating leukaemia of pre-B type (pre-B ALL). also WA. 7R), low-expression of which was independently the mechanism of CTGF gene deregulation by plays a role in osteoblast proliferation and predictive of relapse in T-ALL patients. In T-ALL genetic and epigenetic mechanisms. Analysis differentiation, and these cells are known to cell lines, low IL-7R expression was correlated of the CTGF locus by Southern blotting ruled control haematopoietic stem cells (HSCs) via Outcome prediction of paediatric with diminished growth response to IL-7 and out rearrangements disturbing the CTGF locus. production of factors essential for renewal and patients with acute T-cell lymphoblastic enhanced glucocorticoid resistance. Analysis of A combination of bisulfite sequencing and maturation. The balance of HSC self-renewal and leukaemia at diagnosis biological pathways identified the NF-κB and methylation-specific PCR identified epigenetic differentiation is highly regulated by intrinsic WNT pathways, and the cell adhesion receptor regulation of CTGF in our panel of pre-B ALL factors together with cues from the surrounding AL Cleaver, AH Beesley, NC Sturges and UR family, particularly integrins, as being predictive cell lines. Demethylation of CpG dinucleotides microenvironment, including growth factors. Kees, in collaboration with MJ Firth and RA

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 21 of relapse. Outcome modelling using genes potential markers of drug-resistance could this model, relapse/CCR patient status could develop resistance and which pathways are from these pathways identified patients with improve patient stratification and further be predicted with >75% accuracy in each of deregulated. We predict that modulation significantly worse relapse-free survival in improve cure rates. Over the past 20 years the three independent cohorts. Predictions of glucose metabolism pathways may be each T-ALL cohort. We have therefore used our laboratory has developed a panel of of relapse were driven by contributions from associated with drug resistance and evasion two different approaches to identify, for paediatric ALL cell lines that retain critical different drug combinations in each of the of apoptosis. To assess the bioenergetic the first time, robust gene signatures that features of the primary disease. Using the cohorts, indicating particular importance in phenotype we examined a panel of GC- can successfully discriminate relapse and MTT viability assay we have measured the T-ALL therapy. These findings demonstrate resistant and sensitive T-ALL cell lines using continuous complete remission patients at sensitivity of these cell lines to 13 commonly that biological pathways correlating to in vitro in vitro cell culture assays to provide insights the time of diagnosis across multiple patient used ALL chemotherapeutic agents and drug resistance may have prognostic potential into the modulation of glucose metabolism cohorts and platforms. Such genes and have measured gene-expression profiles by in patients and highlight the importance and association with GC-sensitivity. These pathways represent markers for improved Affymetrix HG-U133A microarray. In contrast of understanding how individual patients studies identified that glucocorticoid resistant patient risk stratification and potential targets to many of the cell lines that are available relapse. These genetic features contribute leukaemia cells alter their central metabolism for novel T-ALL therapies. commercially, our cell lines generally grow at to our understanding of drug resistance and and enhance glucose catabolism. We found slow rates similar to the growth of leukaemic represent potential markers for improved that GC-resistance is associated with an This work was supported by the National blasts in vivo. Their drug-resistance profile patient stratification at diagnosis. increased glycolytic phenotype and protection Institutes of Health, USA and the Children’s parallels the spectrum of resistance that has from metabolic crisis in T-ALL. Moreover, Leukaemia and Cancer Research Foundation, This work was supported by the Children’s been observed in primary patient specimens, we have developed novel metabolomic and WA. Leukaemia and Cancer Research Foundation, particularly in regard to dexamethasone. We proteomic profiling techniques to identify WA. have correlated drug-resistance and gene- metabolites and proteins associated with expression profiles to generate an extensive resistance, conducted in collaboration with Models of drug-resistance to database of drug-gene signatures that Metabolomics Australia and Proteomics predict patient outcome in acute Modulation of energy metabolism are currently being analysed for biological International. Preliminary metabolomic lymphoblastic leukaemia pathways associated with function. Comparison of drug-gene signatures analysis also indicates that changes at the glucocorticoid resistance in T-cell with the publicly available Connectivity Map metabolic level are associated with drug AH Beesley and UR Kees in collaboration acute lymphoblastic leukaemia (T-ALL) with RA O’Leary and MJ Firth, Division of has provided potential drug-leads that are resistance; we are currently identifying and Biostatistics and Genetic Epidemiology. under test in our laboratory. We are also in AL Samuels, J Heng, AH Beesley and UR Kees delineating significant differentially expressed the process of developing a gene expression- in collaboration with KW Carter and RW metabolites and pathways. Together these Children with acute lymphoblastic leukaemia algorithm based on our in vitro drug-gene Francis, Division of Biostatistics and Genetic results indicate that drug-resistant leukaemia (ALL) are treated with complex chemotherapy resistance data that can predict outcome in Epidemiology. cells place unique importance on glucose as regimens of up to ten different drugs primary patient specimens. The data was used a carbon source and this relationship may according to risk stratification at diagnosis. Despite significant improvements in to generate a model of predicted resistance provide a novel therapeutic opportunity. Around 80% of patients achieve continuous the treatment of childhood T-cell acute scores that was subsequently assessed in Understanding the metabolic/ proteomic complete remission (CCR) with early response lymphoblastic leukaemia (T-ALL), up to 30% of microarray datasets from three independent mechanisms underlying the development to drug therapy being one of the strongest patients will relapse and most of those face a T-cell ALL (T-ALL) patient cohorts. These scores of drug resistance in T-ALL is of critical predictors of outcome. However, a significant dismal prognosis. Resistance to glucocorticoids were used to predict patient outcome (relapse importance for the identification of novel number of patients continue to relapse and (GC) is known to be a major factor contributing or CCR) in each cohort. The top 50 genes prognostic indicators and the development of for these the outlook is dismal due to the to the poor prognosis of relapsed ALL, correlating with in vitro resistance to each of more effective antileukaemic drugs. development of drug-resistance. Identifying however, it is still unclear how patients the ten drugs were used in modelling. Using

22 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 This work is supported by the Cancer Council of (Samuels AL, Beesley AH, Lock RB, Kees UR contributing to the resistant phenotype. The these cells. DNA was extracted from 12 cell lines WA and the Children’s Leukaemia and Cancer et al. Validation of a Mouse Xenograft Model molecular alterations driving acquired drug and NOTCH1 exons were PCR amplified and Research Foundation, WA. System for Gene Expression Analysis of Human resistance will provide important clues for the sequenced. Activating mutations of the NOTCH1 ALL. BMC Genomics, 2010 Apr 21;11:256). development of new therapeutic strategies for gene were identified in 7 of the panel of 12 cell Using this approach we were able to identify the treatment of T-ALL. lines (58%). One cell line had a mutation in the Targeting drug-resistance in paediatric potential drug-leads that could synergise with juxtamembrane domain, three cell lines had a This work is supported by the NHMRC, Australia acute lymphoblastic leukaemia current therapies to reverse the acquired drug mutation in the heterodimerization domain only, and the Children’s Leukaemia and Cancer resistance. Gene set enrichment and Ingenuity and one cell line had a mutation in the PEST Research Foundation, WA. AL Samuels, AH Beesley, V Peeva, and UR pathways analysis identified key networks, domain, whilst two cell lines had mutations in Kees in collaboration with R Papa and R Lock, including cellular movement, carbohydrate both the heterodimerization and PEST domains. Leukaemia Biology, Children’s Cancer Institute metabolism and cellular death associated The drug resistance profile of the T-ALL cell line Correlation of NOTCH1 activating Australia for Medical Research, New South with drug resistance. The Connectivity Map panel for standard chemotherapeutic agents mutations and sensitivity to Wales. algorithm predicted small molecule inhibitors to used in the clinic to treat T-ALL (including 6-mercaptopurine in T-cell acute reverse the resistant phenotype, including those cytosine arabinoside, 6-mercaptopurine, Drug resistance continues to be a significant lymphoblastic leukaemia cell lines problem in childhood T-cell acute lymphoblastic directed at histone deacetylase, beta-oxidative 6-thioguanine, methotrexate, dexamethasone, leukaemia (T-ALL), yet few novel therapies have respiration and hydroxy-methyl-glutaryl AD Schoof, AH Beesley, NG Gottardo and UR methylprednisolone, daunorubicin, doxorubicin, emerged over the last decades. To identify genes Coenzyme A reductase (HMG-CoA). In vitro and Kees in collaboration with JD Jago, Curtin L-asparaginase and vincristine) were then and pathways deregulated in drug resistance, in vivo screenings were conducted to assess University of Technology, Perth. correlated to NOTCH1 mutation status. as well as small molecule inhibitors that could the efficacy of several small molecule inhibitors This revealed that cell lines with NOTCH1 Acute lymphoblastic leukaemia (ALL) is the synergise with current therapies, we have targeting cellular metabolism pathways activating mutations were more susceptible to most common cancer in children, with T-cell ALL established and validated a T-ALL non-obese particularly fatty acid and lipid synthesis. One of 6-mercaptopurine and 6-thioguanine than cell (T-ALL) occurring in about 15% of cases. Using diabetic/severe combined immunodeficient the most promising drugs, an HMG-CoA inhibitor lines without NOTCH1 activating mutations, the current Children’s Oncology Group protocol (NOD/SCID) xenograft model of leukaemia was evaluated in vivo as both a single agent and indicating that they may be more important 5-year event free survival rates approaching relapse. We have developed a novel, clinically in combination with VXLD. Interestingly, we have in T-ALL therapy than has been previously 80% can been achieved. However, for the relevant four-drug regimen to mimic in mice the found this modulator plus VXLD notably reduced appreciated. We are currently expanding this patients that relapse many become resistant initial phase of therapy in paediatric patients. leukaemic infiltration of the bone marrow 2 research to include additional T-ALL cell lines to the current chemotherapeutic drugs and Each xenograft was treated with vehicle control weeks post treatment initiation, this finding is and to study mutations in the FBW7, PTEN, P53, a cure remains hard to achieve. NOTCH1, a or a combination of vincristine, dexamethasone, currently being further evaluated. The results and TPMT genes, which have relevance either critical developmental gene, was implicated in L-asparaginase and daunorubicin (VXLD) to from our study indicated that patients develop for NOTCH1 signalling or thiopurine sensitivity. T-cell leukaemogenesis by the discovery of a derive drug resistant clones in vivo. Importantly, distinct yet definable patterns of acquired Such studies have important implications for t(7;9) translocation. More recently, activating the pattern of drug sensitivity in xenografts drug resistance. Therefore to gain a thorough improved risk stratification and the development mutations of NOTCH1 have been demonstrated mirrored the progression of disease in the understanding of the mechanisms driving drug of individualised treatment strategies. in over 50% of T-ALL patient specimens. patients from whom they were derived. resistance and ALL relapse we are generating Based on these observations we wished to (i) This work was supported by the Children’s more xenografts. Primary engraftment for an We compared gene transcriptional profiles determine the mutational status of NOTCH1 in Leukaemia and Cancer Research Foundation, additional 10 new T-ALL xenografts is underway. among the in vivo drug-selected T-ALL xenografts our unique panel of T-ALL cell lines and (ii) to WA. We will use transcriptional profiling to examine and controls to identify genes and pathways correlate the presence of NOTCH1 activating common and individual patterns among the associated with drug resistance and ALL relapse mutations with the drug resistance profiles for xenografts to identify genes and pathways

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 23 Infant acute lymphoblastic leukaemia studying to obtain further evidence regarding midline carcinoma (NMC). These cancers patient data from PMH and have identified and the mixed lineage leukaemia (MLL) the pathogenesis of this disease. Molecular are characterised by translocations between another NMC case and two other carcinoma gene analysis and sequencing has confirmed chromosome 15 and 19 and in most cases the cases of interest. We have developed cell the breakpoint as a novel translocation breakpoint on chromosome 19 contains the lines from these patient specimens and are RS Kotecha, UR Kees, AH Beesley and NG breakpoint between the MLL and EPS15 BRD4 bromodomain gene and the NUT gene conducting high-throughput drug screening Gottardo in collaboration with CH Cole and T genes and we are continuing to analyse the on chromosome 15. This translocation was in conjunction with the ACRF Drug Discovery Carter, Department of Haematology-Oncology, features at the genomic level. DNA analysis present in the cell line PER-403 established Centre for Childhood Cancer, Children’s Cancer Princess Margaret Hospital and A Murch, King using Affymetrix 2.7M Cytogenetic Arrays has from an 11-year old girl diagnosed at PMH Institute Australia, Sydney, to find alternative Edward Memorial Hospital for Women, Perth. provided evidence for additional copy-number several years ago. The 16-year old patient therapeutic strategies to treat this disease. variations affecting the leukaemias in both received combination chemotherapy at PMH In modern medicine, treatment of paediatric This work was supported by the Cancer twins, challenging the concept that a single and she initially responded well, however acute lymphoblastic leukaemia (ALL) Council Western Australia, Apache Energy, and genetic defect is sufficient for overt disease died from disease 8 months after diagnosis. represents one of the many success stories, the Children’s Leukaemia and Cancer Research in infant MLL. The identification of additional We generated cell line PER-624 from her with significant improvements in event free Foundation, WA. and overall survival. However, infant ALL is a genetic abnormalities in such cases may cancer cells and have determined that they heterogeneous group with distinct biological provide opportunities for the development of contain several karyotypic abnormalities, and clinical characteristics, which continues novel targeted therapies in this disease. including t(6;19) and t(1;18;7) but not the The novel T-ALL agent flavopiridol: standard translocation. FISH experiments mechanisms of action and resistance to be resistant to this success. Infant ALL This work is supported by the Children’s were performed using whole chromosome represents 2-5% of paediatric ALL cases. The Leukaemia and Cancer Research Foundation, paints, BACs, sub-telomere and PCR probes AH Beesley, E Ferrari, J Ford, and UR Kees. most common genetic aberration in infant WA, and the Whiteman Fellowship. ALL involves the mixed lineage leukaemia to determine the nature of these karyotypic Our recent studies in ALL cell lines have (MLL) gene, located on chromosome 11q23, abnormalities. These studies have shown revealed that the novel agent flavopiridol (FP) which is involved in up to 80% of cases. Most that in this case BRD4 and a region of 19p is highly effective in steroid-resistant cells. chromosomal rearrangements are associated Carcinomas were cryptically inserted into chromosome When administered in a pharmacologically- with leukaemias of a particular lineage. 15, co-localising next to the NUT gene. To derived schedule in adults and children, FP has Novel BRD4 translocation in However, 11q23 rearrangements are unique further characterise this carcinoma we been shown to achieve marked clinical efficacy undifferentiated carcinoma in that they occur in both ALL and acute used RNA sequencing to investigate the in refractory haematopoietic malignancies, myeloid leukaemia (AML), hence the term K Thompson, AH Beesley and UR Kees, in transcriptome. We identified that there is a including acute leukaemias and relapsed high- mixed lineage leukaemia. Since discovery collaboration with E Baker and A Murch, King BRD4-NUT fusion gene in the PER-624 cells risk chronic lymphoblastic leukaemia (CLL). of the MLL gene in 1992, its recombinome Edward Memorial Hospital for Women, Perth, but that it has a novel breakpoint which is Liposomes containing FP have recently been has been the subject of significant scientific and AK Charles and M Phillipps, Princess different to the standard NMC cases. We have produced and this formulation has achieved research. There have been > 100 translocation Margaret Hospital, Perth. confirmed this breakpoint using RT-PCR. This significantly improved pharmacokinetics. partner genes identified, many of which have novel fusion breakpoint, coupled with the However, the evidence that development of been characterized at the molecular level. Five years ago a 16-year old female patient FISH data suggests that there is alternative steroid resistance in ALL contributes to relapse MLL-EPS15/AF1P, t(1;11)(p32;q23) is a rare was diagnosed at Princess Margaret Hospital splicing occurring at the RNA level. We are makes it highly likely that clinical resistance to fusion, with a paucity of cases reported in (PMH) with a poorly differentiated lung currently undertaking genomic sequencing of FP would also ultimately evolve, as has been the literature. We have recently reported carcinoma which had the hallmarks of a the PER-403 and PER-624 cell lines to identify the case for the drug Gleevec. The objectives infant monozygotic twins harbouring the rare but almost invariably fatal carcinoma the exact nature of the genomic breakpoints of this study are to study the biological actions t(1;11)(p32;q23) translocation which we are arising in the midline organs, known as a NUT in these cells. We also conducted a review of of FP and to derive FP-resistant ALL cell lines

24 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 with which to investigate potential mechanisms survivors often face serious long-term quality of and SHH-driven MB and CD133+ NSCs, as well Interestingly, several of the over-expressed of FP-resistance before the phenomenon life issues that can profoundly affect patient and as between MB with neuronal differentiation miRNAs were predicted to target FOXO1A is known in the clinic. Over a period of two family. The relatively poor outlook for children characteristics and foetal germinal matrix cells. raising the possibility that down-regulation of years we have grown cell lines in increasing with brain tumours can be largely explained by Importantly, these data suggest that CD133+ FOXO1A expression in MB may be linked to concentrations of FP to generate clonal sublines the fact that the molecular pathogenesis of MB NSCs represent a valuable in vitro model system deregulated miRNA expression. We are currently with increased resistance to the drug. We is only partially understood. The main priority of for the study of the pathogenesis of SHH and investigating this possibility. Several deregulated now have 4 cell lines displaying approximately the brain tumour research program is to address WNT dependent MB and the development of miRNAs mapped to chromosome 14q32 and 2-fold higher resistance to FP than the parental this problem, and ultimately develop safer and more efficient subgroup-targeted treatment integrative analyses with inversely correlated lines. To establish the molecular basis for this more effective drugs and treatment strategies regimes in the future. predicted target genes revealed enrichment of change in phenotype, DNA extracted from that are urgently required. To achieve this goal pathways related to neuronal migration, nervous This work was supported by the NHMRC, these lines was analysed by Illumina TruSeq we are employing a variety of approaches to system development and cell proliferation. We Australia and the Children’s Leukaemia and Exome Sequencing (AGRF, Brisbane). This data investigate the molecular biology of MB. anticipate that ongoing research based on these Cancer Research Foundation, WA. is currently being analysed and is expected to data will rationalise our understanding of the A subset of MB is thought to arise from the reveal the first genetic clues to the evolution of fundamental molecular mechanisms that initiate deregulated proliferation of neural stem cells FP resistance. This knowledge will contribute and maintain the brain tumour phenotype. (NSCs) in the developing foetal brain. Hence, The characterisation of deregulated to the application of this novel therapy to the the development of MB is likely to be linked microRNA expression in paediatric brain This work was supported by the Raine Medical treatment of drug-resistant ALL. to the aberrant activity of signalling pathways tumours Research Foundation and John Lillie Fellowship This work is supported by the Children’s that control NSC proliferation, self-renewal (PBD). Leukaemia and Cancer Research Foundation, and differentiation. As part of our approach LA Genovesi, K Carter, NG Gottardo, and PB WA. to identifying the genes that regulate these Dallas in collaboration with KM Giles of the pathways, we have analysed chromosomal Western Australian Institute for Medical Development of a mouse ependymoma aberrations in a panel of paediatric brain Research, Perth. model tumour cell lines using cytogenetic analysis, MicroRNAs (miRNAs) are a large class of short Paediatric Brain Tumours H Hii, R Endersby, and NG Gottardo. representational difference analysis, and non-coding RNAs that regulate growth and The identification of deregulated microsatellite mapping. To further refine our development in eukaryotic cells. It is now clear Ependymoma is the third most common genes and pathways involved in the focus to specific regions of the human genome, that deregulated miRNA expression plays an brain tumour affecting children and remains pathogenesis of childhood embryonal we have correlated our extensive cytogenetic important role in the pathogenesis of many incurable in 40% of patients. As is often the tumours. data with the gene expression profiles of our different types of cancer, including adult brain case with paediatric brain tumours, survivors panel of brain tumour cell lines, primary tumour tumours. Recent data suggest that deregulated are frequently left with devastating long-term CM Bertram, LA Genovesi, UR Kees, JP McGlade, specimens, and human NSCs generated using miRNA expression may also play a significant neuro-cognitive sequelae. There is an urgent R Endersby, NG Gottardo, and PB Dallas. Affymetrix HG-U133A microarrays. Cross- role in the pathogenesis of MB. To address need for more effective and safer therapies. Medulloblastoma (MB) is the most common comparison of MB expression profiles with this issue in more detail we analysed the Transgenic mouse tumour models are important type of malignant paediatric brain tumour. normal NSCs and differentiated neural tissues expression levels of a panel of 754 miRNAs in tools to facilitate the study of tumour initiation Although the five-year survival rate for standard distinguished expression signatures associated MB specimens and neural stem cells (NSCs) and progression and are invaluable for pre- risk MB patients is encouraging, the prognosis with MB pathogenesis from signatures reflecting using qRT-PCR in a low-density array format. We clinical studies. A genome-wide analysis of remains dismal for those with recurrent or developmental variation. In addition, the study identified 33 differentially regulated miRNAs human ependymoma specimens demonstrated metastatic disease. In addition, brain tumour highlighted a genetic relationship between WNT in primary specimens relative to CD133+ NSCs. that all cerebral ependymomas exhibited

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 25 activated NOTCH signalling and INK4A/ARF CL Burchill, PB Dallas, R Endersby, and NG lomustine (CCNU) and temozolomide. These Novel peptide based drugs for deletion and that radial glia (RG) were the Gottardo. profiles will form the basis for combinatorial the treatment of sonic hedgehog putative cell of origin of ependymoma. Based studies using novel therapies. In addition, to dependent medulloblastoma Medulloblastoma, pineoblastoma and on these observations we generated the uncover novel genes and biological pathways ependymoma constitute the most common first mouse model of ependymoma, which involved in the development of resistance to PB Dallas, J Varano, NG Gottardo, R Endersby malignant brain tumours of childhood. Many phenocopies the human disease precisely these drugs, we are also correlating the drug in collaboration with N Milech, B Longville, R children with these tumours remain incurable by over-expressing NOTCH1 in RG cells sensitivity profiles with the gene expression Hopkins, Drug Discovery Group, TICHR and survivors are often left with devastating using the Blbp promoter and concurrently profiles. long-term side effects. Whilst many novel Medulloblastoma (MB) is the most common deleting Ink4a/Arf. However, the penetrance targeted anti-cancer agents have been We are currently assessing two novel malignant brain tumour in children, and a of ependymoma formation was low (1 to developed, to date only a small number have compounds, alone and in combination with leading cause of paediatric cancer related 5%) with a long latency (6 to 18 months), revealed clinical efficacy. One reason is due the chemotherapeutics above. The first mortality and morbidity. The disease is suggesting that additional genetic mutations to the lack of model systems that accurately compound, PF-00299804, developed by difficult to treat because there is a limited are required for ependymoma formation, reflect the disease in children. To address this Pfizer, irreversibly targets the ERBB signalling understanding of the molecular biology making the current model unsuitable issue, we have previously generated a panel of pathway, which has been shown to be over- of these tumours. This has hampered for pre-clinical testing. A more extensive unique cell lines, which have been cultured in expressed in the majority of medulloblastomas the development of drugs that target the genomic analysis using high resolution SNP the absence of drug selection, representative and ependymomas. The second compound, tumours specifically and minimise damage genotyping of a larger cohort of human of the various medulloblastoma subtypes and CDDO-IM, a synthetic triterpenoid has shown to normal tissues. Recently, drugs that target ependymoma specimens (n=230) revealed pineoblastoma. In addition, to more closely anti-tumorigenic activity in many cancer Smoothened (SMO), which is a component frequent focal deletions in the tumour model the tumours natural microenvironment, types and been demonstrated to inhibit the of the sonic hedgehog (SHH) pathway, have suppressor gene PTEN. Array comparative we have established an orthotopic xenograft anti-apoptotic protein CFLAR/FLIP. We found shown great promise for the treatment of MB. genomic hybridisation analysis of mouse mouse model system representative of the CFLAR/FLIP was significantly up-regulated However, there are drawbacks with these new ependymomas demonstrated numerous large various medulloblastoma subtypes and in medulloblastoma samples relative to SMO targeting drugs, particularly associated chromosomal copy number alterations (CAN) pineoblastoma. We have also acquired a their putative normal cellular counterpart, with the development of resistance. Phylomers as well as focal CAN, common to all tumours, transgenic mouse model of medulloblastoma, implicating this gene in the development are a unique type of peptide-based drug which included the Pten locus. Thus, to more the Smoothened (Smo) mouse, which of medulloblastoma. We speculate that developed by the drug discovery company faithfully recapitulate the human disease, develops spontaneous medulloblastoma due up-regulation of CFLAR in MB may be Phylogica, which may be particularly suitable we are modifying the existing ependymoma to the over-expression of the sonic-hedgehog responsible for resistance to cytotoxic agents for avoiding the drug resistance problem. mouse model by additionally deleting Pten. pathway component Smo. We hypothesise and that inhibition of CFLAR may sensitise Phylomers have major advantages over other The development of such a model will be an that the use of these models will accelerate cells to apoptosis. The best combinations, as types of drugs, including the capacity to target important tool to enhance our understanding the investigation of combined conventional determined from in vitro experiments, will large protein interfaces reducing the likelihood of the biology of this disease and facilitate pre- agents with targeted agents in clinical trials. then be assessed in our mouse model systems. of the development of resistance, and the clinical studies of novel targeted therapies. Using the MTT cell proliferation assay we relative ease by which Phylomers can be This work is supported by the John Lillie This work was supported by the John Lillie have determined the drug sensitivity profiles engineered to access and enter tumour cells. Fellowship (NGG), a grant from Pfizer Inc., Fellowship (NGG). for our panel of brain tumour cell lines to In animal models, Phylomers have been shown and a Princess Margaret Hospital Foundation conventional anti-cancer therapies currently to be effective for the treatment of burns, Testing novel therapies in childhood Translational Research Grant. used in the clinic for these tumours, including stroke and traumatic brain injury. The unique brain tumour models vincristine, cyclophosphamide, cisplatinum, characteristics of Phylomers may open new avenues for effective MB therapeutics that

26 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 have yet to be exploited. In addition, Phylomers Amy Samuels, PhD, BSc (Hons), status”. Curtin University of Technology, WA (Co- Nicholas Gottardo. Children’s Oncology Group. that are effective for the treatment of MB may supervisor Dr U Kees and Prof M Garlepp) Central Nervous System Tumour Committee Katherine Thompson, PhD, Bsc (Hons), also be effective for other types of cancer, Mathew Welch [Ph.D. 2011] “Molecular National including basal cell carcinomas, the majority of Meegan Howlett, PhD. mechanisms underlying aberrant expression of which are associated with altered SHH pathway Jacqueline McGlade, PhD. connective tissue growth factor in paediatric Ursula Kees, Member, The Cancer Council of activity. Phylomers that target SMO, and other pre-B cell acute lymphoblastic leukaemia.” Western Australia, Research and Scientific SHH pathway components, will be assessed for Mathew Welch, PhD Curtin University of Technology, WA (Co- Advisory Committee. their ability to block tumour growth in cancer Jennifer Bearfoot, PhD supervisors: Dr U Kees and Dr W. Greene) cell lines and animal models. Ultimately, this Amy Samuels, Deputy convenor ASMR WA approach may radically improve the outlook Alex Gout, PhD Cornelia Bertram [Ph.D. 2011] “A human Peter Dallas. Australasian Society for Stem Cell for MB patients by providing new treatment Jasmin Heng, BSc (Hons), neural stem cell model for the study of Research conference organising committee. options and opening up new avenues for drug medulloblastoma pathogenesis” University of Nicholas Gottardo. Medical Advisory Committee. development. Emannuela Ferrari, BSc (Hons) Western Australia (Co-supervisors: Dr P Dallas and Dr U Kees). The Cure Starts Now Foundation. This research is supported by the Telethon Hilary Hii, BSc (Hons) Nicholas Gottardo. Australian Children’s Cancer Adventurers. Laura Genovesi. [Ph.D. 2011] “Characterisation of deregulated miRNA expression in paediatric Trials (ACCT) Principal Investigator. Postgraduate Students brain tumours”. University of Western Australia. Nicholas Gottardo. Australian Children’s Clinical (Co-supervisors: Dr P Dallas and Dr K Carter, and Staff and Students Laurence Cheung, BSc (Hons), PhD candidate Trials (ACCT) group. Board member and Principal Dr K Giles, WAIMR) Investigator for Western Australia. Head of Division Ashley Schoof, BSc (Hons), PhD candidate Raelene Endersby. Australian Early-Mid Career Rishi Kotecha, MB ChB(Hons), MRCPCH, PhD Ursula R Kees PhD Researchers Forum, Australian Academy of candidate Adjunct Professor University of Western Awards Science. Australia Julia Wells, BSc (Hons), PhD candidate Alex Beesley, Children’s Leukaemia and Cancer Consultant, Department Haematology/Oncology, Chantel Burchill, BSc (Hons), PhD candidate Research Foundation (CLCRF) Travel Grant Princess Margaret Hospital for Children $4000. Invited Presentations

Raelene Endersby. Professional Scientists Poster Kees UR. 2011 OMICS Meet Cell Biology, Research Support Research Staff Award, Combined Biological Sciences Meeting, Alpbach, Austria. May 2011 Profiling Drug August 2011 Stewart Cattach Resistance in a Mouse Model of Leukaemia Alex H Beesley, PhD Relapse Peter B Dallas, PhD Beesley AH (Invited Speaker 2011). High- Nicholas Gottardo, MB ChB FRACP (Paeds.) PhD, Theses passed External Committees throughput RNAi screening to dissect the molecular profile of NUT-Midline carcinoma. International Raelene Endersby, PhD. Misty-Lee Palmer [Ph.D. 2011] “Paediatric acute Perth Cancer Club, WAIMR. lymphoblastic leukaemia cell lines to model Jette Ford, BApplSc, Grad Dip Comp, Ursula Kees, Chair COG-B969 Study Committee Dallas PB. Cancer stem cells and brain tumours. clinical drug resistance and investigate MLL (Children’s Oncology Group), Arcadia, CA USA. Stem cells and their clinical applications: now

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 27 and the future. NSW stem cell network Endersby R. Use of a novel mouse glioma PMH Foundation Translational Research Leukaemia Biology Program, Children’s Cancer workshop. QEII Medical Centre. Perth, WA. Oct model for preclinical drug evaluation. Grant. NG Gottardo and PB Dallas. Targeting Institute Australia for Medical Research, 2011. Australian Children’s Clinical Trials Symposium. apoptosis pathways in medulloblastoma. Sydney (Prof R Lock; NHMRC Project Grants Melbourne, Vic. June 2011. $48401 ID513765 and ID1011499 collaboration with Dallas PB. Novel peptide based drugs for the Alex Beesley and Ursula Kees) treatment of sonic hedgehog dependent Pfizer Investigator initiated grant. NG Gottardo, medulloblastoma. Australian Children’s Clinical PB Dallas, DM Ashley, TG Johns. A preclinical ACRF Drug Discovery Centre for Childhood Trials Symposium. Melbourne, Vic. June 2011. Research Funding awarded study of the effects of the pan-Her inhibitor Cancer, Children’s Cancer Institute Australia PF-00299804 (PF) on the growth of brain for Medical Research, Sydney (Dr G. Arndt Gottardo NG. Testing novel therapies using (recent) tumour cells. $60400 collaboration with Alex Beesley and Ursula paediatric brain tumour models Australasian Kees) Biospecimen Network Association Annual NHMRC Project Grant APP1011499 (2010): Meeting. Perth, WA, Australia. Nov 2011. ‘Targeting drug-resistance in childhood Department of Paediatric and Adolescent leukaemia’ (Kees UR, Lock RB, Beesley AH, Haematology and Oncology, Princess Margaret Gottardo NG. The Children’s Oncology Group: ACTIVE collaborations $626,732 over 3 years). Hospital for Children (Prof C. Cole, Dr M A blueprint for biobanking from clinical trials?. Children’s Oncology Group, Arcadia CA, USA Phillips and Dr A Charles; NHMRC Project Clinical Oncological Society of Australia (COSA) NHMRC Project Grant APP1007586 (2010): (Prof S Hunger and Dr S Winter collaboration Grant ID 1007586 collaboration with Alex ASM, Biobanking workshop. Perth. WA. Nov ‘The role of connective tissue growth factor with Alex Beesley and Ursula Kees) Beesley and Ursula Kees) 2011. in the pathobiology of lymphoid tumours and response to therapy’ (Kees, UR, Beesley AH, St Jude Children’s Research Hospital, Memphis Lead Discovery Centre GmbH, Dortmund, Gottardo NG. Testing novel therapies using Charles AK, $601,732 over 3 years). TN, USA (Prof C Mullighan collaboration with Germany (NMC Carcinoma Project paediatric brain tumour models. Cooperative Ursula Kees) collaboration with Alex Beesley and Ursula Trials Group for Neuro-oncology (COGNO) Children’s Leukaemia and Cancer Research Kees) Annual Scientific Meeting. Sydney. NSW. Aug Foundation (CLCRF) Research Fellowship Walter and Eliza Hall Institute of Medical 2011. (2010): ‘Targeting therapy and disease Research, Melbourne (Prof W Alexander and Novartis Pharma AG, Basel, Switzerland (NMC outcomes in paediatric cancer’ (Beesley AH, 3 Dr R Dickins collaboration with Ursula Kees) Carcinoma Project collaboration with Alex Gottardo NG. Tumour Banking, a Clinicians years). Beesley and Ursula Kees) Perspective. National Paediatric Tumour Children’s Research Institute, Columbus OH, Banking Network Inaugural meeting. NHMRC. NG Gottardo, R Endersby, U Kees. USA (Prof D Brigstock collaboration with Ursula GlaxoSmithKline R&D, Brentford, UK (NMC Melbourne. Vic. Feb 2011. 2012-2014. Testing novel therapies using Kees) Carcinoma Project collaboration with Alex paediatric brain tumour models 2012-2014. Cancer Genome Project, Wellcome Trust Beesley and Ursula Kees) Gottardo NG. Testing novel therapies using $371,175.00 paediatric brain tumour models. Australian Sanger Institute, Hinxton, UK (Dr M Garnett Women and Brigham’s Hospital, Boston Children’s Cancer Trials (ACCT) Symposium. University of Western Australia Near Miss collaboration with Alex Beesley and Ursula (Dr Christopher French, Pathologist and Australian Children’s Clinical Trials Symposium. Safety Net Grant. NG Gottardo, 2011; $70,000 Kees) International Expert in NUT-Midline Carcinoma Melbourne, Vic. June 2011. Cancer Council of Western Australia. PB Dallas, Experimental Therapeutics Program, Children’s collaboration with Alex Beesley and Ursula Kees) Endersby R. Developing novel mouse models NG Gottardo, K Carter, K Giles. Project Grant Cancer Institute Australia for Medical for paediatric ependymoma. University of 1006115. 2011-2012. The role of deregulated Research, Sydney (Prof M Haber and Prof M Cytogenetics Department, King Edwards WA, Department of Pathology and Laboratory microRNA expression in the pathogenesis of Norris collaboration with Alex Beesley and Memorial Hospital, Perth (Dr A Murch Medicine. Perth, WA, Nov 2011. medulloblastoma. $80000. Ursula Kees) collaboration with Alex Beesley and Ursula

28 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Kees) Western Australian Institute of Medical Research, Perth (Prof Peter Leedman and Dr Keith Giles; miRNAs and cancer project collaboration with Peter Dallas, Raelene Endersby and Nicholas Gottardo) Monash Institute for Medical Research, Melbourne. (Prof Terry Johns; New drugs for the treatment of paediatric brain tumours collaboration with Nicholas Gottardo, Raelene Endersby and Peter Dallas) Pfizer Inc, New York, USA (New drugs for the treatment of paediatric brain tumours collaboration with Nicholas Gottardo, Raelene Endersby and Peter Dallas)

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 29 diabetes and obesity

Overview benefits of incorporating a 12 week combined Diabetes Database, and Western Australian with knowledge our which patients may be at cardio and resistance training on microvascular Midwives’ Notification System . The study higher risk of severe hypoglycemia. The team conducts research in collaboration and macrovascular health, of adolescents with population will be all children diagnosed with The aims of this study are: with the Department of Endocrinology Type 2 diabetes. The Bioenteric Intragastric childhood-onset diabetes before the age Report the incidence of severe hypoglycemia and Diabetes in Princess Margaret Hospital Balloon study for weight management and of 15 years, who were resident in Western over the past decade in the WA childhood T1D for Children Perth, the School of Sports health improvement in obese adolescents Australia at the time of diagnosis. The study onset cohort Science and Exercise Health, Psychology, is now almost half-way though recruitment. period will be from January 1985 to December University of Western Australia; the Western Studies examining approaches to prevent 2010. There are over 1500 cases in the Calculate the relative risk for the association Australian Institute for Medical Research, hypoglycamia during exercise in patients with diabetes register at Princess Margaret Hospital of demographic, lifestyle and management the Juvenile Diabetes Research Foundation Type 1 Diabetes are also ongoing. that meet these inclusion criteria. Cases in factors (including but not limited too age, and collaborators from diabetes research the Western Australian Children’s Diabetes length of diagnosis, BMI, insulin regime) with centres interstate and overseas Our research Database at Princess Margaret Hospital the incidence of severe hypoglycemia. into Type 1 diabetes, childhood onset Type Type 1 Diabetes Epidemiology will be linked to records in the Western 2 diabetes and obesity aims to improve the Australian Midwives’ Notification System lives of children and adolescents affected Epidemiology of childhood-onset type using the unique personal identification Investigating mortality rates and the by these conditions. Our research addresses 1 diabetes in Western Australia number assigned to individuals in the Western incidence and risk factors of diabetes relevant clinical questions and encompasses Australian Health Department databases. complications and co-morbidities epidemiology, clinical investigations, clinical Liz Davis, Aveni Haynes, Matt Cooper, Carol during early adult life in a population trials, new technology in disease management Bower based childhood onset diabetes Epidemiology of hypoglycaemia in cohort and prevention studies. Funding Source: Department of Endocrinology childhood-onset diabetes in Western In the year 2011, type 1 diabetes research has & Diabetes, PMH Australia Liz Davis, Matt Cooper, Aveni Haynes, Tim seen the commencement of a series of clinical The objectives of this study are: Jones trials with the ultimate aim of implementing Tim Jones, Liz Davis, Matt Cooper Funding Source: Diabetes Research Fund the closed-loop system of managing Type 1 To study the epidemiology of childhood Funding Source: Internal Funds diabetes using pump therapy. The year 2011 onset diabetes in children aged 0-16 years in The education and treatment regimes for has also seen the culmination of a series of Western Australia from 1985 onwards. Hypoglycemia and the subsequent effects children with Type 1 Diabetes (T1D) are clinical trials in collaboration with AIMedics To test for differences in incidence rates of hypoglycemia remain the primary fear constantly evolving, and the introduction Pty Ltd, contributing to the development of a by year of diagnosis, age of diagnosis, sex, for children and their parents in adequately of and improvements to new technologies non-invasive monitoring system (HypoMon) month of diagnosis, birth month and place of managing the treatment of Type 1 Diabetes adds to the complexity of the management for the detection of nocturnal hypoglycaemia. residence at diagnosis. (T1D). It is reported that over the past of T1D. Studies have been done in the past The Adolescent type 1 diabetes Cardio- decade the overall incidence of severe to provide insight into the complications renal Intervention Trial investigating the To identify potential antenatal and perinatal hypoglycemic events has declined relative and co-morbidities in adulthood for this use of statin and ace-inhibitor to prevent antecedents to childhood-onset diabetes e.g. to the previous decade. In this study we with childhood onset type 1 diabetes, but diabetes complications is well underway, and birth weight, gestational age, birth order and investigate the demographic, lifestyle and little is known about how the changes to recruitment to this study closes June 2012. maternal age. diabetes management factors associated diabetes management affect the incidence of these complications and co-morbidities, as The group has also commenced a trial These aims will be achieved by means of data with the incidence of severe hypoglycemia this is something that can only be revealed investigating the immediate and sustained linkage using the Western Australian Children’s to provide clinicians and diabetes educators

30 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 with time. This project will use the Western To examine the impact of risk factors observed genetic markers associated with T1D. The primary outcome of this prospective cohort Australian Data Linkage System (WADLS) to during childhood on the incidence of diabetes study is the development of diabetes as defined 2. To examine the accuracy of TrialNet measures provide novel information of the incidence complications, co-morbidities and cause of by the American Diabetes Association (ADA) in predicting future T1D. and relative risk of T1D co-morbidities and death in early adulthood (<40 years) in a based on glucose testing, or the presence of mortality during early adulthood in a modern childhood onset T1D population-based cohort. 3. To characterize the progression of symptoms and unequivocal hyperglycaemia. clinical setting. The primary source of the study immunologic abnormalities in the development Participant eligibility: (1) Having a first degree population is the Western Australian Children’s of T1D by serially studying islet autoantibodies relative (parent, sibling, child) with T1D, and Diabetes Database. The WADLS contains data TrialNet: Pathway to Prevention and immune mechanistic studies. aged 1 – 45 years; (2) having a second and third uploaded from the Hospital Morbidity Data 4. To characterize the progression of metabolic degree relative (nieces, nephews, aunts, uncles, Collection; the Emergency Department Data Tim Jones, Liz Davis, Julie Dart, Heather Roby; decompensation in the development of T1D grandparent, cousins, half-siblings) with T1D and Collection; the Mental Health Information Nirubasini Paramalingam; Adam Retterath by serially studying insulin, C-peptide, other aged 1 – 20 years. System; the Birth, Death and Marriages Registry Funding Source: The National Institute islet hormones, HbA1c and glucose levels, and the Western Australia Electoral Commission of Diabetes and Digestive and Kidney and to identify immunologic and other factors records. The WADLS will enable the selection Diseases (NIDDK), the National Institute of associated with this decompensation. Early environmental determinants of matched controls from the birth registry. All Allergy and Infectious Diseases (NIAID), the of pancreatic islet autoimmunity: a subjects in WA diagnosed with T1D prior to age 5. To determine the incidence of severe acute National Institute of Child Health and Human pregnancy to early life cohort study in 16 who were 18 years or older at 30th June 2010 metabolic decompensation as the initial clinical Development (NICHD), the National Center children at risk of type 1 diabetes (T1D) (n=1,376) are considered eligible for entry into for Research Resources (NCRR), the Juvenile presentation in individuals who have been this analysis. Diabetes Research Foundation International identified as being at increased risk for T1D. Tim Jones, Liz Davis, Niru Paramalingam (JDRF), and the American Diabetes Association 6. To identify individuals who qualify for TrialNet Funding Source: NHMRC 1025082 The aims of this study are: (ADA) T1D prevention trials. This is a multi-centre study involving researchers To identify the incidence of diabetes The overall objective of this multi-centre 7. To accrue additional information about in South Australia, Victoria, New South Wales, complications and co-morbidities seen in early international study is to perform baseline and immunologic and metabolic factors related Western Australia and Queensland. The study adulthood (<40 years) in a childhood onset T1D repeat assessments over time of the metabolic to the pathogenesis of T1D and validate new is coordinated by Prof Jenny Couper in South population-based cohort. and immunologic status of individuals at risk methods or tests that mark disease progression Australia. To calculate the risk (relative to age and for type 1 diabetes (T1D). This is in order to:(a) or response to therapy. This prospective cohort follows children who are sex matched controls) for incidence of characterize their risk for developing T1D and 8. To accrue additional information about at risk of developing T1D from the gestational diabetes complications and co-morbidities identify subjects eligible for prevention trials, (b) genomic markers associated with risk for the period into the first 3 years of life. Pregnant in early adulthood (<40 years) associated describe the pathogenic evolution of T1D, and development of T1D. women who have type 1 diabetes or where with childhood onset T1D in a population- (c) increase the understanding of the pathogenic their unborn child has a first degree relative based cohort. factors involved in the development of T1D. 9. For those participants who participated in with T1D are recruited to the study. The infants The specific objectives of this study are: the DPT-1 study, to examine associations of To compare the all-cause mortality rate, and characteristics (e.g. demographics, immunologic, are monitored for genotype, weight gain, cause of death in early adulthood (<40 years) in 1. To determine the risk for the occurrence metabolic, etc.) assessed during the DPT-1 study insulin sensitivity, changes in the metabolome a childhood onset T1D population-based cohort of T1D according to glucose tolerance tests, with characteristics and outcomes assessed in and microbiome, vitamin D and omega 3 fatty to general population age and sex matched C-peptide levels, islet autoantibodies, HbA1c TrialNet. acid status, and the timing and frequency of controls. levels, markers of cell-mediated immunity, and viral infections. This is in order to determine

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 31 the relationship between weight gain, This study aims to measure changes in diabetes who are on multiple daily injections particularly for patients who have lost some of insulin sensitivity, nutritional status and viral molecular systems at the time of onset of or insulin pump therapy. The study design is the symptoms that would normally alert them infection, and the development of persistent childhood T1D, and relate these changes a randomised 4 armed cross-over trial, where to a low blood glucose level. In a subgroup islet autoimmunity in these children. to the patients’ genotype for known T1D the glycaemic fluctuations in the 180min of 16 adolescents, we will also look at their risk genes. The systems of interest are gene following the meal is traced using a continuous hormone and symptom responses during The primary outcome measure is islet expression (transcriptome) in circulating WBCs sub-cutaneous glucose monitoring system. hypoglycaemia. autoimmunity defined as persistent elevation and plasma protein composition (the plasma investigating the of > 1 islet autoantibodies on consecutive 6 Patients aged between 4 years and 50 years proteome) circulating WBC IFNγ production. monthly tests, including the most recent. This 58 children between the two participating with T1D on insulin pump therapy with will exclude transient, low titre autoantibodies. The approach of correlating gene expression sites having the following inclusion criteria, impaired awareness of hypoglycaemia will be and underlying genetic variation has recently will be recruited: aged- 7-18 years inclusive; eligible to participate. been termed “systems genetics”. The approach on 4 or more insulin injections per day, or on Patients will be randomised to either the Identifying molecular signatures of has been pioneered in rodent models, but insulin pump therapy; diagnosed with type Paradigm Veo (low glucose suspend feature type 1 diabetes has not been applied to proteomics, diabetes 1 diabetes, at least over 6 months ago; with and continuous glucose monitoring) or research or to research in humans. HbA1c ≤ 8.0% at last clinic visit. Exclusion continue on their standard pump (no low Prof Grant Morahan, Tim Jones, Liz Davis, criteria are: Coeliac disease; Hyperlipidaemia; The strength of this approach lies in the lack glucose suspend capability and no continuous Heather Roby history of poor compliance or attendance; of assumptions that are taken into the data glucose monitoring). Unable to commit to full study protocol. Funding Source: NHMRC 305500; Diabetes gathering process. Hypotheses are generated Research Foundation of WA after data gathering and analysis. These hypotheses can then be validated using Effect of exercise intensity on the rate We aim to identify genes and genetic Low glucose suspend study pathways associated with the autoimmune alternate “hypothesis-testing” experimental of glucose administration required destruction of beta cells, and characterise the designs. Tim Jones, Trang Ly, Jennifer Nicholas, Adam to maintain stable glycaemia when transcriptomic and proteomic changes of the Retterath plasma insulin is at basal levels T1D process. This will potentially in individuals with type 1 diabetes Funding Source: Juvenile Diabetes Research mellitus increase our understanding of the Type 1 Diabetes Management Foundation pathophysiology of T1D; Vinutha Shetty, Paul Fournier, Tim Jones, How do high protein and/or high fat A new pump has just been released, the Liz Davis, Nirubasini Paramalingam, Adam allow us to more finely stratify people most at meals affect postprandial glycaemic Paradigm Veo pump. This pump has the Retterath, Heather Roby; Kaitie McNamara risk of developing T1D; control in children using intensive new feature of detecting low glucose levels insulin therapy? (hypoglycaemia) and automatically switching Funding Source: Pfizer APEC Research Grant; discover biomarkers of the activity of the T1D off insulin infusion for 2 hours if the blood PMH Foundation Grant process, which may allow clinical intervention Liz Davis; Megan Evans glucose level is low. This will be helpful in the “honeymoon period” before all beta cell Regular exercise provides a number of well in reducing the severity of an episode of mass is lost. Funding Source: Pfizer APEC Research Grant documented health benefits for individuals hypoglycaemia. with type 1 diabetes. Unfortunately for insulin 100 patients presenting to PMH with onset This dual-site study is investigating the effect The aim of this study is to see if using the treated type 1 diabetes individuals, particularly of T1D will be recruited to the study. Blood of fat and protein content of a standardized Paradigm Veo pump for a period of 6months those in good glycaemic control, exercise samples will be collected at diagnosis and at carbohydrate meal, on the post-prandial can reduce the rate of severe hypoglycaemia, increases the risk of severe hypoglycaemia. the 3-18 month follow-up clinic. glycaemic response in children with type 1

32 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 This increased risk of hypoglycaemia occurs not Type 1 Diabetes Technological conditions we will generate such data. In This is an international clinical trial with the only with exercising, but also for several hours addition, although previous studies have utilized primary objectives of determining whether during recovery. One approach to reduce the Advances increased basal insulin delivery as a method intervention with Angiotensin Converting risk of hypoglycaemia associated with exercise is of inducing hypoglycaemia, in our study we Enzyme Inhibitors (ACEI), Statins, or a Predictive low glucose suspend study – to reduce insulin dose before exercise. Another will utilize increased bolus insulin delivery-the combination of both, when compared with Stage 1 is to consume extra carbohydrates during and/ scenario more likely to be encountered in a real- placebo, will: (1) reduce albumin excretion after exercise, but the current guidelines for Michael O’Grady; Trang Ly; Liz Davis; Tim Jones, life setting. as assessed by six monthly measurement treatment of hypoglycaemia do not provide of albumin/creatinine ratio (ACR) in 3 early Nirubasini Paramalingam; Julie Dart; Heather Study participants will be: adolescents and practical practical information about the amount morning urines; (2) reduce the incidence of Roby; Adam Retterath young adults age from 12 to 26 years with type of CHO necessary to prevent hypoglycaemia microalbuminuria (MA) (ACR log mean > 3.5 mg/ 1 diabetes; duration of diabetes > 1 year and on during exercise. Funding Source: JDRF mmol (males) or > 4 mg/mmol treatment with an insulin pump; HbA1c < 8.5% This proposed study aims to determine more The availability of continuous glucose monitoring (females) in 2 out of 3 urines) at the end of the The aims of this study are: (1)To determine precisely the amount of glucose intake that systems is an important advancement in the study period; (3) reduce the incidence of MA the blood glucose profile with a predictive is required to prevent hypoglycaemia during pursuit of a fully automated closed-loop system. during the six month run out period following low glucose suspend (PLGS) algorithm exercise; under basal insulin conditions. In An initial stage in the development of such a the completion of intervention phase. versus no insulin suspension (control) addition, we will investigate how glucose system has been the availability of a system that following hypoglycemia induced by a bolus This study will aim to recruit 500 adolescents requirements is affected by exercise intensity automatically suspends basal insulin delivery of subcutaneous insulin; (2)To determine the with the following criteria: adolescents aged and how this relationship responds to for a pre-determined period if patients do not blood glucose profile with a PLGS algorithm 11-16years; with type 1 diabetes of >1year confounding factors such as prevailing insulin respond to alarms. Whilst this is a major step versus no insulin suspension (control) following duration; identified as being at high risk for the and glucose levels. This study will involve forward, the capacity to suspend insulin delivery hypoglycemia induced by moderate intensity development of DN and CVD as predicted by one group ten healthy, active type 1 diabetic when impending hypoglycaemia is predicted exercise; (3) To analyse the pattern of blood albumin excretion in the upper tertile after individuals (male and female) aged between 13 offers the additional advantage of reducing the glucose and ketone levels following pump and 25 years old. All participants will undergo actual time spent hypoglycaemic. If effective appropriate adjustment for age, sex, age at suspension in both scenarios, and use these four testing sessions involving cycling on a and safe this system is likely to reduce the diagnosis and duration of disease. Recruitment to assist with determination of parameters for stationery bike at four different workloads – burden of diabetes care as well as allow more closes in June 2012. It is a four-armed insulin pump resumption. 35%, 50%, 65% and 80% VO2 Peak. intensive attempts to improve glycaemic control. randomised clinical trial involving: (1) Quinapril: starting dose 5mg increased to 10mg daily Primary outcome : Precise estimate of the This study will aim to test a novel algorithm after 2 weeks ,(2) Atorvastatin, 10mg daily, (3) glucose requirements to maintain stable glucose for hypoglycemia prediction, under conditions Type 1 Diabetes Complications Quinapril + Atorvastatin, (4) Placebo. levels over a range of exercise intensities under of excess insulin and moderate intensity exercise, to determine if the response of insulin basal insulin condition. Adolescent type 1 diabetes cardio-renal suspension to these different conditions which Intervention trial Secondary outcome : Determining the extent predispose hypoglycaemia differs. Crucial to the Aussi-AdDIT to which changes in glucose requirements effectiveness of a preventive system and the Tim Jones; Liz Davis, Barbara Sheil; Julie Kendall; result from changes in glucose production and Tim Jones; Liz Davis, Julie Kendall; Julie Dart; prevention of post suspend hyperglycemia will Heather Roby; Trang Ly; Vinutha Shetty; Michael utilisation rates. Adam Retterath be a complimentary algorithm that activates O’Grady; Adam Retterath; Jennifer Nicholas the resumption of insulin delivery. By studying Funding Source: NHMRC Grant #632521 Funding Source: JDRF; BHF post suspend glucose values under controlled This multi-centre study is investigating the

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 33 changes in retinopathy, aortic intima media Funding Source: PMH Foundation; APEG grant the hypothesis that if there are cognitive the pancreas. This time provides a potential thickness (aIMT) and heart rate variability deficits associated with T1DM, they are opportunity to prevent further destruction which are indicators of macrovascular disease more likely to be found in measures of fluid of the beta cells and thus the onset of type 1 and autonomic neuropathy respectively; which Previous research has indicated that children intelligence and executive (frontal) functions. diabetes. are complications of type 1 diabetes. with type 1 diabetes mellitus (T1DM) may This study is run in collaboration with the INITII is recruiting relatives of people with type experience deficits in their neurocognitive Neurocognitive Development Unit at the The study’s aims are: (1)To determine whether 1 diabetes. Relatives have an increased risk of development compared with healthy children. School of Psychology, UWA. adolescents with T1DM found to be at high developing diabetes, which can be assessed Whilst the impact that T1DM has on the risk of microalbuminuria have evidence of by a simple blood test. Only 2% of the people developing brain remains controversial, accelerated atherosclerosis, retinopathy tested will be considered at high risk of evidence suggests that these deficits may and autonomic neuropathy as compared to developing diabetes and be eligible to enter reflect the occurrence of episodes of severe Type 1 Diabetes Prevention adolescents at lower risk of microalbuminuria. this trial. Testing for this study is free and can hypoglycaemia. Previous studies have found (2) To determine whether ACE inhibition Intranasal Insulin Trial II be done either at PMH or at the local blood a link between hypoglycaemia history and and or statin therapy during puberty will collection centre. cognitive ability on a number of cognitive Liz Davis; Tim Jones, Julie Kendall; Trang Ly; slow the progression of microvascular and domains including verbal IQ, verbal memory Vinutha Shetty; Michael O’Grady; Nirubasini macrovascular disease in T1DM short-term memory and attention. These Paramalingam; Jacqueline Curran; Adam Oral Insulin Trial The study population is adolescents aged findings are not always replicated and, as yet, Retterath 11.0y to 16.9y, and with type 1 diabetes there is no consensus as to how episodes of Funding Source: NHMRC; JDRF Tim Jones; Liz Davis, Julie Dart; Heather Roby; mellitus; screened as being at low risk or severe hypoglycaemia affect the developing Nirubasini Paramalingam; Adam Retterath high risk for developing diabetic nephropathy brain. Our previous study however indicated The Type 1 Diabetes Prevention Trial, also and cardiovascular disease. Throughout that performance on tasks of executive known as the Intranasal Insulin Trial (INIT II), is Funding Source: NIDDK; NIAID; NICHD; NCRR; Australia 370 adolescents deemed at high function and fluid intelligence was significantly part of a coordinated global effort to develop JDRF; ADA and 200 adolescents deemed at low in the poorer in individuals with T1DM, and there is a a vaccine for type 1 diabetes. The trial, The TrialNet Oral Insulin Diabetes Prevention Microalbuminuria Screening Study. The study suggestion of associated differences in frontal which began in 2006, is jointly funded by the Study is being conducted internationally, to duration functioning as indicated by ERP (event-related National Health and Medical Research Council see if giving insulin by mouth (in a capsule) will potential) studies. (NHMRC) and the Juvenile Diabetes Research Is 6 years, and includes a two year recruitment delay or prevent T1DM in people at increased Foundation, through the Diabetes Vaccine period and a 4year follow-up period. The study The main aim of the Neurocognitive Outcomes risk of developing diabetes. Development Centre. endpoints are changes in retinal images, aIMT study is to conduct an analysis of children with Participants attend the hospital for an initial, a and heart rate variability measures, after 4 TIDM’s cognitive profile at an age in which If successful, this vaccine could prevent type baseline (Randomization), a 3-month follow- years duration from baseline. both cognition and cortical development 1 diabetes and the need for daily insulin up visit and then follow-up visits 6-monthly are still maturing (7-11 years). This will be injections in people at risk. Over the past 5 for the rest of the study. At each study visit, achieved through the use of neurocognitive years, over 6,500 people have been screened participants are asked questions about their Neurocognitive outcomes of children assessment, electroencephalogram (EEG) in Australia. Before someone is diagnosed health, activity, diet and about diabetes in with type 1 diabetes mellitus technology and magnetic resonance imaging with diabetes, there is a period of time, often their family and will also have a physical (MRI) screens. We are also analysing many years, when there are no symptoms, examination and blood tests. At the Baseline Tim Jones; Mike Anderson; Liz Davis, Kaitie the cognitive profile of a healthy sibling but the body’s immune system has already Visit, participants are randomly assigned to McNamara; Nooshi comparison group. In particular we will test begun attacking the insulin-producing cells in receive either active treatment with insulin

34 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 capsule (7.5 mg insulin) or an inactive dummy blood glucose control within the first few years to sustainable weight loss and improved health Adjustable Gastric Banding or bypass surgery. capsule called placebo. of diagnosis. One way of improving blood in children and adolescents participating in the Likewise there are no reliable predictors to glucose control is through exercise. Department’s lifestyle intervention programs, determine which adolescents will have a good and participants in the trial of a new weight loss response from surgery, there is no available risk We are studying how exercise in young people device. benefits data. Type 2 Diabetes Epidemiology with T2DM, and obese young people at risk of developing type 2 diabetes, affects: (1) The A less invasive option is the gastric balloon, Epidemiology of T2DM in childhood and function of small and large blood vessel, and achieving a temporary restriction of food intake associated disease complications whether an exercise training program can Intervention in combination with lifestyle and behavioural improve function, (2) How well the body uses changes the aim being to achieve long term Liz Davis; Rachelle kalic insulin, and (3) Whether exercise training can Bioenteric Intragastric Balloon weight loss. This has been achieved in adults Funding Source: Internal improve blood glucose control. with the use of a gastric balloon that floats in Jacqueline Curran; Liz Davis; Colin Sherrington; the stomach giving the individual the sensation This study is investigating the incidence of Tim Jones, Rachelle Kalic; Luise Russel; Deanna of continued satiety, reducing their requirement childhood Type 2 Diabetes in the Western Messina; Anna Tremayne Australian community, and the incidence of and desire for food. While there have been large Obesity Funding Source:: NHMRC # 634308; Pfizer APEC diabetes-related complications and related studies on the successful use of the BIB in obese Grant cardiovascular risk factors such as hypertension Liz Davis adults. Only one small (n=5) retrospective study and hyperlipidaemia in that population Weight loss treatments for adolescents who has been performed in adolescents with the The 2007-2008 Australian National Health use of the BIB. The purpose of this randomized Survey found that 25.1% of children aged 5-17 are overweight or obese include lifestyle changes that includes diet, exercise, parental clinical trial is to determine whether the use of years in Western Australia are overweight or the BIB aids weight loss in obese adolescents. Type 2 Diabetes Management obese (ABS, 2011). The Obesity Research Team involvement, reinforcement, stimulus control at Telethon Institute for Child Health Research and self-monitoring as targeted interventions. Specifically, that: Can exercise training Improve health in These lifestyle interventions in children have together with the Department of Endocrinology 1.The BIB aids weight loss in obese adolescent young people with type 2 diabetes? found to result in a mean sustainable excess and Diabetes at the Princess Margaret Hospital patients. for Children, are researching the causes of weight loss of 8%. Pharmacotherapy has a very Liz Davis; Danny Green; Louise Naylor, Norhaida obesity and interventions to combat obesity. limited role in the treatment of adolescent 2.The BIB will be well tolerated in obese Mohd Yusuf; Nirubasini Paramalingam; Mary obesity, compliance is often poor and drug adolescent patients. Abraham; Rachelle Kalic Investigators are collecting DNA and serum to choices are limited. investigate the genetic factors and biomarkers 3.The BIB will reduce the severity and frequency Funding Source: Pfizer APEC grant # WS1836718 that are potential risk factors for weight gain in Studies of bariatric surgery highlight the of obesity related co-morbidities in obese Over the last few years, T2DM and obesity is children and adolescents, the development of potential weight loss that can be achieved in adolescents. obese patients with the subsequent improved becoming more common in young people. obesity-related complications, and protective 50 adolescent patients (male and female), health, complication rates unfortunately remain Individuals with T2DM and obesity often have factors against these complications. By collecting age 12-17 years attending Princess Margaret high. In obese adolescents who fail to lose high blood glucose, the effects of which can information on the development of obesity and Hospital (PMH) will recruited to the study. cause other major health problems such as successful interventions, investigators hope to weight with lifestyle alone surgery is increasingly heart or kidney disease. However studies have alleviate the burden of childhood obesity being considered. However there are currently shown that we may be able to avoid the effects no predictors to determine which adolescents The team is also investigating physical, of constant high blood glucose by improving will get complications from Laparoscopic psychological and dietary factors contributing

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 35 Repositories and Databases of diabetes genes is important as it will help appropriate ethics approval and sample details mechanisms. us to understand better why some people can only be accessed by authorised personnel. The data is collected using a questionnaire, Type 1 and Type 2 Diabetes DNA bank become diabetic, and help researchers to either at the time of diagnosis for newly develop new treatments. diagnosed patients, or during routine follow- Tim Jones; Liz Davis Western Australian Children’s The Australian Childhood Diabetes DNA up appointments, for patients attending the Diabetes Database Funding Source: Department of Endocrinology Repository (ACDDR) is aiming to collect DNA diabetes clinic. Data access will be restricted & Diabetes, PMH samples from Australian families affected by Tim Jones; Liz Davis to relevant clinical and authorised research A prospective population-based diabetes diabetes. Families with a child with either type staff only. Consent is obtained from newly Funding Source: Internal Funds register that conforms to international 1 or type 2 diabetes are invited to participate. diagnosed patients or their parents prior to standards, and which stores demographic DNA for the Repository is collected once via This diabetes register was established at the collection and storage of incidence data and clinical data on all patients attending the saliva samples. To participate, both biological Princess Margaret Hospital (PMH) in 1987 and family history data in the diabetes register. diabetes clinic at Princess Margaret Hospital. parents and the child with diabetes provide which stores data on all consenting patients Patient confidentiality is maintained. The database also records family history, in the about a teaspoon of saliva in a special pot that attending the hospital’s diabetes clinic. In first degree relative, of autoimmune disease we supply and can be collected in clinic or at Australia, all children diagnosed with type and atopic disease As PMH is the only tertiary home. 1 diabetes (T1DM) are admitted to hospital A Database of the Complications of Obesity in Children paediatric referral centre in Western Australia, The Repository stores samples of DNA, so that at the time of diagnosis. As PMH is the the case ascertainment of this register has only children’s teaching hospital in Western Diabetes researchers, with the approval of Liz Davis, Rachelle Kalic consistently been over 99%. This complete, relevant Ethics Committees, can then apply to Australia (WA), all children diagnosed with population-based data source is invaluable for access this Repository rather than asking your diabetes are seen by the diabetes department Funding Source: Internal studying the epidemiology of childhood onset at this hospital. Since the diabetes register child and you for more blood samples. The Obesity Database records the diabetes in Western Australia. was set up, over 99% of children newly characteristics and medical complications diagnosed with T1DM have consented to being of children with obesity who present to registered in the register. This means that the Longitudinal Type 1 and 2 Diabetes treatment at Princess Margaret Hospital, in Australian Childhood Diabetes DNA register contains data on almost all children Plasma and Serum Repository an on-site database. The database records Repository diagnosed with T1DM under the age of 15 demographic and anthropometric data about Tim Jones; Liz Davis, Adam Retterath years in WA, and can be used to accurately participants in the study, as well as features Grant Morahan; Tim Jones; Liz Davis, Heather describe their characteristics. Roby Funding Source:Internal Funds of complications of obesity. Complications A history of T1DM in the parents and siblings of obesity include an abnormal lipid profile, The Serum & Plasma bank was established Funding Source: NHMR Enabling Grant of children diagnosed with T1DM has been hypertension, glucose intolerance, fatty to provide a store of samples from subjects collected by the diabetes clinicians since 1992. liver, musculoskeletal issues and obstructive Both types of diabetes tend to run in families. with diabetes as well as their families. This Since 2005, this data collection has extended sleep apnoea, among others. Analysis of this This means that certain genes we inherit from resource will allow researchers to carry out to include type 2 diabetes and other diseases data quantifies the complications of obesity our parents may increase or decrease the risk scientific studies looking at the genetic causes associated with T1DM. This population in children who are overweight and obese, of developing diabetes. for diabetes. The ultimate aim is to improve on based database for childhood is a valuable and will be used to develop guidelines for current practice for prevention and monitoring By testing DNA samples from families affected resource which will allow us to investigate the investigation and treatment. of complications related to diabetes. Samples by diabetes, we can identify genes which relationship between associated diseases may can only be accessed by research teams with increase the risk of this disease. Identification add to the understanding of their underlying

36 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Western Australian DNA and ethics approval, to identify susceptibility genes Research Staff Awards Longitudinal Serum Bank for Weight and biomarkers related to obesity and its Regulation complications. Raymond Davey PhD Tim Jones, Diabetes Australia Research Trust Megan Evans APD, BSc, Post-Grad Dip (Nutrition Award 2005 Liz Davis; Tim Jones; Sue Byrne; Jacqueline and Dietetics) Curran, Rachelle Kalic; Adam Retterath Tim Jones, Mary Jane Kugel Award: Medical and Staff and Students Rachelle Kalic BPsych Scientific Review Committee, Juvenile Diabetes Funding Source: NHMRC Enabling Grant & Research Foundation 2004 Internal Funds Head of Division Kaitie McNamara BA(Hons) Tim Jones, APEG: Norman Wettenhall Medal for The establishment of this resource will allow Tim Jones MBBS, DCH, FRACP, MD Jennifer Nicholas BSc (Nursing), CDE, MSc Excellence in Research & Innovation – Paediatric researchers in the future to carry out scientific Clinical Professor, The University of Western (Diabetes Education) Endocrinology 2011. studies which will look at the genetic causes of Australia Nirubasini Paramalingam HDip (Children’s Liz Davis, Prize for Clinical Medicine, University excessive weight gain (how excessive weight Practitioner Fellow, National Health & Medical Nursing), Grad Cert (Diab Edu), BSc(Hons) of Western Australia, 1985 gain runs in families), and to identify biomarkers Research Council (special molecules) in blood that help predict Head, Department of Endocrinology and Adam Retterath BSc(Hons) Liz Davis, Award for best scientific paper at individuals at risk of becoming overweight or Diabetes, Princess Margaret Hospital for Heather Roby BSc West Australian College of Paediatrics Research at risk of developing obesity related diseases. Children Seminar. 1993. Barbara Sheil PhD Eventually the aim is to improve on current Faculty Member - Senior Principal Investigator, Ray Davey, Young Investigator Award, ADS-ADEA practice for prevention and monitoring of Centre for Child Health Research, Telethon meeting. 2011 complications related to obesity. Institute of Child Health Postgraduate Students The individuals that will be eligible for Adjunct Professor, Institute for Health & recruitment to the study will be overweight Rehabilitation Research, The University of Note Matthew Cooper BSc, PhD candidate children their siblings and parents seen for Dame Australia External Committees Aveni Haynes BA(Hons), MBBChir, PhD candidate their weight problem at Princess Margaret International hospital, and families enrolled in the Growth and Development study through Institute of Child Senior Team Leader Research Support Tim Jones. APEG Australasian Children’s Diabetes Health research. Liz Davis MBBS , FRACP, PhD Network – Chair 2011 Mary Flynn Grad Dip(Counseling), BA (Fine Art) DNA will be extracted from blood/saliva; serum Clinical Associate Professor, University of Tim Jones. JDRF Artificial Pancreas Consortium – & plasma from the blood samples The samples Western Australia Member 2011 collected will be coded so that no one outside Head, Diabetes and Obesity Services, Princess Tim Jones. Medtronic Advisory Board Clinicians the PMH research team will be able identify who Margaret Hospital for Children Theses passed – Member 2011 the sample belongs to. Associate Professor, School of Paediatrics and Child Health, The University of Western Australia Liz Davis, PhD, University of Western Australia: Tim Jones. Australasian Paediatric Endocrine Fractions of DNA and protein results may be Faculty Member - Senior Principal Investigator, Glucokinase – From kinetic analysis to clinical Council Research Grant Review Body – Chairman provided to properly qualified researchers, with Telethon Institute for Child Health Research, The application and a novel therapeutic potential 2011-12. PMH ethics approval, to identify susceptibility University of Western Australia genes and biomarker results may be provided Tim Jones. Australasian Paediatric Endocrinology to properly qualified researchers, with PMH Group Council - Member - 2001-2005

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 37 Tim Jones. Royal Australasian College of Tim Jones. Australian Growth Hormone Liz Davis. Royal Australian College of May 2001. Physicians – Clinical Examiner - 2002,2004 Advisory Committee Member 2000, Physicians - Written Examination committee - Tim Jones. Risks of Hypoglycaemia in Type Chairperson 2003-2005 2000-2007 Tim Jones. JDRF International - Scientific 1 diabetes, International Conference of Review Committee Member - 2001- 2004 Tim Jones. Type 1 Diabetes Guidelines Expert Liz Davis. Diabetes Research Foundation – Paediatric Endocrinology, Montreal, Canada Advisory Group – Member board member 2004 July 2001 Tim Jones. JDRF Professional Advisory Panel- 2007 Tim Jones. JDRF Australia, Scientific Advisory Liz Davis. Brightspark Foundation (formerly Tim Jones. New Zealand Diabetes Conference, Committee – Member - 1999-2004 Child Health Research Foundation)Board “Challenges in managing diabetes in the Liz Davis. Consensus Guidelines on Insulin Member 2005 young”, September 2004. resistance in children - Invited member of Tim Jones. Australian National Association of International committee 1998 Diabetes Centres - Paediatric Representative Tim Jones. International Society of Paediatric 1999-2005 & Adolescent Diabetes Congress, Singapore Liz Davis. Australasian Paediatric Endocrine Local 2004. Group’s Annual Scientific Meeting – local Liz Davis. APEG annual scientific Meeting – organiser - 1997 member of scientific organising committee Tim Jones. New Children’s Hospital WA Tim Jones. Growth in children born SGA, 1998-2011 Advisory Group – Member 2011 Symposium, Magdeberg Germany, June 2005. Liz Davis. Australasian Paediatric Endocrine Group - 2011-Member of Executive Council Liz Davis. Consensus Guidelines on Insulin Tim Jones. Paediatric Medical Clinical Care Unit Tim Jones. Hypoglycaemia in Early Diabetes. 2011 - 2012 resistance in children - Invited member of WA Medical Advisory Committee – Member American Diabetes Association, Washington, International committee 1998 2011 USA 2006. Liz Davis. Australasian Paediatric Endocrine Group - 2005- Member Diabetes Liz Davis. Australian Consensus Guidelines on Tim Jones. Diabetes Research Foundation of Tim Jones. Hypoglycemia in Children. Database Committee – 2005 - 2012 Polycystic Ovary Syndrome - Invited member Western Australia - Member Medical Advisory Presented at the American Diabetes of national committee – 2010 Panel, 2002- Association, Washington USA 2006. Liz Davis. Australian Paediatric Endocrine New Children’s Hospital WA Advisory Group – Tim Jones. Neurocognitive Findings Do Not National Council Research Grant Review Body – Member 2011 Provide Evidence for Upper and Lower Glucose Tim Jones. Type 1 Diabetes Guidelines Expert Chairman – 2011 - 2012 Liz Davis. PMH-KEMH - Accreditation Targets in Children. Presented at the American Diabetes Association 67th Annual Scientific Advisory Group – Member 2011-2012. Liz Davis. SAC Endocrinology, RACP - Member committee - 2001-02 Meeting, Chicago IL, June 2007. Tim Jones. Diabetes & Endocrine Health – 2010 - 2012 Tim Jones. Treatment of Paediatric Networks Advisory Group – Member 2011- Liz Davis. Australian Tertiary Obesity Clinical Diabetes. Presented at the China Paediatric 2012 Network - Member of Executive committee – Invited Presentations Endocrinology Association Annual Meeting, 2009 - 2012 Tim Jones. Best Practice in Paediatrics Tim Jones. Risks of hypoglycemia in childhood Huan Gsang, 14th November 2007. Committee. Organising Committee – 2010 Liz Davis. Endocrine training and curriculum Australian Diabetes Association. Investigators Tim Jones. Workshop. Exercise in Diabetes development subcommittee, APEG - Member Research Symposium, New Mexico, 1997. Tim Jones. Royal Australasian College of Children. International Society of Paediatric 2009 - 2012 Physicians - Clinical Examiner 2002,2004 Tim Jones. International Diabetes Federation Endocrinology. South Africa 2008. Liz Davis. Birth Defects Registry - Advisory Congress, Mexico 2000. Tim Jones. Diabetes Australia Research Trust - Tim Jones. Intensive Insulin Therapy. Lawson member – 2004 - Member Scientific Review Committee 2004- Tim Jones. NZSSD Annual Scientific Meeting, Wilkins Paediatric Endocrine Society/European

38 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Society for Pediatric Endocrinology, New York NY Tim Jones. Pump Therapy in Children and Diabetes Twenty Meeting, Melbourne, Australia 1 Diabetes in Children. JDRF Symposium. USA, September 2009. adolescents. Directions in Diabetes. Invited 2006. Australian Paediatric Endocrinology Group speaker, Queensland. March 2002. Annual Scientific Meeting, November 2008. Tim Jones. Barriers to Achieving Glycaemic Tim Jones. Transitioning type 1 from childhood Targets and Risks of Hypoglycaemia, Session Tim Jones. Hypoglycaemia in Children. Invited to young adult. Presented at the, Diabetes Tim Jones. Insulin Pump Therapy. Australian A1C Targets in Pediatric Diabetes – Ideal vs Real. speaker. JDRF Seminar. Melbourne, March 2002. Association of Western Australia Annual General Paediatric Society, 3rd Annual Insulin Pump American Diabetes Association 70th Scientific Meeting, Subiaco Oval, 25th October 2007. Workshop, Newcastle, NSW. March 2009. Tim Jones. Management of diabetes in Children. Sessions, Florida, June 2010. Invited speaker. JDRF Type 1 Seminar. Adelaide, Tim Jones. Effects of exercise on glucose. Tim Jones. Paediatric Endocrine Disorders and Tim Jones. Diabetes in Children (Plenary); September 2002. Australasian Paediatric Endocrine Group 2007. Fertility. Fertility Nurses Association of Australia, Technology in Type 1 Diabetes Therapy; Pediatric Perth, WA. October 2009. Tim Jones. Glucose Sensing Invited speaker. Tim Jones. Paediatric Endocrine Cases. Care (Discussions) Diabetes Asia 2010, Kuching, Australian Diabetes Society Annual Scientific Presented at the 2008 Chemical Pathology Tim Jones. Closing the Loop – Australian Malaysia Oct 2010. Meeting, Adelaide, September 2002 Course. Fremantle Western Australia, February perspectives on Artificial Pancreas Project. ADS Tim Jones. Insights into the Future of Glucose 2008. Medtronic Symposium. Adelaide, 2009. Management - Managing Hypoglycemia: a Tim Jones. Research Advances: hypoglycemia. prospective view of GCM technologies. at Invited speaker. Australian Diabetes Society Tim Jones. Common and Uncommon Tim Jones. Intensive Insulin Therapy of Type 5th International Conference, Advanced Annual Scientific Meeting, Adelaide, September Presentations. Presented at the Continuous 1 Diabetes and Hypoglycaemia. Novo Nordisk Technologies & Treatments for Diabetes, Spain. 2002. Professional Development GP Weekend- Diabetes Nurse Educators Symposium, Perth, Feb 2012 Great Southern GP Network. Albany, Western May 2010. Tim Jones. Australian Diabetes Educators Australia, February 2008. Tim Jones. Hypoglycaemia in Children and Association Annual Scientific Meeting, Tim Jones. Lilly 11th Annual Diabetes Regional Adolescents. Invited Lecture. Adelaide September 2003. Invited speaker. Meet Tim Jones. Advances in Insulin Therapy. Pumps Medical Conference, Sydney, May 2010. November, 1995. the Expert: CGMS it has a place in diabetes and CGMS. Presented at the 9th Annual Tim Jones. Diabetes in Youth, Aboriginal Health management. Directions in Diabetes Regional Medical Tim Jones. Challenges and Advances. Asia Conference, Perth, July 2010. Conference, Melbourne Australia, Sebel Albert Pacific Paediatric Endocrinology Workshop, Tim Jones. Australasian Paediatric Endocrine Park Hotel, 23-25 May 2008. How to Achieve tight controls without Sydney, March 1996. Group, Melbourne, September 2003. Invited Hypoglycaemia. Australian Paediatric Society 5th Speaker: Hypoglycaemia in children - ?an Tim Jones. Insulin Pump Services. Best Practice Tim Jones. Achieving Metabolic control in Annual Diabetes Workshop Jul 2011. uncommon problem. in Diabetes Centres. 2008. adolescent with IDDM. Invited lecture, ADS Tim Jones. Exercise in Diabetes. Australian Annual Scientific Meeting, Sydney 1996 Tim Jones. Australian Association of Clinical Tim Jones. Exercise in Diabetes. ADEA/ADS. Paediatric Society 5th Annual Diabetes Biochemists Annual Scientific Conference. Melbourne 2008. Tim Jones. Childhood Diabetes. Invited Lecture. Workshop Jul 2011. September 2003. Invited Speaker: In vivo Diabetes Australia Symposium, Sydney 1997. Tim Jones. Kimmelsteil meeting, Improving continuous glucose monitoring. Tim Jones. Hypoglycaemia and Exercise in standards of care for children with Type 1 Tim Jones. Hypoglycaemia, JDF Research Diabetes. 9th Australian Paediatric Endocrine Tim Jones. Consequences of hypoglycaemia. Diabetes. Melbourne, October 2008 Seminar, Perth, Australia, 1998. Group – Clinical Fellows School. Aug 2011. Presented at the Australasian Paediatric Tim Jones. Prefer to Improve, Exercise Tim Jones. Hot topics in Diabetes. Annual Endocrine Group Annual Meeting, Tasmania, Tim Jones. Assessing Glycaemic Variability: and Glucose and Practical Pump Therapy, Scientific Meeting of the Australian Paediatric Australia September 2006. Does it Make a Difference in Paediatrics? Sanofi Queensland, November 2008. Endocrine Group, 1999. Diabetes Expert Forum, Melbourne, Oct 2011. Tim Jones. Hypoglycaemia. Presented at the Tim Jones. Advances in the Treatment of Type

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 39 Liz Davis. Obesity and Type 2 diabetes in Presentation and panel discussion. APA WA Liz Davis. T2DM in Youth – Management: Dr Dennis Daneman: Hospital for Sick Children, adolescents, Kimberley Regional Medical Biennial State Conference, May 2005 Rural Health West Annual Conference. Invited Toronto, Canada Conference, 2002 speaker. May 2008 Liz Davis. Obesity, super size me in the under Prof Paul Fournier: School of Sports Science Liz Davis. Obesity in Children and Adolescents, 18’s. Endocrine Nurses Society of Australia, Liz Davis. T2DM in WA – Annual meeting of WA and Exercise Health, UWA RACGP Annual Seminar, 2002 September 2005 Diabetes Educator Association. Invited speaker, Winthrop Prof Danny Green: School of Sports May 2009 Liz Davis. Obesity – prevalence, investigations Liz Davis. Diabetes thru the ages. Australian Science and Exercise Health, UWA and management, Annual RACP update, May Diabetes Educator Association State Liz Davis. Lawson Wilkins Paediatric Prof Grant Morahan: Western Australian 2003 Conference- Keynote speaker, March 2006 Endocrine Society/European Society for Institute for Medical Research Pediatric Endocrinology in New York, NY USA, Liz Davis. Diabetes and hypoglycaemia: Liz Davis. Obesity and T2DM in Children: September 2009 : Invited symposium speaker. Mr Victor Skladnev: AIMedics Pty Ltd, NSW Australasian Association of Clinical South Metro Region Diabetes Update, Invited Biochemists, May 2003 speaker, March 2007 Liz Davis. Management of Diabetes Mellitus in Prof Hung Nguyen: University Technology, Isolated Aboriginal Populations. Sydney, NSW Liz Davis. Childhood overweight and obesity: Liz Davis. Obesity and T2DM in childhood: WA Australian Pediatric Review Training Program, Annual Scientific meeting of Pharmacologists, Liz Davis. Australasian Paediatric Endocrine Winthrop Prof Mike Anderson: School of June 2003 Perth, May 2007 Group Annual Meeting, Symposium speaker: Psychology, UWA Insulin Resistance Consensus Update: 2009 Liz Davis. Management of Type 2 diabetes in Liz Davis. Clinical Aspects of Childhood Dr Lim Ee Mun: Clinical Biochemistry, Childhood, West Australian Diabetes Forum, Obesity: Childhood Obesity: Prevention and Liz Davis. Maturity Diabetes of The Young: PathWest, Sir Charles Gairdner June 2003 Treatment Seminar, WA, May 2007 Diabetes Nurse Educators Professional update meeting, Perth 2010 Liz Davis. Diabetes: What’s new? Institute for Liz Davis. T 2 Diabetes in Indigenous Youth. Child Health Research Seminar Series, June Australasian Paediatric Endocrine Group 25th Liz Davis. Endocrine Society of Australia- 2003 Annual Scientific Meeting, Broome. October Australasian Paediatric Endocrine Group, Liz 2007 Davis. Combined ESA-APEG orals – Diabetes Liz Davis. Australasian Paediatric Endocrine (Clinical – 6 presentations). Invited Session Group ASM, Symposium speaker: Insulin Liz Davis. Obesity and Emerging Policy: Chair - Annual Meeting, 2011. pumps in children, September 2003. Community Health Nurses Clinical Practice Update. Invited speaker. Feb 2008 Liz Davis. Australian Diabetes Society ASM Liz Davis. Obesity - current trends: annual Symposium speaker: Clinical significance of scientific update WA Dental Society, May 2004 Liz Davis. European Society for Paediatric genetics in Diabetes, 2011 Endocrinology Conference, Turkey, 2008 Liz Davis. The neonate of the diabetic mother: WA branch of Perinatal Society of Australia and International Society of Paediatric and New Zealand, August 2004 Adolescent Diabetes Conference, Durban 2008 ACTIVE collaborations Liz Davis. Development of a multisite protocol Liz Davis. European Association for the Study for bisphosphonate treatment of children with of Diabetes Conference, 2008 A/Prof Maria Craig: Australian Clinical Trials Chronic neurological disability, August 2004 Network; NSW Australasian Paediatric Endocrine Group Liz Davis. Childhood Obesity: Have Annual Meeting, Canberra 2008 Prof David Dunger: Addenbrooke’s Hospital, Physiotherapists missed the boat? Cambridge, UK

40 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 drug discovery

Overview of protein fragments that are encoded by the successfully yielding high quality functional Extracellular Targets (Gpcr’s natural genes of evolutionary diverse microbes primary hits (pM- nM affinity), against multiple The Drug Discovery Technology Unit (DDU) and that often exist in extreme environments classes of intracellular and extracellular and other receptor) its commercialization vehicle Phylogica Ltd. such as deep sea volcanic vents and geysers. drug targets as well as in direct phenotypic Blocking the inflammation target CD40 Typically, these peptides, which are known screens. Phylomer® libraries have a number of The Drug Discovery Technology Unit is focused Ligand (CD40L) as Phylomer® peptides, are comprised of 15 advantages against a range of alternate random on developing therapeutic approaches against to 50 amino acids. The inherent diversity of peptide screening technologies for biologic disease-associated protein interaction targets Katrin Hoffmann, Shane Stone, Paula the genetic sources of Phylomer® peptides discovery. This leads to their diverse application both inside and outside of cells as well as the Cunningham and Richard Hopkins means that libraries contain multiple classes in a range of distinct areas (see figure 1 below). development of ‘mimetic’ vaccines against of subdomain and supersecondary structures The CD40L receptor on T-cells is critical for discontinuous epitopes. The research of the unit across thousands of distinct structural families. many inflammatory diseases, including Asthma, is funded by contracts with large pharmaceutical Phylomer® peptides can show excellent Inflammatory Bowel Disease, Rheumatoid companies via a commercial entity named specificity can function as high affinity disruptors arthritis and Lupus erythematosis. We have ‘Phylogica’ which was the first spin-off company of protein-protein interactions and binders of identified potent Phylomers, which are able to from the Telethon Institute for Child Health protein targets. Since Phylomer® libraries have block the interaction between CD40L on T-cells Research. the most comprehensive collection of distinct and CD40 on antigen presenting cells or on Phylogica (http://www.phylogica.com) which protein-based structures available this gives B-cells. These new lead compounds are currently is listed on the Australian Stock Exchange, is them a key versatility advantage over other being fast-tracked into animal models of disease a specialist drug discovery company, which peptide libraries This feature of high structural to determine their biological activity and indentifies new prototype drugs for large drug diversity has resulted in Phylomer® libraries potency - key end points of interest to the large company customers (www.phylogica.com). It pharmaceutical companies, who are considering achieves this by drawing from its own huge licensing these compounds for inflammatory source of billions of unique compounds from diseases. nature, the world’s largest and most diverse collection (see below). These are strongly protected by a portfolio of 16 patent families, Discovering new antimicrobials against including granted patents in the US and Europe. multi-resistant microorganisms The peptide drug class which Phylogica controls Tatjana Heinrich and Richard Hopkins access to is known as “Phylomers’. The Drug Discovery Technology Unit has Phylomers: The world’s most structurally diverse had extensive experience in the discovery library of peptides of antimicrobial peptides from its phylomer Phylogica’s proprietary Phylomer® libraries libraries. Some of these peptides have activity contain billions of distinct peptides that on multiresistant isolates of Acinetobacter represent a rich source of biologically active baumanii, an important cause of hospital drug leads for a broad range of intracellular and acquired infections of burns patients. We have extracellular disease targets. The Phylomer® also screened Phylomer libraries to identify libraries are based on expressed sequences and characterize antimicrobial peptides

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 41 against the related pathogen Pseudomonas Intracellular Targets and Novel Phylogica has screened its Phylomer® libraries Immunodeficiency Virus. We have also aeruginosa, which is involved in hospital- to identify peptides that can deliver drugs into identified cell specific Phylomer® peptides and acquired catheter and burns infections as Delivery Approaches cells. These efforts yielded approximately 1000 others that are aligned to bacterial virulence well as lung infection, particularly in children unique candidates, highlighting the structural factors known to be involved in cell invasion Discovery and Characterisation of suffering from cystic fibrosis. The group and functional diversity present within our (for example: the fibronectin binding protein Novel Cell Penetrating Phylomers has investigated the biophysical properties Phylomer® libraries. After screening a sub-pool from Staphylococcus aureus). of antimicrobial Phylomer peptides by a of 166 Phylomers, a total of 17 peptides were Katrin Hoffmann and Richard Hopkins Our ability to enrich for different classes of technique known as circular dichroism. These confirmed as having cell penetrating activity, peptides with natural cell penetrating activity studies measure the extent of formation of The emerging field of cell penetrating peptides corresponding to a functional hit rate of 11%. is unique to our Phylomer® technology and the alpha helix structure in model membranes (CPPs) is generating considerable excitement Most importantly, our recent analysis has has generated considerable interest with incorporating various phospholipid mixtures in the pharmaceutical industry. Not only can identified multiple classes of novel cell prospective Pharma partners. which mimicking different types of bacteria this class of peptide be used to deliver existing penetrating Phylomers (Table 1). These or mammalian cells. These studies found drugs inside cells but they also provide access Phylogica is currently developing a second peptides range from the traditional short, good agreement between prediction in silico to an entirely new landscape of intracellular generation screening platform, which promises positively charged CPPs, to Phylomer® and biophysical measurements. We also targets. Indeed, estimates suggest that 80% to improve significantly on the diversity and peptides that mimic invasive viral peptides were able to optimize antimicrobial Phylomer of ‘druggable’ targets are located inside cells. quality of cell penetrating Phylomers that can involved in cell entry and escape into the peptides - reduced length to approximately Combined with the fact that CPPs can deliver be isolated. cytoplasm. 20 amino acids and improving the activity new classes of drugs such as biologics into (MIC) to the high nanomolar range. Recent cells, one can appreciate why CPPs have the For example, the sequence of one of our potential to significantly expand the landscape studies have explored the potential synergy novel cell penetrating Phylomers is analogous Intracellular Projects and Target between clinical antibiotics and antimicrobial of targets currently considered druggable. to a viral peptide found in the Simian Phylomer peptides and found at least one Discovery potent combination. We have found a number Anticancer Phylomers: targeting of peptides with antimicrobial activity against ‘Sonic Hedghog’ the nosocomial infective agent Pseudomonas. aeruginosa. We have established a control Nadia Milech and Richard Hopkins in panel of recently published, highly active collaboration with Peter Dallas and Nick natural antimicrobial peptides and compared Gottardo, Division of Children’s Leukaemia and them with antimicrobial Phylomer peptides Cancer Research under different salt conditions (different broths), and have identified Phylomer The ‘Sonic hedgehog’ pathway earned its derivatives which are more active than a name after researchers observed that cells potent antimicrobial peptide known as of fruit flies, which carry a mutation in the Tachyplesin which is isolated from the horse- gene encoding hedgehog ligand, have a spiky shoe crab. appearance. The mammalian equivalent of this gene was named ‘Sonic hedgehog’ (Shh) as a humorous reference to a video game of the same name. Inappropriate inactivation of this

42 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 pathway causes cancer and is associated with PHENOTYPIC SCREENING FOR TARGET It has subsequently been shown that a phylomer Nadia Milech BSc (Hons), PhD Intracellular malignancies such as basal cell carcinoma, which DISCOVERY & VALIDATION can be used both to identify a candidate target Projects and Target Discovery is a form of skin cancer, and a childhood brain as well as to validate that target via ‘protein Shane Stone BSc (Hons), PhD Structural Biology/ cancer known as medulloblastoma (Figure 2). Paul Watt, Nadia Milech and Richard Hopkins, in interference’. It is expected that this target Modeling &Bioinformatics Collaboration with Cambridge University validation at the protein level, will be very useful Screens of our Phylomers against two as it provides an opportunity to block disease- Paula Cunningham BSc (Hons), PhD independent targets in the Shh pathway The Drug Discovery Technology Unit has relevant interfaces of target proteins while not Inflammation and Bioassay Development have yielded over 100 potentially interesting been collaborating with Ashok Venkitaraman, blocking their normal functions. peptides. Having screened approximately half of the distinguished Professor of Oncology of Tatjana Heinrich BSc (Hons), PhD Antimicrobial these hits for functional activity in two industry- the Hutchison MRC Unit at the University of To commercially exploit this opportunity, a new Discovery standard in vitro assays, we have identified Cambridge in the UK. commercial entity named ‘Phenomica’ has been some very promising lead candidates for further The objective of this collaboration has been created as a joint spin-off between Phylogica development. to test if Phylomer libraries might assist in and the University of Cambridge. There is Research Staff identifying new cancer targets for the discovery already interest from the Pharmaceutical These Phylomer® leads will be further evaluated Mark Anastasas BSc (Hons) industry in accessing the expertise of Phenomica to determine their suitability for assessment of new drugs. The Hutchison group has shown in phenotypic screening for target discovery and Allan Beveridge BSc, MSc, PhD in a predictive preclinical in vivo model of the Phylomers can bind to defined targets validation. medulloblastoma that has been established by linked to cancer cells, and that the hit-rate in a Tracy Chai BSc (Hons) our collaborators within the Telethon Institute of phenotypic mammalian screen of a Phylomer Clinton Hall BSc (Hons) Child Health Research. library is superior to that from traditional approaches used Staff and Students Suzy Juraja BSc (Hons), MSc, PhD by pharmaceutical companies. Principal Program Manager Maria Kerfoot BSc (Hons) Paul Watt BSc.(Hons) D.Phil (Oxon) Having achieved this Brooke Longville BSc (Hons), PhD Member of Faculty, Drug Discovery Division aim, the next relevant Adjunct Professor, University of Western Marie Scobie BSc (Hons) step was to use the Australia target binding as a Sarah See BSc (Hons), PhD tag to identify the key Yew-Foon Tan BSc (Hons), PhD biological step in a Research Staff pathway for which new Susan Turner BSc (Hons) drugs might be built. Program Manager Scott Winslow BSc (Hons) The success of the target Richard Hopkins, BSc. (Hons) PhD identification using Member of Faculty, Drug Discovery Division the Phylomers in this Support Staff collaboration highlights the usefulness of this Team Leaders Farzana Khan BSc (Hons) approach for target Leanne Neville discovery. Katrin Hoffmann BSc (Hons), PhD Cell Penetrating Peptide Discovery/Phage

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 43 Awards America Boston Professor Ashok Venkitarman, Cambridge University (Hutchison MRC Research Paul Watt December 5-7th , Natural Peptides Paul Watt, 2011 WA Finalist for the Ernst and Insititute), Phenotypic screening and target ID To Drugs (N2PD) Zermatt,Switzerland Young Entrepreneur of the Year Awards and Professor Greg Weiss , University of California one of 3 finalists nationally for the Rio Tinto Richard Hopkins Feb, 2011: Roche Peptide at Irvine CA, USA Protein Engineering Commercialisation of Innovation Eureka Award Symposium, Colorado of the Australian Museum. Professor Una Ryan, Murdoch University, WA. Richard Hopkins June 2011: IBC Next Cryptospiridium Paul Watt, 2011 Winner of Asia Pacific Frost Generation Protein Engineering Summit, San and Sullivan New Product Innovation Award Francisco Associate Professor Marie Bogoyevitch, for Phylomer Technology University of Melbourne (Bio21 Institute), VIC Stone, S.R., Hoffman, K., See, S., Milech, N., Anastasas, M., Hall, C., Hellsten, R.L., Professor Adrian West, University of Tasmania, Thompson, C.A., Juraja, S., Cunningham, TAS P.T., Scobie, M.N., Winslow, S.G., Watt, P.M., External Committees Adjunct Associate Professor Bruno Meloni and Hopkins, R.M., (2011), Anti-CD40L and Professor Neville Knuckey, Australian Paul Watt, University of Western Australia, Phylomers®: De Novo Modelling of Phylomer®- Neuromuscular Research Institute, WA ‘Pathfinder’ commercialization CD40L Interactions, 9th Australian Peptide Richard Hopkins, Ausbiotech, Western Conference: Peptides – by Discovery and Australian Committee Design, Hamilton Island QLD, October 2011. Stone SR, Hoffmann K, Milech N, Anastasas M, Hall C, Hellsten RL, Thompson CA, Juraja Invited Presentations S, Cunningham PT, Scobie MN, Winslow SG, Watt PM, Hopkins RM., (2011), Anti-CD40L Paul Watt Feb 22-24th 2011, Biocom Global Phylomers®: De Novo Modelling of Phylomer®- Life Science Partnering Meeting, La Jolla CD40L Interactions, Drug Discovery Chemistry: Peptide-Peptide Interactions, San Diego CA, California USA April 2011. Paul Watt April 12-14, 2011, BioTrinity 2011 Meeting, Newbury Paul Watt May 23-25, 2011, IBC TIDES Collaborations Conference, Boston Dr Erica Golemis, Fox Chase Cancer Centre Paul Watt June 8-9th, 2011, Oxford Global R&D (Philadelphia) - (Blocking protein interactions, Leaders Summit, Zurich Yeast Two Hybrid Screening Paul Watt June 20-22, IBC Protein Therapeutics Dr Reto Crameri Swiss Institute of Allergy and Summit, San Francisco Asthma Research (SIAF, Davos), Mimetopes of Paul Watt September 7th-9th, Biopharm allergens

44 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 inflammation

Overview We investigated whether inflammation in inflammatory mediator production. These RN, Perron award to RN. other tissues had the same effect on dendritic studies are ongoing. Sunlight is one of the most important cell precursors in the bone marrow. In further environmental agents to which man is exposed. studies, we have shown that inflammation of the Effect of UVB on bone marrow cells The ultraviolet B (UVB) wavelengths are the respiratory system and in the peritoneal cavity Inflammation engrafted into chimeric mice most powerful and cause not only skin cancers, induces the formation of less immunogenic, RLX Ng, NM Scott, SA Bazely, DH Strickland, S but also suppression of immune responses regulatory dendritic cells from bone marrow by Effect of UV irradiation of skin on Gorman, PH Hart. to antigens introduced at distant body sites. a prostanoid-dependent process. dendritic cells generated by culture We have previously shown that UVB light In parallel studies we have investigated the from the bone marrow Regulatory dendritic cells are generated by administered to the shaved dorsal skin of mice effects of UV-induced vitamin D in control of culture of bone marrow from UV-irradiated mice can suppress models of allergic airways disease. 3 NM Scott, J Bisley, RLX Ng, PH Hart immune cell activity and asthma models in mice. and results suggest the induction of regulatory This suggested that UV-induced changes in Humans obtain 90% of their vitamin D from We have previously shown that signals sent cells. We are uncertain of the potential artificial the skin could signal downstream systemic 3 UV irradiation of skin so it has been proposed from skin irradiated with erythemal UV to the effect of bone marrow cell culture. In 2011, responses to allergens in respiratory tissues. by us, and others, that UV-induced Vitamin bone marrow stimulate the development of chimeric mice were established; mice were In 2011, we focussed on the effects of UV D may contribute to the immunomodulatory dendritic cells that are poorly immunogenic gamma-irradiated to destroy their bone marrow irradiation of skin on dendritic cell precursors 3 effects of UV. We have examined the effect of and cannot induce a strong immune response. cells and then injected with bone marrow cells in the bone marrow. This was important as vitamin D in excess (painted onto the skin of The phenotype and function of cells generated from non-irradiated or UV-irradiated mice. The the bone marrow produces haematopoietic 3 mice with normal levels of vitamin D ) and in by culture from the bone marrow of animals re-establishment of their bone marrow was cells that replace those that are dying in the 3 deficiency (mice were fed diets restricted in administered a single inflammatory dose of UV followed and by 8 weeks, the peripheral lymph peripheral organs. Erythemal UVB irradiation vitamin D ). We discovered that male vitamin have been studied. Different growth factors nodes had been re-populated. After 16 weeks, of skin stimulated the production from bone 3 D -deficient mice were unable to respond to have been added to the cells in culture to the efficiency of the engrafted dendritic cells has marrow of poorly functioning dendritic 3 UVB irradiation of skin for vitamin D production. generate these poorly immunogenic dendritic been sought as we wish to know whether the cells. Further, UV-induced prostanoids were 3 Thus, if the male mice responded to UVB for cells. Both GM-CSF and FMS-related tyrosine effects of the UV exposure are long-lived. When responsible for the effects of UV irradiation of regulation of immunity, this was not via the kinase 3 (Flt3-L) have been used and represent an inflammatory antigen is painted on the skin skin on dendritic cell precursors in the bone modulatory properties of vitamin D . This finding inflammatory and steady-state conditions, of the chimeric mice, there is an inflammatory marrow. This result suggested that UV-induced 3 has given us an exciting and ongoing approach respectively, and stimulate different progenitor response in mice engrafted with bone marrow inflammation per se was responsible for this to analyse the relative contribution of vitamin populations to differentiate. As poorly cells from non-irradiated mice but a very poor effect and that it was a homeostatic response D and other UV-induced mediators to the immunogenic dendritic cells are generated response if the mice were engrafted with bone that ensured that the inflammation in the 3 immunomodulatory properties of UV irradiation. under all differentiative conditions, we speculate marrow cells from UV-irradiated mice. This result skin was restricted and did not progress out We have also shown that vitamin D -deficient that early progenitors are altered by UV suggests a long lasting effect of UV irradiation on of control. We have also tested these bone 3 mice express worse symptoms of asthma. irradiation of skin. The dendritic cells generated dendritic cells in the bone marrow. marrow cells in controlling models of established in culture have also been able to actively down- In 2011, our studies of the mechanism of Funded by NHMRC, UWA Postgraduate Award to inflammation. The dendritic cells generated regulate immune responses in mice already action of interleukin-4 as an anti-inflammatory RN & SB, Perron award to RN & SB. from the bone marrow of UV-irradiated mice sensitised and responding to antigen. Thus, the cytokine for human monocytes and actively suppressed ongoing responses in bone marrow-derived dendritic cells from UV- antigen-sensitised mice and suggested that the macrophages continued. Gene arrays gave irradiated mice are regulatory dendritic cells. Effect of UVB on bone marrow dendritic cells were not only poor in function but new candidate molecules that may be involved subpopulations actively regulatory. in the mechanism by which IL-4 suppresses Funded by NHMRC, UWA Postgraduate Award to

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 45 SA Bazely, R Ng, N Scott, DH Strickland, S skin, bone marrow derived dendritic cells are vitamin D were more important when lower Mechanisms of regulation by IL-4 for Gorman, PH Hart. regulatory. To determine whether the effect concentrations of allergen were used to reduced inflammatory mediator is unique to skin inflammation, the effect of develop the model. Studies are in progress production by human monocytes The effect of mature dendritic cells in the bone inflammation at other tissue sites has been to examine the effect of vitamin D deficiency marrow on the development of regulatory examined. In response to inflammation in the on the various immune cell types, particularly EA Woodward, PH Hart. dendritic cells in culture has been investigated airways and in the peritoneal cavity (due to dendritic cells. by their removal prior to culture of the We have been studying the mechanisms administration of the inflammasome activator, bone marrow cells. No consistent effect was Funded by the Brightspark Foundation and the by which interleukin-4 (IL-4) can suppress alum), bone marrow derived dendritic cells measured. As poorly immunogenic dendritic Raine Foundation inflammatory cytokine production by activated are regulatory. Further their development is cells are generated under all differentiative human monocytes and macrophages. Using blocked by the administration of indomethacin conditions (namely upon culture with GM-CSF gene arrays, we continue to search for and again suggests that inflammation- or FLT-3L), we speculate that an early dendritic Vitamin D in deficiency – Effect of UV molecules that may be involved in the anti- induced PGE , and possibly prostanoids, are cell progenitor is altered by UV irradiation of 2 irradiation of skin inflammatory properties of IL-4. Candidate responsible. We propose that the formation skin. We have FACS-sorted early dendritic cell molecules studied in 2010 include RP-105 of regulatory dendritic cells in the bone progenitors (Lineage negative, CD117 positive) S Gorman, C Weedon, NM Scott, PH Hart (CD180), IL-10, RIPK2 and the transcription marrow is part of a homeostatic mechanism factor c-Maf. from bone marrow of mice obtained 3 days When vitamin D -deficient mice are UVB to limit the destructive properties of tissue 3 after UV-irradiation of the shaved dorsal skin irradiated, only the female mice are able to inflammation. Funded by Murdoch University Students of the mice. RNA was extracted from the respond with systemic vitamin D3 levels. We stipend, Perron award to EAW cell populations and we have recently sent Funded by NHMRC, UWA Postgraduate Award do not fully understand why male vitamin D3- RNA preparations externally for microarray to RN, Perron award to RN deficient mice are unable to make circulating analysis. We propose that differences in the vitamin D3 although they are able to make transcriptomes of the dendritic cell progenitors Staff and Students vitamin D3 if it is provided in their diet. We Vitamin D in deficiency – Effect of diets from the bone marrow of non-irradiated and believe that we have developed a powerful Research Staff UV-irradiated mice will help us understand deficient in vitamin D3 model to determine which immunoregulatory how the developmental programme of the responses measured following UVB Prue H Hart BSc (Hons) MSc PhD, NHMRC S Gorman, C Weedon, PH Hart dendritic cells is altered by UV-irradiation of Principal Research Fellow irradiation of skin are vitamin D3-dependent. skin. To study vitamin D deficiency, we have In assays of both systemic and local contact 3 Shelley Gorman BSc (Hons) PhD Funded by NHMRC, UWA Postgraduate Award established colonies of BALB/c mice fed a hypersensitivity, and OVA-induced asthma, Naomi M Scott BSc (Hons) to SB & RN, Perron award to SB & RN. vitamin D restricted diet. The ovalbumin- male and female mice have responded to UV driven model of allergic airways disease has irradiation to a similar extent. We have not Jacqueline Bisley BSc (Hons) been established in these mice. Detailed detected responses to UV in male vitamin D3- studies suggest that the models of disease deficient mice that are vitamin D -dependent. Clare Weedon BSc (Hons) Effect of experimental allergic 3 airways disease and the inflammasome are worse in the vitamin D-deficient mice To better understand why the skin of male activator, alum, on bone marrow- supporting the hypothesis that vitamin D has mice cannot respond to UV irradiation, the Postgraduate Students derived dendritic cells a regulatory role in systemic immune diseases expression of the enzymes responsible for the such as asthma. Effects of vitamin D deficiency development and breakdown of vitamin D are Eleanor A Woodward BSc (Hons), PhD NM Scott, J Bisley, RLX Ng, PH Hart. have been measured in both the lymph nodes being investigated. Candidate and the lungs and airways. The effects of In response to UV-induced inflammation of the

46 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Royce LX Ng BSc (Hons), PhD Candidate by the Cancer Council WA, Perth, November Research (ASMR), Annual State Meeting, Curtin 2011. University – June 2011 Scott A Bazely BSc, PhD Candidate PH Hart, Invited symposium speaker, Japanese Royce Ng, TICHR Institute presentation – June Society for Investigative Dermatology - Asia- 2011 Oceania Symposium, Kyoto, Japan, December Awards Royce Ng, TICHR Postgraduate forum – August 2011. 2011 Prue Hart, Adjunct Professor, University of WA, S Gorman, Research Presentation, secondary- Royce Ng, Australasian Society for Immunology, NHMRC Principal Research Fellowship aged school students from Ashdale Secondary Annual State Meeting – October 2011 Shelley Gorman, Brightspark Research College and year 12 students attending the Fellowship 2011-1013. National Youth Science Forum visiting TICHR, Royce Ng, Australasian Society for Immunology, January 2011. Annual National Meeting, Adelaide - December Royce Ng, Best Student Presentation, 2011 Australasian Society for Immunology, Annual S Gorman, Invited presentation, Australian State Meeting, October 2011 Society for Dermatology Research National Naomi Scott, Australian Society for Medical Conference Perth, May 2011. Research (ASMR), Annual State Meeting, Curtin University – June 2011 S Gorman, Public Lecture, Telethon Institute for Presentations Child Health Research, July 2011. Vitamin D: Super nutrient or super fad? PH Hart, Poster Presentation, Keystone External Committees Symposium, ‘Immunoregulatory Networks’, S Gorman, Research Presentation, primary-aged Beaver Run Resort, Breckenridge, USA, April school students at St Hilda’s Anglican School as PH Hart, Invited Member, NHMRC Academy 2011. part of National Science Week (Being a Scientist, September 2011). PH Hart, Invited Member, NHMRC RGMS PH Hart, Public Lecture, Telethon Institute for working group. Child Health Research, July 2011. Vitamin D: S Gorman, Seminar, Perspectives in Child Health Research Seminar, TICHR, August 2011 PH Hart, Sole External Member, Royal Perth Super nutrient or super fad? Hospital Medical Research Foundation Scientific PH Hart, Invited Seminar speaker, WAIMR, S Gorman, Perth Immunology Group Meeting, Committee. August 2011 Australasian Society for Immunology, Perth, October 2011. PH Hart, President, Australasian Society for PH Hart, Invited speaker, European Society Dermatology Research S Gorman, Australasian Society for Immunology for Photobiology 14th Congress, Geneva, PH Hart, Chair, Organising Committee, Switzerland, September 2011. Annual Scientific Meeting, Adelaide, December 2011. Australasian Society for Dermatology Research PH Hart, Invited speaker, Australian Thoracic Annual conference, Perth, May 2011. Society, WA Conference, Mandurah, October Royce Ng, The Australasian Society for 2011. Dermatology Research (ASDR), Annual National Meeting, Perth – May 2011 PH Hart, Symposium on ‘Giving Advice on How Much Sun Exposure Should We Get’, organised Royce Ng, Australian Society for Medical

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 47 lung growth and respiratory environmental health

Overview Gilmour, US EPA). We also combine our Early life determinants of lung is being pursued by Rachel Foong who began measures of lung function with structural a PhD in 2011 examining the role of vitamin D We have three major research themes 1) early (stereology and in vivo imaging) and genetic growth deficiency airway remodelling in chronic lung life determinants of lung growth, 2) respiratory studies (Collaborators: Dr Anthony Bosco, disease. Vitamin D deficiency and lung growth environmental health and 3) mechanisms TICHR; Dr Kim Carter, TICHR) with a view to Funding: NHMRC, Asthma Foundation of W.A. of airway dysfunction in asthma. These understanding critical pathways involved in Rachel Foong, Shelley Gorman, Prue Hart, research themes overlap in several areas and lung growth and development and how these Graeme Zosky underpin our overall goal to understand the may be altered by early life insults resulting in The effects of in utero tobacco smoke early life factors that contribute to respiratory a predisposition for disease. These studies on There has been a dramatic increase in recent exposure on lung growth and health disease. These factors include environmental early life factors that impact on lung growth decades in the prevalence of vitamin D exposures, viral infection, allergic sensitization, and disease are complemented by our ongoing deficiency in Australia and worldwide. Vitamin Alexander Larcombe, Graeme Zosky, Rachel nutritional deficiencies and genetic variability work examining the mechanisms of airway D deficiency is associated with a number of Foong, Peter Sly (UQ). hyperresponsiveness in obstructive disease. diseases including, 1) the bone disorder rickets in innate lung function responses. It is Unborn children exposed to tobacco smoke These studies are largely driven by Dr Peter (due to the importance of vitamin D in calcium becoming increasingly clear that early life are more likely to suffer respiratory disorders Noble’s in vitro and in vivo (human/animal homeostasis), 2) autoimmune disorders and exposures make a substantial contribution to such as bronchitis and wheeze and are more model) work which tests new concepts of 3) cardiovascular disease. Recent prominent respiratory morbidity and by understanding likely to be admitted to hospital for respiratory airway smooth muscle physiology and how publications have also implicated vitamin D in key lung development processes we aim problems. Exposure to cigarette smoke before these impact airway function in health and the pathogenesis of obstructive lung diseases to design interventions that will ultimately and directly after birth affect a child’s lung disease (Collaborators: A/Prof Alan James, such as asthma and COPD. Additionally, prevent the onset of respiratory disease and function, however, a mother’s smoking during SCGH; Prof Howard Mitchell, UWA; Dr Peter epidemiological studies have shown a strong improve lung health. pregnancy, rather than her smoking status McFawn, UWA; Prof David Sampson, UWA; A/ association between serum vitamin D levels This research relies heavily on mouse models after the birth is more highly correlated with Prof Robert McLaughlin, UWA). and lung function suggesting an important and the state of the art techniques for the development of childhood asthma and link between vitamin D status and lung health. assessing lung function and structure that have The two key highlights of 2011 were the wheeze. There is an association between in However, there had been no study showing a been developed in our laboratory through expansion of our research program to utero exposure to cigarette smoke to reduced direct lung between vitamin D deficiency and ongoing collaborations with Prof Zoltan Hantos include studies specifically designed to lung function and childhood asthma, however lung growth/structure/function. In 2010 we (University of Szeged, Hungary) and Prof Peter assess environmental factors that may be the mechanisms for this are unknown. published a study in the leading respiratory Sly (University of Queensland). These studies contributing to the gap in health between journal (American Journal of Respiratory and This project began in 2008 when we involve a multi-disciplinary approach whereby indigenous and non-indigenous Australians Critical Care Medicine) on the lung structure characterized our commercially available epidemiological and clinical studies inform (Collaborator: A/Prof Roz Walker, TICHR) and function of mice raised on vitamin D cigarette smoking machine using adult mice. the design of mechanistic animal studies; and the development of a key collaboration deficient and replete diets (established by Dr We showed that a regime of 3 cigarettes twice which are in turn used to identify issues with engineers from Monash University Gorman and Prof Hart). We showed for the per day for 13 days was optimal for in utero that require further investigation in terms (Collaborator: Dr Fouras, Monash) examining first time that vitamin D deficiency alters lung cigarette smoke exposure studies. of clinical outcomes and public health. This novel imaging technologies for respiratory structure resulting in significant deficits in lung approach is facilitated through collaborations disease. Following characterization of the smoking function. This study received considerable with researchers examining clinical outcomes machine, we began exposing groups of dams public interest resulting in an international (Collaborators: A/Prof Graham Hall, TICHR; to mainstream cigarette smoke. Control media release by the American Thoracic Prof Steve Stick, PMH; Prof Peter Sly, dams were exposed to medical air only. Society and interviews for ABC Radio National. UQ) and environmental exposure studies When the resultant pups were two weeks These studies are ongoing and we now plan to (Collaborators: A/Prof Merci Kusel, TICHR; A/ old, we weighed them, measured their lung identify the mechanism of vitamin D deficiency Prof Angus Cook, U.W.A; Dr Andrea Hinwood, volumes, baseline lung function and lung induced alterations in lung growth. This work ECU; A/Prof Dean Bertolatti, Curtin; Dr Ian mechanics over 20cm H2O inflation/deflation

48 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 manoeuvres and assessed lung morphometry. life As exposure and the development of lung adulthood demonstrating the importance of hrs and 7 days post inoculation. Additional We showed that two week old mice exposed disease in later life we conducted a series of early life environmental and viral exposures in groups of mice were exposed to 100 µg of 10 to cigarette smoke in utero were significantly experiments using mouse models of in utero determining adult lung health. µm silica or inert polystyrene beads as controls smaller and had significantly lower lung volumes As exposure. We began pilot studies in 2008 Funding: NHMRC Project Grant for generic responses to inhaled particulate than control pups. As a result of their smaller which involved exposing pregnant mice from matter. To date we have completed the analysis size, cigarette exposed pups had significantly three strains (C57BL/6, C3H/HeARC, BALB/c) of cell numbers (and type) from lavage samples impaired lung function, although lung structure to 100 ppb (or 0 ppb as a control) via their Regional environmental determinants from mice in all groups. The magnitude of the was not altered. These data were the first to drinking water from gestational day 8 (prior to of lung health influx of inflammatory cells was dependent show impaired lung function in mice exposed the development of the lung buds at day 9.5) on the dose and sample used. The silica and to tobacco smoke in utero using appropriate until birth. The offspring of these mice had Graeme Zosky, Russell Wong, Robert Woodward polystyrene preparations resulted in a minor techniques. their lung function measured at 2 weeks of age. (U.W.A.), Lucia Guiterrez (U.W.A.), Brian Devine (barely detectable) inflammatory response. We found that there was no difference in lung (U.W.A.), Fiona Maley (U.W.A.), Angus Cook In contrast a significant influx of neutrophils mechanics corrected for lung volume in BALB/c (U.W.A.) (polymorphonucleocytes) was observed in the mice exposed to As compared to controls. In mice exposed to PM from both Kalgoorlie Respiratory environmental Exposure to mining dust in towns close to 10 contrast C3H/HeARC mice exposed to As had and Newman with a greater response in open cut mines in Western Australia has significantly higher airway resistance for a mice exposed to PM from the latter. We are health been identified as a public health concern. In 10 given lung volume compared to controls and As currently measuring cytokine levels in lavage particular, children have been identified as Arsenic induced non-malignant lung exposed C57BL/6 had higher tissue damping and fluid from these mice and have begun Phase 2 a subgroup that is at high risk of respiratory disease elastance for a given lung volume compared to which involves exposing mice to samples from disease as they are active close to the ground, controls. These experiments provided the proof other sites and measuring lung function at have higher ventilation rates than adults and Kathryn Ramsey, Peter Sly (UQ), Alexander of concept data required to demonstrate the key timepoints (6 hr, 24 hr and 7 days post- often play in areas (e.g. community playgrounds Larcombe, Graeme Zosky potential of As to alter lung development which inoculation). and outdoors) where dust levels are high. This may explain the link between early life arsenic The contamination of groundwater with arsenic study is the first to directly assess lung responses In 2011 we extended this study to include exposure and poor lung health in later life. (As) is a global health problem. In the Ganges to inhaled “real world” particles from mining particles obtained throughout W.A. including We have since completed an indepth genetic Delta (West Bengal, Bangladesh) over 80 million sites in Australia. We will determine whether Tom Price, Port Hedland and Karratha. This analysis of lung tissue samples from these mice people have been exposed to unsafe levels of exposure to dust in communities close to mines study (data currently being analysed) is the first and found that genes related to lung branching As from shallow tube wells that were installed causes a level of inflammation in the lung that is comprehensive examination of the potential and mucous clearance were altered by arsenic to prevent the epidemic of waterborne diseases of concern and also whether the response varies respiratory health impacts of geogenic particles exposure. These are important findings as they in infants. This exposure event is a public health depending on the mineral/metal content of the obtained directly from communities exposed to provide, for the first time, a direct mechanism catastrophe and has been described as the dust. These studies will assist in informing public high dust loads. For the first time we hope to that may explain the association between lung biggest mass poisoning in human history. Arsenic health and safety policy in these communities. identify the key elements of these particles that is a well recognised carcinogen and is listed by disease and arsenic exposure via drinking water have the greatest impact on respiratory health In 2010 we completed Phase 1 of the in vivo the International Agency for Research on Cancer observed in human populations. with a view to designed remediation programs animal exposure studies associated with this (IARC) as a category 1 carcinogen. However, In 2011 we also completed a series of studies in these communities. project. In these studies adult BALB/c mice recent evidence from an exposure event in examine the effect of combining arsenic were exposed to varying (0, 10, 30, 100 µg) Funding: CRC for Asthma Chile has suggested that As is linked to the exposure with an additional respiratory concentrations of PM (< 10 µm) collected development of non-malignant obstructive lung insult using a mouse model of influenza 10 from Newman and Kalgoorlie suspended in disease. In particular, in utero exposure to As infection. These data clearly demonstrate 50 µL of saline by intranasal inoculation under Environmental health of remote via drinking water has been linked to increased that arsenic can exacerbate influenza induced light anaesthesia. Mice were assessed for indigenous communities mortality due to bronchiectasis in young adults. inflammation and alterations in lung function. inflammatory responses in the lung 6, 12, 24 In order to investigate the link between early These respiratory deficits also persisted into Graeme Zosky, Roz Walker

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 49 There is a significant gap in health between also measured increased levels of a number lung using highly coherent synchrotron based and lung function at the peak of the response indigenous and non-indigenous Australians. of cytokines including MIP-2 and MCP-1 post radiation. These studies are conducted at the (3-4 days post-infection). We found that there This is particularly true for respiratory exposure. Cellular inflammation had largely third generation synchrotron in Japan and are was no difference in responses between the health and in individual living in remote resolved 48 hours post exposure. We also yielding novel insights into the regional effects two groups of mice suggesting that NE is not communities. In 2011 we commenced a measured lung volume, baseline lung function of bronchoconstricting agents. involved in the induction of influenza related

research program designed to assess the role and lung mechanics over 20cm H2O inflation/ AHR. of the environment, with a focus on water deflation manoeuvres for these mice 6 and DEP and influenza; As part of our ongoing Viral induced airway quality and dust exposure, in contributing 24 hours post exposure. We noted impaired interest in respiratory responses to hyperresponsiveness to this disparity in respiratory health. We lung function at 6 hours, which had returned environmental exposures we have developed travelled to several communities of the Martu to normal after 24 hours. A significant Rachel Foong, Alexander Larcombe, Anthony and characterized a mouse model of acute people in the eastern Pilbara and collected component of this project was assessing DEP exposure. DEP is one of the major water and dust samples for analysis of heavy uptake of DEP by alveolar macrophages. We Kicic, Steve Stick, Peter Sly, Peter Noble (KEMH), Graeme Zosky contributors to atmospheric particulate metal contamination. We are now expanding measured a distinct bi-phasic uptake of DEP matter in urban areas. There are strong this program to conduct real-time monitoring at levels comparable to those seen in children These studies span a number of different epidemiological associations between levels of the inhalable dust with a view to estimating chronically exposed to soot / DEP, indicating projects and involve infecting mice with of particulate matter in the atmosphere and exposure levels in the community. the real-world relevance of these studies. respiratory viruses (primarily rhinovirus and respiratory morbidity and mortality. One Funding: Thoracic Society of Australia and New In 2011 we combined this DEP model with our influenza) at different ages and under different explanation for this observation may be DEP Zealand (Rob Pierce) established model of influenza infection and conditions (e.g. in the presence of other induced exacerbation of respiratory disease. clearly demonstrated that DEP can enhance respiratory insults). In 2010 we focused on In order to test this we exposed mice infected viral replication and exacerbate influenza 2 aspects; the role of neutrophil elastase in with influenza, at the peak of inflammation Diesel exhaust particle exposure and induced inflammation. This observation has the progression of influenza induced airway (day 4), to DEP and measured responses 6 its effects on lung function and the potential to influence how people who hyperresponsivness (AHR) and the impact of hours later. We found that mice exposed to exacerbations of airways disease are hospitalized with influenza are treated diesel exhaust particle (DEP) exposure during both DEP and influenza had higher levels of and to inform public health warnings on high acute influenza infection. inflammation compared to mice exposed to Alexander Larcombe, Rachel Foong, Graeme pollution days. Neutrophil elastase; We have shown either DEP or influenza alone. Additionally, Zosky previously that influenza induced AHR is due to DEP exposure increased viral titre suggesting This ongoing project is designed to directly disruption of the epithelial barrier resulting in that it enhanced viral replication. These address the issue of whether acute exposure Mechanisms of airway increased access of bronchocontrictor agents studies are ongoing and we plan to extend to diesel exhaust particles (DEP) results in to the airway smooth muscle. Neutrophils are the measurement timepoints to determine exacerbation of existing respiratory illness. hyperreponsiveness in asthma one of the primary response cells involved whether DEP exposure prolongs the resolution In 2009 and 2010 we established a mouse in the inflammatory response to influenza. of influenza symptoms. Novel imaging modalities for the model of acute DEP exposure using intra- Neutrophils release a number of key products Funding: UWA Research Development Award nasal instillation of DEP (ie small amounts assessment of regional airway including neutrophil elastase (NE) which, of DEP in solution are placed on the nose of contriction when in excess, can damage the lung tissue. mice and inhaled). At a variety of time-points We hypothesized that NE, by disrupting the Emerging models of asthma post exposure (ranging from 3 hours to 4 Graeme Zosky, Andreas Fouras (Monash), epithelial barrier, was responsible for influenza weeks) we took bronchoalvelar lavage fluid Stuart Hooper (Monash) induced AHR. To test this we used a genetically Alexander Larcombe, Graeme Zosky, Peter for assessment of inflammation and uptake In 2011 we established a collaboration with modified mouse which lacks neutrophil Noble (KEMH) of carbon black by alveolar macrophages. We researchers at Monash University who are elastase (NE-/-). NE-/- mice and wild-type Experimental mouse models of aeroallergen identified significant cellular inflammation developing novel methods for imaging the littermates were infected with influenza A sensitization have helped advance our which peaked ~6 hours post exposure. We and studied for inflammation, viral replication

50 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 understanding of respiratory diseases such as hyperresponsiveness for HDM exposed mice. Alexander Larcombe PhD Graeme Zosky. Thoracic Society of Australia & asthma. Traditional mouse models, however, The impacts were greatest 24 hours after Catherine Boylen BSc(Hons) New Zealand (WA) Executive Committee. have a number of inherent draw-backs and the final exposure. We also took blood and Russell Wong BSc(Hons) Graeme Zosky. Thoracic Society of Australia & are far from the ideal model of human allergic bronchoalveolar fluid from these mice for New Zealand ASM Organising Committee. airways disease. Typically, mouse models of analysis of total IgE and cellular inflammation. Luke Berry BSc “asthma” involve systemic sensitization of adult These mice showed significantly increased total Kathryn Ramsey. Thoracic Society of Australia & Dr Peter Noble PhD (Honorary member) animals where allergen (usually ovalbumin, IgE and eosinophilia, two key features of allergic New Zealand (WA) Associates Committee. from chicken eggs) is used in conjunction with airways disease. Kathryn Ramsey. Thoracic Society of Australia & powerful chemicals to enhance the response. One of the most striking abnormalities in Postgraduate Students New Zealand ASM Organising Committee. Whilst still an extremely valuable tool for patients with obstructive lung disease is a loss Rachel Foong. Thoracic Society of Australia & the investigation of allergic airways disease of the bronchodilation that normally occurs Rachel Foong BSc(Hons) PhD Candidate New Zealand (WA) Associates Committee. in mice, this situation does not mimic the in healthy individuals when they take a deep Kathryn Ramsey BSc(Hons) PhD Candidate process in humans, which happens at an early inspiration (deep inflation, DI). In both asthma age across the nasal mucosa. To address this, and COPD, the protective action of DI fails. we have designed a project to validate and It is argued that an impaired response to DI Research Support Invited Presentations to further characterize two mouse models of is intimately related to disease morbidity Graeme Zosky. Australian Physiological Society house dust mite (HDM) sensitization and by Marina Stubbs including airway obstruction and airway Conference 2011. “Alterations in lung structure this assess the impacts of such sensitization/ hyperresponsiveness (AHR). The general aim exposure on respiratory health. Mouse models can perpetuate inflammation leading to chronic of this on-going project is to examine the lung disease” of HDM exposure have strong links to human underlying mechanisms governing beneficial Awards allergic airways disease and are potentially a responses to DI and to determine the considerable improvement on other mouse susceptibility of the system to interference in Kathryn Ramsey, Maurice Blackburn models. This is because HDM, unlike ovalbumin, disease. In 2011 we demonstrated the capacity International Travel Award ACTIVE collaborations is a cosmopolitan guest in human habitation, for a DI to modify both the timing (rate) and Kathryn Ramsey, Lung Institute of Western Assoc Prof Angus Cook, University of Western and naturally causes allergic airways disease magnitude of constriction following exposure to Australia Junior Medical Scientist Award Australia in humans. Unlike earlier studies by other the bronchoconstrictor MCh. researchers, we will use an array of specialised Kathryn Ramsey, Australia Society for Medical Prof Alan James, Sir Charles Gairdner Hospital, in-house techniques suitable for measurement Research (W.A.) Murdoch Award W.A. of lung function in mice, allowing us to reveal Kathryn Ramsey, Thoracic Society of Australia important physiological effects of HDM that may Staff and Students Prof Zoltan Hantos, University of Szeged, and New Zealand Travel Award have been previously overlooked. Hungary Head of Group Rachel Foong, Thoracic Society of Australia and To date, we have exposed adult BALB/c mice Prof Peter Sly, University of Queensland, QLD New Zealand Travel Award to 25μg HDM protein in saline daily for ten Graeme R Zosky PhD MBiostat Prof Steve Stick, Princess Margaret Hospital, sequential days. Control mice received saline Principal Investigator, Telethon Institute for Child Catherine Boylen, Thoracic Society of Australia W.A. only. The mice receive the HDM intranasally, Health Research and New Zealand Travel Award Dr Andrea Hinwood, Edith Cowan University, mimicking the route of exposure in humans. Associate Professor, Centre for Child Health W.A. We then measured lung volume, baseline Research, The University of Western Australia lung mechanics and hyperresponsiveness to External Committees Dr Andreas Fouras (Monash) methacholine 24, 48 and 72 hours post the Professor Stuart Hooper (Monash) final exposure. We have shown significant Research Staff Local impacts on lung function, including airway Dr Ben Mullins, Curtin University

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 51 molecular biotechnology

Overview virus and hence an immunological insufficiency A preschool (CAS) cohort was used to tract infection and asthma in children. In vitro or if there are increased titres that might be study antibody responses to the P4 and P6 cultivation of the type C is difficult so the Childhood respiratory infections: Immune expected from increased infection, for example antigens from Haemophilus influenzae and production of the recombinant polypeptide is responses to childhood respiratory infections due to increased exposure. Antibody titres can Psp-A and Psp-C antigens of Streptococcus the only avenue available to produce antigens have become a major subject of investigation also show the prevalence of infection from pneumoniae. Children that became allergic to measure immune responses and conduct by the Division of Molecular Biotechnology. the three species of rhinovirus, HRV-A, B and to house dust mite allergens had a delayed seroepidemiology. DNA encoding the two This follows from the finding that nearly C, and might provide a diagnostic method for development of IgG1 responses to all the representative VP1 antigens from each species all infants that become allergic to inhalant identifying recent infection associated with a bacterial antigens examined and, especially has been obtained by gene synthesis and allergens show developmental delays in clinical episode. The production of structurally for the H. influenzae allergens, children who expressed as recombinant proteins by several the production of antibodies to common authenticated recombinant proteins for became asthmatic (judged at 5 years) had strategies. Recombinant VP1 assembled as colonising bacteria, and that when the major VP1capsid antigens has now been early and persistent low IgG1 titres. The same a discrete multimer has been produced and low responses persist, the children have accomplished and pilot studies have already was found for S. pneumoniae but not to the purified by several chromatographic steps. It a high propensity to develop asthma. show the interesting result that antibodies to same degree. This corroborates the results is by circular dichroism highly structured with Indeed children with the worst asthma HRV-C are found infrequently in adults. from a previous emergency room study. The the beta-sheets expected from the natural have the lowest anti-bacterial responses, Allergens of the house dust mite: The unusual association of IgE antibody and antigen. Pilot studies with adults show that along with a poor IgE/IgG profile for their measurement of IgE antibody titres to Der low risk for asthma was found in 5 year old in contrast to the type A VP1 protein only a responses to allergens. These discoveries p 15 and Der p 18, allergens expected to children corroborating results from an older few individuals have high titres of antibodies were dependent on the development of bind chitin, has demonstrated that immune aged cohort. There was additionally an inverse binding to type C. It may therefore only be recombinant and highly purified antigens so responses to different house dust mite association between IgE anti-house dust a paediatric infection or the observations defined reproducible observations can be allergens are regulated by different pathways. mite allergen titres and IgE anti-P6 bacterial made by PCR-based virus detection from made and the development of methods for The IgE titres to these allergens correlated protein, which indicates protection from hospitalised children may have overestimated absolute quantitation. To date the emphasis strongly with each other but not to responses allergic sensitisation, is part of the mechanism. the prevalence in the community. has been to establish the reproducibility of to other house dust mite allergens. These The size of the anti-bacterial IgE and the anti- the findings in different cohorts of children, form a separated group that correlate with bacterial IgG1 titres were correlated indicating Der p 15 and 18 and independent with different antigens and with antigens from each other. The results emphasise the need they are part of the same mechanism or regulation of IgE responses to different bacteria, Haemophilus influenzae to investigate immune responses to different markers for the same mechanism that is now and Streptococcus pneumoniae. Not only have house dust mite allergens separately and not being investigated. different groups of house dust mite the associations with the low IgG1 responses with extracts. allergens been reproduced but so has the unusual association of reduced risk of asthma with IgE Rhinovirus antigens and antibodies W. Smith, C, E. Elliot, L. Y. Chai, L. A. Hazell, B. antibody production to bacterial proteins. The J. Hales, W. R. Thomas with S. Stone from Drug J. Iwasaki, W. Smith, W. R. Thomas, C. E. Elliot, mechanisms responsible for these effects are Molecular Biotechnology Discovery and S. Piboonpocanun, T. Tipayanon LY Chai, L. A. Hazell, B. J. Hales now being explored. and S. Thanyaratsrisakul, Mahidol University, Development of anti-bacterial IgG The VP1 proteins are the most antigenic Bangkok Rhinovirus infection: There has been increasing and IgE antibody in house dust mite capsid antigens of the type A, B and C species recognition that rhinovirus infection is not only Der p 15 and Der p 18 which are respectively allergic children of human rhinovirus. Each has about 80% found frequently in exacerbations of asthma a chitinase-like protein and a chitin binding sequence identity within the species but but that children who become asthmatic domain protein were produced in the yeast B. J. Hales, L. Y. Chai, C. E. Elliot L. A. Hazell, only 20% between species, which would have more frequent rhinovirus infections. Pichia pastoris. From their molecular size W-A Smith, T. K. Heinrich, W. R. Thomas with not be expected to cross react. The type C It is proposed that serological studies will they were glycosylated to a similar level M.M.H. Kusel, P. D. Sly and P. G. Holt from Cell is a newly identified species that has been be able to show if the increased infection is to the natural allergens that included the Biology and Clinical Sciences especially associated with lower respiratory associated with lower antibody titres to the extensive glycosylation of Der p 15. Circular

52 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 dichroism revealed a high degree of secondary fluoroimmunoassay (DELFIA). Studies with the structure with the expected amount of beta Fel d 1 allergen showed that the IgE binding sheet and alpha helix demonstrated for the was only detected when both the IgE antibody family 18 hydrolases homologous to Der p 15. and allergen were present and there was no IgE binding with adults showed that antibodies binding when IgE was depleted with IgE receptor were restricted to subjects that had anti-Der p transfected RBL cells. IgG depletion in contrast 1 and 2 antibodies but that the titres to Der p increased the CD23 binding titre. Mouse CD23 15 and 18 correlated with each other but not to did not bind human IgE-allergen complexes Der p 1 or Der p 2. They also did not correlate showing the expected species specificity. with responses to the Der p 5 and 7 allergens, which correlate with each other and Der p 1 and 2. Since Der p 15 and 18, which only have Invited Presentations 29% sequence identity, do not cross react the results show a coordinated regulation of W. R. Thomas. Guest workshop speaker. responses to these allergens that is different to American Academy of Allergy Clinical the coordinated regulation of Der p 1, 2, 5 and Immunology, Dust mite allergens. Molecular 7. The regulation of IgE responses to allergens mimicry of lipopolysaccharide-binding proteins therefore depends on the allergen and not and allergic sensitization. San Francisco, USA just to host factors or on non-specific adjuvant activity associated with the source of the allergen. External Committees. W. R. Thomas. IUIS-WHO International Allergen CD23 binding assay in cat allergy Nomenclature Committee L. Y. Chai, C. E. Elliot, T. K. Heinrich, W. R. Thomas W. R. Thomas. World Allergy Organization and B. J. Hales Committee on Aeroallergens The ability of complexes of IgE antibodies and allergen to bind to the low affinity CD23 IgE receptor was studied. The extracellular portion of human CD23 was produced as a recombinant polypeptide fused to a coiled coil leucine zipper that promotes the formation of trimers, similar to how they are found in found in nature. The CD23 was isolated by size exclusion chromatography as a trimer and coated onto microtitre wells and used to capture IgE immune complexes produced by the incubation of allergen and sera from allergic subjects. The binding was read out with anti-IgE antibodies in a dissociation enhanced lanthanide

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 53 paediatric respiratory physiology

Overview parenchymal mechanics as assessed by the • Assess the impact of early life exposure are more severe and sensitive to respiratory low-frequency forced oscillation technique to air pollution on respiratory symptoms symptoms in those with BPD. The Paediatric Respiratory Physiology (LFOT) and by ventilation inhomogeneities during infancy Funded by: Princess Margaret Hospital research group was established in mid 2010 as determined using multiple breath In 2011 we continued to recruit for this Foundation with the appointment of A/Prof Graham washout (MBW). Further, we hypothesise project with ~80% of eligible (non-smoking) Hall by the Telethon Institute of Child Health that those infants with increased pulmonary pregnant women agreeing to participate. Research. The primary aim of the group is the inflammation will have correspondingly poorer Ongoing research is aimed at integrating the Investigation of the influence preterm assessment of lung growth and development peripheral respiratory function. The goals of assessments of air pollution during pregnancy birth on lung structure and function this study are to evaluate these established in both health and in respiratory disease, and lung function measures in infancy. in school age children including asthma, cystic fibrosis and chronic standardised, objective measurements of Funded by NHMRC lung disease of prematurity. respiratory function and their combined ability Graham Hall, Andrew Wilson, Jane Pillow, to detect and monitor the presence of lung Andrew Maiorana, Shannon Simpson, Karla disease early in the life of infants and young Logie. children with cystic fibrosis. Cystic Fibrosis Long term outcomes following Bronchopulmonary dysplasia (BPD) remains Funded by NHMRC, USA Cystic Fibrosis preterm birth the most significant chronic lung complication Evolution of airway function and Foundation of premature birth. Contemporary BPD is inflammation in early CF lung disease Characterising respiratory health of dominated by peripheral lung abnormalities young children born preterm including failed alveolarisation with a Graham Hall, Stephen Stick, Sarath Indoor air pollution and lung decreased number of large and simplified Ranganathan (VIC), Shannon Simpson Graham Hall, Maureen Verheggen, Andrew alveoli and abnormal pulmonary vascular and Karla Logie as part of the AREST CF health Wilson, Stephen Stick, Jane Pillow development. The few studies to examine collaboration (www.arestcf.org) the long term respiratory outcomes in Impact of exposure to air pollutants Advances in neonatal care have resulted Cystic Fibrosis (CF) is a condition of chronic in the survival of increasingly premature new BPD have demonstrated impaired during the prenatal period on lung inflammation and infection resulting in infants and changed the clinical presentation gas transfer reduced cardiopulmonary function in infancy destruction of lung architecture eventually of bronchopulmonary dysplasia (BPD). The exercise capacity, gas trapping and increased leading to death. We and others have shown respiratory morbidity. None of these studies Graham Hall, Peter Franklin, Zoltan Hantos long-term respiratory outlook for young that infants and young children with CF show children born premature is not known. We undertook a comprehensive assessment evidence of early inflammation and infection and Mark Tan with the Peel Child Health Study of lung structure, peripheral lung function (www.peelchildhealthstudy.com.au) aimed to characterize the lung function of and reduced lung function highlighting this young children born preterm in the surfactant and respiratory morbidity and examined the as a crucial period for intensive and new This project aims to assess the impact of era, who are now aged between 4 and 7 influence of neonatal history on the long term treatments to prevent progression or even prenatal environmental exposures on lung years by measuring lung function using outcomes of new BPD. Studies of this nature reverse lung disease. However, the evolution function in infancy. In particular we wish to: Forced Oscillation Technique, Multiple Breath are essential and will provide an improved understanding of the pathology of new BPD of peripheral airway pathology in early • Determine the impact of air pollution, Washout, Diffusing Capacity, and Spirometry. and its long term outcomes and allow a more infancy is poorly understood and ongoing particularly indoor air pollution, during We found children born preterm have worse targeted approached to the treatment and relationships between peripheral respiratory the prenatal period on lung function in lung function than healthy controls and management of infants with BPD through the function and measurements of pulmonary infancy. that lung function worsened with increasing inflammation or infection remain unknown. severity of disease. Symptom prevalence was neonatal period and into childhood. The aims • Investigate the different measures of We hypothesise that infants with cystic similar in preterm children irrespective of BPD of this project are to: infant lung function for detecting early fibrosis will demonstrate abnormal peripheral status. These results suggest that children born • obtain novel information regarding lung changes in response to prenatal lung function manifested as altered lung preterm have distal lung abnormalities which lung structure in preterm children environmental exposures.

54 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 with and without a history of new Asthma Staff and Students Theses passed bronchopulmonary dysplasia BPD using HRCT scanning of the chest. Characterising objective lung function Head of Division Maureen Verheggen; Master of Medical Science • assess peripheral lung function using tests in young children with recurrent “Respiratory outcomes in young children born sensitive to the pathophysiological changes wheeze Graham L. Hall; BAppSci, PhD, CRFS, FANZSRS preterm in the surfactant area” encountered in children with BPD Associate Professor (Adjunct), Centre for Child Graham Hall, Andrew Wilson, Stephen Stick, Health Research, University of Western Australia • determine the response to a maximal Shannon Simpson, Afaf Al Bloushi Associate Professor (Adjunct), Faculty of Health cardiopulmonary exercise test (CPET) in Sciences, Curtin University Awards Summary: Asthma results in episodic wheezing children with and without BPD. Senior Respiratory Scientist in Charge, and is associated with cough and shortness of Graham Hall, Telethon Institute for Child Health Respiratory Medicine, Princess Margaret • assess the importance of the relative effects breath. In the majority of cases of persistent Research PhD Supervisor of the Year of prematurity, neonatal lung disease and Hospital asthma, symptoms begin in early life with Chris O’Dea, “Excellence in respiratory other perinatal factors on alterations in longitudinal studies suggesting that ~40% of measurements” at ANZSRS ASM lung structure, function and respiratory children who wheeze in the first 3 years of Research Staff Chris O’Dea, Curtin Award at ASMR WA annual morbidity. life were still wheezing at 6 years. Patterns symposium Key findings in 2011 were that of wheeze prevalence and lung function are Mr Chris O’Dea B. Med Sci (Resp Hsci) Hons – Shannon Simpson, European Respiratory Society • All preterm children have abnormal lung established by 6 years and do not change Senior Respiratory Scientist significantly by age 16. The pre-school years Young Scientist Fellowship structure, irrespective of the presence of Ms Judy Park BSc MBiostat BPD. are therefore the time in which the most Shannon Simpson, Ian Potter Foundation Travel Dr Shannon Simpson PhD – Research Officer important alterations in lung function develop Grant • Children with a history of BPD are twice in susceptible individuals. In most asthmatics Ms Maureen Verheggen M Med Sci – Senior a likely to exhibit exercise flow limitation Shannon Simpson, Australasian Cystic Fibrosis airway obstruction and its reversibility Respiratory Scientist when compared to preterm children are quantified using spirometry. However Conference; Best Poster Award Dr Andrew Wilson Paediatric Respiratory without BPD. spirometry requires considerable patient Maureen Verheggen, Maddison Scholarship coordination and is not feasible for widespread Physician • Respiratory symptoms such as wheeze Maureen Verheggen, WA Respiratory Science use in young children. Lung function techniques, Ms Georgia L Banton BSc – Research Assistant and shortness of breath with exercise are Travel Award significantly increased in children born such as the forced oscillation technique (FOT) preterm. do not require active cooperation and are ideal for use in young children The use of these Postgraduate Students Funded by NHMRC, Raine Foundation and techniques to assess lung function in young External Committees Princess Margaret Hospital Foundation children with recurrent wheeze may have major Ms Afaf Al Bloushi BSc PhD Candidate implications for our understanding of asthma Ms Karla M Logie BSc(Hons) PhD Candidate International pathophysiology in this age group. This study Mr Chris O’Dea PhD, B. Med Sci (Resp Hsci) Graham Hall, Joint American Thoracic Society - is investigating the influence of respiratory Hons European Respiratory Society Working Party on history and symptoms on lung function and Infant Lung Function Testing (2003- ) bronchodilator responsiveness (BDR) in young Mr Mark Tan MSc PhD Candidate children using the FOT and MBW techniques. Mr Tim Rosenow BSc Grad Cert Paed Resp Sci – Graham Hall, European Respiratory Society Global Lung Initiative Task Force: Co-Chair (2008 Honors Student - ) Graham Hall, Joint American Thoracic Society -

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 55 European Respiratory Society Task Force for “Respiratory Mechanics in the ventilated child: Provocation testing guidelines (2010 - ) The role of the forced oscillation technique” Graham Hall, European Respiratory Society Annual Congress Paediatric Respiratory Physiology Abstract review committee ACTIVE collaborations Graham Hall, Editorial Board; Respirology (Jun Royal Perth Hospital, Respiratory Medicine, 2011 – Ongoing) Perth - Dr Kevin Gain Graham Hall, Editorial Advisory Panel; Expert King Edward Memorial Hospital, Neonatology, Review of Respiratory Medicine (Oct 2006 – Perth - Prof Jane Pillow, Assoc Prof Noel French Ongoing) and Dr R Hagan, Dr Mary Sharp University of Western Australia, Perth - A/Prof National Dr Peter Franklin, A/Prof Sunalene Devadason Royal Children’s Hospital, Melbourne - Dr Graham Hall, Thoracic Society of Australia and Sarath Ranganathan New Zealand Professional Standards Sub- committee (2008 - ) University Children Hospital, Zurich Switzerland - Dr Alex Moeller Graham Hall, Thoracic Society of Australia and New Zealand Paediatric Special Interest Group: University Children Hospital, Vienna Austria - Convenor (2007 – Mar 2011) Dr Fritz Horak Institute for Child Health, London UK - Prof Janet Stocks Local University of Szeged, Hungary - Prof Zoltan Graham Hall, Western Australian Health Hantos Department: Health Professions Strategic Erasmus University, Rotterdam, The Reference Group (2007 - ) Netherlands - Prof Philip Quanjer Graham Hall, Asthma Foundation of Western Australia Board member (2010 – )

Invited Presentations Graham Hall, ANZSRS Progression of Cystic fibrosis lung disease mini-symposium: “Respiratory physiology and Cystic Fibrosis lung health: Which test for what age?” Graham Hall, ATS Workshop: Evaluation of respiratory mechanics and function in the ICU

56 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 population sciences

Overview working relationships with government and remained the same. Pneumonia is a serious Common stressful events included financial and community partners with the overall aim of illness and a common reason for children to relationship problems, difficult pregnancy, job The Division of Population Sciences is the ensuring that Western Australian’s children are be admitted to hospital. Around one-fifth of loss and issues with other children while major largest Division within the Telethon Institute. happy and healthy. This means that Western childhood deaths globally – approximately life stressors were events such as a death in the The Division conducts a wide range of research Australian families are supported to enable their 2 million per year – are due to pneumonia. family. This study found that the overall number with a focus on multidisciplinary studies in the children to achieve an optimal level of social, The research team supports the continued of stresses is most related to child behaviour areas of developmental disorders, nutrition, emotional, academic, and vocational wellbeing. monitoring of pneumonia trends in high-risk outcomes. Two or fewer stresses during indigenous health, developmental health, populations to fully understand the impact of pregnancy are not associated with poor child childhood cancers, services for children and pneumococcal vaccination and other public behavioural development, but as the number families, and mental health. Highlights for 2011 health interventions. of stresses increase to three or more, then the risks of more difficult child behaviour increase. The Division has a staffing mix of around 200 In April, the results of the Australian Early In February, researchers from the Division What this study says is that we as a community staff and students that include a wide range Development Index (AEDI) were released. uncovered more evidence for a link between need to target pregnant women with support of different research specialists including Researchers within the Division have played early testosterone levels and autism. The study programs to ensure stress does not negatively epidemiologists, clinicians, developmental an integral role in the planning and delivery used data from the long-running Raine Study to affect their unborn child. psychologists, biostatisticians, sociologists and examine the relationship between autism-like of the AEDI in collaboration with the other social scientists. The Division has a focus behaviours in early childhood among otherwise Australian Government and State and Territory In July, a new study from the Division showed on collaboration in particular with government typically developing girls and the timing of their Governments and working in partnership with that late-talking toddlers are no more likely agencies as a means of translating the results first period. The research found that girls with the Centre for Community Child Health at to experience behavioural and emotional of our research into policy and practice where autism-like symptoms such as poor eye contact Murdoch Children’s Hospital. The AEDI results difficulties during childhood and adolescence it can make a real difference to the lives of and repetitive behaviours were older at the time report on 261,147 children (97.5 per cent of the than children who have normal language Western Australians. of their first period. These findings suggest a estimated five year old population) throughout development. Dr Whitehouse said the results Australia from data collected during their first offer reassurance to parents of late-talkers that The Division prides itself on the breadth of common developmental mechanism underlying year of school in 2009 to provide a snapshot of their language delay is not in itself a risk factor research methods utilized across our research both autism and the later onset of puberty. children’s health and development in different for later behavioural and emotional problems. groups. Our quantitative researchers use This study is in line with previous findings by communities. The AEDI results provide The findings of this study suggest that parents mathematical modelling and other biostatistical researchers within the Division which has shown communities with rich information about how should not be overly concerned that their techniques to identify patterns and trends a positive association between concentrations their young children are developing. This late-talking toddler will have language and in child health. They may be working with of testosterone taken from umbilical cord information can be used to encourage parents, psychological difficulties later in childhood. databases that have thousands and thousands of blood and autism-like symptoms in 10 year old families and leaders to come together and focus records collected over decades. Our qualitative children. Also in July, researchers from the Division on specific things that can be done to enrich researchers will utilise mixed methods including showed that parents have an important role to Also in February, research from the Division and extend developmental opportunities and focus groups, one on one interviewing and play in teaching their children to understand showed that the Western Australian expectations for families and children that are participatory action research techniques to another person’s feelings and point of view. pneumococcal vaccine program has contributed doing less well than others. explore the opinions, perceptions and views of to closing of the gap in serious infections in The study found that mothers who have parents and families on a variety of issues. Aboriginal children. This study found that Also in April, researchers from the Division found higher levels of empathy were more likely to a link between the number of stressful events encourage their children to think how others The Division’s commitment to prevention and hospitalizations for pneumonia across Western experienced during pregnancy and increased might be feeling, which in turn was associated early intervention is seen by our collaborative Australia have declined in Aboriginal children while rates for non-Aboriginal children have risk of behavioural problems in children. with greater development of empathy skills in

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 57 the child. What this means is that children caesarean for other than medical reasons. Australia, which together with Sweden had This exposure model was then “tested” by with more advanced perspective-taking skills the lowest rates. There was little variation application to a study on asthma emergency In November, a study by Divisional researchers behave more positively with other people. between countries in the rate of maltreatment department presentations, published in the found more evidence that reading books to The study reinforces the importance of parents related injury admissions and officially Medical Journal of Australia (2010). Exposure young children and helping them visually to in modelling good social behaviour in early recognised physical abuse or neglect. New to traffic-related air pollution was associated follow the story improves a child’s language. childhood. It supports previous research that Zealand and USA has substantially higher child with increases in emergency department The study investigated the factors that found that warm and responsive parenting protection investigations while placement presentations, and the observed effects facilitate children’s language (vocabulary) in infancy also promotes the development of in out of home care was ten times higher in were considerably greater than previously development between 9 and 34 months of prosocial behaviour. Manitoba, Canada than in other countries, reported in Australia. A new method to age using data from Growing Up in Australia: and twice as high for infants in England, New generate a map of disease risk was also In October, a study within the Division found the Longitudinal Study of Australian Children Zealand and the USA than in WA or Sweden. developed and published in Health and Place a link between traffic emissions and reduced (LSAC). The study found that higher levels of This research reinforces the need to improve (2009). The impact of geographic variation of fetal growth. The study showed that a parent-child book reading are associated with the evidence base for child protection policies. socioeconomic status using these maps, which neonate who would have otherwise attained significantly better child language (vocabulary) was peer reviewed as a full paper at the State an optimal birth weight of 3.5 kg would be development. Also children with more of Australian Cities Conference (2009). expected to be born 58 g lighter. The results educated mothers have larger vocabularies reflect about half of the effect observed for because they engage in more parent-child Air pollution We examined whether proxies, such as traffic maternal smoking during pregnancy among book reading. The study also confirmed counts, were appropriate substitutes for direct this group. These results were surprising previous research demonstrating a gender gap The influence of ambient air pollution measurement of air pollutants but found that because these effects were observed when air favouring girls, who had a significantly greater from traffic emissions and pregnancy this was not the case; International Journal quality guidelines met national standards. vocabulary than boys at around 3 years of age. outcomes of Health Geographics (2009). Consequently, funding was obtained from the CRC for Asthma Also in October researchers from the Division Finally, a study released in December found Gavin Pereira (ICHR), Angus Cook (UWA), and Airways and passive air sampling (nitrogen found that babies born by elective caesarean that rates of child maltreatment over the Natasha Nassar (USyd), Carol Bower (TICHR), dioxide) was undertaken throughout the Perth are more likely to be admitted to hospital with last two decades in developed countries has Nick de Klerk (TICHR), Phillip Weinstein metropolitan area in 2010. During this period the serious respiratory infection, bronchiolitis, not consistently decreased despite a raft (UniSA), Eve Blair (TICHR), Fatima Haggar of field work, a computer model (dispersion in the first year of life. Although the effect of policy initiatives. The study used three (Ottawa Hospital, Canada). model) for traffic emission exposure was was relatively modest, it is the first study types of indicators of child maltreatment - International research and animal studies applied to investigate fetal growth restriction to link elective caesareans to bronchiolitis. violent deaths in children, injuries related indicate the potential for adverse effects among a small population. We found that Bronchiolitis, generally caused by the common to maltreatment and involvement by child of traffic emissions on various pregnancy traffic-related air pollution (carbon monoxide) respiratory syncytial virus (RSV), is one of protection agencies, and compared these outcomes, as summarised in our review was associated with restricted fetal growth, the most common reasons for babies to across different countries. The study found article published in the journal Surveys although the effects were limited to one of the be admitted to hospital. Bronchiolitis also large variations between countries in the and Perspectives Integrating Environment three study areas; Australian and New Zealand has been shown to be associated with an frequency of involvement by child protection and Society (2010). A statistical model for Journal of Public Health (2011). A study on increased risk of asthma in children. This study agencies, but much less variation in rates of ambient air pollution (criteria pollutants) the seasonal variation in fetal growth was also has implications to the rising caesarean rates maltreatment-related injury or violent death, was developed and peer-reviewed as a full conducted to distinguish whether the variation in Australia and this potential impact on the reflecting differences in government policies. paper through submission to the International in growth was due to pollutants or weather, immune system might be another factor that It also found that violent deaths in the USA Clean Air and Environment Conference (2009). and found that fetal growth restriction parents and doctors may consider if choosing a were more than five times higher than in

58 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 was associated with higher temperatures, award, Commercialisation Training Scheme contributions to policy and practice; other Alcohol and Pregnancy: Educational independently of pollution; American Journal award, UWA GRST grant alcohol and pregnancy projects in Australia; Resources for Health Professionals of Obstetrics and Gynecology (2011). At the alcohol and pregnancy publications involving completion of the field work, a exposure model Telethon Institute researchers; resources; Jan Payne, Carol Bower, Kathryn France, Nadine Henley, Heather D’Antoine, Anne Bartu, Colleen was developed using field measurements of a Birth Defects and Developmental community participation; alcohol guidelines; marker for traffic emissions (nitrogen dioxide), living with a child with a FASD; where to go for O’Leary, Elizabeth Elliott, Elizabeth Geelhoed, traffic counts, temperature and a range of Disorders assistance and links to sources of Australian Lynda Blum, Roslyn Giglia, Janet Hammill, Ray other inputs. The papers reporting the effects and international information for parents/ James (dec’d), Christine Jeffries-Stokes, Anne of this exposure on fetal growth, preeclampsia Alcohol and Pregnancy: carers, health professionals, workers in health, Mahony, Daniel McAullay, Anne McKenzie, Raewyn Mutch. and stillbirth are currently under review. To In the late 1960’s researchers in France and education and justice sectors, politicians summarise these studies, we observed strong the US were documenting the development and researchers. The Alcohol, Pregnancy The Alcohol and Pregnancy Project (2006-2008) support for (i) a weak effect of traffic-related air of children born to alcoholic mothers. Dr and FASD website can be viewed at http:// provided educational resources for Western pollution on fetal growth, (ii) a weak effect on Kenneth Lyons and Dr David Weyhe Smith alcoholpregnancy.childhealthresearch.org.au. Australian (WA) health professionals to inform risk of preeclampsia, and (iii) a strong effect on from the University of Washington Medical In 2011 submissions were made to the House them about the prevention of prenatal alcohol stillbirth. School identified a pattern of facial, limb and of Representatives Standing Committee on exposure and Fetal Alcohol Spectrum Disorder We also conducted a study to validate a cardiovascular defects in 1973 and called it Fetal Social Policy and Legal Affairs Inquiry into Foetal (FASD). Studies conducted in WA in 2002 and measure used to assess fetal growth using serial Alcohol Syndrome (FAS). Over time research Alcohol Spectrum Disorder and the Western 2004 showed that WA health professionals were ultrasound scans from the RAINE cohort (under has identified a range of effects (including Australian Government Health Standing poorly informed about alcohol consumption in review). physical, behavioural and cognitive) that can Committee Inquiry into improving educational pregnancy and Fetal Alcohol Syndrome (FAS). arise from prenatal alcohol exposure. The outcomes for Western Australians of all ages The majority of these health professionals The findings of these studies were presented term Fetal Alcohol Spectrum Disorders (FASD) (specifically item 5 Fetal Alcohol Syndrome: requested educational resources for themselves at national and international conferences, has developed to include FAS as well as other prevalence, prevention, identification, funding and information to give to clients. These including: the Conference of the Royal Society conditions resulting from prenatal alcohol and treatment to improve education, social and results led to the formation of the Alcohol and of Public Health (London, 2011), the Conference exposure. The first studies of FAS in Australia economic outcomes). Pregnancy Project. of the International Society of Environmental were published between 1978 and 1983. The Epidemiology (Barcelona, 2011), the Annual A highlight of 2011 was the introduction of We developed educational resources for WA Alcohol and Pregnancy team at the Telethon Meeting of the Australasian Epidemiology the Social Security and Other Legislation health professionals using formative research. Institute has been at the forefront of research Association (Sydney 2010, Perth 2011), the Amendment (Miscellaneous Measures) Bill into We used project management and incorporated and involvement in the translation into policy Annual Meeting of the CRC for Asthma and the Federal Parliament. This Bill called for the consumer and community representatives’ and practice. Between 2000 and 2011 Telethon Airways (Sydney 2010), the Pacific Basin Parliament to continue to facilitate and support expertise into all aspects of the project. In 2007, Institute researchers have been authors on 46 Consortium Conference (Perth, 2009) and the the development of a FASD national diagnostic the educational resources were distributed published papers on alcohol and pregnancy. As Australia-China Biomedical Research Conference tool for use by medical professionals and other to 3,348 health professionals (Aboriginal part of our aspiration to provide information (Tianjin China, 2009). health service providers, to give FASD the status health workers, allied health professionals, on alcohol and pregnancy a new website of a recognised disability in Australia, and to community nurses, general practitioners and Funders of the project: Australian Postgraduate was launched in 2011. The website includes institute a national awareness campaign, among obstetricians), and to 159 paediatricians. Award, University Postgraduate Award, Perron general information on alcohol and pregnancy other calls. FASD is currently not recognised as a Six months later, we surveyed 1,483 health award, CRC for Asthma and Airways award, in addition to the following: current Telethon disability by the Australian Government. professionals and 133 paediatricians. We Australia China Society for Biomedical Research Institute projects on FASD; previous projects; compared health professionals’ responses

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 59 with results from 2002 and paediatricians’ in pregnancy (based on very small numbers). reports on consumer and community Australia. A panel of 139 health professionals with results from 2004 using prevalence rate Fifteen researchers (93.8%) and seven (53.8%) participation and project management in from Australia (92.2%) and overseas (7.8%) ratios and 95% confidence intervals. At the consumer and community representatives health and medical research. Our research were recruited based on their expertise or end of the project we conducted a survey to completed an evaluation questionnaire and has made a unique contribution to knowledge involvement in FASD screening or diagnosis. evaluate researchers’ (n=16) and consumer both thought that consumer and community and the evidence base about the role The response rates for rounds 1 and 2 of the and community representatives’ (n=13) participation had significant influence on the of educational resources in the primary survey were 74.1% and 85.4% respectively. Of perceptions of the process, context and impact success of project outputs and outcomes. prevention of prenatal alcohol exposure and these health professionals 74.8% were female of consumer and community participation in Fifteen researchers (93.8%) completed a FASD, and to good practice in health and and 25.2% male with the majority (43.7%) the project. We also conducted a post-project post-project review and reported that project medical research in the areas of consumer being paediatricians. Only 25.7% of health review of researchers’ (n=16) opinions on management increased the effectiveness of and community participation and project professionals had completed any specific project management and whether it made a the project, communication, teamwork, and management. training on FASD diagnosis. Community difference to the project. application of researchers’ expertise. The conversations were held in Perth and Cairns Funders of the project: Health Promotion evaluation of the project showed that although with 32 women who expected their health The response fraction for health professionals Foundation of Western Australia, Healthway the measure of effect was not large, the professional to provide information on alcohol was 67.7%. Of these, 69.8% had seen the Project Grant #15177; NHMRC Program Grant extent of change has public health significance use in pregnancy. The women also saw merit educational resources and of these, 77.1 #353514 (JP, HD’A, CO’L); NHMRC Enabling because the reach was extensive. in having a standard set of questions for all % had used them. Comparing results from Grant #402784 (EE); NHMRC Fellowships pregnant women that included a question 2002 with 2007, there was a 35% increase Following the distribution of the educational #353628 (CB) and #457084 (EE). about alcohol use in pregnancy. A final in the proportion who knew all the essential resources to WA health professionals, we report was submitted to the funding body, features of FAS and there was a 52% increase demonstrated some improvement in their the Department of Health and Ageing (DoHA) in the proportion who had diagnosed FAS. knowledge, attitudes and practice in relation Development of a Diagnostic in September 2011. Papers based on the There was no increase in the proportion who to alcohol consumption in pregnancy and Instrument for Fetal Alcohol research are being prepared for publication. routinely asked about alcohol consumption, FAS. FASD is a serious public health problem. Spectrum Disorders in Australia (FASD but there was a 31% increase in the proportion The educational resources have potential Project) Funders of the project: Department of Health that routinely provided information about to increase health professionals’ capacity and Ageing; NHMRC Program Grant #572742; the consequences of alcohol consumption to reduce prenatal alcohol exposure and Winthrop Research Professor Carol Bower NHMRC Fellowship #634341 (CB) in pregnancy. The response fraction for FASD. They are novel products that have & Professor Elizabeth Elliott AM (lead paediatricians was 61.7%. Of these, 65.9% had been evaluated and sustained into routine investigators), Dr Rochelle Watkins & Heather seen the educational resources and of these, organisational practice. We also demonstrated Jones (project staff) and the Steering Group: Evaluation of information and 66.7% had used them. Comparing results that consumer and community participation Dr Lucinda Burns, Maureen Carter, Heather services for parents/carers of from 2004 with 2007, there was no increase made a difference to this research and D’Antoine, Dr James Fitzpatrick, Associate children with a Fetal Alcohol in the proportion who knew all the essential participation was valued by community and Professor Jane Halliday, Lorian Hayes, Spectrum Disorder features of FAS or who had diagnosed FAS, and consumer representatives and researchers. Associate Professor Jane Latimer, Anne no increase in the proportion who routinely Project management was comprehensively McKenzie, Sue Miers AM, Dr Raewyn Mutch, Dr Amanda Wilkins (lead investigator), asked about alcohol consumption when taking endorsed by researchers and contributed Dr Colleen O’Leary, Jan Payne, Dr Elizabeth Winthrop Research Professor Carol Bower and a pregnancy history. There was a 93% increase substantially to the research and benefited Peadon, Elizabeth Russell, Dr Amanda Wilkins. Heather Jones in the proportion that provided information both management and scientific outcomes. A modified Delphi process was used to assess Focus Groups have been held in Perth and on the consequences of alcohol consumption There are very few previously published expert consensus on the diagnosis of FASD in Bunbury to explore events that prompted

60 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 parents/foster carers to consider FASD, what criminal justice system Research and Education (FARE) Funders of the project: Australian Postgraduate initial advice they received, what screening Award (LC). NHMRC Program Grant #572742; and diagnostic services they were advised to Dr Raewyn Mutch (lead investigator), Winthrop NHMRC Fellowship #634341 (CB) utilise, what the nature of diagnostic services Research Professor Carol Bower and Heather Pharmacovigilance in pregnancy using has been, what therapeutic services have been Jones population-based linked datasets used, what information and services have they In response to comments from lawyers about Harmful Maternal Alcohol Lyn Colvin, Linda Slack-Smith, Fiona Stanley, found on their own initiative and finally what the inevitability of some children ending up in Consumption and Cerebral Palsy in the Carol Bower are the key elements for new resources and the criminal justice system Retired District Court offspring support services. A further two focus groups Chief Judge, Justice Antoinette Kennedy stated Recent studies have reported links O’Leary CM, Watson L, D’Antoine H, Stanley F, are planned with Aboriginal foster carers in the “If we know it’s inevitable, why aren’t we doing between prenatal exposure to the group of Bower C Perth metropolitan area. A survey will also be more about it.” In 2011 research commenced antidepressants known as selective serotonin conducted with staff within key government looking at the ‘Knowledge, attitudes and practice reuptake inhibitors (SSRIs) and increased risk Heavy alcohol use by pregnant women places and non-government foster care and support of FASD within the WA criminal justice system’. of adverse pregnancy outcomes. Using data the baby at risk of a range of poor outcomes agencies on what resources and information This project aims to find out what people within linkage of population-based health datasets classified as Fetal Alcohol Spectrum Disorders. they have available to provide to foster carers the justice sector know about FASD, their from Western Australia and a national Cerebral palsy has for many years been thought and for their own professional development. attitudes towards children and adolescents pharmaceutical claims dataset, we investigated to be one of these outcomes but the evidence A Reference Group with representatives from who may have a disorder in the spectrum and the morbidity and mortality outcomes in to support this assumption was weak. As the South West Foster Families, Foster Care their current practices in dealing with FASD. A children born to mothers who were dispensed cerebral palsy is very rare, research examining Association of WA, Wanslea, NOFASARD and Reference Group comprising representatives an SSRI in pregnancy (3,703 women; 3,764 this association is difficult to undertake and Child and Adolescent Community Health from WA Police, Law Society of Western children). previous studies had small numbers of children Aboriginal Health Team is aligned with the Australia, Legal Aid, Department of Corrective with cerebral palsy. We used routinely collected Mean birth weight, length, and APGAR score at Telethon Institute’s policy that consumers and Services, Children’s Court Judge, National health data to identify the children of mothers 5 minutes were significantly lower in children researchers collaborate and draw on each Organisation for Fetal Alcohol Syndrome and with an alcohol-related diagnosis, a proxy for of women dispensed an SSRI, regardless of other’s knowledge to build on and strengthen Related Disorders (NOFASARD) and the Foster heavy alcohol consumption, and a randomly whether the SSRI was dispensed in trimester the quality of health and medical research. Care Association of WA is guiding the project selected group of children of mothers without 1, or, trimester 2 or 3 only. 0.9% of the live The outcomes from the focus groups will and assisting with the development of questions an alcohol-related diagnosis. The birth data for born children exposed to SSRIs had died before be analysed and reported back to the focus for the survey of staff within the justice sector. the children were then linked with data from the the age of 1 year compared with 0.5% of the group participants prior to a final report being The survey will have two components: a general Cerebral Palsy Register to examine the risk of unexposed children (odds ratio (OR) 1.8; 95% submitted to the funding body the Foundation section for all participants on demographics and cerebral palsy in these two groups of children. CI 1.3-2.6). Before the age of two years, 42.9% for Alcohol Research and Education (FARE) in knowledge of FASD and a sector specific set of There were 23,880 children of mothers with an of the exposed children had been admitted to June 2012. questions for police, judges and magistrates, alcohol-related diagnosis and 293 children with hospital after their birth admission, compared corrective services staff and lawyers. The project cerebral palsy in our study. Funder of the project: Foundation for Alcohol with 34.1% of the unexposed children (1.4; 1.3- also aims to identify training and information Research and Education (FARE) 1.6). This may reflect their prenatal exposure We found a three-fold increased risk of pre/ needs relating to FASD across the justice sector to SSRIs, be related to maternal depression, or perinatally acquired cerebral palsy in children so people with a FASD receive appropriate SSRI use may be a proxy for an environmental of mothers with an alcohol-use disorder. We consideration and referral for services. Knowledge, attitudes and practice of exposure such as smoking, or a combination of also found an eight-fold increased risk of post- FASD within the Western Australian Funder of the project: Foundation for Alcohol these factors. neonatally acquired cerebral palsy for non-

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 61 Aboriginal children of mothers with an alcohol of children identified with an intellectual heavy alcohol consumption during pregnancy which are of comparatively low prevalence. diagnosis, but not for Aboriginal children. disability from the Department of Education and intellectual disability in the offspring; Despite numerous studies investigating This study provides the strongest evidence and the Disability Services Commission to the pregnancy and birth factors associated the association between pre- and perinatal that harmful maternal alcohol consumption end of 2008. These records are linked by the with intellectual disability and autism; factors and autism, many relationships remain is a potentially modifiable risk factor for both Western Australian Data Linkage Unit (DLU) hospitalizations in children with intellectual unclear, often because sample sizes are small pre/perinatally and post-neonatally acquired to each other and to all current notifications disability and autism: and the pattern of and methodologies vary across research cerebral palsy. on the database in order to minimise any hospitalizations for children with Down groups and countries. To overcome these duplications. Medical information on cause syndrome. limitations, the International Collaboration Funders of the project: This study was of intellectual disability is provided from for Autism Registry Epidemiology (iCARE) supported by an Australian National Health The IDEA Database is overseen by the IDEA Disability Services Commission. was established among researchers from and Medical Research Council (NHMRC) Public Advisory Council. The current members Denmark, Sweden, Finland, Norway, Western Health (Australia) Fellowship (594451) (Dr. Analysis of prevalence rates for intellectual are Professor Carol Bower (Chair), Dr Australia, Israel and the US. The aim of this O’Leary), NHMRC program grant number disability calculated on the WA births from Helen Leonard, Jenny Bourke, (TICHR), initiative is to demonstrate the capabilities of a 353514 (2005-09), and an NHMRC Research 1983-2003 and ascertained up to 2008 gives Dr Vera Morgan (UWA), Richard Sanders multi-national registry approach to investigate Fellowship (353628) (Dr Bower). Dr. O’Leary a rate of 17.6/1000 live births. This is an (Department of Education), Robyn Cooksey pre- and perinatal factors and autism, autism was partially funded by infrastructure grants increase on the previous prevalence rate of (Department of Education), Kerry Stopher trends and variation across countries. As all from Curtin University and the Western 14.3/1000 live births, calculated using births (DSC), Nick Cantatore (DSC), Dr Peter Chauvel sites have access to complete birth population Australian Drug and Alcohol Office. from 1983-1992 and ascertained up to 1999. (Paediatrician), Dr Peter Rowe (State Child data for their respective countries/states from Whilst more recent data are not yet available, Development Centre) and Charlie Rook which the cases of autism are ascertained, further analysis undertaken suggests that (Consumer). data from the multi-national registries have the prevalence of mild-moderate intellectual Intellectual Disability Funders of the project: Disability Services been used to create a common, harmonised disability may have increased among children Commission set of variables across all sites. Using a born in the nineties. This will be further IDEA - Intellectual disability exploring computational infrastructure designed by investigated to try to identify the reason for answers the bioinformatics team at the Institute, the this rise and whether it might relate to an Multi-Registry Analyses of Pre- and data, which is stored and managed at each Carol Bower, Helen Leonard, Ami Bebbington, increase in the diagnosis of autism spectrum Perinatal Risk Factors for Autism international site, is retrieved on demand and Amanda Langridge, Patrick Fitzgerald, Geoff disorders or another cause. pooled to create a virtual dataset. Analysing Hammond, Jenny Bourke. Michaeline Bresnahan, Kim Carter, Richard Recent articles published in the scientific this dataset allows us to use the power of Francis, Mika Gissler, Raz Gross, Nina Gunnes, The IDEA Database provides an infrastructure literature using data from the IDEA data from all countries/states to investigate Geoffrey Hammond, Mady Hornig, Christina for population-based epidemiological research database have covered the areas of autism, the relationships between pre and perinatal M Hultman, Amanda Langridge, Helen into the causes and prevention of intellectual child maltreatment, evaluation of family- factors and autism. This virtual dataset also Leonard, Anastasia Iliadou Nyman, Erik Parner, disability as well as the outcomes for those centred care for children with intellectual allows cross-country comparisons, and ensures Manuel Posada, Abraham Reichenberg, Diana affected. Information in the database disability, hospital admissions of children that common methodologies are used. There Schendel, Sven Sandin, Andre Sourander, is sourced from data from the Disability and adolescents with single gene and are several papers currently being prepared for Camilla Stoltenberg, Pål Surén and Ezra Susser. Services Commission (DSC) since 1953, as chromosomal disorders and variation over publication. well as information from the Department time in health conditions of children with Population-based disease registry systems Funders of the project: Autism Speaks of Education for births since 1983. IDEA Down syndrome. Investigations currently are extremely important research resources is currently updated with notifications underway include the relationship between especially for conditions such as autism

62 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 The natural history of the CDKL5 disorder register using our InterRett database their days. The study is investigating the factors transition (23-31 years). Two years later in disorder: development of an and study processes as a model. This register at an individual, educational, family, and societal September 2011, follow-up questionnaires were international register aims to collect information from additional level which contribute positively and negatively administered to 228 families and the subsequent cases with the CDKL5 disorder from families to a ‘good’ outcome for the young person and response to date has been pleasing. About the Helen Leonard, John Christodoulou, Meredith and their clinicians to increase the precision of their family. same time, questionnaires were sent out to Wilson, Alison Anderson, Ami Bebbington, our description and will be used to describe the 147 families and care workers of young women This study involves young people with Stephanie Fehr and Jenny Downs natural history of the disorder. As part of this with Rett syndrome aged 16 years and over intellectual disability aged 16 years and over study, a consumer reference group has been throughout Australia, who are also participating The CDKL5 disorder, which is caused by from four separate sources: (i) Down syndrome established comprising mothers of a child with in the transition study. mutations in the cyclin-dependent kinase-like NOW cohort in WA, (ii) the Queensland the CDKL5 disorder from the USA, UK, Australia 5 (CDKL5) gene, is a newly identified cause Centre for Intellectual and Developmental In consultation with the WA research team and and the Netherlands. of early-onset seizures and gross motor and Disability’s ASK study (a five year project aiming based on our model of collection and storage intellectual impairment. In the past some Funders of the project: International Rett to improve the health of young people with of data, the Queensland group developed a children and adults with mutations in the CDKL5 Syndrome Foundation intellectual disability by implementing and questionnaire which they administered to the gene may have been diagnosed with atypical evaluating the effectiveness of a combined parents of the young people, aged between 17 Rett syndrome or infantile spasms. education and health intervention package); and 23 years, in the ASK cohort. The response to In 2011, however, we studied questionnaire The transition from secondary (iii) the Australian Child to Adult Development date is 65% with 54% of these being male. Using and genetic data from 86 families living in 14 school to adulthood: Experiences Study at the University of Sydney and (iv) the the existing ACAD data previously collected different countries (majority being USA and and life outcomes for youth with an Australia-wide Rett syndrome cohort. We used in New South Wales and Victoria we hope to UK) who were participating in our InterRett intellectual disability and their families the World Health Organization’s International compare the effects of legislative and policy Database. We found that only a minority of Classification of Functioning, Disability and differences on employment options between Helen Leonard, Carol Bower, Nick de Klerk, children and adults with the CDKL5 disorder Health (ICF) framework which enables us to states. Gwynnyth Llewellyn, Stewart Einfeld, Trevor take into account the complexity of life and did meet the clinical criteria for Rett syndrome. Preliminary findings from our study suggest Parmenter, Vivienne Riches, Bruce Tonge, acknowledges that many issues come into play We therefore suggest that the CDKL5 disorder that the employment needs of about one third Nick Lennox, Ron Chalmers, John Brigg, Greg which may affect a person’s participation in all is an independent clinical entity. We also of the young people with Down syndrome Lewis, Jackie Softly, Jenny Bourke, Paula Dyke, aspects of life. Environmental factors, which will collected photographs of the face, hands and are not being met, suggesting that services Marie-Louise Collins, Sarah Tocker, Kitty Foley, include family characteristics such as income, feet of the children in 67 families to investigate and interventions may not be adequate or Katherine Bathgate, Terri Pikora, Sonya Girdler availability of transport, parental health and whether these children have any characteristic appropriate for enabling young adults with family functioning, as well as the health of facial features. This work was carried out in This project, which developed from an ARACY Down syndrome to enter the work force. the young person and their individual level of collaboration with Professor John Christodoulou Seed-funding grant, seeks to explore the Based on the 2009 Down Syndrome NOW functioning, may all contribute to the young and clinical geneticist/dysmorphologist Dr challenges faced and outcomes achieved by data, among those who had left school (n=164) person’s participation in society. Meredith Wilson, both from the Children’s young people with an intellectual disability as the most common main day occupation was Hospital at Westmead, Sydney. Examination they move from secondary school into adult In 2009/10 questionnaires were administered sheltered employment (39.0%), followed by of the photographs confirmed that these life. There are likely to be major life changes to 269 families of young people with Down open employment (25.6%) and alternatives to children shared similar features of the face and for these young people as they move into syndrome in Western Australia. Of the 203 employment (ATE) (25.0%) while the remainder hands. In 2011 we also began collaboration adulthood with respect to work, where they (75.0%) returned, 164 (80.8%) had left school (10.4%) attended training. We have found that with the International Foundation for CDKL5 live, who cares for them, how their health and with ages varying from pre-transition (16-17 functioning was related to the type of post- Research to establish a new international CDKL5 therapy needs are managed and how they spend years), early transition (18-20 years) to late school occupation among those who had left

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 63 school. Not unexpectedly young adults who Jenny Downs, Elizabeth Geelhoed, Elizabeth are currently being completed by clinicians children and adults with Rett syndrome. The were reported as functioning better within Elliott, Peter Jacoby, Ian Torode, Gordon Baikie, who request MECP2 testing from one of the decision to proceed with these surgeries self-care, community and communication Mark Davis, Ian McPhee, Madhur Ravikumara, three Australian accredited laboratories. is often difficult for families and there is a skills were more likely to be participating Sue Thompson, Margaret Thomson Carol These are completed prior to the result of need to provide accurate information to both in open employment or training than those Philippe, Ami Bebbington, Amanda Jefferson, genetic testing being known. The goal is to clinicians and families of the short and long in sheltered employment or alternatives to Olivia Knight, Sonya Girdler, Anna Urbanowicz, develop tools to support clinical decision term risks and benefits of these procedures. employment. However we did not find any Kingsley Wong, Katherine Bathgate making to facilitate timely diagnostic testing Currently, there are gaps in our knowledge evidence that poor health status adversely for girls with Rett syndrome, thereby assisting of outcomes. Collection of data from the Rett syndrome is a rare neurological disorder impacted on workplace participation. families in the often stressful early stage when follow-up questionnaire and hospital records generally affecting females and caused by a seeking a diagnosis. has commenced to address these gaps in Further analysis will explore additional mutation in the MECP2 gene. AussieRett, as knowledge and will continue throughout 2012. issues related to employment outcomes to the Australian Rett Syndrome Study is known, As part of the longitudinal study follow- We will also collect additional video data explain why some young people find suitable is a population-based study which, since up questionnaires were administered in throughout 2012. employment while others do not. These data 1992, has followed a cohort of Australian September 2011 to 269 families enrolled in will also be explored to identify issues related Rett syndrome cases born since 1976. The the study. The response fraction from parents The AussieRett study has continued to involve to accommodation and respite needs among study aims to describe the natural history of and care-workers has been excellent at over consumers through the Consumer Reference this group as well as exploring the longitudinal Rett syndrome and assess the impact of the 70% and we anticipate further returns in 2012. Group, biannual newsletters and online via aspects of parental emotional and physical condition on resource utilisation as well as to Information is being collected on the affected the new website and Facebook page. The health. examine the economic and social burden for individual’s functional ability in daily living, Consumer Reference Group, involving family families and the community. behaviour, hand function, medical conditions, members from across Australia via regular A lay summary booklet of the findings use of health and education services, and teleconferences, is an opportunity to discuss of previous Down syndrome research In 2011, a new three year NHMRC funded family health and functioning. Questions and give valued feedback on all facets of the undertaken within the group has been study commenced to facilitate best practice in have also been included to assess parental study. This year one focus of the meetings published and distributed to all families who clinical decision making, laboratory procedures satisfaction with spinal fusion and gastrostomy has been the planning of a national family have participated in current and previous and counselling in relation to the diagnosis procedures for those children and adults who conference to be held in Brisbane in May Down syndrome studies. This publication and management of Rett syndrome. This study have undergone these procedures. 2012, to coincide with the International Child has also been widely distributed among a aims to: Neurology Conference. In November 2011 the range of disability service providers as well Scoliosis is a common complication of Rett • develop recommendations for the new AussieRett website went live and included as special and local libraries. A copy of the syndrome, however little is known about diagnosis process for Rett syndrome; information about Rett syndrome and the report is available on the website at www. the natural history of curve progression and AussieRett study, links to published research childhealthresearch.org.au. • identify longitudinal changes in gross the relationship with the type of genetic abstracts, information about media and motor abilities, hand function and mutation, age and mobility level. X-ray data current events and links to the online follow- development of scoliosis and; on the progression of the spinal curve of up questionnaire. Importantly, lay summaries Towards evidence based care for Rett children and adults with scoliosis has started • evaluate the clinical effectiveness of of publications or ‘research snapshots’ are syndrome: a research model to inform to be collected and will continue throughout scoliosis and gastrostomy surgery in available. management of rare disorders 2012. Spinal fusion (for scoliosis) and children and adults with Rett syndrome. gastrostomy insertion (feeding tube into the The study has a multi-disciplinary investigative Helen Leonard, John Christodoulou, Carolyn For the diagnostic study questionnaires stomach due to problems with swallowing team from the fields of medicine, Ellaway, Lakshmi Nagarajan, Helen Woodhead, relating to the characteristics of their patients or poor growth) are surgeries faced by many physiotherapy, epidemiology, biostatistics,

64 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 dietetics and occupational therapy. It has disease research. This project allows clinicians Promotion of the InterRett project is ongoing We are also developing a set of guidelines for national collaborations with the Children’s and families caring for an individual with Rett and encourages clinician and family participation optimal bone health in Rett syndrome. Our Hospital at Westmead, Sydney, the Royal syndrome to directly contribute to the global in accordance with the website motto: “Every methods have thus far included assessment Children’s Hospital, Melbourne, the Mater research effort by completing web or paper- individual contribution adds to our collective of the perspectives of parents on these issues, Children’s Hospital, Brisbane and the Royal based questionnaires. The resulting data understanding of Rett Syndrome.” systematic review of the literature and the Children’s Hospital, Brisbane. repository, which now contains 2,496 cases, creation of a document for circulation in the Funders of the project: International Rett affords investigation of a wide variety of issues first phase of the Delphi process. We are During 2011 eleven articles relating to the study Syndrome Foundation and our current analysis is concerned with now recruiting an expert panel which is both were published or accepted for publication. epilepsy. international and muli-disciplinary in nature who These articles investigated gross motor and will participate in the Delphi process and provide hand function over time with video data; the In addition to the analysis of questionnaire Developing clinical guidelines for feedback on the first and subsequent drafts until attainment of early developmental milestones data, we have over the course of 2011 collected the management of gastro-intestinal a consensus is reached. and their relationships with regression and qualitative data about the period of regression disorders and bone health in patients diagnosis; health and related services use in interviews with mothers of girls with Rett with Rett syndrome Funders of the project: Rett Syndrome and costs; physical activity measured by syndrome. The interviews are providing a Association UK. accelerometry, and trends in diagnosis over developmental profile prior to and over the Jenny Downs, Helen Leonard, Gordon Baikie, time. One article was written by an Australian course of the regression period. Regression Madhur Ravikumara, Nusrat Naseem, Amanda mother together with researchers on her is a core feature of Rett syndrome but as yet, Jefferson, Helen Woodhead, Sue Fyfe, Aris WA Register for Autism Spectrum experiences of diagnosis and this paper was has not been the topic of focussed research. Siafarikas Disorders published as a companion piece to an article Research publications over the last few years Rett syndrome is often associated with poor Emma Glasson, Katherine Russell-Smith, Ainsley looking at pathways to diagnosis by families have included: the characteristics that influence growth, in part from feeding difficulties and/ Read, Carol Bower. with a daughter with Rett syndrome in China diagnosis; pain sensitivity; the influence of DNA or gastro-oesophageal reflux. Co-morbidities recruited through the InterRett database. variations in the BDNF gene on severity; and such as constipation and abdominal bloating The aim of the WA Register for Autism Spectrum comparisons of clinical outcomes between those Funders of the project: Current: NHMRC Project are also common. There is limited literature Disorders is to monitor diagnostic trends of with different types of mutations in the Rett Grant (1004384), NHMRC Program Grant of management strategies for these common conditions characterized by autism (autism, syndrome gene MECP2. Strong collaboration (572742), NHMRC Senior Research Fellowship- gastro-intestinal disorders in Rett syndrome and Asperger syndrome, Childhood Disintegrative with colleagues in China continues to be fruitful Helen Leonard (572568) we have used the Delphi technique to develop a Disorder, and Pervasive Developmental Disorder with a recent publication on the parental consensus for items that describe how to assess Not Otherwise Specified (PDD-NOS)). These origin and recurrence risk in Rett syndrome and manage these gastro-intestinal disorders. disorders develop in young children and have and an article about barriers to diagnosis of International Rett syndrome study: We recruited an expert panel of clinicians significant life-long effects in the areas of social a rare neurological disorder in China. The InterRett and researchers who reviewed two drafts interaction, communication and behaviour. The InterRett project website was recently updated of the guidelines. We have know identified WA Autism Register is ongoing and between Helen Leonard, Alison Anderson, Ami and includes lay term snapshots of these the consensus for each of the items and are 1999 and 2011 information has been collected Bebbington, Sally McIlroy, Nada Murphy, and other research outcomes. Members of currently preparing three manuscripts for on more than 4,000 individuals. Stephanie Fehr, Jenny Downs, Heidi Meyer, the Rett syndrome team, who manage the publication. As well as existing for the purpose of local Joanne Lee InterRett project, continue to work with the Rett syndrome is also associated with and national information, Register data were international research community to harmonise The InterRett project is now in its 10th year and osteoporosis and a greater likelihood of fracture used in an international collaboration making data collection initiatives across countries. continues to be an exemplary model for rare in comparison with the general population. comparisons with a Danish autism register. This

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 65 project was awarded funding from Autism two years. decisions about placing their child on this typical development (controls). Newborns Speaks (USA, value $128,000) and findings medication as a way of managing their umbilical cord blood is collected to further Funders of the project: National Health & were published during 2011: symptoms of ASD. Similarly, the results will study the DNA and examine their exposure Medical Research Council inform physicians and provide sound clinical to pregnancy hormones. Children’s growth Parner E, Thorsen P, Dixon G, de Klerk N, guidelines and practice related to the use of and development is monitored via standard Leonard H, Nassar N, Bourke J, Bower Fluoxetine and its appropriateness for RBs measures and direct observations at four time C & Glasson E (2011). A comparison of The Fluoxetine for Autistic Behaviours including the plausible side-effects of this points until their second birthday. autism prevalence trends in Denmark and Trial medication for this population. The FAB trial is Western Australia. Journal of Autism and Over 30 women are now participating in expected to finish in 2013. Developmental Disorders, 41(12):1601-1608. Andrew Whitehouse, John Wray, Jo Granich, this research across both arms of the study. Dinah Reddihough, Catherine Marraffa, Philip Funders of the project: National Health and By the end of 2015, we aim to recruit over Funders of the project: Autism Speaks Hazell, David Dossetor Medical Research Council 200 pregnant mothers. The findings of this Repetitive behaviours (RBs) constitute one research may provide insight into the early onset and atypical development of fetal brain Western Australian Autism Biological of the three core impairments that affect Pregnancy Investigation of Siblings growth. In addition, the study outcomes Registry children and adolescents with an autism spectrum disorder (ASD). These behaviours and Mothers of Children with Autism may lead to a breakthrough in identifying Andrew Whitehouse, John Wray, David Ravine, are typically initiated and exacerbated by (PRISM) specific biological risk factors for autism Anna Hunt, Rachel Jones associated anxieties that can significantly early in life. This may have implications Andrew Whitehouse, Murray Maybery, Cheryl impact upon daily life. The Fluoxetine for for the development of preventative in- The aim of the Western Australian Autism Dissanayake, Martha Hickey, Craig Pennell, Jo Autistic Behaviours (The FAB Trial) is a multi- utero measures. Collectively, the results of Biological Registry (WAABR) is to collect Granich, Anna Hunt, Lisa Unwin site randomized controlled trial seeking this study will bear significant implications detailed information on children with autism to investigate the use of Fluoxetine (anti- Studying fetuses ‘at risk’ for autism is the on early diagnosis of autism and possible in WA and their families and to centralize depressant medication also known as Prozac) aim of a world-first longitudinal research commencement of early intervention this information so that it is accessible to for the treatment of RBs for the first time in study named PRegnancy Investigation of therapies for the treatment of autism among those who are involved in autism research. Australia. Lack of gold standard evidence for Siblings and Mothers of children with autism much younger children than ever before. The study has three components to allow the effectiveness, optimal dosing and safety (PRISM). This NHMRC funded study is seeking Overall, the PRISM findings are likely to have us to obtain the best information about the of Fluoxetine has meant that this medication to investigate specific in utero bio-markers enormous impact on the future outcomes of child with autism. These are questionnaires, is commonly used “off the label” as treatment for autism by looking at aspects of fetal young children affected by autism and their clinical assessment and blood samples of the for RBs and anxieties among the paediatric development, such as fetal brain growth and families. child and parents. The WA Autism Biological population living with ASD. The recruitment the prenatal hormone environment. State- Registry began its recruitment in early 2011, Funders of the project: National Health and for eligible participants (aged 8-17 years) of-the-art ultrasound technology used at with our first participant coming through the Medical Research Council across all sites (WA, NSW and Victoria) has six gestational time points (12, 18, 24, 28, doors in March 2011. In late 2011, we had been wide-spread and continuing with over 40 32 and 36 weeks) is enabling this aspect seen our 100th participant. To date, we have children participating in this trial to date. of pregnancy to be examined among two seen 150 participants with another 50 booked WA Cerebral Palsy Studies groups of women. Pregnant mothers with in to be seen over the next few months. This The findings of this trial will provide evidence- subsequent pregnancies who have an existing Eve Blair, Linda Watson, Fiona Stanley makes WAABR the largest biobank of autism based information for individuals with ASD child with autism (cases) are compared information in the southern hemisphere. Our and their families. The research outcomes Cerebral palsy (CP) is a chronic neurological with mothers who have a child with neuro- aim is to reach 500 families within the next will enable families to make better informed condition affecting movement and posture,

66 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 ranging in severity from barely noticeable Grant #572742 Early developmental pathways funds the extension of training across Australia Haber, Rodney Scott, John Attia, Murray Norris, to severely disabling. For most, the cause is linking health, disability, education, welfare and Lin Fritschi, Margaret Miller, Judith Thompson, Case Control Studies of CP in term and unknown. CP results in life-long disability, and justice (2010-2014) Frank Alvaro, Catherine Cole, Luciano Dalla pre-term infants in WA, 1980 to 1995 as there is no cure, prevention and effective Pozza, John Daubenton, Peter Downie, Marie management are top priorities. Eve Blair, Sarah McIntyre, Linda Watson, Nadia Kirby, Liane Lockwood, Glenn Marshall, Elizabeth Developing a reliable system of Badawi, Karin Nelson Smibert, Ram Suppiah classifying CP Researchers in the Childhood Cancer The Western Australian Cerebral Palsy Comprehensive maternal, birth and neonatal Epidemiology program have been analysing Register Sarah Love, Noula Gibson, Eve Blair, Linda information on CP cases, matched controls, and Watson a sample of unexplained perinatal deaths born the data collected between 2003 and 2007 in Linda Watson, Eve Blair, Fiona Stanley 1980-1995 was collected from birth hospitals this national case-control study of the causes The cerebral palsies include a wide range of throughout the State providing a wealth of of childhood acute lymphoblastic leukaemia The WA CP Register, now in existence more than motor impairments across the spectrum of data enabling causal pathways to the different (ALL). The primary hypothesis of this study was 30 years, is used to monitor the occurrence severities, and research therefore depends outcomes to be compared. The primary aim of that maternal folate supplementation during of CP in WA, carry out research to investigate on consistency in classifying CP subgroups. these studies is to prevent the occurrence of pregnancy protects against ALL in the offspring, its causes and evaluate treatment strategies, International attention has been focused on brain damage responsible for CP by identifying with the effect modified by genetic factors in identify CP as a long-term outcome in other WA the challenge of standardising the recording of points on each causal pathway to CP at which it folate metabolism. studies and assist in the planning of services motor impairments for several decades, and WA may most effectively, efficiently and ethically be for people with CP. A birth cohort is included has long been at the forefront in developing a The following papers were published in 2011: interrupted. Data analysis continues with the in analyses after case data are updated at age 5 reliable system of describing the clinical features intent to explore causal pathways and report Parental prenatal smoking and risk of childhood years; the Register is now considered complete of CP. We are continuing to introduce and research findings at international forums. ALL to 2006. trial an innovative diagrammatic limb-by-limb CP Description Form which incorporates the Funders of the project: In this paper we reported that maternal smoking The WA Register is now also responsible for Australian Spasticity Assessment Scale (ASAS) during pregnancy was not related to risk of contributing data to the Australian CP Register This case-control study has been s funded by devised by Sarah Love and Noula Gibson, who ALL but that paternal smoking of 15 or more (ACPR), a national collaboration initiated by NHMRC Program Grants #353514 (2005-2009) have led this work. A booklet which defines cigarettes per day in the preconception period the WA team which was established to provide and #572742 (2010-2014). An Innovative every aspect of the form is currently being was moderately related to risk of ALL. When information about CP throughout Australia as Research Grant from the CP Institute provides compiled. A Training and Reference video our results for paternal smoking were combined well as a larger study population to enable more additional funds for analysis and travel demonstrating the use of the ASAS as well as with others from around the world there was effective research. The administrative centre the features of different forms of CP is close to evidence that smoking 20 or more cigarettes a has now moved to the Cerebral Palsy Institute completion. day increased the risk of childhood ALL. in NSW where it continues to flourish. The first Childhood Cancer report of the ACPR was published at the very Funders of the project: PLAN Australia has Exposure to house painting and the use of floor treatments and the risk of childhood acute end of 2009, Eve Blair presented the results of generously funded the development of the Australian Study of Causes of Acute lymphoblastic leukemia this report both at the AusACPDM meeting in ASAS, the CP Description Form and the Training Lymphoblastic Leukaemia in Children Christchurch, New Zealand and at the AACPDM and Reference DVD. A PMH Foundation Special In this paper we reported some suggestion of meeting in Washington, USA. Project Grant 2007 covers travel to conduct Elizabeth Milne, Carol Bower, Nick de Klerk, an association between house painting and an training sessions throughout WA, and an Ursula Kees, in collaboration with Bruce Funders of the project: The WA Cerebral Palsy increased risk of ALL if more than three rooms Innovative Research Grant from the CP Institute Armstrong, Frank van Bockxmeer, Michelle Register is presently funded by NHMRC Program in the house had been painted, if someone

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 67 other than the parents had done the painting In this paper we reported that we saw no National Case-Control Study of the contacted, and a further 162 were not invited (possibly due to type or quantity of paint used evidence of an association between maternal Causes of Childhood Brain Tumours due to medical or psychosocial reasons. by professionals), or if the mother had painted or paternal antenatal exposure to ELF and risk Control children (that is, children without with oil-based paints outside the house. of childhood leukaemia. Elizabeth Milne, Carol Bower, Nick de Klerk, Peter Dallas, in collaboration with Bruce a brain tumour) and their families were Exposure to professional pest control Parental occupational exposure to exhausts, Armstrong, Frank van Bockxmeer, Rodney recruited through national random digit treatments and the risk of childhood acute solvents, glues and paints and risk of childhood Scott, John Attia, Lin Fritschi, David Ashley, dialling and frequency matched to the case lymphoblastic leukemia leukaemia Lesley Ashton, Judith Thompson, Murray children by age, sex and State of residence. A total of 1363 controls were recruited. We In this paper we reported modest evidence In this paper we reported that antenatal Norris , Richard Cohn, Margaret Miller, Luce received exposure questionnaires from 941 that the use of professional pest control exposure to moderate or substantial levels of dalla Pozza, John Daubenton, Timothy Hassall, control families, food frequency questionnaires treatments during pregnancy and shortly after exhausts by mothers or fathers increased the Maria Kirby, Stewart Kellie, Ross Pinkerton, from 726 control families and DNA samples the child’s birth may increase the risk of ALL. risk of leukaemia in their offspring. Frank Alvaro, Angela Alessandri from 974 control families for genotyping, The risk was highest for exposure after birth Maternal consumption of coffee and tea during The Australian Study of Childhood Brain which is complete. between the ages of two and three years, and pregnancy and risk of childhood ALL: Results Tumours (AUS-CBT) was a national case-control was also higher if the house had been treated The following paper was accepted for from an Australian case-control study. study into the causes of childhood brain for termites. When results from other studies tumours (CBT). It aimed to investigate genetic, publication in 2011: around the world were combined with the In this paper we reported that children of dietary and environmental risk factors for CBT, Participation in population-based case–control current results, there was an increased risk of mothers who drink at least two cups of coffee and is the sister study to the Australian Study studies: does the observed decline vary by pest control treatments during pregnancy. a day during pregnancy and do not smoke may of Causes of Acute Lymphoblastic Leukaemia socio-economic status? be at increased risk of leukaemia. In addition, Refueling of vehicles, the use of wood burners in Children (AUS-ALL). The study recruited the risk of specific types of leukaemia involving In this paper we compared the socioeconomic and the risk of childhood acute lymphoblastic case and control families between 2006 and chromosomal translocation was higher among status of recruited controls in the Aus-ALL leukemia 2010; data collection was completed in 2011. children of mothers who drank at least two study and the Aus-CBT study. We found that In this paper we reported no association with cups of coffee or tea per day during pregnancy. The study involved children aged 0-14 years. participation rates were lower in Aus-CBT than the refueling of vehicles by the mother before Case children and their parents were recruited Aus-ALL, and that controls from both studies Analysis is also under way to examine whether or during the pregnancy or the father in the from the nine paediatric oncology units had higher socioeconomic status than that of there are links between risk of ALL and: year before the pregnancy and risk of ALL. nationwide. In total, we were notified of the general population, but were quite similar There was a moderate association between • the mothers’ diet during pregnancy; 734 eligible cases, of whom 568 were invited to each other. using a closed wood burner in the year before (77%) to participate and 374 consented, • the types of jobs that parents had Analysis and manuscript preparation are or during pregnancy, which was slightly less for with 335 providing either self-administered under way to examine whether there are links after birth. There was no increasing risk with • parental alcohol consumption questionnaires or doing short telephone interviews to provide demographic and basic between risk of CBT and: greater usage of wood burners, which might • variations in genes that influence the way exposure data. 302 case families returned full • Maternal folate supplementation indicate that these results are due to chance. the body processes food and chemicals exposure questionnaires, and 295 did a food Risk of childhood acute lymphoblastic • Parental alcohol consumption prior to or • medication use before/during pregnancy frequency questionnaire. We received DNA leukaemia following parental occupational during the pregnancy and by the child samples from 355 families for genotyping, exposure to extremely low frequency which is complete. A total of 194 families • Parental smoking prior to or during electromagnetic fields Funders of the project: NHMRC Grant declined to participate or could not be re- pregnancy #254539, and Cancer Council WA

68 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • Maternal consumption of coffee and tea biomarkers of DNA damage. The blood sample Database System, Birth and Death Register, from the birth cohort. Bronchiolitis and during pregnancy was also used to identify genetic polymorphisms Emergency Department Data Collection, Birth croup were the most common reasons for related to nutrient metabolism and DNA repair. Defects Register and the PathWest Laboratory presentation. However, there are some Funders of the project: NHMRC Grant #404089 Saliva samples collected from the child were Database. This project is the first to link limitations of the available emergency used to measure cortisol and cotinine levels, as statewide laboratory data for respiratory department datasets. indicators of psychological stress and exposure pathogens to other datasets within the Western Nutrition and Genome Health in • Children born with birth defects have an to environmental tobacco smoke, respectively. Australian Data Linkage System. Data analysis Children increased risk of hospitaliation before age Parents were given feedback on their child’s diet, was completed in 2011 and results are now 2 years for ALRI than children without birth and dietary advice was provided by a dietician being disseminated. Major findings in 2011 Elizabeth Milne, Michael Fenech, Bruce defects. This increased risk remains after where needed. were: Armstrong, Nick de Klerk, Margaret Miller adjusting for other known risk factors for The Nutrition and Genome Health in Children In all, 464 participants provided data. Statistical • 43,003 laboratory records for respiratory hospitalisation. analysis of these data is currently in progress. pathogen testing between 2000 and 2005 Study aimed to identify key nutritional and The majority of these findings have now been from children in the birth cohort were genetic factors associated with DNA damage Funders of the project: NHMRC Grant#572623 published in international and national peer- identifed. Of these, 89.7% have a coded in children. It aimed to describe the nature reviewed journals. A further manuscript result for 30 bacterial and viral respiratory of the interaction between nutritional and describing metropolitan emergency department genetic factors in determining level of DNA pathogens. Infectious Diseases presentations for respiratory infections is damage in children, and also the associations • Linking laboratory data and hospital currently under review and a manuscript between body mass index, DNA damage and Aetiology, burden and causal pathways data, we reported that 57.9% of linked describing the relationship between birth micronutrient levels in children. of acute lower respiratory infections hospitalisation records for ALRI had tested defects in children and hospitalisations for This study was a cross-sectional study of 450 using population linked data positive for a respiratory pathogen. Of ALRI is in advanced draft stage. In 2011, these Western Australian children, conducted between these, respiratory syncytial virus was the findings were presented at the Exploiting 2009 and 2011. Participants were children Hannah Moore, Deborah Lehmann, Khadra most common (39.5%) and was identified Existing Data for Health Research International aged 3, 6 or 9 years at recruitment who had Jama-Alol, Peter Jacoby, Nicholas de Klerk in in 63.7% of bronchiolitis admissions for Conference in Scotland, the 7th World Congress never been diagnosed with asthma, diabetes, collaboration with Peter Richmond, David Smith, children under 6 months. Many respiratory of the World Society for Paediatric Infectious cancer, arthritis or epilepsy. Participants and Anthony Keil, Christopher Blyth pathogens were found across different Diseases in Melbourne, the Communicable their parents were recruited via primary schools, Acute lower respiratory infections (ALRI), or clinical diagnoses. Disease Control Conference in Canberra and the Australasian Epidemiological Association posters displays and flyers, advertisements chest infections like influenza and pneumonia, • Non-Aboriginal children delivered by Annual Scientific Meeting in Perth. This project in local newspapers and information letters are a major cause of illness in young children. elective caesarean have an increased risk of also contributed to the completion of Hannah distributed to a wide range of organisations. The primary objective of this project is to repeated hospitalisations for bronchiolitis Moore’s PhD which was awarded in July 2011. These include crèches, day care centres, describe the aetiology, burden and causal compared to those non-Aboriginal children playgroups, sports centres and libraries. pathways of ALRI in Aboriginal and non- who were delivered through spontaneous Funders of the project: NHMRC Project Grant The child’s diet and macro- and micro-nutrient Aboriginal children from a 10-year birth cohort vaginal delivery. This finding attracted #572590. intake was assessed using parent-completed (245, 249 births) using population linked data widespread local and national media. from the Western Australian Data Linkage Food Frequency Questionnaires (FFQs). A • Through the analysis of linked emergency System. Datasets include the Midwives’ sample of the child’s blood was taken and used department data, we investigated the Notification System, Hospital Morbidity to assess micronutrient levels and specific out-of-hospital burden of ALRI in children

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 69 Hospitalisation for diarrhoea among Monitoring carriage of Streptococcus international data. Our data help to inform health services for routine examination, Western Australian children pneumoniae among Aboriginal policy on optimal vaccine schedules and immunisation or illness and also through children and adults in Western formulation. home-visiting or community links. To date Deborah Lehmann, Hannah Moore Australia we have collected 1578 pernasal swabs and Pneumococci are carried in the back of the 58 swabs of discharge from the middle ear Diarrhoea is a significant reason for nose of healthy as well as sick individuals. Deborah Lehmann, Anke Hoskins, Deirdre from a total of 559 children aged < 5 years and hospitalisation in Australian children. This Surveillance of pneumococcal carriage offers Collins, in collaboration with Jacinta Bowman, 1010 older children and adults. Most of the study utilising the total population-based important complementary information to Natalie Thomsen, Jade Jones, Tom Riley, collected swabs (1518) have been cultured. databases from the Maternal and Child Health data on IPD since it can quickly provide a Carolien Giele, Paul Effler, Amanda Leach, Kim Recruitment has taken place in Wiluna, Research Database investigates the trends in large amount of information on serotypes Hare, Heidi Smith-Vaughan, Peter Richmond Kalgoorlie, Coolgardie, Laverton, Leonora, Mt hospital admissions for diarrhoeal diseases circulating in the population, thereby Margaret, Coonana, Norseman, Roebourne, (gastroenteritis) in Western Australian children Streptococcus pneumoniae (pneumococcus) informing public health programs. It also gives Wickham, Kununurra, Broome, Beagle Bay, aged <15 years between 1983 and 2006. can cause middle ear infections and invasive a conservative estimate of antibiotic resistance Halls Creek, Carnarvon, Jigalong, Meekatharra, Hospitalisation rates for gastroenteritis are pneumococcal disease (IPD) resulting in of invasive pneumococcal strains. This study Burringurrah, Bunbury, Geraldton and at highest in children aged 6-12 months. Over meningitis, pneumonia and septicaemia aims to monitor pneumococcal carriage by Aboriginal Medical Services in the Perth the last two decades, we have seen diverging (blood poisoning). The Australian Aboriginal collecting 600 pernasal swabs from Aboriginal Metropolitan area (Perth, Armadale, Bentley, trends in hospitalisations for gastroenteritis population has among the highest reported adults and children in urban, rural and remote Maddington, Swan District and Kwinana). between Aboriginal and non-Aboriginal IPD rates worldwide. The existence of over areas of Western Australia annually. We also children. In Aboriginal children aged 6-11 90 known types (serotypes) of pneumococci collect ear swabs from children with middle In children under 5 years of age pneumococci months, rates have fallen from 304 per 1000 increases the challenge of prevention. A ear discharge and data on vaccination status of were grown from 70% of pernasal swabs. population in 1983-1994 to 214/1000 in 1995- pneumococcal conjugate vaccine (Prevenar™, children in the study. Haemophilus influenzae from 62% and 2006 with similar declines in other age groups. PCV7 ) covering the 7 most common serotypes Moraxella catarrhalis from 68%. In people Other study aims include: In non-Aboriginal children, hospitalisation causing IPD in a 2-4-6-month schedule and aged ≥5 years 35% of pernasal swabs grew rates for gastroenteritis have increased from an 18-month booster with a pneumococcal i) describing the prevalence of upper pneumococci, 22% grew H. influenzaeand 27% 1987 to 1999 and then declined from 2001 to polysaccharide vaccine (Pneumovax™) respiratory tract (URT) carriage of other grew M. catarrhalis. 42 different serotypes 2006 when they were approximately 20/1000 covering 23 serotypes have been offered to pathogens identified on primary culture; have been identified. Currently, the most in those aged 6-11 months. There have Aboriginal children since 2001. Pneumovax™ common pneumococcal serotypes in children ii) comparing the distribution of also been diverging trends of gastroenteritis is also offered to adults. While there has under 5 are 6A, 23F and 19A, while 6C, 16F pneumococcal serotypes in the URT with those hospitalisations between the different been a marked reduction in IPD due to the and 6A are most common in older children and causing IPD in Aboriginal adults and children geographical regions of the state. This study near elimination of Prevenar™ serotypes, adults. will be useful in providing baseline data on there has been an increase in IPD rates due annually; In line with data from IPD surveillance in WA hospitalisations for diarrhoeal disease prior to serotypes not included in the Prevenar™ iii) storing pernasal swabs for detection of Prevenar™ successfully eliminated carriage to the introduction of the rotavirus vaccine in vaccine, particularly in young Aboriginal viruses by PCR to describe the prevalence of of serotypes included in this vaccine since 2007. A publication describing the temporal adults. In light of this, Prevenar™ was replaced respiratory viruses; and and seasonal trends over a two decade period with Prevenar-13™ on 1 July 2011, which only 12% of pneumococci were Prevenar™ is now in advanced draft form. covers 6 additional serotypes. The findings of iv) investigating viral-bacterial interactions in serotypes. 66% of pneumococci in the increasing incidence of IPD due to non-PCV7 the URT. URT were serotypes that are not covered Funders of the project: NHMRC Program Grant serotypes in the West Australian Aboriginal by Prevenar-13™. Ongoing surveillance of #353514 We recruit study participants attending population is consistent with national and pneumococcal carriage following the change-

70 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 over to Prevenar-13™ is vital for development of serotype distribution of IPD notifications in the Denise Murphy, Kylie Carville, Stefano Occipinti, • Exposure to environmental tobacco smoke appropriate guidelines for Aboriginal people. WA Aboriginal and non-Aboriginal population. Amanda Leach, Nevada Pingault is an important risk factor for OM. This project involves analysis of the IPD Our findings to date were presented at the Otitis media (OM, middle ear infection) can • Crowding is the strongest and most surveillance data between 1997 and 2007 to Communicable Disease Control Conference seriously affect childhood development, consistent predictor of carriage of OM- investigate the underlying co-morbidities and in Canberra in April 2011, and the 7th World school performance and subsequent social associated pathogens S. pneumoniae, risk factors associated with IPD. These include Congress for the World Society for Paediatric and economic well-being. The Kalgoorlie Otitis nontypeable H. influenzae or M. catarrhalis an investigation of risk factors such as excessive Infectious Diseases in November 2011 in Media Research Project was established in 1999 in the URT, but living in a larger house alcohol use, smoking, diabetes, asthma, chronic Melbourne. to investigate the causal pathways to OM and, attenuates this effect in Aboriginal children. diseases of the respiratory system, chronic specifically, to identify demographic, socio- Funders of the project: Western Australian diseases of the cardiac system and malignancies. • Daycare attendance predicts carriage of economic, environmental, microbiological and Department of Health through the Collaboration This project aims to describe the co-morbidities the same OM-associated pathogens in immunological risk factors for OM in Aboriginal for Applied Research and Evaluation and NHMRC reported in IPD cases according to age, non-Aboriginal children while exclusive and non-Aboriginal children in order to develop Project Grant #545232 (a collaboration with gender, geographical region and Aboriginal breastfeeding for the first 6-8 weeks of appropriate interventions. We followed 100 Menzies School of Health Research) status. We will also investigate the NHMRC life protects children from carriage of Aboriginal and 180 non-Aboriginal children recommendation for the 23vPPV vaccine to be Staphylococcus aureus. from birth to age two years. Field work was given to those individuals aged ≥10 years with completed in 2004 and data cleaning completed • Rhinoviruses (HRV) and adenoviruses were Investigating the risk factors and co- certain risk factors for IPD. Analyses for this in April 2005. Analysis of data has been on- commonly identified in asymptomatic morbidities associated with Invasive project are ongoing and a publication from these going. children, more commonly in Aboriginal than Pneumococcal Disease in the Western descriptive analyses is planned. non-Aboriginal children and are frequently Australian population Major findings: Funders of the project: Western Australian associated with bacterial carriage. Department of Health through the Collaboration • The peak prevalence of OM in the Deborah Lehmann, Aoiffe McLaughlin, Hannah • Human rhinovirus A is the most common for Applied Research and Evaluation Kalgoorlie-Boulder area was 72% in Moore virus type identified in healthy children Aboriginal children aged 5-9 months and and HRV C is associated with presence of The Vaccine Impact Surveillance Network (VISN) 40% in non-Aboriginal children aged 10-14 upper respiratory symptoms and carriage of conducted enhanced surveillance on Invasive The Kalgoorlie Otitis Media Research months. bacteria associated with OM. Pneumococcal Disease (IPD) between 1996 and Project - An investigation into the • Almost one-third of Aboriginal children 2007. Everyone is susceptible to IPD, though causal pathways to otitis media in • Early carriage of H. influenzae increases risk and 5% of non-Aboriginal children had a most at risk are children under the age of 2 Aboriginal and non-Aboriginal children of OM in Aboriginal children, while early perforated ear drum at least once by age 2 years, elderly persons and those with chronic carriage of M. catarrhalis increased risk of years. disease and compromised immune systems. Deborah Lehmann, Peter Jacoby, Wenxing Sun, OM in non-Aboriginal children. Across all age groups incidence rates are higher Alicia Annamalay, Christine Jeffries-Stokes, • 65% of Aboriginal children and 23% of non- • A large proportion of M. catarrhalis strains in Aboriginal people than in non-Aboriginal Annette Stokes, Daniel McAullay, Dimity Elsbury, Aboriginal children have some degree of were resistant to ampicillin and/or co- people throughout Australia. The Australian Janine Finucane, Ruth Monck, Fiona Stanley, hearing loss at age 12-17 months. Aboriginal population has among the highest in collaboration with Bega Garnbirringu Health trimoxazole. Therefore, current therapeutic reported IPD rates worldwide. Since January Services, Ngunytju Tjitji Pirni Inc, Harvey Coates, • Measurement of otoacoustic emissions guidelines, which recommend amoxicillin 2008, CDCD has conducted the surveillance Thomas Riley, Sharon Weeks, Allan Cripps, in early infancy can identify children at for treatment of OM, may need to be of IPD across Western Australia. Our previous Jennelle Kyd, Jacinta Bowman, Amanda Taylor, subsequent risk of OM. revised. We have also documented for the publications reported on the incidence and Gerry Harnett, David Smith, Glenys Chidlow, first time simultaneous carriage of multiple

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 71 strains of M. catarrhalis. by the time they start school. A variety of activities involving adults and Infectious Diseases Community children that promoted handwashing and Reference Group • Early nasopharyngeal colonisation can The objectives of this project are to: keeping children away from cigarette smoke modulate mucosal immune responses (1) Develop and implement a multifaceted ear were organised. Music workshops conducted Deborah Lehmann, Hannah Moore, Kirsten in the upper airways. Total salivary IgA health promotion program in collaboration by a local Indigenous musician in 3 primary Alpers, Glenn Pearson, Anne McKenzie is stimulated by high bacterial load, but with Aboriginal organisations in the Goldfields. schools and a community centre were warmly levels of specific antibodies to bacteria In 2007 we convened an Infectious Diseases received and culminated in performances of associated with OM may be suppressed (2) Evaluate the impact and effectiveness Community Reference Group to inform the stories and ‘The Germ Song’ by the children. by early colonisation in Aboriginal of an ear health promotion program that wider community about research conducted Soap making was offered at community events children. includes (a) an awareness program, (b) training at ICHR around infectious diseases and for and at some screening sessions. Training and of Community Health Nurses and Aboriginal community members to provide researchers Funders of the project: Western Australian encouragement of health workers occurred Health Workers in screening and health with their valuable input into research Health Promotion Foundation (Healthway); during ear screening sessions and as part of promotion and (c) a screening program for projects. This group consists of 13 members NHMRC Project Grant #212044 and as part of the curriculum at Bega Nindila Training Centre. OM. including 8 community members (of which 4 the NHMRC Program Grant #353514 The video-otoscope proved to be very useful are Aboriginal), 2 researchers, 1 representative (3) Evaluate use at primary health care level for helping carers, children and health workers from the Western Australian Department of of a simple tool (which measures otoacoustic understand and visualise the anatomy of the Health, 1 representative from the Vaccine Preventing Otitis Media to Give a emissions) that can detect fluid in the middle ear and the need for regular ear checks. An Trials Group and 1 representative from the Sound Start for School (Pina Palya Pina ear at a very young age and hence identify a interactive inflatable ear that children and Institute for Child Health Research Consumer Kulilku, Good Ears Good Learning) target group of children at subsequent risk of adults can walk through was developed and and Community Advisory Council. The current developing OM. members of this group are: Glenn Pearson Deborah Lehmann, Ruth Monck, Wendy Sun, commissioned with community consultation (Chairperson), Barry Combs, Bev Taylor, Lorraine Sholson, Kirsten Alpers, Margaret (4) Evaluate the overall program in terms of taking place in November 2011 and a multi- Helen Martin, Jane Jones, Karen Ziegelaar, Wallam, Daniel McAullay, Tanyana Jackiewicz feasibility and sustainability. agency community event scheduled for the Linda Gibbs, Maude Walsh, Natasha Indich, in collaboration with Anne Mahony, Charles launch of the ‘Big Ear’ in early 2012. During 2011, enrolment continued and ear Patricia Nyaga, Rae Young, Trish Laitt, Anne Douglas, Michelle Forrest, Bega Garnbirringu screenings were conducted in Kalgoorlie, Media interest in the study included radio McKenzie, Deborah Lehmann and Hannah Health services, Ngunytju Tjitji Pirni Inc, Coolgardie, Norseman, Laverton, Mt Margaret interviews and articles in the Kalgoorlie Miner Moore. This group met four times in 2011 and Francis Lannigan, Sharon Weeks, Annette and Leonora. Over 200 Aboriginal children newspaper on the children’s musicals and the discussed the progress of the research projects Stokes, Christine Jeffries-Stokes under 5 years of age have been enrolled development of the Big Ear. associated with infectious diseases at ICHR. This 3-year project follows on from findings and 330 ear examinations performed. For The study was presented at: Funders of the project: Jointly funded by the of the Kalgoorlie Otitis Media Research examinations where a diagnosis could be Meningitis Centre and NHMRC Project Grant Project. We reported very high rates of otitis made, 51% were found to be normal in both The 11th National Rural Health Conference, #572590 media (OM) and associated hearing loss, high ears and in 49% OM was found in one or both March 13-16, Perth ears with perforations of the eardrum present carriage of bacteria in the upper respiratory Funders of the project: Western Australian tract (which predisposes to OM) from a very in 37% of these examinations (19% of the total Health Promotion Foundation (Healthway) Neonatal immunisation with young age in Aboriginal children and an valid examinations). Early screening enabled pneumococcal conjugate vaccine in increased risk of OM among children exposed many children to be seen by ENT specialist Dr Papua New Guinea to environmental tobacco smoke. The overall Francis Lannigan at clinics in Kalgoorlie and aim is to have Aboriginal children hearing well Leonora.

72 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Deborah Lehmann, Anita van den Biggelaar, Pat • 7vPCV in a neonatal (0-1-2 months) or early Preliminary results from investigation of the role of the 23-valent pneumococcal Holt, in collaboration with Peter Siba, William infant (1-2-3 month) schedule primes for associations between genotype and acute polysaccharide vaccine (PPV) in infants following Saila Pomat, Suparat Phuanukoonnon, John immunologic memory for 7vPCV serotypes lower respiratory infections suggest that several priming with a pneumococcal conjugate Reeder, Peter Richmond, Amanda Leach, David with booster response to 23-valent genetic variants for known immune pathways vaccine due to a potential immunological Smith, Ingrid Laing, Glenys Chidlow pneumococcal polysaccharide vaccine (PPV) may play a role in the frequency of lower hypo-responsiveness (i.e. a poorer immune at age 9 months. Serotype-specific antibody respiratory tract infections in children in PNG. response to subsequent immunisation or natural Throughout the world an estimated 820,000 concentrations are generally sustained to exposure). In PNG we have previously found children die annually from pneumococcal At PathWest Laboratory Medicine WA multiplex age 18 months. that (a) PPV given from age 6 months onwards disease, the majority in early infancy in third PCR has been used to identify viruses in (without priming with conjugate vaccine) world countries. This study was designed • PPV induces good antibody responses for the nasopharynx of sick and healthy trial prevents death and severe morbidity due to to investigate the safety, immunogenicity some non-PCV pneumococcal serotypes participants. Influenza virus A, respiratory acute lower respiratory tract infections up to age and priming for immunologic memory of which commonly cause disease. syncytial virus and adenoviruses and detection 5 years and (b) serotype-specific pneumococcal pneumococcal conjugate vaccine (PCV) in Papua of multiple viruses were more common during • 60% of infants were colonised with antibody responses are generally sustained up New Guinean infants at 1-2-3 months of age episodes of acute lower respiratory tract Streptococcus pneumoniae by age 1 month. to age 18 months with a PPV booster at age 9 and to find out whether neonatal immunisation infections than when children were healthy. months following priming with 3 doses of 7vPCV. in the first week of life would provide earlier • 51 different pneumococcal serotypes have Assays to measure mucosal immunity to Nevertheless it is important to ensure the protective antibody responses. The study is been identified in the upper respiratory pneumococcal polysaccharides are currently immunological safety of the PPV in infants. also assessing the impact of a 7-valent PCV tract. being optimized in the laboratories in Goroka. (7vPCV) on early pneumococcal nasopharyngeal This study aims to determine whether PPV given • At age 9 months, 68-78% of pneumococci colonisation. We are investigating the Funders of the project: This study was funded at 9 months of age: were non-7vPCV serotypes. development of mucosal and T-cell immunity by the NHMRC/Wellcome Trust International 1) provides enhanced persistence of antibody to non-capsular pneumococcal protein antigens • PCV has limited impact on upper Collaborative Research Grant #303123 levels associated with protection from invasive and how this may be affected by early onset of respiratory tract carriage in this population. disease at 3 to 5 years of age compared to colonisation. We have assessed the impact of • Early pneumococcal carriage may result unvaccinated controls Investigation of serotype-specific neonatal immunisation on humoral and cellular in enhanced disease susceptibility antibody persistence and B-cell memory 2) has an impact on the development of immune responses to concomitant vaccines and suboptimal vaccine responses at age 3 - 4 years following 23-valent serotype-specific B-cell memory at 3 to 5 years (diphtheria toxoid, tetanus toxoid and measles) by modulating the development of pneumococcal polysaccharide vaccine of age and whether PCV interferes with normal pneumococcal immune responses. maturation of the immune system. at age 9 months in Papua New Guinean 3) enhances antibody persistence and B-cell • Analysis of cellular immune responses has children previously primed with A total of 318 children were enrolled; 80% memory for those serotypes included in 7vPCV shown that neonatal PCV vaccination is 7-valent pneumococcal conjugate completed follow-up at 18 months of age. among children who received 7vPCV in early safe and not associated with immunological vaccine infancy Results to date show tolerance. Peter Richmond, Deborah Lehmann, Peter 4) has an effect on long-term pneumococcal • No deleterious effect of neonatal 7-valent In an extension of this project IA Laing Jacoby, Anita van den Biggelaar in collaboration carriage in children primed or not primed with PCV (7vPCV). investigated the contribution of human genetic with Peter Siba, William Saila Pomat, Andrew 7vPCV. • 7vPCV is immunogenic in PNG neonates susceptibility to nasal bacterial carriage, Greenhill, Christine Opa, Gerard Saleu and young infants. development of immune/vaccine responses and We are assessing immune function (by the incidence of pneumonia in this population. Recently, concerns have been raised about measurement of serotype-specific antibody

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 73 concentrations, opsonophagocytic antibodies disease, the majority in early infancy. While time points. the approach taken with US Promoting Healthy and memory B-cell responses) and many industrialized countries have had Development Survey-PLUS (PHDS-PLUS) and Recruitment into the study began in November nasopharyngeal carriage at age 3-5 years pneumococcal conjugate vaccines in their the child health literature. Emphasis in this 2011. prior to and one month after a challenge dose routine immunisation schedules since 2001 study will be given to identification of access to (0.1ml) of PPV in children who took part in and a 23-valent pneumococcal polysaccharide Funder of the project: Exxon-Mobil developmental health information, preferred the previous neonatal 7vPCV trial (described vaccine (PPV) has been shown to be Governance and Public Affairs sources of this information, and attitudes to above) and in 150 age-matched controls. efficacious in preventing death and severe child health services. disease from age 6 months onwards in Papua We enrolled 130 of the children who had The third proposed component is a sequence New Guinea (PNG), no pneumococcal vaccine previously received PPV (primed or not primed Collaboration for Applied of focus group sessions, with parents to be is currently offered to children in PNG. The with 7vPCV) and 150 controls. recruited from the quantitative study. Focus Global Alliance for Vaccines and Immunisation Research and Evaluation group questions will be informed by the first Preliminary data show continuing high (GAVI) and the World Health Organization Are child health services meeting the community forum and the literature. pneumococcal carriage up to age 5 years (WHO) have committed to the introduction needs of WA parents and children? (>70%, predominantly non-PCV serotypes) of pneumococcal conjugate vaccine (PCV) for Objectives of the proposed study irrespective of vaccination history, and high infants in GAVI-eligible countries (including In collaboration with Child and Adolescent 1. A diverse range of parents/carers are serotype-specific pneumococcal antibody PNG) and introduction of a PCV is planned for Community Health Policy Branch (WA) involved with and inform research directions concentrations. Preliminary analyses show 2013. and lines of inquiry so as to ensure that the no evidence of impaired antibody responses Care Leads: Kim Clark, Judy Donnelly, Jordan The primary aim of this study is to determine research study reflects the priorities and following a challenge dose of PPV. Fisher and Tanyana Jackiewicz whether PCV10 and PCV13 (which include 10 concerns of the WA community. Funders of the project: Papua New Guinea or 13 pneumococcal serotypes, respectively) The purpose of this research project is to 2. A diverse range of parents/carers are Institute of Medical Research Internal are safe and immunogenic in Papua New assess whether the current child health invited to participate in the research study Competitive Research Award Grant Guinean infants for the serotypes in the services meet the needs of WA parents and as survey respondents, interview and focus respective vaccines. identify why parents are not accessing child health services at key developmental ages group participants, so that the felt needs of This is an open randomised trial. We aim to WA parents for child health information and A study to determine the safety and (scheduled contacts at 18 months and 3 years). enrol 200 children at age 1 month. Half will be services are identified. immunogenicity of 10-valent and randomised to receive PCV10 and the other The proposed study will have three interlinked 13-valent pneumococcal conjugate 3. The barriers and facilitators to WA parents half PCV13 a 1-2-3-month schedule. At age 9 components. The first is two ‘community vaccines in Papua New Guinean accessing and engaging with child health months half in each group will be randomised conversations’ or forums that will respectively children services, particularly the scheduled contacts, to receive 23vPPV and the other half no play a role in both informing and shaping are identified. Deborah Lehmann, Andrew Greenhill in PPV. To specifically address the possibility of subsequent qualitative and quantitative collaboration with Peter Siba William Pomat, hyporesponsiveness following PPV, all children research and exploring final recommendations 4. Strategies and processes to improve the Audrey Michael, Vela Solomon, William Lagani, will receive a challenge dose (0.1ml) of PPV and suggested processes for managing any delivery of child health services are identified. change. The second proposed component is a Lea-Ann Kirkham, Peter Richmond, Trevor at age 23 months and followed up 4 weeks In 2011, a project reference group was quantitative study of parents of children aged Duke, Megan Passey later. Blood for antibody studies as well as formed to discuss a review of processes and and B- and T-cell responses will be collected 0 to 4 years. It is proposed that the form of Throughout the world an estimated 820,000 develop questions for surveys, interviews at ages 1, 4, 9, 10, 23 and 24 months of age. this study will be guided by both information children die annually from pneumococcal and focus groups. The scientific protocol and Pernasal swabs will be collected at the same gathered from the first community forum, by

74 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 ethics application was submitted and ethics delivery that enable increased parental At the age of 16-17 years, children whose and methods sections of the report are currently approval via the DoH HREC has been received. engagement with, and responsiveness to, parents received the Triple-P Parenting Program being prepared. Whilst awaiting ethics approval The questionnaire design is complete and the evidence-based child health information will have: the personal information from the WA Triple-P instrument was trialled before use in the field. and guidance; Evaluation Database has been extracted and 1) lower number of hospital/emergency Field work has progressed, with approximately formatted to provide to the Data Linkage Unit. • Options for improving accessibility department admissions two thirds of the planned survey data actually Some cleaning of Triple-P database was required and acceptability of well-child health obtained. Field work, however, stalled in 2) lower levels of teenage pregnancy (removal of duplicate cases, ID of non-response/ information and support to WA parents. December as a consequence of insufficiency of missing items). In preparation for receipt of 3) lower levels of school absenteeism and lower the sample of contact numbers obtained from Funders of the project: Department of Health linked data and data analysis, the distribution risk of suspension/expulsion from school the DoH data linkage group as a result of a and completeness of key covariates is currently poorer-than-expected success rate in contacting 4) higher performance on literacy and numeracy being examined (and key literature examined) to parents. Survey data is expected to be delivered Triple-P Parenting Program: long-term tests determine what will be included in analyses. in March 2012. outcomes and economic benefits 5) less contact with the justice system A report will be prepared for the Department A Community Conversation was undertaken in In collaboration with Child and Adolescent 6) less contact with the mental health system of Health, WA outlining the key findings of the October in Mullalloo. Planning for an additional Community Health Policy Branch research. An article outlining the results of the conversation to be undertaken in Kwinana is 7) lower incidence of problematic drug/alcohol research for submission to a scientific journal CARE Leads: Grant Smith underway. Focus group questions and format use will also be prepared. At this stage, these has been developed. A trial focus group was This research project will evaluate the Triple-P It is hypothesised that improved outcomes outputs will be delivered by December 2012. undertaken in December and the results of this Program’s long term effectiveness, using data associated with the Triple-P program will Funders of the project: Department of Health will be used to guide the approach to be taken collected in the initial effectiveness trial and data translate into significant cost savings to the with subsequent focus groups. A report on this on the children and their family up to 13 years Western Australian government and that the was sent to the project reference group which following the intervention (children of parents delivery of the program will be associated with a The development of a novel antenatal will meet again in February 2012 to approve to enrolled in the program are now at least 16 net positive economic impact. education programme for first-time approach to be taken with focus group research. years old). obese mothers-to-be on their intention Focus groups are planned at the completion of A reference group has been formed, ethics The WA Triple-P study database will be linked to manage their gestational weight the survey component of the research. documentation prepared and feedback received to a number of administrative databases (e.g. from the DOHWA Ethics has been received gain and foster a healthy lifestyle The project output will be a comprehensive education, health, mental health, justice, child and addressed. The correspondence with In collaboration with Professor Yvonne Hauck report into the provision of well-child health protection, drug and alcohol, mortality) to the committee has indicated that approval (KEMH) information and services to Western Australian determine whether the program was associated will be given out of session. Data linkage will parents of children under 5 years old. This with better long-term outcomes for children. commence immediately following this approval. Dr Lisa Gibson will lead the project with support report will include discussion on: from Kim Clark and Tanyana Jackiewicz The project will also use costing algorithms The project is also currently awaiting approval • The expressed needs, priorities, barriers to determine how these outcomes translate from the Department of Corrective Services The aim of this project is to develop an and facilitators to accessing child health into costs/savings to the WA government and Ethics Committee (this approval is not required evidence-based and field-tested antenatal care information and services (particularly at key develop an overall cost-benefit model of the for linkage to begin and will be received whilst and education package based on the ‘Centering developmental stages) for WA ; Triple-P Parenting Program. data linkage is being conducted). The literature Pregnancy’ model that is acceptable to pregnant review has commenced and the introduction women with a body mass index (BMI) of ≥30 • Processes and modes of child health service The specific hypotheses for this research are:

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 75 kg/m2. The package is to be designed with periods. current outpatients from KEMH and conduct Through meeting with the KEMH clinic referral the goal of positively influencing participants’ the session trials at KEMH from the WNHS triage midwife, we have formed a recruitment • Preliminary trial of antenatal package intention to manage and thus minimise their Ethics Committee. This was approved on plan involving identification of eligible women content with women to assess acceptance gestational weight gain whilst fostering the October 4, 2011. using the hospital patient management of material covered and method of adoption of a healthy lifestyle. system. delivery. Governance approval for consumer reference The project is consistent with the group formation The next steps to be completed in 2012 are: • Evaluation of the intervention with the Department’s strategic objectives and would primary target group through conducting The project gained approval by King Edward Drafting of package content progress the following strategic objectives focus groups post each trial session. Memorial governance committee to form a of the Western Australian Health Promotion Using the literature review findings and the consumer reference group using current and Strategic Framework 2007-11 and the National The project objectives are: feedback from the consumer reference groups recent outpatients. This was approved in Preventative Health Strategy (2009), that is: each session will be drafted. The proposed Objective 1: Review of evidence on October 2011. content for each session will be reviewed • Ensure women planning pregnancy and interventions that have potential application in Formation and meeting of the consumer by the consumer reference group to refine pregnant women receive information, addressing obesity among pregnant women. reference groups approaches and to obtain guidance on the education and support to reduce lifestyle Objective 2: Design of a draft antenatal care acceptability of the proposed content and risks of excessive weight and poor After consulting with Anne McKenzie and lifestyle education package for obese delivery methods. nutrition. (Consumer Research Liaison Officer, UWA) mothers-to-be. to determine the method of forming such Recruitment of participants • Provide consistent and clear information Objective 3: Pilot-testing of each session in a group, eligible women (BMI ≥ 30 kg/m2) to parents to support them to establish Recruitment will begin in February 2012. the maternal obesity education package with were contacted and recruited. Two consumer appropriate eating and physical activity members of the target group recruited from reference groups were formed; one south Trial and re-trial of antenatal session content patterns in children and to better KEMH. of the river (Rockingham) and one north of according to focus group outcomes understand the risks of unhealthy the river (Joondalup). In November 2011, a weight in early life through targeted During 2011 the following has been achieved: Trial of the sessions will begin in March 2012. focus group/morning tea was conducted with interventions for parents. Post each trial session a focus group will be Formation of steering committee and project each of these groups to discuss the maternity conducted to evaluate the acceptability of the The overall project will comprise: managers experience of obese women, how their care content. Each session will be re-trialled in the could be improved, how they could be more • Research and consultation: Formation of The project’s steering committee is comprised case of significant changes/improvements. supported to achieve a healthy gestational a consumer reference group to inform of Yvonne Hauck (Curtin University), Anne Rae weight gain and the perceived acceptability of Funders of the project: Department of Health the type of information required and how (KEMH), Hanna Burbidge (KEMH), Kim Clark a group-based educational package. to present it within a group antenatal (TICHR), Barbara Loury (KEMH), Lisa Gibson (TICHR) and Ms Tanyana Jackiewicz (TICHR). Preliminary literature review education package. The psychosocial determinants of The project managers, Joan Jones (KEMH), a • Development of an antenatal education A literature review has been conducted to health outcomes in young children midwife and Anna Fletcher, a dietitian (KEMH) package: Development of approximately establish evidence-based content to inform with cystic fibrosis (CF) meet regularly with the steering group to 4 education sessions along with support the development of each session in the discuss and review project progress. In collaboration with Dr Tonia Douglas materials and resources for the target intervention package for obese mothers-to-be. and Catherine Gangell from Cystic Fibrosis group to cover healthy family lifestyle Ethics Approval Participant recruitment plan Research Group at PMH, CARE Leads: Grant issues in the pre-natal and post-natal The project gained ethics approval to recruit

76 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Smith the study protocol that required resubmission 2) the risk factors for severe respiratory A mailout of invitation letter to be involved of the application. A literature review has been problems, in the study has been sent to clients who The primary aim of this pilot study is to gather prepared. fitted the eligibility criteria (N=627). A media data to inform the design and implementation 3) the prevalence of known risk factors for release has been prepared and submitted to of a longitudinal research project examining the Findings of this primary cross-sectional study severe respiratory problems, and the TCCP newsletter ‘Brand News’ to assist in relationships between psychosocial factors and will be presented to the CF clinic at Princess 4) the relationships between selected risk recruitment. A mailout of information sheet the progression of CF lung disease. Margaret Hospital and interpreted within the factors, respiratory symptoms and respiratory and questionnaires to TCCP clients who had not context and limitations of the study design. To meet this aim, a primary cross sectional study morbidity. opted out of study (N=568). We anticipate that results will inform the of preschool children diagnosed with CF through CF multidisciplinary team of significant links The study will produce prevalence data on Data collection has commenced and as at 31 NBS and their families in Western Australia between disease progression and specific respiratory symptoms, morbidity and risk December 2011 the project has collected 100 will be conducted to gain insight into the psychosocial domains within this population of factors for children, adolescents and young completed questionnaires (~18% response rate). relationships between psychosocial factors and children. We anticipate that this information adults with CP by severity of impairment, age Progress is on track for the delivery of the final disease progression. Information will be gained will provide the foundations for design of and feeding method used. Such data are not report by June 2013. through one-to-one interviews of parents of psychosocial screening tools and intervention currently available in the published literature. children with CF and through self-administered Funders of the project: Department of Health strategies on a local level, which will be further The data can be used for early identification questionnaires. developed with the results of the longitudinal and intervention in order to prevent the The specific objectives for the project are: study. development of serious respiratory problems. Long-Term outcomes associated with • To identify the cross-sectional relationships Funders of the project: Department of Health The project will provide a method for tracking the use of stimulant medication in the between child health measures (designed changes in these problems over time with a view treatment of ADHD: outcomes at 17 years to measure the progression of CF), and to identifying early risk factors and protective of age the following psychosocial measures: Respiratory symptoms in children with factors for later serious respiratory problems. family functioning, parental mental health, Cerebral Palsy In collaboration with Craig Russell In 2011, a project reference group was formed parental reflective functioning, and dyadic (MICADHDWA), Brad Jongeling (Child with considerable discussion of questions in relationships. In collaboration with The Centre for Cerebral Development Service) and Lou Landau (DOH). Palsy and Associate Professor Eve Blair (TICHR). questionnaire amongst group members. An CARE Lead: Grant Smith • To use novel and sensitive techniques to CARE Leads: Grant Smith application has been submitted to the PMH detect and quantify disease progression/ Health Research Ethics Committee (HREC) for This project will replicate the methodology used severity in young children with CF. The aim of this study is to determine the permission to amend the questionnaire and in the report: Raine ADHD Study: Long-term prevalence of respiratory problems in children approval was provided by the PMH HREC in outcomes associated with stimulant medication • To determine the value and precision of 1 and adults with CP in Western Australia. October 2011. Scientific protocol and ethics in the treatment of ADHD in children . However, each of the psychosocial instruments as This information will be used to identify and application has been submitted and ethics where the previous report examined outcomes correlates of health status in early life and intervene as early as possible in order to prevent approval via the DoH HREC has been received. measured at the 14-years of age, this project will inform the choice of instruments for the serious respiratory problems from developing. The questionnaire has been piloted and finalised examine outcomes measured at 17 years of age. longitudinal study. The objectives of this study of children and with the development of an electronic online Specifically, this project will aim to use Ethics documentation has been prepared and young adults with CP are to determine: questionnaire. A recruitment poster has been longitudinal data from the Raine Study to tools have been designed. HREC has yet to prepared and printed as well as information examine the long-term associations between 1) the prevalence of respiratory symptoms and approve the study due to essential changes to sheets and final questionnaire tool (6 versions). stimulant medication-use during childhood morbidity,

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 77 and adolescence and a number of outcomes Integrated Early Years Services Project process; interpret quality audit/checklist data. with improved infant feeding practices in WA, for children with ADHD. These outcomes, A report has been prepared to the steering/ and 3) obtaining a reliable baseline measure measured at 17 years of age, include: Social, In collaboration with Child and Adolescent reference group on quality audit/checklist on prevalence of breastfeeding in WA. Emotional, Educational, Growth Measures, Community Health Policy Branch results and obtain agreement on audit The initial (baseline) survey of 1054 mothers and Cardiovascular Function. The 17 year recommendations. Planning with both WACHS CARE Lead: Kim Clark with children aged 9 months across Western follow up also provides an opportunity and CACH led to the identification of 3 rural Australia was conducted in 2010 using to examine addition variables such as This project seeks to characterise whether sites for assessment as part of the project and computer assisted telephone interviewing employment and employment related training, there are factors within the design and 1 metropolitan site. with the assistance of the ECU Survey if these additional variables are available. operation of integrated early years services The report format agreed by the project Research Centre. Mothers were asked about It is hypothesised that different patterns that lead optimise developmental outcomes steering group will be a manual for the their experiences in hospital that relate to of medication use will be associated with for pre-school children and best support development and evaluation of integrated BFHI practices; they were asked about their different outcomes. their families. An output of the project will be a framework for assessing the quality of early years services. A review/synthesis of infant feeding practices including duration, Approval from the Raine Executive Group early years service integration. This was to integration literature has been completed. introduction of formula and other liquids was received in October 2011 for both stages be developed via a detailed analysis of the Ethics approval for interviews was obtained and the introduction of solids. Finally they of the research. The delay was a result of literature, interviews with early years service through the ECU Research Ethics Committee. were also asked about their experiences with additional time spent on ensuring appropriate staff in a range of metropolitan and rural Focus groups and key informant discussions community services aimed to improve infant support and engagement from all stakeholders settings, and discussions with parents and have taken place. The focus group and key feeding practices. in this project. The use of medication for the informant data has been including in a report other stakeholders. The framework will enable A report has been prepared that provides a treatment of ADHD is a controversial topic to steering group. This workshop has taken the Department of Health to better assess the description of the results collected via Phase and therefore a considerable amount of time place and a draft report to steering group for potential benefits of service integration and I of a project aimed at evaluating the WA was spent ensuring that the analysis plan endorsement of program logic and evaluation consequently aid policy making. Department of Health’s Baby Friendly Health addressed all concerns of the stakeholders recommendations has been prepared. Initiative policy (the WA Hospital Breastfeeding before the application was submitted to the Proposed tasks in the development of the Funders of the project: Department of Health Policy) rollout. The report provides 2010 Raine Executive Group. Data is currently being quality and evaluation framework included data for infant feeding practices in WA and extracted. an analysis of the literature, focus groups and key informant interviews with a range of staff experiences of Baby Friendly Hospital Initiative The timeline for the delivery of the project working in integrated early years services Infant Feeding in Western Australia: (BFHI) practices in hospital for mothers who final report has been amended to reflect centres across WA, and focus groups and Establishing a Baseline and Evaluating gave birth prior to the introduction of the WA delays as a result of our engagement strategy key informant discussions with parents and the WA Department of Health’s Baby Hospital Breastfeeding Policy. with all relevant stakeholders in the project. Friendly Health Initiative Policy (BFHI) community stakeholders regarding early years These results will be compared to data to be Progress is now on track for the delivery of services. collected in 2012 as a means of evaluating the the final report by the end of June 2012 and a Grant Smith and Tanyana Jackiewicz Field work for the project was to include site WA Hospital Breastfeeding Policy. The infant paper by the end of August 2012. To undertake a state-wide population- visits to 4 rural locations that have integrated feeding data gathered indicated that a large representative survey with the aims of 1) Funders of the project: Department of Health early years services in operation (site selection portion of infants did not receive the optimal determining the relationship between hospital under the direction of WACHS). infant nutrition during the first six months practices (and community services) and of their life. Whilst almost all WA mothers A steering group has been formed and has met breastfeeding practices 2) identifying whether initiated breastfeeding their infant (98.3%), to endorse the quality audit/checklist review the DOH BFHI policy rollout was associated

78 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 only 67.1% of infants were still receiving some hospitals. Funders of the project: Department of Health by the Human Research Ethics Committee. Both breast milk at six months of age. aspects of the project rely on receipt of linked Mothers who had greater experience of BFHI data through the Developmental Pathways The duration of ‘full’ breastfeeding (providing practices whilst in hospital were significantly Deliberate Self Harm in Western Project at the Telethon Institute for Child Health no source of nutrition other than breast milk more likely to ‘fully’ breastfeed their infants Australia Research. Our expression of interest has been or water) of WA infants was examined and the to the age of four months. This relationship approved by their governance group; however, following key baseline results gathered: remained significant after adjusting for key Grant Smith and Dr Tracy Reibel this data will not be available until 2012. sociodemographic covariates. • 69.9% of infants were ‘fully’ breastfed This project will use qualitative and quantitative Following receipt of the DPP data, linkage to the beyond the first week of life Younger maternal age, lower levels of maternal methods to examine the effectiveness of the newly gathered data from the ED records will education, being a single mother, and giving take approximately 6 -8 months through the • 45.9% of infants were ‘fully’ breastfed up to various referral pathways (on separation from birth to first child were all associated with WA Data Linkage Unit. Given the time taken for four months of age EDs) with regard to reducing the likelihood lower percentages of mothers reporting they of readmission. The qualitative element of data receipt and linkage, it is expected that this • Only 12.6% of infants were ‘fully’ breastfed had breastfed their infant to four months the project will involve interviews with first- project will be completed by December 2012. up to six months of age of age. Infants residing in the Northern and time DSH ED clients and clients who have Funders of the project: Department of Health Southern regions had the highest percentage of The duration of exclusive breastfeeding been admitted to ED for DSH injuries multiple infants ‘fully’ breastfed to four months of age. (providing no source of nutrition other than times. Elements of the referral pathway that The lowest rates were observed in the South breast milk) of WA infants was examined and the were helpful and those that were not helpful Immunisation Consent Research Project Metropolitan and Central areas. following key baseline results gathered: in preventing further episodes of DSH will ‘Full’ breastfeeding and ‘full’ breastfeeding with be identified. The quantitative aspect of the CARE Leads: Kim Clark, Judy Donnelly, Jordan • 68.7% of infants were exclusively breastfed occasional supplementation indicated that there project will involve the collection of data Fisher and Tanyana Jackiewicz beyond the first week of life on referral pathways data from the written was a significant number of infants who received The output of the research will be evidence ED records of DSH clients. This data will be • 34.6% of infants were exclusively breastfed formula in the first week of life (usually in the based recommendations on the design of linked to Data provided by the Developmental up to four months of age hospital, presumably by medical indication) immunisation consent resources and procedures Pathways Project (specifically the WA Emergency but were nevertheless considered to be ‘fully’ for use in WA. • 8.7% of infants were exclusively breastfed Department Data Collection, the Hospital up to six months of age breastfed to four or six months. A comparison of the durations of true exclusive breastfeeding Morbidity Data Collection, and Mortality) This research is intended to engage Western A scale was developed to measure a mother’s and exclusive breastfeeding with occasional to determine which referral pathways are Australian parents and immunisation providers experience of Baby Friendly Hospital Initiative supplementation yielded similar observations. associated with a lower likelihood of repeat DSH to inform the development of both improved (BFHI) practices. This scale indicated that, on admission (or suicide). immunisation consent resources and a protocol Phase II for use by WA immunisation providers. The average, mothers have a high experience of BFHI In 2011, support was sought from hospitals with project has a sequence of stages. The scope of practices in WA hospitals. Out of a possible 40 The survey will be repeated in 2012 to EDs in the Perth Metropolitan area. The majority the current project entailed the following: points (indicated a high BFHI experience) the determine whether the rollout of the WA of these have agreed to take part in the research average experience of WA mothers was 33.1. Hospital Breastfeeding Policy is associated following approval of the projects by Human (1) Audit and Literature Search with statistically significant increases in BFHI Research Ethics Committees. The applications There was a significant proportion of mothers, This stage of the project was to examine the Experiences of WA mothers and the proportion for ethical review have been submitted to the however, who reported a hospital experience current state of immunisation consent, giving of infants ‘fully’ and exclusively breastfed to the Princess Margaret Hospital Scientific Advisory that was not in line with BFHI practices; emphasis to the types of resources used by ages of four and six months. Sub-Committee and are currently under review indicating room for improvement in some WA Australian and overseas providers. The literature

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 79 was to be examined to highlight discussion be analysed in February 2012. service providers within these services. the outreach services, the approach of the of, and research into, immunisation consent workers in not being too pushy, and being Focus group research for the project will be This study confirmed that young people in procedures for parents with young children. accepting of the clients own situation was also undertaken in Feb-March 2012. metropolitan Perth share many of the views An audit of protocols used in WA by different important to young people. The young people and opinions of their peers reported in other service providers, in both metropolitan and Funders of the project: Department of Health: also reported that they had trust in the service studies. That is, what makes IHSHY services regional areas, was also to be undertaken. Communicable Disease Branch personnel and were confident that their accessible to young people is that they either confidentiality was protected. At the same (2) Experiences, perceptions and offered an outreach/home visiting approach or time they did require continuity of service recommendations of consumers provided transport as required (for intensive Innovative Health Services for providers and were quick to point out that social support models) or in the case of Street This stage of the project was to explore the Homeless Young People (IHSHY) relationships and trust are important. Most Doctors, these services were located in places experiences and perceptions of Western Evaluation young people talked about IHSHY services and that were easy for young people to access such Australian parents regarding the consent the service personnel as being easy going, fun Dr Tracy Reibel and Tanyana Jackiewicz as on transport lines or close to community process followed with their children’s and informal with non-judgemental attitudes. centres. The client results showed that young immunisation. Qualitative and quantitative The purpose of this research was to identify The area that remained problematic for many people access IHSHY services because they methods of data collection were to be the attributes of WA IHSHY services, by asking young people was in accessing mainstream are conveniently located or offered a home undertaken to establish an indication of the the users of the services and those who work services either because they felt they did visiting/outreach service, which makes access views that Western Australian parents have of within the service, what makes these services not need the services or because they were straightforward. Other factors include clients current approaches to consent as well as their able to work successfully with marginalised not confident in keeping appointments not having to incur a cost to receive the opinions about improvements in this area. young people with complex needs, including or approaching these services without an service, and importantly, the informal and Indigenous young people. Five IHSHY services advocate. The study has been overseen by a reference relaxed atmosphere of services. Aboriginal were involved in the evaluation including: group and has ethics approval via the DoH clients particularly referred to feeling secure The service personnel interviews provided for Perth Street Doctor; Fremantle Street Doctor, Health Research Ethics Committee (HREC). The accessing Fremantle Street Doctor as it an in depth perspective of the services; and Adolescent Mothers Support Service, RUAH reference group played a substantial role in all did not require them to sit in unfamiliar or providers noted that for their services to be Young Women’s Program and Hills Community aspects of project development. unwelcoming places such as doctors surgeries. very accessible to young people – location is Support Service. Unbooked appointments or having the service important. There was reflection from Street The project literature review has been come to them, particularly when public Doctor personnel that integration with other completed. Questionnaire design for the Qualitative research is particularly useful transport is not available, was also a factor community services is an essential aspect of survey aspect was completed and the in understanding the socio-cultural context in ease of access to these services by both building relationships with local Aboriginal instrument was trialled before use in the field. of complex behaviours particularly in Aboriginal and non-Aboriginal clients. communities in particular. Co-location Subsequently, field work was completed and marginalised populations such as homeless youth and an informal interview based provides an opportunity to expose young study data is currently being analysed for In regard to acceptability for young people, structure was used in this evaluation as the people to other services but also makes reporting. A “Community Conversation” was the fact that the services are of no cost, have most appropriate means to elicit information the Street Doctor services visible in places undertaken and reported upon. A further an informal and relaxed atmosphere was a from at risk and homeless youth. A total of 49 where young people are known to frequent. conversation will be held in February 2012. An draw card for young people, particularly in interviews were conducted with young people Service participants noted their respect and audit of current practice has been completed relation to the drop in nature of the Street (15-24 years) recruited across 5 IHSHY services admiration for the young people who use and a report written on this aspect. An online Doctor mobile primary care ‘clinics’. Aboriginal in the Perth metropolitan area. In addition, their services. To understand what drives survey of WA immunisation providers has also clients reported that they felt accepted by a total of 18 interviews were conducted with their commitment, we asked service providers been completed and data from this survey will the staff and that they felt understood. For

80 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 what qualities they think are imperative for staff and psychology services, as well as drug and sleeping/bed-sharing policy (OD). The research of its recommendations seems on the surface to have to work in their type of service. Not alcohol agencies, youth workers and childcare. idea originated from the Women and Newborns quite effective. Whilst many women and health surprisingly, the qualities or attributes service Mental health issues were a common theme for Health Network (Department of Health) in professionals know and understand what the personnel identified were similar to young both young people and service personnel. consultation with the Telethon Institute for key messages about co-sleeping are, there are people’s views on provider qualities. These Child Health Research. The purpose of the multiple reasons for non-compliance or only Importantly, access to acceptable and are, being non-judgemental, philanthropically evaluation was to assess the effectiveness of the partial adherence to the OD recommendations. accessible mental health has been identified inclined, passionate, respectful, easy going, implementation and dissemination processes of These may include the philosophical beliefs in this evaluation as a prevalent issue with with a sense of humour and empathetic with the OD across state government maternity units, and attitudes about bonding and attachment homeless and at risk young people. It is clear the client group. Additionally, the service private hospital maternity units, child health by health professionals and women, pragmatic that there is a need for better integration personnel discussed the necessity to work as and community health services in Western considerations such as lack of sleep, limited between youth oriented mental health services a team to build relationships with their clients Australia. This was achieved through a multi access to material resources such as cots, and IHSHY services, with defined referral acknowledging that the work is challenging. method research design involving service audit, overcrowded living conditions experienced pathways to ensure timely engagement, but Even though the work is demanding, interviews and focus groups with health workers by mothers and cultural beliefs (co-sleeping also for psychologists and counsellors to be unpredictable and at times overwhelming, and interviews with WA mothers. The evaluation is normalised) by both health workers and incorporated as part of the IHSHY service model it was emphasised that being in a team and also included the identification of other sources mothers. Some health professionals and women multidisciplinary teams. This aspect of providing making even a small difference in people’s lives of co-sleeping information, policy guidelines also question the scientific basis for the OD and holistic care to disadvantaged youth is one of makes the work worthwhile. A combination of and directives used across maternity and child require more clarity around the absolute risk of the most resource poor of all service gaps. The team work and working with the clients with health services. Key findings of the evaluation co-sleeping deaths when all other risk factors lack of referral pathways to appropriate mental knowledge and empathy was noted as essential included the barriers and facilitators for health have been taken into account. The evaluation health services and indeed the lack of these to making the services work so that young workers in providing co-sleeping information also identified key areas of confusion and services for youth is a key area of need identified people will return. and highlighted the complexities and dilemmas information gaps that are not directly addressed by both clients and service personnel and fully in interpreting the intent and practice of by the OD, particularly around the issues of the Clients were asked to identify any improvements supported in the literature and is highlighted the OD. Health workers and WA mothers use of safe sleeping aids and side cots, wrapping, to services and a number of young people from here as a significant barrier to addressing informed suggestions and recommendations stroller sleeping and mattress fumes. These were the Street Doctor sites recommended more homeless and at risk youths’ full spectrum of for developing and disseminating co-sleeping all issues identified by both health professionals access to warm clothing and coffee, onsite health needs. education that responds to the diverse cultural and mothers as requiring clarification and the pharmacy and free scripts, and more services in Funders of the project: Department of Health and life-style backgrounds of WA families. development of appropriate information. more locations. Many clients also asserted the need for a 24 hour/7 day a week availability of Overall the evaluation has shown that generally Funders of the project: Department of Health services, particularly drop-in centres for short the OD is well disseminated throughout An evaluation of the implementation term, safe accommodation, showers and meals. government and private maternity units, and dissemination processes for the Clients from outreach services tended not to however, is less well distributed or known To investigate the resources and Western Australian Operative Directive suggest any improvements when interviewed, about in community health and Aboriginal support available for women (including for co-sleeping which was taken to mean that the service they Community Controlled Health Organisation Aboriginal and CALD) accessing were provided with was sufficient for their Dr Jenny Dodd (ACCHO) settings. The manner in which the maternity system services, who are at needs. Importantly, however, and a key finding OD has been interpreted and responded to risk of domestic violence This evaluation assessed the effectiveness of the in this research, is that young people identified by the health professionals/workers in this implementation and dissemination processes the need for access to counselling, mental health evaluation has shown that the implementation Dr Jenny Dodd of the WA Operational Directive State wide co-

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 81 This research project reviewed and mapped and appropriate accommodation services development and emotional support. There The results of this research process has led the current processes, guidelines and particularly for young pregnant women, are some areas where maternity health to the formation of inter-agency leadership protocols that are in place that respond to Aboriginal women, CaLD women (particularly services and community support services such group with representatives from the range pregnant women, at risk of family domestic those on accompanying and/or student visas) as housing and counselling are already working of government and community agencies to violence (FDV), who are accessing maternity and women living in rural areas. well. However, there are also areas where consider how pregnant women at risk of FDV system services in Western Australia. The increased collaboration and integration are can access additional services and support Further, well established referral pathways are referral pathways that are utilised was required particularly in meeting the needs of both within and external to the maternity reported between some major government identified through analysis of guidelines and these women: health services. maternity units in metropolitan Perth and protocols used by a range of maternity health social worker support, counselling, domestic • Young women – accommodation, Funded by the Department of Health system services and through interviews with violence advocacy and young women’s counselling, legal representation, Health professionals/workers and Social accommodation and support services. substance misuse. workers. These are generally less developed in some • Aboriginal women – culturally relevant Developmental Pathways in A mixed methods approach was used including regional and rural areas particularly where responses, information, accommodation, policy and literature overview, audit, focus communities may be dispersed. However, WA Children Project support services for men, substance group and interviews with a range of health some smaller regional towns have good misuse and increased ability to remain in and community sector workers across health, integration and relationships between Fiona Stanley (University of Western Australia their own homes. child protection, immigration, communities, maternity services and external services, (UWA), Telethon Institute for Child Health legal, drug and alcohol and housing sectors. although demand for services is often greater • Culturally and linguistically diverse Research (TICHR)); Helen Leonard (UWA, These methods resulted in a comprehensive than availability and are more likely to be women – culturally appropriate TICHR); Nicholas de Klerk (UWA, TICHR); and in-depth overview of the key issues and subject to workforce shortages and mobility. information, support and services Jianghong Li (Curtin University of Technology, concerns for pregnant women at risk of FDV for women on accompanying and/ TICHR); Natasha Nassar (UWA, University The majority of maternity health services and the maternity service workers who they or spousal or student visas, access to of Sydney); Stephen Zubrick (UWA, TICHR); workers report feeling generally supported come in contact with. The methods used publicly funded health, housing and Catherine Taylor (UWA, TICHR); Amanda by their management, however, also identify enabled the identification of processes and income support services, culturally Langridge (UWA, TICHR); Eddie Bartnik (WA that FDV professional development, space strategies that are currently working well as appropriate information and responses to Mental Health Commission); Cheryl Gwilliam for confidential screening and “burn out” well as those requiring further development. contraception, termination and unwanted (WA Department of the Attorney General); of health professionals are issues requiring pregnancies. Ian Johnson (WA Department of Corrective This project reported that formal and informal attention. The majority of health workers Services; Tim Marney (WA Department of screening methods are used by a range of describe FDV guidelines and screening tools Overall, this research project reminds us Treasury and Finance); Karl O’Callaghan (WA government, private and community-based as useful starting points, along with the that there is no one solution, screening tool Police); Sharyn O’Neill (WA Department of maternity services. Formal methods are ability to refer pregnant women to social or process that is applicable to all pregnant Education); Grahame Searle (WA Department less useful for Aboriginal and CaLD women workers and counsellors in the first instance, women at risk of FDV. Family and domestic of Housing); Ronald Chalmers (Disability and health workers recommended the use as most important. The majority of health violence is a complex area and ensuring that Services Commission WA); Jenni Perkins (WA of informal and trust building processes workers feel constrained by mandatory the needs of pregnant women in all their Department for Communities); Cliff Weeks for these. Referrals to external support reporting requirements and require more diversity are met often requires referrals to a (WA Department of Indigenous Affairs); Diana services from these different methods of support from management in negotiating wide range of health, community and support Rosman (Department of Health WA); and Kim screening are effective when they occur, but and discussing cases with the Department services outside the immediate remit of Snowball (Department of Health WA) there is also unmet demand for counselling for Child Protection, including professional maternity services.

82 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 The Developmental Pathways Project is a interrelationships among them. Through neglect; determine the mental health and with risk, protective and resilience factors that landmark project taking a multidisciplinary and the effective communication of the research juvenile justice outcomes of children who have contribute to juvenile delinquency in Aboriginal holistic approach to investigate the pathways to findings, future government agency policies, contact with the child protection system; and and Torres Strait Islander Children. health and wellbeing, education, disability, child practice and planning initiatives will be more investigate the child, family and community abuse and neglect, and juvenile delinquency preventative, culturally appropriate and cost characteristics which increase or reduce outcomes among Western Australian children efficient, and we have encouraged cross-agency vulnerability to child abuse and neglect. Juvenile delinquency and youth. To achieve this, researchers from collaboration to ensure improved health, well- the Telethon Institute for Child Health Research being and development of children and youth, Conducted by Anna Ferrante and the University of Western Australia have their families and their communities. Aboriginal health research Anna Ferrante is an Associate Professor at been working in collaboration with a number of Funders of the project: The Developmental the Centre for Data Linkage, Curtin University, state government departments, including the Conducted by Glenn Pearson Pathways Project was made possible by the formerly a Research Associate Professor at the WA Departments of Health, Education, Child generous cash and in-kind contributions made Glenn Pearson, a Noongar from Western Crime Research Centre, University of Western Protection, Corrective Services, Communities, by all of the collaborating organisations and Australia, and Manager of Aboriginal Health Australia. As part of the Developmental Indigenous Affairs, Treasury and Finance, government departments, which has been Research at the Institute, is completing his Pathways Project, Anna is undertaking a Housing, Attorney General, the Disability matched by the Australian Research Council Doctorate on the Developmental Pathways population-based study of the dimensions Services Commission, the Mental Health (ARC) through two consecutive ARC Linkage Project. His qualitative research PhD project and development of delinquency in Western Commission, and WA Police. The project has Project Grants. explores how the delivery of health, education Australian children. The aim of the project is established the process of linking together de- and child protection services provided by the to contribute to a better understanding of the identified longitudinal, population-based data The Developmental Pathways Project supports WA State Government to Aboriginal clients is dimensions of juvenile delinquency and of the collected and stored by a large number of these several postgraduate students and postdoctoral mediated by the perceptions Non Aboriginal impact of various factors on the development of WA government departments and the Telethon fellows, to conduct individual research projects and Aboriginal people hold of themselves and delinquency over the life-course. By exploring Institute, to create a fantastic cost-effective which answer specific research and policy each other in the provision and receipt of these the interactions between risk factors and their research and policy planning/evaluation relevant questions within and across the themes services. effect on offending, it may be possible to map resource. The project has also established a and scope of the overall project. ‘pathways’ from early childhood to juvenile Directors’ General Steering Committee who delinquency and later criminal behaviour. meet twice a year to discuss how to best use Conducted by Jocelyn Jones these joined up data and joined up agency Child abuse and neglect Jocelyn Jones is completing her doctorate resource. In 2011 the project also established Attention Deficit Hyperactivity Disorder Conducted by Dr Melissa O’Donnell through the Developmental Pathways Project. a Consumer and Community Reference Group Her project is titled ‘Exploring the pathways who meet four times a year to provide an Dr Melissa O’Donnell is an NHMRC Early Career Conducted by Dr Desiree Silva to contact with juvenile justice in Aboriginal oversight role for governance, standards Fellow and a Psychologist who completed and Torres Strait Islander children: developing Dr Desiree Silva is a paediatrician, and Professor and practices relating to the project from a her PhD in 2009 through the University a profile of the risk and protective factors to of Paediatric Medicine at Joondalup Health community perspective. of Western Australia. Her research uses support a strategy for change’. Using linked Campus and UWA. Due to the escalation longitudinal population data provided through The linked data are being used by researchers longitudinal population data provided through of mental health issues in children, Desiree the Developmental Pathways Project. This and the respective departments to the DPP this project seeks to develop a profile commenced a PhD through UWA and the administrative data is being used to: investigate identify multi-level and early determinants of the developmental, health, socio-economic, Telethon Institute for Child Health Research emergency department presentations and of developmental outcomes and the racial and demographic factors associated on the risk factors and outcomes of children hospital admissions related to child abuse and

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 83 and adolescents diagnosed with Attention Children who are vulnerable to mental In this study we brought a bioecological behaviour. In this study we investigated the Deficit Hyperactivity Disorder (ADHD) in health problems are subsequently at risk of approach to children’s early vocabulary hypothesis that more empathic mothers are Western Australia. Her PhD project uses experiencing interference with development, development using data for 2,188 children more likely to encourage their child to take longitudinal population data provided through and more specifically, with schooling, and the (1,119 male) from the Longitudinal Study of the perspective of others and that this is the Developmental Pathways Project. This development of their identity. Results of this Australian Children. These children had a associated with increased child empathy and administrative data, along with questionnaire study will potentially inform the development median age of 9 months (M = 9.3 months, prosocial behaviour. Participants were 72 data, is being used to: identify potential of suitable interventions, ultimately with the SD = 2.1 months) at Wave 1 and a median typically developing children (66 Caucasian, antenatal and early neonatal risk factors aim to decrease the prevalence of mental age of 34 months (M = 34.2 months, SD = 2.5 6 Asian) aged between 47 and 76 months (M associated with children requiring treatment health issues and improve educational months) at Wave 2. We found that the effects = 61.5 months, SD = 8.3 months). Results with stimulant medication; explore hospital outcomes. of individual (e.g., parent) and environmental supported the hypothesis. Thus, the role and emergency morbidity, accident related (context) characteristics on children’s played by parents in the development of The Developmental Pathways Project also hospitalisation risk, criminal and antisocial vocabulary development are primarily prosocial behaviour extends beyond warm/ facilitates the provision of de-identified behaviour, and service needs associated with indirect, mediated through their impact on sensitive/responsive parenting in infancy. non-health linked population level data to a children on stimulant treatment for ADHD; the proximal processes of joint attention and Together these forms of parenting are key number of other research projects conducted examine education outcomes of children parent-child book reading. Thus, the findings factors that facilitate the development of within other research institutions, including diagnosed with ADHD and their level of of our study add to the growing evidence that prosocial behaviour. those led by Prof Jablensky (Pathways of Risk stimulant medication treatment; and explore joint attention and parent-child book reading from Conception to Disease: A Population- Funders of the project: University of Western the mental health burden of parents and are important facilitators of children’s early Based Study of the Offspring of Women with Australia Hackett postgraduate scholarship family functioning of children diagnosed and vocabulary development. Bipolar Disorder and Schizophrenia); Assoc (BF), University of Western Australia treated with pharmacotherapy for ADHD in Prof Tony Butler (Does Traumatic Brain Injury Funders of the project: NHMRC Program Grant completion scholarship (BF) NHMRC Program WA. (TBI) lead to offending behaviour?); and Dr #572742 (BF) Grant #572742 (BF). Colleen O’Leary (Investigating the effect of a maternal alcohol-related diagnosis on Mental health the educational, juvenile justice, and child Empathy, Perspective Taking, and Getting Our Story Right Conducted by Janice Wong protection outcomes of their children and Prosocial Behaviour: The Importance Examining the effect of the dose, pattern, of Parenting Practices David Lawrence, Francis Mitrou, Daniel Janice Wong is completing her doctorate on and timing of prenatal alcohol exposure on Christensen, Glenn Pearson the Developmental Pathways Project. Her Brad Farrant, Tara Devine, Murray Maybery, educational outcomes). The Getting Our Story Right project is a project is titled ‘The relationship between Janet Fletcher collaboration between the Telethon Institute educational and mental health outcomes for It has long been argued that empathy for for Child Health Research, the Australian Western Australian children: A longitudinal others’ plight and the associated altruistic Bureau of Statistics (ABS) and The Department population study’. Using linked longitudinal Human Capability behaviour are key facilitators of social life. of Health WA (DoHWA) and aims to explore population data provided through the DPP Early vocabulary development: The Social scientists emphasise the important and develop different methods for deriving this subproject seeks to explore the dynamic importance of joint attention and role that parents play in the socialisation of Indigenous status from multiple data sources relationship between children’s educational parent-child book reading empathy and prosocial behaviour and research using the WA Data Linkage System and outcomes and their mental health, whilst has found that positive parenting practices are examine the impact of these methods on a taking into account variables that have Brad Farrant, Steve Zubrick. associated with higher levels of child prosocial sample of health and educational outcomes been shown to impact on this relationship.

84 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 among the Indigenous population. of SSB, consumption patterns and the dietary Berthelsen more likely to use other child services, like a and demographic profile of SSB consumption in maternal child health nurse. Various methods of deriving consistent Though thousands of parents and children children was available. We used data from the Indigenous status from a linked data source will attend playgroups each week, there is little Funders of the project: NHMRC program grant 2007 Australian National Children’s Nutrition be explored and the impact of these methods evidence around the extent to which playgroups #572742 and Physical Activity to address these issues. examined against a selection of health and achieve their objectives of enhancing child educational outcomes such as mortality rates, We found that SSB consumption was high and development, supporting parents and hospitalisation rates, and school-based reading patterns of consumption varied by age. The encouraging community participation. Using How multiple generations of mental and writing scores from standardised tests. primary source of SSB was from supermarkets data from around 5,000 families participating in health problems in families influences with less than 17 per cent of products being Growing Up in Australia: The Longitudinal Study the wellbeing of children The overall aim of the project is to produce sourced from fast-food establishments and of Australian Children, we found that children a set of recommendations for agencies and school canteens. Further, the majority of SSBs from disadvantaged families were less likely Kirsten Hancock, Francis Mitrou, David Lawrence researchers responsible for the provision of were consumed at home. We found children to access playgroups than other children, yet and Stephen Zubrick with Megan Shipley Aboriginal and Torres Strait Islander Statistics, whose parents had lower levels of education these were the children who benefitted most particularly with reference to COAG ‘Closing Research has consistently shown that children consumed more SSB on average, while children from attending. Children from disadvantaged the Gap’ indicators. It is envisaged that these of parents with mental health problems are at whose parents had higher education levels families scored higher on measures of learning recommendations will help agencies and greater risk of also developing mental health were more likely to favour sweetened juices and competence and social-emotional functioning researchers produce consistent, reproducible problems. Yet there is limited research around flavoured milks. at age 4-5 years if they persistently attended and meaningful statistics in order to assess the how these mental health relationships evolve playgroup when aged 0-1 and 2-3 years health and wellbeing of Aboriginal people. This research highlights the need for public over multiple generations, beyond the initial compared to children from disadvantaged health interventions which are evidence based parent-child relationship. In this study, we used Funders of the project: COAG, ARC Discovery families who did not attend. and target the primary source of SSBs in order data collected from 4,600 families participating Grant DP0877513 Growing Up in Australia: The Longitudinal to reduce current levels of intake by Australian In a second phase of research, we found in Study of Australian Children children. Additionally, education of parents and that mothers of 4-5 year old children who to examine the children regarding the health consequences of persistently attended playgroup were more likely mental health relationships across three Sugar Sweetened Beverage consumption high consumption of both carbonated and non- to have consistently good support from friends, generations of Australian families. by Australian children: Implications for carbonated SSBs is required. or to have improved support from friends public health strategy Our results show that the mental health of compared to mothers whose children did not Funders of the project: NHMRC program grant grandparents matters for children, even in the attend, suggesting that socially isolated parents Katherine Hafekost, Francis Mitrou, David #572742 absence of problems in the parent generation. Lawrence and Stephen R Zubrick may find playgroups a useful resource to build Compared to children with no family history of their social networks. mental health problems, the risk of social and Consumption of sugar sweetened beverages emotional wellbeing problems in 4-5 and 8-9 has been linked to unhealthy weight gain and Playgroup participation and the Finally, we found that compared to children who year old children was 1.3 times (95% CI 1.07- nutrition related chronic disease. Despite public associated outcomes for children and never attended playgroup, children who did 1.64) higher for children who had a grandparent, health efforts to reduce consumption, such as mothers attend playgroups tended to have more books in but not a parent, with a history of mental health limiting sales of these products in schools and the home, attended more activities outside the Kirsten Hancock, David Lawrence, Francis problems; 3.2 times higher (95% CI 2.3-4.5) for restrictions on marketing, Australian children’s home (e.g. swimming pools, museums, movies), Mitrou, Stephen Zubrick children with only a parent with a mental health intake remains high. In addition, little up-to-date lived in safer neighbourhoods, lived in places problem and 2.6 times higher (95% CI 1.9 – information about the primary purchase source with David Zarb , Jan Nicholson and Donna with good access to basic services and were 3.5) for children who had both a parent and a

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 85 grandparent with a history of mental health approach to informing the evidence base for problems. The broad aims of the National Survey of problems. these interventions. Key research findings Mental Health and Wellbeing initiative have • Investigation of data on food production from the study include: been to determine how many Australians have In our next phase of work we are examining and food imports into Australia has which mental disorders, what is the impact of how multiple generations of joblessness and • teenage pregnancy was found to be identified that sugars in processed these disorders (on individuals, families and divorce impact upon a range of outcomes for significantly associated with family type, manufactured foods imported communities), and what services are being children. highest school year completed by primary into Australia are not included in used by people with mental disorders. carer, combined carer income, whether estimates of sugar consumption. This Funders of the project: NHMRC program grant the primary carer was a smoker and is traditionally estimated from the size The development work for this study included #572742 whether the girl displayed aggressive and of the sugar crop minus sugar exports. reviewing surveys of child and adolescent delinquent behaviours during childhood As importation of manufactured foods mental health and wellbeing internationally, and adolescence. Aggressive and with high sugar content has increased reviewing relevant instruments and Measuring and modelling the delinquent behaviours were predictive of dramatically over the last 15 years, this questionnaires in the field, and facilitating childhood determinants of human teen pregnancy even when observed at may have downplayed the role of sugar consultation with relevant stakeholders to capital formation and human young ages. consumption in the increasing rate of help refine and articulate the goals for the capability expansion obesity and metabolic diseases. survey. Methodological work to develop an • deliberate self-harm was found to be appropriate sampling strategy to achieve Stephen Zubrick, Sven Silburn, Dennis Trewin, significantly associated with female sex, Funders of the project: COAG, ARC Discovery these goals was undertaken. The work also Ann Sanson, Bill Louden, David Lawrence. primary carer being a smoker, being in Grant DP0877513. identified emerging content areas relevant to This study uses archival data sources and a step or blended family, having more the social and emotional wellbeing of children data linkage capacities to focus on the emotional or behavioural problems than and young people including the impact of new measurement of human capability across other children, living in a family with Child and Adolescent Component of and emerging technologies on peer relations the life course. Specifically the study aimed inconsistent parenting style, and having a the National Survey of Mental Health and bullying behaviours, and the role of social to integrate archival data with population teenage mother. and Wellbeing inclusion in fostering emotional wellbeing. data registers in the health, education and • people with common mental disorders Jennifer Hafekost, David Lawrence, Stephen Funders of the project: Australian Government social services sectors to study patterns such as anxiety or depression smoke Zubrick Department of Health and Ageing of participation (or non-participation) at substantially higher rates than the associated with specific education, health remainder of the community, and The National Survey of Mental Health and and developmental burdens; and to use represent about one-third of Adult Wellbeing includes three main components - a Early life influences on child and national data sources such as the Longitudinal smokers in Australia. People with these population-based survey of adults, a service- adolescent mental health problems: Study of Australian Children to compare and disorders are more likely to start smoking, based survey of people with low-prevalence A life-course approach to prevention validate findings across settings. This study less likely to quit, and smoke on average psychotic disorders, and a population survey and intervention seeks to document the relationship of human for longer duration, despite wanting of children. The first Child and Adolescent capital growth to educational attainment, component was conducted in 1998, and the to quit and trying to quit as much as Dr Monique Robinson (Supervisor: W/ employment and occupational skill level across Institute is participating in sample design and anyone else. Mainstream anti-smoking Professor Stephen R Zubrick) the lifespan and how this relates to human campaigns that have been successful in content development work in preparation for capability expansion. The study also sought the broader population have had lesser a second national survey of children and young My current work explores the early life to inform population health interventions success for people with mental health people. influences on mental health development and health promotion through a lifecourse in order to inform both prevention and

86 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 intervention. It has been suggested that the of children’s development in communities across has now taken ownership of the AEDI National Health Research, Perth, to deliver the AEDI. best method for avoiding poor mental health Australia. Teachers complete the checklist for Program and has committed to undertake an outcomes is to build and promote positive children in their first year of full-time schooling. AEDI Census of child development once every outcomes right from the very start of life. The AEDI measures five developmental domains: three years. Thus, in 2012, the AEDI will be Early Child Development, The goal then shifts from treating problems completed nationwide for a second time. Data • Physical health and wellbeing after they have occurred, to a model enabling will be collected between May and July 2012, Program Evaluation: the formation and promotion of positive • Social competence with results made public in early 2013. This mental health outcomes. However, we have second round of data collection will provide the Randomised cluster control trial • Emotional maturity predominantly used early childhood as the start first opportunity to explore change in the level evaluating the impact of an Early point for development. My research exists • Language and cognitive skills (school-based) of developmental vulnerability for children living Childhood Education and Development initiative across Indonesia within this new paradigm, exploring the early • Communication skills and general in different communities, states and territories within Australia. life influences on behavioral development. I knowledge Sally Brinkman, Menno Pradhan, Amanda continue to research numerous novel risk factors In 2011, the Australian Government Department Beatty, Amelia Maika, Elan Satriawan present in the prenatal period that are linked The AEDI is based on the Canadian Early of Education, Employment and Workplace to an increased risk for mental health problems Development Instrument (EDI) which was With a greater scale for improvement in school Relations (DEEWR) awarded $1.5 million in throughout childhood, including stress, maternal developed by Dr Janus and Dr Offord at the readiness outcomes, the evaluation of ECED funding directly to TICHR to explore the 2009 obesity, preterm birth, cigarette smoking, Offord Centre for Child Studies, Mc Master programs in the developing countries affords and 2012 AEDI data and deliver on policy alcohol consumption, low levels of Vitamin D University. In Australia, the Canadian EDI a greater scope for investigation into the focused research. The research will focus on a and hypertension. I am also actively involved in checklist was first trialed in the northern facilitators and barriers for success. This ECED range of questions pertinent to early childhood collaborations with Columbia University (USA), metropolitan suburbs of Perth in 2002 and 2003, program that we are evaluating represents a development such as:- McMaster University (Canada), the Murdoch with around 4,300 children. Since 2004 the significant investment on behalf of the Republic Children’s Research Institute (Melbourne) adaption of the EDI - now called the Australian • Are there jurisdictional differences in the of Indonesia and the World Bank. EDI, or AEDI has been carried out by the Centre level of developmental vulnerability across and the School of Population Health (Perth) With significant economic growth over the last for Community Child Health in partnership with Australia? on various projects looking at psychological 5 years, Indonesia is currently classified as a outcomes following adverse early life exposures. the Telethon Institute for Child Health Research. • Is there a differential impact of living in lower to middle income country. Despite this Funders of the project: Australian Rotary Health In 2009, the AEDI was completed nationwide for mining towns vs. non-mining towns for fact, there are over 35 million people living Colin Dodds Postdoctoral Research Fellowship the first time with the Australian Government Aboriginal child development? below the poverty line – representing 16% of the providing $21.9 million for the implementation population. In addition it is estimated that up • How does the AEDI predict later outcomes of the AEDI in recognition of the need for all to half the population are vulnerable to poverty during the primary school years? Australian Early Development Index communities to have information about early with the inequality between rich and poor vast. childhood development. Between 1 May and Acknowledgement: A large disparity in socio-economics, nutrition, Sally Brinkman, Stephen Zubrick, Tess Gregory 31 July, information was collected on 261,203 education and health exist between districts, The Australian Government and State and Louisa Santucci children (97.5 per cent of the estimated national with infant and child mortality rates significantly and Territory Governments are working five-year-old population). The initial results higher in the poorer communities. In addition, The Australian Early Development Index (AEDI) in partnership with The Royal Children’s provide a snapshot of the early childhood children from the poorer villages start school is a population measure of young children’s Hospital Centre for Community Child Health in development outcomes for children in later, complete fewer years of schooling and development. Like a census, it involves Melbourne, the Murdoch Childrens Research communities across Australia. The government have higher drop out and repetition rates. collecting information to help create a snapshot Institute, and the Telethon Institute for Child

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 87 The objective of the Early Childhood Education and abroad. In addition the evaluation will International Consortium for the are deemed to be of critical importance. This and Development program is to improve poor utilize outcome instrumentation that can Monitoring of Child Development calls for longitudinal data collection to improve children’s overall development and readiness be internationally referenced and thus the knowledge base for identifying children for further education by (i) increasing the rigorous piloting and cultural adaptation of Magdalena Janus, Sally Brinkman, Clyde at risk of adverse mental health and social delivery of ECED services in targeted poor internationally recognized instruments will be Hertzman, Mary Young outcomes in childhood, adolescence, and early communities using a community-driven required. As international interest and acknowledgment adulthood. Research has shown that 75% of approach and (ii) developing a sustainable mental disorders commence before the age The AisAID ADRA Grant has enabled the grows around the importance of monitoring system for delivering ECED services. The of 25 years, and that 46% of adults report the employment of two early career academics child development various countries are project will reach approximately 738,000 occurrence of at least one psychiatric disorder based at the University of Gadja Mada (UGM) looking for support in initiating monitoring children aged 0 to 6 and their parents/ over their lifetime (with 25% reporting a in Indonesia. As both academics are teaching activities. As such an International Consortium caretakers living in about 6,000 poor current psychiatric disorder). university students, building their capacity, for the Monitoring of Child Development has communities (dusuns) located in 3,000 villages skills and knowledge will not only benefit been formed between the Offord Centre at The NSW Child Development Study is being within 50 districts. Participating districts have themselves but their current and future McMaster University and the Human Early designed as a 15-20 year project to identify been selected according to poverty level students. There is a clear and recognised Learning Partnership in Canada along with the potential health-related vulnerability and and their commitment to developing ECED deficit in Indonesia in the knowledge and Telethon Institute for Child Health Research protective factors in children, and to examine services. capacity regarding high quality research and the Centre for Community Child Health their relationships to a variety of health, The outcomes of the research will enable us: methods, research application, instrument in Australia, with the WorldBank as a partner wellbeing and social outcomes in adolescence to determine (if and to) what extent the ECED development, statistical/analytical skills and organisation. Currently we are involved in and young adulthood. Improved knowledge project improved children’s development, the importance of good quality evaluations supporting Indonesia, Peru, Ireland, the of these factors will enable the identification attendance and readiness for school; to what of programs (such as this ECED program) as United Arab Emirates, Chile and Brazil in their of children at risk of a variety of negative extent the ECED project improved parental well as simply a lack of understanding of the endeavors to adapt the EDI. health, wellbeing and social outcomes, and awareness and practices; if the project importance of early child development and Funders of the project: Supported by: may lead to the development of effective early increased the availability and utilisation of education. Building local capacity will decrease WorldBank, Van Leer Foundation and UNICEF. intervention and prevention programs. ECED services and if so, how those impacts the current reliance on “fly-in consultants”. The main outcomes of interest are in the differed by gender, wealth, and level of service Over the time of this research our aim is to following domains. delivery at baseline. It is essential that the ensure that Dr Elan Satriawan and Ms Amelia Five-Up Study (NSW) research will be able to determine what factors Malika will independently have the skills, • Mental health (e.g., early onset severe contributed to any success or failures by the knowledge and confidence to be able to Vaughan Carr, Kristin Laurens, Rhoshel mental illnesses, drug and alcohol abuse) ECED program. By including local academics design, undertake and manage such large scale Lenroot, Patricia Michie, Allyson Holbrook, • Health (e.g., early onset chronic diseases) in the research we will facilitate cultural research programs and have the confidence Melissa Green, Sally Brinkman, Frini relevance, local knowledge and contextual to disseminate the research findings to Karayanidis, Miles Bore, Helen Stain, Carmel • Education (e.g., academic achievement, relevance to the research (instrument government, donors and other stakeholders Loughland, John Attia, Stephen Lynn, Max failure to complete high school education) Smith, Richard Matthews, Michael Tarren- development, fieldwork nuances through to including within the academic literature. • Welfare (e.g., DoCS notifications and identification of key stakeholders etc). A well Sweeney, David McKie, Felicity Harris Funder of the project: Australian Development interventions) designed and implemented impact evaluation A healthy start to life is one of Australia’s key Research Award (ADRA) awarded by AusAID • Workforce (e.g., unemployment) will provide a unique opportunity to inform goals and primary research priorities. Where at the current and future practices in Indonesia all possible, prevention and early intervention • Criminal offending (e.g., arrests, charges,

88 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 court outcomes, imprisonment) LOOKING at Language Funders of the project: USA National Institutes research between Raine Study Principal of Health Investigators. National and international Using a NSW population cohort, this project Mabel Rice, Cate Taylor, Stephen Zubrick, Shelley collaborations with the Raine Study are aims to identify vulnerability and resilience Smith continuing to develop and add value to the factors, emerging from birth to 10 years of The Western Australian Pregnancy cohort and expand research opportunities. age, that relate to developmental functioning A child’s ability to communicate is one Cohort (Raine) Study – not complete 2011 saw the cohort members participate in the (social, emotional, behavioural, physical and of their most important developmental accomplishments and builds the foundation 20/21 year cohort follow up at LEI consisting cognitive functioning) and school achievement. The Raine Study began in 1989 at King Edward for success at school and beyond. LOOKING of comprehensive eye testing, a DEXA scan, a The research has two key components: 1) a Memorial Hospital with the recruitment of 2900 at Language is a population based longitudinal fibroscan, follow up of longitudinally collected comprehensive inter-agency record linkage; and pregnant women in early pregnancy. These study of individual differences in language anthropomorphic measures (height, weight, 2) a cross-sectional child and parent assessment. families were followed through pregnancy and development from infancy through adolescence. body measurements), blood pressure and Record linkage is being conducted under the child birth, and 2868 families were recruited The study is an international collaboration questionnaire data. Male cohort members also auspices of the Centre for Health Record Linkage for long term follow to study the origins of between Professor Mabel Rice from the participated in the Male Fertility Study which (CheReL), in which the use of probabilistic record health and disease. After birth, The Raine University of Kansas, Professor Cate Taylor and was conducted separately to the Eye Health linkage techniques help to ensure strict privacy cohort participants been reviewed in detail on Winthrop Professor Stephen Zubrick from the Study. protocols are adhered to. ten occasions at ages 1, 2, 3, 5, 8, 10, 14, 17, Telethon Institute for Child Health Research 18 and during 2011 at 21 years of age. This In February 2011 the Raine Study PhD top-up To supplement the information available and the University of Western Australia and cohort review has been conducted at the Lions scholarships were awarded to Nicole Warrington through record linkage, the research includes a Professor Shelley Smith from the University of Eyes Institute by the TICHR Raine Study Team, and Lauren Hollier. cross-sectional child and parent assessment to Nebraska Medical Center. be administered to the cohort in 2014 (during ophthalmologists and orthoptists from LEI and On Sunday 6th November 2011, the Raine Grade 5). This assessment will be developed Data collection for this project is based entirely UWA medical students. Study organized a public exhibition event at in WA and involves 1000 families, 800 are and administered in partnership with the NSW The Raine Study is one of the largest successful the Government House Gardens in Perth as families with twins. We established that 13% of Department of Education, and in collaboration prospective cohorts of pregnancy, childhood and a celebration and exhibition of the 21 years single-born children are late to start to talk at 24 with educational experts and other stakeholders adolescence in the world. 80% of the original of research in the Raine Study. Raine Study months and that one in five of these children is (e.g., teachers unions). participants are still active and committed to participants and their families were invited, as at risk for language impairment at 7 years. We the project. The Raine cohort demographics are well as the Raine Study Research Community. There will be significant opportunities for are currently writing a paper on the prevalence representative of the wider Western Australian The Event was a celebration of the commitment partnership and collaboration for TICHR of late language emergence in twins. We are population. Each member of the cohort has and amazing dedication of the Raine Study researchers as such linked databases build set to realize the publication opportunities from over 85,000 measures of health and disease and Cohort participants over the past 21 years. On across the country. this study over the next few years when data information on more than 2.5 million genetic display were the achievements of the Raine from successive birth cohorts is available from Funders of the project: Australian Research variants. The Raine Study is a unique resource Study over the past 21 years. Exhibition stands each wave of follow-up (i.e., 2, 4, 6 and 9 years). Council, NSW Department of Health, NSW for WA, Australian and International researchers. were created by some the 24 Raine Research Department of Education and Community The study provides a unique multidimensional Groups displaying their research and findings. Services. population based longitudinal dataset for The Raine Study is governed by the Raine Study studying the many factors that influence Executive Committee and managed by Raine The Governor of Western Australia, His language development and reading from infancy Study Manager and Scientific Director. There Excellency, Mr Malcolm McCusker AO QC and Mrs Tonya McCusker, joint patrons of the Raine to adolescence. are 24 research groups utilizing the Raine Study Cohort data and there is growing collaborative Study, formally opened the event. His Excellency

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 89 presented awards to Professor John Newnham sleep disordered breathing 13. Hypothalamic-Pituitary-Axis • Canadian Institute of Health Research for outstanding contribution to Science, and 1022134, Prof W Oddy et al, Nutritional 14. Infectious Disease to Professor Leon Straker, Professor Peter determinants of cardio metabolic risk and O’Sullivan and Dr Anne Smith for outstanding 15. Language Development Scientific Director: Associate Professor Craig mental health: from infancy to adulthood contribution to public health. Professor Fiona Pennell 16. Mental Health Stanley presented awards to some of the Raine 1030148, Profs D Hunt, D Mackey, Myopia and Study Manager: Ms Jenny Mountain Study Participants who had made a substantial colour vision: potential impact of colour vision 17. Musculoskeletal gene variation on susceptibility to myopia Data Managers Dr Louise Mckenzie, Ms Angela effort in participating in the Raine Study. The 18. Ophthalmology day was an outstanding success. Jacques 1037966, Prof W Oddy et al, Analysis of 19. Otolaryngology The Raine Study Annual Scientific day was Metabolic Profiles in young adults from Team Leader: Ms Diane Wood the Western Australian Pregnancy Cohort 20. Physical Activity held at UWA Club on 18 November 2011. Raine Study Team 2011 This was an extremely successful meeting (Raine) Study by Metabolomics: Biomarkers 21. Pregnancy & Birth with posters and presentations from over 20 for Metabolic Consequences of Early Jenny Mountain, Louise McKenzie, Angela Raine Study Researchers. The Raine Medical Programming by Infant Feeding Type. 22. Reproductive Health Jacques, Diane Wood, Alex Baptista, Emilly Research Foundation prize for best poster was Hockley, Natasha Larter, Jessica Hall, Annegret In 2011, there were 47 Raine Study 23. Risk Taking Behaviour awarded to Dr Monique Robinson and the Harries, Sue Greene (phlebotomist), Denny publications in peer reviewed journals. Raine Medical Research Foundation prize for 24. Sleep Craig, Carolyn Smargiassi, Amy Smithies best presentation was awarded to Ms Carly Raine Study Research Groups Herbison. 1. Anaesthesia Core Management funding: The Raine Study 20 year follow up - The In November 2011, the Raine Study was 2. Asthma & Allergy • The Telethon Institute for Child Health Raine Eye Health Study: An Ophthalmic successful in being awarded six NHMRC follow-up study of a longitudinal 3. Cardiovascular & Metabolic Research funded Grants. Planning was started for the birth cohort at age 20/21 years 23 year follow up of the cohort examining 4. Cognitive Neuroscience • The University of Western Australia sleeping disorders and asthma in young adults. David Mackey, Alex Hewitt, Alla Soloshenko, • Raine Medical Research Foundation, UWA 5. Dental Health Sandra Oates, Seyan Yazar, Alex Tan, Hannah Successful Grant Applications - Raine Study 6. Developmental Origins of Health and • UWA Faculty of Medicine, Dentistry and Forward, Charlotte McKnight, Craig Pennell, 1021105, Prof D Mackey et al, MRC Genome- Disease Health Sciences Jenny Mountain, Raine Study Team wide association study (GWAS) for juvenile- • Women and Infants Research Foundation The Raine Study commenced the 20 to 21 onset myopia and its component measures to 7. Eating Disorders year follow up of the cohort participants in identify molecular pathways to prevent myopia • Curtin University 8. Endocrinology 2010 carried on in 2011. The Raine Eye Health 1021858, Prof G Hall et al, Transition from 9. Epigenetics • Research Funding Study is examining eye health in an age group childhood to adult asthma: Predicting for which very little data exist. It is presumed • National Health and Medical Research persistent and adult‐onset asthma in young 10. Gastrointestinal & Heptology that young adults have the best vision and Council of Australia adults in the Raine longitudinal birth cohort 11. Genetic Epidemiology thus very few people have studied people of • National Hearth Foundation this age group. The primary aims of this study 1027449, Prof P Eastwood, The evolution of 12. Growth & Nutrition are: (1) To document the prevalence of the childhood obesity and its relationship to adult • Rotary Health Research

90 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 eye conditions: refractive error, amblyopia and The Raine Study 20 year follow up - DEXA such as Fibroscan® (Echosens™, France) a large and well-established cohort prospectively strabismus, in young adults; (2) To determine scan in the RAINE cohort have recently been developed. A FibroScan followed from intrauterine life through the population distribution of endophenotypes/ fulfils many criteria required for non-invasive adolescence into adulthood to investigate key biometry related to eye diseases in young Craig Pennell, Leon Straker, Raine Study Team assessment of liver fibrosis. It is quick; taking on fetal and childhood events leading to reduced adults; (3) To determine genetic and early Bone mineral content, body composition and average five minutes, has good reproducibility, is semen parameters and decreased testicular environmental factors that influence ocular percentage body fat are assessed from dual most importantly, acceptable to the patient, and volume. Recruitment began in April 2010 biometry and predispose to ophthalmic disease; energy X-ray absorptiometry (DEXA) scans. examines a relatively large sample of the liver. and continued through 2011. Results and and (4) To investigate the interaction of early During the 20 year follow up visit, each Raine As part of the 20 year follow up, Fibroscan® is clinical support if necessary, are provided to life, familial, lifestyle, demographic and genetic participant has a whole body DEXA scan using a being used in the Raine cohort to non-invasively participants. risk factors with these conditions, and their quantify hepatic fibrosis in the Raine cohort and Norland XR36 Quickscan machine. DEXA is the Funders of the project: NH&MRC 634457. endophenotypes. Raine Study participants are most widely used clinical tool for the assessment establish norms in this age group. invited to the Lions Eye Institute to undergo a of skeletal integrity owing to its efficiency, Funders of the project: NH&MRC 634445 comprehensive set of eye tests checking eye precision and accuracy. The DEXA provides Raine Study 20 year follow up – Early sight and vision and the health of the eyes. measures of body composition (lean mass, influences on adult behaviour and The results of all these tests are given to the fat mass, bone mass) as well as bone density. Raine Study 20 year follow up - The thinking styles participant during the follow-up, and where The DEXA is considered the ‘gold’ standard early life origins of impaired testicular necessary glasses prescriptions or treatment measurement of adiposity. function Andrew Whitehouse, Martha Hickey, Raine are provided. In addition participants complete Study Team Funders of the project: Canadian Institute of a questionnaire which includes information Roger Hart, Stephen Junk, Dorota Doherty, Health Research CIHR (Lye et al, MOP‐82893) This study is examining autism-like behaviours on sociodemographics, relationships, mental Michelle Pedretti, Raine Study Team in the general population to test the two health, spinal pain, physical activity, asthma and Over the last few years there have been reports most prominent biological theories of atopy, risk taking behaviour and medical history, The Raine Study 20 year follow up - that male sperm counts are diminishing and Autism Spectrum Disorders (ASDs), namely, and the Cancer Council short food frequency FIBROSCAN in the RAINE cohort that this is beginning to be obvious at a younger that ASDs are caused by (1) early brain questionnaire. Participants also have physical age. Many of these findings are based on sperm overgrowth, or (2) exposure to elevated levels measurements (height, weight, anthropometry) Eng Gan, Leon Adams, John Olynyk, Oyekoya counts from people seeking infertility treatment, of fetal testosterone. There is agreement that and blood pressure testing. Ayonrinde, Raine Study Team and not from healthy groups of people. It is autism-like symptoms, including social and During the assessment the participants have a The prevalence of Non-alcoholic fatty liver not known why some people have low sperm communication difficulties, are on a continuum DEXA scan, which measures body composition disease (NAFLD) in the Raine cohort at 17 counts. It may be through exposure to passive in the general population, with Autism Spectrum (fat mass, lean mass and bone density). years was 13 %, placing these subjects at smoking, or early life events. Obesity is one of Disorder (ASD) representing the extreme end of Participants also provide a fasting blood sample possible risk of further complications. The the factors that lead to a reduced sperm count, the distribution. This study examines autism- at a domiciliary visit by the Raine Phlebotomist. major determinant of severity and outcome for and it is believed that there might be other like behaviours in the general population by Funders of the project: NH&MRC 634445, NAFLD is the degree of hepatic fibrosis (tissue possible contributors in childhood health and requesting the Raine Study Cohort to complete 634457, 634509, 1003424, CIHR_MOP‐82893, scarring in the liver). Assessment of fibrosis diet. As a population we are being exposed a 50-item questionnaire measuring systematic Raine Core Management Funding Australian has traditionally required the use of a liver to increasing amounts of chemicals in the (logical and organised) and empathetic Foundation for the Prevention of Blindness, biopsy. However, due to its invasive nature environment (endocrine disrupters) which may (understanding and sympathetic) patterns of Lions Eye Institute, Alcon Research Institute and problems of sampling error, variability in have an effect. This study of male participants in thinking. Raine Study participants are given interpretation and cost, non-invasive alternatives the Raine Study cohort is the first study to utilise the opportunity to either log onto the Raine

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 91 Study Website with a unique identifier and risk-taking in adolescence. foods were linked from the Nutrient Tables for This 4-year project commenced in June password and complete the questionnaire use in Australia, the University of Minnesota 2010 and aims to determine the prevalence Initial analyses show higher scores for Total online or to complete a paper copy. Measures Nutrition Coordinating Centre Food and of eating disorders at two time points in Behaviour Problems and the Externalizing of head circumference and fetal testosterone Nutrient Database and the Canadian Nutrient adolescence, in a population-based cohort Behaviour subscale of the Child Behaviour are available on the cohort from prenatal File. We found that fructose contributed followed over time; identify factors that Checklist (CBCL) in participants who had ultrasounds and cord blood. 9.1% of total energy intake for the group. predict the persistence of eating disorders already engaged in sexual intercourse Boys reported higher absolute fructose across adolescence; and identify prospective Funders of the project: Research Funds from compared to those who did not. In addition, intakes than girls (58.9 g ± 26.6 g vs 48.3 g risk factors for early and later-onset adolescent Prof Martha Hickey participants who were identified with clinically ± 20.1 g, respectively, p<0.001), while girls eating disorders. The research utilises data recognized delinquent and aggressive had higher energy adjusted fructose intakes from the Western Australian Pregnancy Cohort behavioural problems at ages 5, 8, 10 and 13, than boys (55.7 g ± 16.1 g vs 51.8 g ± 20.2 g, (Raine) Study. Eating disorder symptoms were Raine Study: Risk Taking Behaviour were more likely to have engaged in sexual respectively, p=0.002). Major food sources of assessed at the 14, 17, and 21-year Raine Group intercourse. These unique data indicating fructose in the Raine cohort were beverages, Study follow-ups, and data from the 14 and early predictors of risky sexual behaviour in in particular soft drinks, followed by fruit and 17-year follow-ups have now been analysed. Childhood determinants of risky adolescence may help determine how and at confectionery. No significant associations were The 21-year data will become available for use sexual behaviour in adolescence: a what ages interventions may be effective. prospective cohort study found between fructose intake and level of in 2012. Funders of the project: NH&MRC 634509 physical activity, BMI or socio-economic status We found that the prevalence of full and Rachel Skinner, Martha Hickey, Eugen Mattes, indicators in unadjusted analyses, however partial eating disorders in the Raine Study Dorota Doherty, Anthony Smith, Susan adolescents from higher socio-economic cohort increased from 6% at age 14 to Rosenthal, Spring Cooper, Michael Smith Fructose intake and food sources in groups consumed more fructose from fruit 9.5% at age 17. Of the adolescents with an West Australian adolescents whereas adolescents from lower socio- This research project aims to identify eating disorder at age 14, approximately economic groups consumed more fructose childhood factors which influence an Therese O’Sullivan, Wendy Oddy, Jill Sherriff, half continued to report significant eating from beverages. To our knowledge, this is the adolescents’ likelihood to initiate sexual Susan Woolley pathology three years later. These participants first study to describe fructose intake and food activity at a young age, and engage in also reported significant and persisting Fructose is widely distributed within the sources in Australian adolescents. Our results sexual risk taking. Risky sexual behaviour problems with depression and anxiety. Fewer Australian food supply; however data on are similar to those previously reported in contributes to unplanned teenage pregnancy, than 20% of the Raine Study participants fructose intakes is limited, particularly in studies of US adolescents. sexually transmitted infections (STIs) and identified as meeting criteria for an eating children and adolescents. Excessive fructose adverse social, emotional and physical health Funders of the project: NH&MRC Program disorder had been diagnosed with, or treated consumption may have implications for outcomes in adolescence into adulthood. We Grant #353514. Heart Foundation/ Beyond for, an eating disorder in the community. dyslipidemia, fatty liver disease and obesity. have little understanding of early determinants Blue Strategic Research Initiative grant Raine Study children who were perceived of risky sexual behaviour. This research aimed to quantify fructose consumption and identify major food sources as overweight by their parents at age 10 The Raine Study provided extensive biological, years were three times more likely to have of fructose, in adolescents participating in the Eating disorders in Western Australia: psychological, psychosocial, family, individual developed an eating disorder by age 14 14 year follow-up of the Western Australian Prevalence, maintaining factors and and environmental characteristics collected at than children who were not perceived as Pregnancy Cohort (Raine) Study. Dietary prospective risk factors all ages. This unique dataset is currently being intake was assessed by 3-day food records overweight by their parents. Parent-perceived utilised to undertake a world first analysis of and entered in the FoodWorks dietary analysis Karina Allen, Sue Byrne, Wendy Oddy child overweight was a more powerful causal pathways through early life to sexual program. Total fructose values for individual predictor of eating disorder development

92 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 than children’s measured weight and height, eating disorders. A84ow7rn). suggesting that it may be concern and Funders of the project: National Health and Parental work and child health and Maternal stressful events in pregnancy awareness about weight status, rather than Medical Research Council (NHMRC) development and numeracy and literacy at grade 5 overweight status per se, that is associated with eating disorder risk. Jianghong Li, Garth Kendall, Lyndall Strazdins, Jianghong Li, Monique Robinson, Anke van Over the last year, we have found that Mike Dockery, Sonia Andrews, Sarah Johnson, Eekelen, Jonathan Foster, Eva Malacova. Social determinants of child Rachel Skinner, Wen-Jui Han (The US). adolescents with an eating disorder report This study examines the timing and number of a significantly lower intake of key macro and health/social epidemiology The project aims to investigate the impact of stressful events in pregnancy and their link with micronutrients when compared to adolescents parental employment status and non-standard numeracy and literacy achievement in a subset Parental work hours and quality of diet without an eating disorder. Adolescents with work schedules on the health and wellbeing of the Raine Cohort children in grade 5 who in adolescents an eating disorder and pronounced depressive of Australian children/adolescents and to attended government schools in WA. The aim of symptoms also report a significantly lower intake Jianghong Li, Wendy Oddy, Therese O’Sullivan, shed new light on the social and economic the study is also to demonstrate the importance of fatty acids than adolescents with an eating Sarah Johnson causes of the high prevalence of mental health of examining gender difference in the impact disorder but no pronounced depression. Low problems in today’s children. The proposed of maternal stressful events in pregnancy on fatty acid intake has been linked to depression The study investigates the association of research will be based on data from Longitudinal offspring’s school achievement and to elucidate previously, and our findings highlight the mother’s and fathers’ work hours and other Study of Australian Children (LSAC) and the the need to distinguish between confounding importance of considering this variable in socioeconomic factors with diet quality in a Western Australian Pregnancy Cohort Study factors from mediating factors in the causal relation to depressive symptoms in eating cohort of adolescents followed from pregnancy (Raine). The project draws on multidisciplinary pathway. disorders. to age 13 in Western Australia (the Raine Study), expertise from sociology, social epidemiology, using a diet quality index and dietary patterns Funders of the project: We have also found that a subset of adolescents developmental epidemiology, clinical psychology developed at the Institute for Child Health and labour economy. We have conducted a Projects undertaken by Dr Jianghong Li and with eating disorders experience neurocognitive Research. difficulties, with a tendency to focus on detail at comprehensive review of the literature on non- supported by her Curtin Research Fellowship, the expense of the bigger, global picture. This Funders of the project: standard work schedule and child mental health Curtin Health Innovation Research Institute, and behavioural problems and the review will Centre for Developmental Health, Curtin neurocognitive style (known as weak central Projects undertaken by Dr Jianghong Li and inform specific research aims and questions. University. coherence) has been documented in clinical supported by her Curtin Research Fellowship, samples of eating disordered participants but Curtin Health Innovation Research Institute, This program of research investigates the This work has resulted in a journal article this is the first time it has been identified in a Centre for Developmental Health, Curtin following outcomes: Mental health, risk taking currently under revision for resubmission to community sample. University. behaviours, body mass index, and school Journal of Pediatrics in April 2012. achievement. Our findings have added to the small body of This work has now been published in Public prospective research on risk and maintaining Funders of the project: Health Nutrition HIV vulnerability in out-of-school factors for eating disorders. Analysis of the 21- adolescents and youth in Yunnan, China year data will allow us to extend these results Jianghong Li, Therese O’Sullivan, Sarah Johnson, Projects undertaken by Dr Jianghong Li and Fiona Stanley, Wendy Oddy. Maternal work supported by The Foundation for Children and further, and the latter stages of the project Lijun Yang (China), Jianghong Li. will focus on translating research outcomes hours in early to middle childhood link to later her Curtin Research Fellowship, Curtin Health into practical strategies to facilitate effective adolescent diet quality. Public Health Nutrition Innovation Research Institute, Centre for This is a UNICEF funded project based in prevention and early intervention efforts for (accepted 25 October 2011: published online Developmental Health, Curtin University. China and I am a collaborator on the project. first: http://journals.cambridge.org/repo_ The project aims to understand the level of

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 93 knowledge about HIV transmission and the effect of housing location and housing Projects undertaken by Dr Jianghong Li and with mothers of primary school children. Also, prevention and risk taking behaviours in a quality and ownership on child developmental supported by The US Studies Centre at the for the purposes of this project, modules random sample of out-of-school adolescents outcomes. University of Sydney and her Curtin Research focusing on parenting skills, educating parents in Yunnan Province. Cross-sectional data has Fellowship, Curtin Health Innovation Research about eating and exercise behaviours in Funders of the project: been collected and the project is at the stage Institute, Centre for Developmental Health, children and promoting psychosocial wellbeing of analysis. Australian Housing and Urban Research Curtin University. in children have been added to the original Institute CBT. Funders of the project: This project has been completed and a final report submitted to the funder in April 2012. Assessment protocols have been developed Projects undertaken by Dr Jianghong Li and for the trial of the intervention program. supported by her Curtin Research Fellowship, Determinants of Child Poverty in the These assessment protocols include self-report Curtin Health Innovation Research Institute, US questionnaires and semi-structured interviews Centre for Developmental Health, Curtin Childhood Obesity which will be administered to mothers and University. Jianghong Li, Joachim Singelmann (the US). Investigating methods for managing children both prior to commencing the The proposed project will build on the This work has been accepted for publication in childhood obesity intervention program and at completion of the analyses of family poverty in the Mississippi World Journal of AIDS (5th April 2012): intervention program. Delta and the Texas Borderland recently Lisa Gibson Jianghong Li, Lijun Yang, Zhouyang Ren , carried out by Singelmann and his associates. In 2011 we attempted to implement the Chongbin Mo, Dingwen Chen, Fuqiang Dai, A key finding of their research has been the Currently there are no satisfactory treatments intervention program in the City of Gosnells Mingzhong Jiang, Zhijie Tang, Peter Jacoby. HIV importance of poverty-intervention programs or prevention strategies for overweight and to help families manage weight and eating Vulnerability in out-of school adolescents and that target specific socio-demographic groups. obese children. New treatment approaches issues. The program (HELP: Healthy Eating and youth in Yunnan, China. World Journal of AIDS Their results show that the correlates of to the management of childhood obesity Lifestyle Program) was advertised in a range (accepted 5th April 2012). poverty differ among race and ethnic groups are needed. This project aims to develop, of different locations (local newspapers, radio, as well as among family types (both parent test and disseminate a new intervention for school newsletters etc). Unfortunately, we vs. single parent). The proposed project will childhood obesity. The approach is novel in were not able to attract the number of families Housing and children’s health and extend these analyses to the third high- that mothers will be the primary agents of we had hoped to participate in the program. development change. There are several compelling reasons poverty region in the United States, which is Work has now begun on finding out why for this. Mothers play a critical role in shaping Central Appalachia. All three regions have a families did not respond to the program as M Dockery, G Kendall, J Li, L Strazdins, F Chan, children’s eating behaviours, and influence poverty rate exceeding 20 %.The focus of the we would have hoped. This has involved two R Ong, R Seymour, A Mahendran food choice through role modelling. It is proposed project will be on the determinants components. Firstly, a questionnaire was sent This is a scoping study that provides a review likely that changes in the mother’s eating and of child poverty and differences in these out to all parents of primary school children of international research literature on the exercise habits will lead to a parallel change determinants by race, ethnicity and household in the City of Gosnells to obtain feedback on link between housing and children’s health in the pre-pubertal child’s eating and exercise type. By focusing on the three poverty the methods of advertising and the format and development and it proposes a research behaviours. regions mentioned above, such race/ethnic of the program. Secondly, focus groups were plan for developing this area of research in differentiation will be possible, given the high The intervention program is based on a conducted with community health workers Australia. Further funding has been obtained concentration of blacks in the Delta and of cognitive behavioural treatment (CBT) for from the Gosnells Early Years Action Group from Australian Housing and Urban Research Latinos in the Borderland. obesity developed at the University of Oxford. (GEYAG). The information gathered from the Institute to carry out the research plan in Funders of the project: The existing CBT has been modified for use focus groups and the questionnaire will be 2011 and beyond. The project will investigate

94 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 used to help understand why families are not Alicia Annamalay B Med Sci (Hons) Marie-Louise Collins, BA, BD (Hons) Dr Emma Glasson, BPsych, BSc(Hons), PhD participating in our weight reduction program Malissa Baddeley, BSc (Biomedical Science), Lyn Colvin, BCom, MPH Dr Rebecca Glauert, BPsych(Hons), PhD and also to develop a program that is acceptable Hons to families experiencing eating and weight Matthew Cooper, BCA/BSc Jackie Goldfinch issues. Helen Bailey, BSc (Nursing), MPH Denny Craig, DipSecStudies Jo Granich, BSc MPH Funders of the project: Western Australian Dr Stephen Ball, BSc (Hons), PhD Somer Dawson, BEcons, BHlth Sci (Hons) Suzanne Green, REN, Phleb Health Promotion Foundation (Healthway) Katherine Bathgate, BSc (Nutr & Food Sc), Grad Michelle de Klerk Andrew Greenhill Dip Diet, Grad Cert Teach, MPH, APD, PhD candidate, Curtin Sarah de Klerk, BSc Dr Kathryn Greenop, BA (Hons) (Psych), PhD (Psych) Staff and Students Ami Bebbington, BSc (Hons), MBioStats Aditya Deshpande, Bachelor of Dental Surgery candidate, University of Melbourne Tess Gregory Head of Division Dr Jennifer Dodd, PhD, BA Soc Sci (Hons) Assoc.Prof Eve Blair, BSc (Hons), PhD (Chem), Kristen Haas, BA Professor Stephen Zubrick, MSc, MA, PhD Dr Jenny Downs, BApplSci (Physio), MSc, PhD PhD (MedSci) Jennifer Hafekost, BSocialSc, Grad Dip Ed Laura Drummy, BSc (Nutrition & Human Biol) Jade Bogdanovs Katherine Hafekost, BSc(Hons) Head of Epidemiology Katrina Duncan Laura Bond, MPH, BHSc Dr Erika Hagemann, BSc(Speech and Hearing Paula Dyke, BAppS (Physio), MPH Winthrop Research Professor Carol Bower Jenny Bourke, BE, MPH Science)Hons, PhD MBBS, MSc, PhD, FAFPHM, DLSHTM, FFPHA Alex D’Vauz, BSc (Hons) Sally Brinkman, BA, MPH Dr Geoffrey Hammond, BSc, PhD Rachel Earl Larina Bromley, BA(SocSc), Kirsten Hancock, BA(Hons) MSc Candidate Head of Biostatistics and Genetic PostGradDip(HlthProm),M HlthCouns Dr Kristjana Einarsdottir Epidemiology Jessica Hall, B.Psych Jessinta Brown Janis Evans Michèle Hansen, MPH, BSc Professor Nick de Klerk, BSc, MSc, PhD Dr Wendy Chan She Ping-Delfos PhD Dr Brad Farrant, BSc (Hons) PhD Annegret Harries Ace Choo, BSc (Biomedical Science), MID Stephanie Fehr, BSc, BMedSci (Hons) Natasha Haynes Research Staff (Tropical Infectious Diseases) Jordan Fisher Carly Herbison Dr Karina Allen, PhD, MPsych (Clinical), BA Daniel Christenson, BAPsych(Hons) Grad Cert Dr Patrick Fitzgerald, BAppSc, GradDip, MAppSc, Dr Siobhan Hickling, BSc, Grad Dip Diet, MPH, (Hons) Applied Statistics PhD PhD Kirsten Alpers Kim Clark Anna Fletcher Sharon Hillman, B Psych, AMAPS Dr Gina Ambrosini, BAppSci, MPH, PhD Michael Clark Kathryn France, BSc (Hons) Emily Hockley, BSc Alison Anderson, BSc (Hons), GradDipPH, PhD Jan Coe, MA, Grad.Dip.Lib & Information Studies Dr Lisa Gibson, BA (Hons)MPsych, PhD candidate, UWA Anke Hoskins, Nurse, MPH Deirdre Collins B.A. (Mod.), MID Dr Sonya Girdler, PhD Denise Anderson Derry Houston, BA/MSocWk

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 95 Dr Rae-Chi Huang, MB BS, PhD, FRACP (paeds), Meg McHugh, BSc, MSc Shawn Phillips, BTh, MSWAP Alicia Watkins, BPsych, PGradDip(Psych) DCH Sally McIlroy Dr Terri Pikora, PhD Dr Rochelle Watkins BSc (Physio), PhD, Anna Hunt, BEdu GradDipMgnt Mary McIllroy Anne Pugh Tanyana Jackiewicz, BSc(Hons) MPH Linda Watson Aoiffe McLoughlin BSc (Health Promotion) BBA Jennifer Quick Peter Jacoby, BA(Hons), MSc Felicity Watt, B.Psych, MSc Heidi Meyer Dr Tracy Reibel, BA (Hons), PhD Angela Jacques Meredith West Associate Professor Elizabeth Milne, BSc, MPH, Wavne Rikkers, BA Caris Jalla PhD Dr Andrew Whitehouse, BSc (Human Phil Riseborough, B.Psych ,M.Soc. Communication Science), PhD Khadra Jama-Alol BSc, PGradDip Biochem, Francis Mitrou, BEc Deborah Robertson, BA, DipEd, Mphil MPH, PGradDip Pub Health Dr Amanda Wilkins MBBS, FRACP, MPH Ruth Monck, RN, RM Dr Monique Robinson, PhD MPsych (Clinical) Dr Sarah Johnson, BA(Soc Sci), PostGradDip Kingsley Wong, MBBS MBA MSc AFCHSM, Dr Hannah Moore BSc(Hons1), BA(Hons)Psych (Social Res), PhD MPH candidate, UWA GradDipClinEpid, PhD Katherine Russell-Smith Heather Jones, B.Ed Dianne Wood, BAppSc(Phys Ed)Dip Ed, Grad Alani Morgan, TA EDWA Louisa Santucci Dip HN Joan Jones Jenny Mountain, BA, MBA Elke Scheepers, BA, AdvCert Tvl Cons Rachel Jones Virginia Muniandy, BEdu (Early Childhood) Carrington Shepherd, BA (Econs) Research Support Staff Dr Amanda Langridge, BSc (Math.Sci), Nada Murphy, BA, Grad Dip Psych, M App Psy BSc(Hons), PhD Dr Adeleh Shirangi, PhD Helen Daley Dr Raewyn Mutch MB ChB, DipRACOG, FRACP, Professor David Lawrence, BSc, PhD, ATCL Lorraine Sholson EN PhD Colette Newcomb Amy Lee Dr Rachel Skoss, PhD Dr Nusrat Naseem MBBS, MPH Leanne Scott Associate Professor Deborah Lehmann, MBBS, Carolyn Smargiassi Cathrine Nemer Kathryn Wilson MSc Grant Smith, BPsych, M Psych Assoc. Prof. Wendy Oddy, BAppSci(Nutr), MPH, Assoc. Clin. Professor Helen Leonard, MBChB, PhD Kristy Staples, BA, Post Grad Dip Counsellor MPH Postgraduate Students Melissa O’Donnell BPsych(Hons), MPsych, Grad Wenxing Sun, BHSc Dr Jianghong Li, BA, MSc, PhD Alison Anderson, BSc (Hons), GradDipPH, PhD Dip Ed, PhD, NHMRC Early Career Fellow Glenda Taylor, EN candidate, UWA Angela Kinnell Dr Colleen O’Leary, RN, BSc, MPH, PhD Associate Professor Cate Taylor, BAppSc, Alicia Annamalay, Hons candidate, UWA Faye Lim, BSc, BMedSci (Hons) Ashleigh Owen, BA PGradDipHlthSc, PhD, FSPA Oyekoya Ayonrinde, PhD candidate, UWA Sarah MacDermott, B.App.Sc (Speech & Jan Payne SRN (UKCC), Post Grad Dip (Health Anna Urbanowicz,BSc(OT)(Hons) Hearing Science), M.A. (Education) Helen Bailey, PhD candidate, UWA Admin), MSc (Public Health) Ellen Walker, BSocialWork (Hons) Jacqueline Mansour, BSc, MPH Katherine Bathgate, BSc (Nutr & Food Sc), Carol Philippe, RN

96 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Grad Dip Diet, Grad Cert Teach, MPH, APD, PhD Katrina Hopkins, BAppSci(Psych), DipEd(Psych), Dr Anett Nyaradi, PhD candidate, UWA Theses passed candidate, Curtin MAppSci(Health Sciences), PhD candidate, UWA Mr Ramin Nikravan, DPH candidate, Curtin Helen Bailey PhD, University of Western Ami Bebbington, BSc (Hons), MBioStats Amanda Jefferson, BSc, PhD candidate, Curtin Afrooz Njafzadeh, PhD candidate, UWA Australia: The relationship between candidate, University of Melbourne Christine Jeffries-Stokes, MBBS, MPH, PhD environmental exposures and the development Jan Payne, SRN(UKCC),PGradDip(Hlth Admin), Sara Beckett, PhD candidate, UWA candidate, UWA of acute lymphoblastic leukemia in children MSc(Pub Hlth), PhD candidate, UWA Sally Brinkman, BA, MPH, PhD candidate, Curtin Jocelyn Jones, BA (Sociology), EN, MAE, PhD Sophia Davidson BSc (OT) (Hons), Edith Cowan Glenn Pearson, BA(Education), PhD candidate, candidate, UWA University: The employment patterns of young Adele Cox, Diploma (Broadcasting and UWA adults with intellectual disability living in Journalism), Masters candidate, UWA Kellie Jones, PhD candidate, ECU Gavin Pereira, MAppStat(Dist) BCM(Hons) GCert Queensland Lyn Colvin, PhD candidate, UWA Milena Jokic, PhD candidate, UWA Res Comm, PhD candidate, UWA Robyn Earl BSc (OT) (Hons), Edith Cowan Sophie Davidson, Hon candidate, ECU Brilliana von Katterfeld BA BSc(Hons) PhD Shawn Phillips, BTh, MSWAP,PhD candidate, University: A normative study of the candidate, UWA UWA Aditya Deshpande, BDS, PhD candidate, UWA participation patterns of young adults living in Olivia Knight, PhD candidate, ECU William Pomat, BSc (Hons), MSc, PhD candidate, Western Australia Jan de Groot, MPH, PGDipNursing (Midwifery), UWA BAppSc(Med Tech), RN, RM, NNT, CHN, PhD Matthew Legge, PhD candidate, UWA Nicola Fenelon, Master of Clinical Psychology, candidate, UWA Carrington Shepherd, BSc, PhD candidate, Curtin University of Western Australia: Maternal stress Lucy Lewis, PhD candidate, UWA in pregnancy and brain functions in adolescence. Jenny Fairthorne, Msc, MPH, PhD candidate, Dr Desiree Silva, MBBS, FRACP, MPH, PhD Faye Lim, Hons candidate, UWA UWA candidate, UWA Jessica Hall, Master of Clinical Psychology, Sandra Louise, PhD candidate, UWA University of Western Australia: Mental health Stephanie Fehr, BSc, BMedSci (Hons), PhD Jessica Simons, PhD candidate, UWA in children and adolescents from culturally and candidate, UWA Miriam Maclean, PhD candidate, UWA Lydia Sung, PhD candidate, UWA linguistically diverse backgrounds. Nicola Fenelon, Masters Candidate, UWA Geraldine Maibani-Michie, PhD candidate, Lauren Taylor, PhD candidate, UWA Brilliana Katterfeld PhD, University of Western University of Qld Anna Ferrante BA (Mathematics), Dip Ed, PhD Australia: Perinatal health in children from Jessica Tearne, PhD candidate, UWA candidate Aoiffe McLoughlin BSc (Health Promotion) BBA culturally and linguistically diverse backgrounds Master of Public Health Anna Urbanowicz, BSc(OT)(Hons), PhD in Western Australia Kitty-Rose Foley, BSc (OT) (Hons), PhD candidate, candidate, ECU ECU Francis Mitrou, PhD Candidate, UWA Matthew Legge PhD, University of Western Sian Williams, PhD candidate, UWA Australia: The genetic epidemiology of Kathryn France, BSc(Hons), PhD candidate, ECU Hannah Moore, BSc(Hons1), GradDipClinEpid, melanocytic naevi PhD candidate, UWA Janice Wong, BSc (Psych) (Hons), PhD candidate, Noula Gibson, BAppSc(Physio)(Hons), M UWA Hannah Moore PhD, University of Western Physio(Develop Paeds), PhD candidate, UWA Jenny Mountain, BA, MBA, Masters candidate, Australia: Epidemiological perspectives of acute UWA Kingsley Wong, MBBS MBA MSc AFCHSM, MPH Michèle Hansen, MPH, BSc, PhD candidate, UWA lower respiratory infections in young Western candidate, UWA Dr Maryam Mozooni, (MD) PhD candidate, UWA Australian Aboriginal and non-Aboriginal Aveni Haynes, Masters/PhD candidate, UWA Paula Wyndow, BSc Postgraduate Diploma, PhD children Barbara Nattabi, PhD candidate, Curtin Lauren Hollier, PhD candidate, UWA candidate, Curtin

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 97 Barbara Nattabi PhD, CurtinU niversity: Fertility Stephanie Fehr, UWA Safety Net Top-up Monique Robinson, Heath Ledger Career RettSearch, International Consortium of Rett desires and intentions of HIV Positive Men and Scholarship 2011 Development Award Syndrome Clinical Researchers (2009-) Women in Post-conflict Northern Uganda Kitty-Rose Foley, Mary Walters Bursary from Monique Robinson, Australian Psychological Jianghong Li. Rural Sociology published by the Ramin Nikravan Doctorate of Public Health, the Graduate Women of Western Australia, Society Early Career Research Award American Rural Sociological Society, Associate Curtin University of Technology: Antioxidant Travel Award 2011 Editor (June 2005-2011) Monique Robinson, UWA Outstanding Young and omega-3 fatty acid intake in the Kitty-Rose Foley, Family Special Interest Investigator Award Elizabeth Milne, Deputy Chair, Management modulation of respiratory illness and asthma Research Group Fellowship to support travel to Committee of the Childhood Leukaemia in children Monique Robinson, Qantas New Investigator IASSID, Nova Scotia, Halifax International Consortium (2006-) of the Year Award Gavin Pereira PhD, University of Western Helen Leonard, Author of UWA’s highly cited Elizabeth Milne, Working party for the Australia: The influence of traffic-related Monique Robinson, WA Winner Young Tall papers 2010 development of international studies air pollution on infant and child health: an Poppy Science Award of embryonal cancers in children, WHO application to fetal growth and asthma Miriam Maclean, The Australian Postgraduate Monique Robinson, UWA Prize for Higher International Agency for Research into Cancer, Award William Pomat PhD, University of Western Degree by Research Achievement (Special Lyon, France (2006-) Australia: Mucosal immunity to Streptococcus Miriam Maclean, The UWA Safety Net Top-Up Commendation) Elizabeth Milne, Brain Tumour International pneumonia Scholarship Monique Robinson, Heart Foundation of Consortium (BTEC), (2010-) Melissa Scott BSc (OT) (Hons), Edith Cowan Elizabeth Milne, Telethon Institute for Child Australia Travel Grant Elizabeth Milne, International Childhood University: The meaning of a good life for Health Research Leadership Award Anna Urbanowicz, Australian Postgraduate Cancer Cohort Consortium (I4C), (2010-) young adults living with Down syndrome Anett Nyaradi. The Raine Study PhD Student Award 2011 Elizabeth Milne, Scientific Programme Advisory Top Up Scholarship Janice Wong, The Australian Postgraduate Committee for the International Society for Melissa O’Donnell, Science meets Parliament – Award Paediatric Oncology (SIOP) in London 2012 and Awards NHMRC Attendee and Travel Award Hong Kong 2013 (Invited) Janice Wong, The Stan and Jean Perron Award Carol Bower, Life Membership, Australasian Melissa O’Donnell, Australian Academy of Melissa O’Donnell, International Society for Epidemiological Association Science – NHMRC Early Career Research the Prevention of Child Abuse and Neglect Jenny Downs, Heath Ledger Career Award, Attendance at Science at the Shine External Committees (2007-present) Dome Development Award, Telethon Institute for Melissa O’Donnell, International Child Child Health Research, November 2011 Jan Payne, Public Health Association of International Maltreatment Data Working Group Australia WA Branch Community Award, Jenny Fairthorne, Australian Postgraduate Carol Bower, International Clearinghouse (2009-present) November 2011 Award 2011 for Birth Defects Surveillance and Research Gavin Pereira, Jan Watt Memorial Prize for Nominating Committee 2011-2012 Jenny Fairthorne, UWA Safety Net Top-up National Excellence in Public Health Field Research, Scholarship 2011 Helen Leonard, Member of Autism Speaks Faculty of Medicine and Dentistry UWA Carol Bower, National Perinatal Statistics Unit Stephanie Fehr, Australian Postgraduate Award International Autism Epidemiology Network Steering Committee for Congenital Anomalies 2011 Monique Robinson, Raine Medical Research Workgroup, (2007-) Foundation Prize for Best Poster Presentation Helen Leonard, Member of Executive of Carol Bower, Australian Paediatric Surveillance

98 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Unit Scientific Review Panel Australian Research Alliance for Children and Network Executive Advisory Group Invited Presentations Youth (ARACY), Mentor Carol Bower, Australian Paediatric Surveillance Helen Leonard, Executive Committee Perth International Unit Board Chair Catherine L Taylor, International Journal of Epidemiology Group, (2008-) Speech-Language Pathology, Member of the Carol Bower, National Perinatal Epidemiology Miriam Maclean, Perinatal Mental Health Anna Ferrante, Using Health Data to Determine Executive Board and Statistics Unit Fetal Alcohol Spectrum Services Research Committee (July 2010 – Gender and Race Differences in the Risk Factors Disorder present) Associated with Delinquency. SHIP Conference, St Andrews, Scotland, September 2011 Rebecca Glauert, International Data Linkage Local Miriam Maclean, Marce Society Conference Conference Organising Committee. Deputy Chair Local Organising Committee (January 2011 – Kitty-Rose Foley, To feel belonged: The voices (2010 – present) Carol Bower, Perinatal and Infant Mortality present) of children and youth with disabilities on Committee Department of Health WA the meaning of wellbeing. 5th Asia Pacific Rebecca Glauert, International Data Linkage Elizabeth Milne, Cancer Council Western Occupational Therapy Congress, Chiang Mai, Carol Bower, Prenatal Diagnosis Committee, Conference Scientific Committee (2010 – Australia Research Sub-Committee Thailand, November 2011 present) Department of Health WA Hannah Moore, Meningitis Centre Management Deborah Lehmann, Invited speaker on tour Jenny Bourke, Committee member, Board Deborah Lehmann, Data safety monitoring Committee of USA in 2011 – New York University; Merck board of the PneuMum Maternal pneumococcal of Management, Parents of Children with Hannah Moore, Australasian Epidemiological & Co, Pennsylvania; Case Western University, immunisation study in Northern Territory (2005-) Disabilities (Inc), Kalparrin Association 2011 Conference Organising Cleveland; Washington University, St Louis; Helen Leonard, Member of Executive, Australian Jenny Bourke, Member of Scientific Advisory Committee – Secretary University of Washington, Seattle Association of Developmental Disability Council, SIDS and Kids WA Monique Robinson, Scientific Advisor to Jianghong Li. Modernity’s paradox and child Medicine, (2002-) Jenny Downs, Human Research Ethics Commissioner for Children and Young People, health and wellbeing in developed countries. Elizabeth Milne, Conference Organising Committee, Princess Margaret Hospital for WA Invited Lecture Yunnan Health and Development Committee for the Annual Australasian Children (2010-) Research Association, Kunming, Yunnan, China, Monique Robinson, Scientific Committee Epidemiology Association Scientific meeting, March 2012 (accommodation, local transport Rebecca Glauert, Ngala Professional Advisory Member for the 7th World Conference on the Perth WA 2011 and food paid by the host). Committee (2011 – present) Promotion of Mental Health and the Prevention Raewyn Mutch, RACP Chapter of Community Rebecca Glauert, Data Linkage Advisory Board of Mental and Behavioural Disorders, Perth Jianghong Li. Causes of rising trends in poor Child Health, Share WebSite Contributor (2010 – present) Australia child outcomes and strategies for reversing them. Invited speech at the Eighth Shanghai Desiree Silva, Head of Department Medical Catherine L Taylor, Intensive Nurse Home Visiting David Lawrence, Heathway Research Committee, International Forum for Children, Shanghai 2-3 Advisory Committee (HOD/MAC) Joondalup (INHV) Project (ARACY and the Centre for (2010-) August 2011 (accommodation, local transport Health Campus Community Child Health), Member of the Expert and food paid by the host). Reference Group Deborah Lehmann, Perinatal and Infant Rochelle Watkins, Member, Board of Directors, Mortality Committee, Ministry for Health, WA, Raewyn Mutch, Vancouver FASD 4th Biennial Neurological Council of Western Australia Catherine L Taylor, ARACY State Convenor (WA) Deputy to Carol Bower (2005-) Conference: Overview of FASD in Australia, Catherine L Taylor, Australian Research Alliance Deborah Lehmann, Meningitis Centre Janice Wong, The Australian Association of March 2011 Cognitive Behavioural Therapy (December 2010) for Children and Youth (ARACY), Councillor Management Committee Monique Robinson, Maternal pre-pregnancy Catherine L Taylor, New Investigators Network, Helen Leonard, Women’s and Newborns’ Health body weight and risk for affective disorders in

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 99 offspring; Infants born at 37 weeks’ gestation Brisbane, October 2011 to delegation from the Shanghai People’s collaborations with China, Presentation are at increased risk for behavioural problems Association for Friendship with Foreign to delegation from the Shanghai People’s Elizabeth Milne, Nutrition and Genome through to adulthood. Developmental Origins Countries (SPAFFC), Perth, November 2011 Association for Friendship with Foreign Health in Children, Royal Brisbane & Women’s of Health and Disease (DOHaD) International Countries (SPAFFC), Perth, November 2011 Hospital Health Care Symposium, Brisbane Katherine Bathgate, Maternal mental health Conference (Portland, US): 18th-21st October 2011 and diagnosis of autism in Rett syndrome. Stephanie Fehr, The CDKL5 disorder: a new September 2011 Disability Services Commission, Perth, October cause of early-onset encephalopathy. Child Elizabeth Milne, Dietary factors contributing 2011 and Adolescent Health Research Symposium, to risk or prevention of childhood cancer, Perth, October 2011 National official launch of the Children’s Health and Katherine Bathgate, Fussy eaters to healthy Environment Program at the University of eating: strategies to prevent nutritional Anna Ferrante, Dimensions of Delinquency: Jenny Downs, Initial assessment of the Queensland, Brisbane, August 2011 deficiencies. Nutrition Australia, Perth, Differences in risk factors for delinquency StepWatch Activity Monitor™ to measure October 2011 across sub-populations in Western Australia. Raewyn Mutch, FASD Training and Seminars: walking activity in Rett syndrome. 3rd WA Department of Corrective Services, Perth, Anyinginyi Health Aboriginal Corporation, Jenny Bourke, IDEA database and Down National Australian Physiotherapy Association November 2011 Conference, Brisbane, October 2011 Tennant Creek, NT, December 2011 syndrome research. Disability Services Commission. October 2011 Geoffrey Hammond, Describing trends in Raewyn Mutch, FASD Training and Seminars: Stephanie Fehr, The CDKL5 disorder: a new gestational age, maternal age, and preterm Drug Education Network, Hobart, Tasmania, Carol Bower, Alcohol and Pregnancy, Perinatal cause of early-onset encephalopathy. 25th birth rates in Western Australia from 1984 to December 2011 Symposium, Joondalup Health Campus Epilepsy Society of Australia Annual Scientific 1999. Australasian Epidemiological Association Meeting, Brisbane, November 2011 Raewyn Mutch, FASD Training and Seminars: Carol Bower, WA Register of Developmental Annual Conference 2011 - Combining Tradition Kitty-Rose Foley, Functioning of young adults Health Ed/ Generation Next, RACGP Anomalies, Perinatal Symposium, Joondalup and Innovation, Perth, September 2011 Accredited, Sydney, NSW Health Campus with Down syndrome transitioning into post Geoffrey Hammond, Child and Adolescent school day occupations. Occupational Therapy Melissa O’Donnell, Rising parental mental Carol Bower, Collaborating with consumers: Health Research Symposium, Perth, October Australia 24th National Conference and health issues and the impact on child a case study in success and satisfaction. 2011 Exhibition, Gold Coast, Queensland, June/July maltreatment risk. International Mental Health Australasian Epidemiological Association Heather Jones, The Development of a 2011 Congress, Brisbane, August 2011 Annual Conference Screening and Diagnostic Instrument for FASD Rebecca Glauert, WA Developmental Pathways Ellen Walker, Carers, emergent adults, and Carol Bower, Consumer participation – a in Australia, Child and Adolescent Health Program: An overview and outcomes. New society: carers’ experience of transition as researcher’s perspective. University of Research Symposium, Perth, October 2011 Horizons for Educational Research, Adelaide, their daughter with Rett syndrome transitions Western Australia, School of Population Health Amanda Langridge, Multinational registry- September 2011. from late adolescence to adulthood. Summer School Consumer and Community based analyses of autism risk factors and Australasian Society for Intellectual Disability Participation in Health and Medical Research: Heather Jones, Alcohol and Pregnancy trends: the International Collaboration Conference, Glenelg, November 2011 A training workshop for researchers Research in Australia, Alcohol and Pregnancy for Autism Registry Epidemiology (iCARE). Community Conversation, Cairns, February Jenny Downs, Medical issues in Rett syndrome. Australasian Epidemiological Association 2011 Disability Services Commission Nurses Study Annual Conference 2011 - Combining Tradition Local Helen Leonard, The value of a population Day, Perth, March 2011 and Innovation, Perth, September 2011 database in the understanding of a rare Alison Anderson, AussieRett & InterRett Jenny Downs, AussieRett & InterRett Amanda Langridge, Maternal conditions and genetic disorder: insights from AussieRett, collaborations with China, Presentation

100 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Perinatal Characteristics Associated with Autism November 2011 Active collaborations Health Microbiology, Forensic and Scientific Spectrum Disorder and Intellectual Disability. Services, Coopers Plains, Qld Raewyn Mutch, FASD Seminars: South West Australasian Epidemiological Association Annual Infectious Diseases Group Foster Families, February 2011 Peter Siba, William Pomat, Andrew Greenhill, Conference 2011 - Combining Tradition and Suparat Phuanukoonnon, Papua New Guinea Innovation, Perth, September 2011 Raewyn Mutch, McCusker Centre for Action David Smith, PathWest Laboratory Medicine, Institute of Medical Research, Goroka, Papua on Alcohol and Youth: “How alcohol affects my Perth WA Amanda Langridge, Maternal conditions New Guinea work” and perinatal characteristics associated with Anthony Keil, Department of Microbiology, Eileen Dunne, Catherine Satzke, Murdoch autism spectrum disorder and intellectual Raewyn Mutch, FASD: School Psychologist Princess Margaret Hospital, Perth WA Children’s Research Institute, Melbourne Vic disability. Child and Adolescent Health Research Association Annual Conference, Perth WA 2011 Peter Richmond, Chris Blyth, School of Symposium, Perth, October 2011 Anita H. J. van den Biggelaar, Crucell, The Raewyn Mutch, FASD: Psychologists of Juvenile Paediatrics and Child Health, UWA, Perth WA Netherlands David Lawrence, Physical health of people with Justice, Department of Corrective Services, Perth Anne Mahony and Charles Douglas, Population mental illness. Unlocking the door to health and Kylie Carville, Epidemiology Unit, Victorian Raewyn Mutch, FASD: Professional Development Health, WA Country Health Services – Goldfields wellbeing: where do we find the key? Webinar Infectious Diseases Reference Laboratory, Day, Child and Community Health, DoH WA for Schizophrenia Awareness Week, Perth, 2011 Melbourne Vic Raewyn Mutch, FASD: Princess Margaret Bega Garnbirringu Health Services, Kalgoorlie David Lawrence, Relating data to events Gillian Hall, National Centre for Epidemiology Hospital Grand Round WA and trends concerning suicide. Prevalence, and Population Health and Medical School, prevention and early response to suicide, Perth, Melissa O’Donnell, Rising parental mental health Harvey Coates and Francis Lannigan, ENT Australian National University, Canberra ACT March 2011 issues and the impact on child maltreatment Specialists, Princess Margaret Hospital for Jennelle Kyd, Central Queensland University risk. Australian Epidemiological Association Children, Perth WA Helen Leonard, Autism and intellectual disability Annual National Conference, Perth, September Trevor Duke, Centre for International Health, are differentially related to socio-demographic Sharon Weeks, Professional Hearing Services, 2011 University of Melbourne background at birth. Asia Pacific Autism Perth WA Conference, Perth, September 2011 Monique Robinson, Prenatal stress events and Christine Jeffries-Stokes, The Rural Clinical Megan Passey, University Centre for Rural behavioural development from age two to 14 Health-North Coast, University of Sydney Helen Leonard, Multi-national registry based School of WA, Kalgoorlie WA years: The influence of the number, type and analyses of autism risk factors and trends: The Heath Kelly, Epidemiology Unit, Victorian timing of stressful life experiences. Australasian Tom Riley, Microbiology and Immunology, The International Collaboration for Autism Registry Infectious Diseases Reference Laboratory, Marce Society Conference Perth, 13th-14th University of Western Australia, Perth WA Epidemiology (ICARE). Asia Pacific Autism Melbourne Vic October 2011 Amanda Leach, Heidi Smith-Vaughan, Menzies Conference, Perth, September 2011 David Burgner, Infection, Immunity & Amanda Wilkins, FASD Seminars: South West School of Health Research, Darwin NT Faye Lim, Rett syndrome in China: Barriers to Environment, Murdoch Children’s Research Foster Families, February 2011 Paul Effler, Communicable Disease Control diagnosis and care. Child and Adolescent Health Institute, Melbourne Vic Directorate, Department of Health, Perth WA Research Symposium, Perth, October 2011 Ngunytju Tjitji Pirni Inc, Kalgoorlie WA Faye Lim, AussieRett & InterRett collaborations Childhood Cancer with China, Presentation to delegation from the Allan Cripps, Gold Coast Campus, Griffith Shanghai People’s Association for Friendship University, Qld Patricia Buffler, University of California, Berkeley with Foreign Countries (SPAFFC), Perth, USA Helen Smith, Public Health Microbiology, Public

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 101 Catherine Mettayer, University of California, Michael Fenech, CSIRO Nutrigenomics, Melbourne, Victoria ACT. Berkeley USA Adelaide. Liane Lockwood, Royal Children’s Hospital, Donna Berthelsen, Queensland University of Jacqueline Clavel Inserm, CESP Centre for Bruce Armstrong, Sydney School of Public Brisbane, Queensland Technology, QLD. research in Epidemiology and Population Health, University of Sydney, NSW Maria Kirby, Women’s and Children’s Hospital, Ben Edwards, Australian Institute of Family Health, U1018, Environmental epidemiology Frank van Bockxmeer, Royal Perth Hospital, Adelaide, SA Studies, Victoria. of cancer Team, F-94807, Villejuif, France; WA Univ Paris-Sud, UMRS 1018, F-94807, Villejuif, Glenn Marshall, Sydney Children’s Hospital, Jan Nicholson, Murdoch Childrens Research France Michelle Haber, Children’s Cancer Institute Sydney, NSW Institute, Victoria. Australia, NSW Claire Infante-Rivard Mcgill University& Centre Elizabeth Smibert, Royal Children’s Hospital, Megan Shipley, Australian National University, Universitaire Mere-Enfant Sainete-Justine, Rodney Scott, Hunter Medical Research Melbourne, Victoria ACT. Quebec, Canada Institute, University of Newcastle, NSW and Ram Suppiah, Mater Children’s Hospital, David Zarb, Playgroup WA (Inc), WA. Hunter Area Pathology Service, NSW Eve Roman Department of Health Science, Brisbane, Queensland Jason Connor, University of Queensland, QLD . University of York, UK John Attia, Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Marty Cooke, University of Waterloo, Canada. Logan Spector Division of Epidemiology/ NSW, Department of Medicine, John Hunter Looking at Language Clinical Research, Department of Pediatrics Steve Kisely, University of Queensland, QLD. Hospital and Hunter Medical Research and Masonic Cancer Center, University of Institute, NSW Mabel L Rice, University of Kansas, USA Sharon Lawn, Flinders University, SA . Minnesota, USA Murray Norris, Children’s Cancer Institute Shelley Smith, University of Nebraska Medical Sybille McKeown, Australian Bureau of Sergio Koifmann National School of Public Australia, NSW Centre, USA Statistics, ACT. Health, Oswaldo Cruz Foundation (FIOCRUZ), Javier Gayan, Neocodex, Spain Ministry of Health, Rio de Janeiro, Brazil Lin Fritschi, WA Institute for Medical Research, Alex Mitchell, University of Leicester, United University of Western Australia, WA Kingdom. Maria Pombo d’Oliviera, Pediatric Hemotology- Oncology Program, Instituto Nacional do Margaret Miller, Edith Cowan University, WA Human Capability David Povah, Australian Bureau of Statistics, Cancer, Rio de Janeiro-Brazil WA. Judith Thompson, WA Cancer Registry,WA Linda Harrison, Charles Sturt University, New Eleni Petridou, Department of Hygiene, Dr Krysta Boylan (McMaster University, Frank Alvaro, John Hunter Hospital, Newcastle, South Wales. Epidemiology and Medical Statistics, University Canada) NSW Raine study team including Martha Hickey, of Athens, Athens, Greece A/Prof. David Burgner (Murdoch Children’s Catherine Cole, Princess Margaret Hospital for Department of Obstetrics and Gynaecology. Joachim Schuz, International Agency for Research Institute, Melbourne) Children, WA University of Melbourne, Victoria. Research on Cancer (IARC), Section of A/Prof. Peter Franklin (School of Population Luciano Dalla Pozza, Children’s Hospital at Rebecca Giallo, Fabrizio D’Esposito, Parenting Environment and Radiation, Lyon, France Health, University of Western Australia) Westmead, NSW Research Centre, Victoria. John Dockerty, Department and Department A/Prof Renee Goodwin (Columbia University, John Daubenton, Royal Hobart Hospital, Sybille McKeown, Australian Bureau of of Preventive and Social Medicine, Dunedin USA) School of Medicine, University of Otago, New Tasmania Statistics, ACT. Prof. Roger Hart (School of Women’s and Zealand Peter Downie, Monash Medical Centre, Suzy Saw, Department of Health and Ageing, Infants’ Health, University of Western

102 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Australia) Dr Ron Chalmers, Disability Services Commission York. Dr Manuel Posada, National Institute for Rare WA, Directors General Steering Committee, Diseases Research, Madrid, Spain Prof. Stephen Lye (Canadian Institute Health Institute of Psychiatry, London, UK. Developmental Pathways Project, TICHR. Research, Canada) Abraham Reichenberg, Institute of Psychiatry, Julie Ireland, Down Syndrome WA Prof John Christodoulou, Children’s Hospital, London,UK A/Prof. S. Rachel Skinner (University of Sydney, Westmead, NSW. Biostatistics, Karolinska Institutet, Stockholm, Sydney) RettSearch Consortium. Sweden. Columbia University, New York, USA. Dr Ryan J. Van Lieshout (McMaster University, Dr Gabriel Ronen, McMaster University, Canada. Prof Walter Kaufmann, Center for Genetic Canada) The Children’s Hospital at Westmead. Disorders of Cognition and Behavior, Kennedy Dr David Roye, Morgan Stanley Children’s Dr Mark Davis, Royal Perth Hospital, Perth. Krieger Institute and Johns Hopkins University Hospital of New York, New York, USA. School of Medicine, Baltimore, UWA. Birth Defects Dr Carolyn Ellaway, Children’s Hospital, Prof Linda Slack-Smith, School of Dentistry, Oral Westmead, NSW. Gwynnyth Llewellyn, University of Sydney, Health Centre of Western Australia, Perth. Australian FASD Collaboration. Lead Investigators Sydney. Winthrop Research Professor Carol Bower Prof Elizabeth Elliott, Paediatrics & Child Sven Sandin, Karolinska Institutet, Stockholm, and Professor Elizabeth Elliott AM, Steering Health, Children’s Hospital, Westmead, FASD Prof Nick Lennox, University of Queensland, Sweden. Collaboration. Queensland. group of health professionals, researchers, Dr Diana Schendel, National Center on Birth epidemiologists and consumers and community Katheryn Frame, The International Foundation Dr Meir Lotan, Israeli Rett Centre, Tel Aviv, Israel. Defects and Developmental Disabilities, Centers members for CDKL5 Research, USA. for Disease. Prof Vera Morgan, University of Western Dr Michael Freilinger, University of Vienna, Australia. Jackie Softly, Down Syndrome WA Austria. Intellectual Disability Dr Lakshmi Nagarajan, Department of Dr Camilla Stoltenberg, Norwegian Institute of Prof Sue Fyfe, Faculty of Health Science, Curtin Neurology, Princess Margaret Hospital, Perth. Public Health, Oslo, Norway. University of Aarhus, Denmark. University, Perth. Dr Natasha Nassar, Kolling Institute of Medical Dr Pal Suren, Norwegian Institute of Public Dr Gordon Baikie, Royal Children’s Hospital, Prof Elizabeth Geelhoed, School of Population Research, University of Sydney. Health, Oslo, Norway Melbourne. Health, UWA. Norwegian Institute of Public Health, Oslo, Prof Ezra Susser, Columbia University, New York, Dr Xinhua Bao, Department of Paediatrics and Dr Mika Gissler, THL National Institute for Health Norway. USA. Obstetrics, Peking University First Hospital, and Welfare, Helsinki, Finland. Beijing, China. A/Prof Anastasia Iliadou Nyman, Department of Dr Andre Sourander, Turku University, Turku, Dr Raz Gross, Columbia University, New York, Medical Epidemiology and Finland Dr Michaeline Bresnahan, Columbia University, USA. New York, USA. Dr Eric Parner, University of Aarhus, Denmark. Dr Teresa Temudo, Hospital Geral de Santo Ronnie Hagan, Department of Neonatology, Antonia, Porto, Portugal. Dr Julie Briody, Department of Nuclear Dr Alan Percy, University of Alabama, USA. School of Women’s and Infants’ Health, UWA, Medicine, The Children’s Hospital at Westmead, Turku University, Turku, Finland. Perth. Dr Mercè Pineda, Centro Médico Teknon and Sydney. Sant Joan de Déu Hospital, Barcelona, Spain. Dr Michael Vitale, Morgan Stanley Children’s Dr Kylie Hill, School of Physiotherapy, Curtin David Burgner, Murdoch Children’s Research Hospital of New York, New York, USA. University, Perth. Dr Rohit Pokharel, Muscular Dystrophy Institute, VIC 3052 Australia. Foundation, Kathmandu, Nepal. Dr Simon Williams, Department of Neurology A/Prof Mady Hornig, Columbia University, New

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 103 and Padiatric Rehabilitation, Princess Margaret Dr Kirsten McKenzie, Queensland University of Hospital, Perth. Technology, Brisbane, Australia Dr Ingergerd Witt-Engerstrom, Swedish Rett Debbie Scott, Australian Institute of Family Centre, Sweden. Studies, Melbourne, Australia Dr Helen Woodhead, Sydney Children’s Hospital, New South Wales. Social determinants of child health/ Dr Xiru Wu, Department of Paediatrics and social epidemiology Obstetrics, Peking University First Hospital, Beijing, China. Associate Professor Wen-Jui Han, School of Social Work, Columbia University, the US Dr Bruria Ben Zeev, Pediatric Neurology, Safra Pediatric Hospital, Tel Hashomer, Israel. Professor Joachim Singelmann, Department of Sociology, Louisiana State University, the US Professor Chun Luo, Yunnan University Developmental Pathways Project Population Research Institute, Kunming, Yunnan Province, China ARACY New Investigator Network, National Collaboration Professor Lijun Yang, Yunnan Police Officers Academy, Kunming, Yunnan Province, China Assoc Prof Leah Bromfield, Australian Centre for Child Protection, University of South Dr Lyndall Stazdins, ANU Australia, Adelaide, Australia Dr Rachel Skinner, Sydney University Discipline Prof Marni Brownell, University of Manitoba, of Paediatrics & Child Health Manitoba Centre for Health Policy, Canada Associate Professor Mike Dockery, Curtin Prof Jane Fisher, The Jean Hailes Foundation, Business School, Curtin University Monash University, Victoria, Australia Dr Garth Kendall, School of Nursing and Prof Ruth Gilbert, University College London, Midwifery, Curtin University Institute of Child Health, United Kingdom Professor Bev McNamara, School of Dr Steven Guthridge, Department of Health Occupational Therapy and Social Work, Curtin and Community Services, Northern Territory, University Darwin, Australia Dr Daryl Higgins, Australian Institute of Family Studies, Melbourne, Australia Dr Melissa Kaltner, Queensland Health, Brisbane, Australia

104 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 vaccine trials group

Overview scientific publications and international The main purpose of the study is to determine continue to assess the safety of the vaccine. conference presentations of our work here in 1) How safe the vaccine is and which side Recruitment for this study commenced in During 2011 our new studies included of an VTG. We have expanded from focusing on ear, effects may occur in children and 2) Whether October 2010 and 74 subjects were recruited Australian designed Ross River Virus vaccine in nose and throat infections into chronic lung the immune system produces special proteins to this site. This study should be completed in adults, and a new vaccine for the prevention disease in both adults and children. These new called antibodies against the flu virus strain in 2012. of Meningococcal B disease in adolescents. A areas are being explored as the host-bacterial the vaccine number of important vaccine studies have interactions appear very similar between these Funders of the project - Sanofi Pasteur SA The required number of subjects for the study also continued this year including the Dengue different types of disease. This is also the first was achieved on the 09th September 2011. Fever, Human Papillomavirus (HPV), Respiratory time in which we are able to take some of the Syncitial Virus (RSV), Meningococcal B, Avian research we have done in the laboratory and At VTG eleven subjects have been recruited. A phase III, double-blind, randomized, Influenza, influenza vaccine effectiveness in apply it in the clinic with the establishment of Ten subjects are enrolled in Stratum A with one controlled study to evaluate the young children (WAIVE) and the Pertussis the Dornase alfa trial for which recruitment will subject enrolled in Stratum B. All visits and study safety, immunogenicity and efficacy vaccine at Birth study. begin in 2012. procedures have been completed of GlaxoSmithKline Biologicals’ HPV 16/18 L1/AS04 vaccine administered Highlights from 2011 must include the VTG has continued to be actively involved in the Funders of the project - Baxter intramuscularly according to a three- conclusion of the first-in-man Staphylococcus areas of vaccine safety, pneumococcal infection dose schedule (0, 1, 6 month) in healthy aureus (Golden Staph) vaccine study in and neonatal immunity. Our staff members have adult female subjects aged 26 years and adults that was presented at an international presented data at international conferences Lot-to-Lot Consistency and Bridging above. conference in Italy. Another achievement has during 2011, published in high impact journals Study of a Tetravalent Dengue Vaccine been the success of the FAST study, which and have also secured ongoing funding for our in Healthy Adults in Australia Dr Tanya Stoney and Associate Professor Rachel monitored the safety of the 2011 Influenza research. Skinner Associate Professor Peter Richmond vaccine in children. This study, sponsored by the Human papilloma viruses (HPV) are viruses Health Department of WA, came about because Dengue is a disease caused by a 4 types of a that cause a common infection of the skin and of high fevers and an increased incidence of virus that is transmitted by mosquito bites. Immunisation genitals in men and women. Several types of convulsions experienced by children < 5 years People who catch the dengue virus may get HPV infection are transmitted by sexual contact during 2010 with the use of Fluvax. The results A Phase l/ll study to assess the safety “dengue fever” – fever up to 40°C for 2 to 7 and, in women, can infect the cervix (the lower showed that the adverse events following and immunogenicity of a Vero cell- days, often with severe headache, vomiting, part of the uterus or womb). This infection often influenza vaccination in 2010 were not observed derived whole virus H5N1 influenza muscle and joint pains, pain behind the eyes, goes away by itself. However, if it does not go during 2011, which was reassuring for both vaccine in Healthy infants, children and and skin rash. Dengue is sometimes more severe away (this is called persistent infection), it can health professionals and parents. We also adolescents aged 6 months to 17 years. and can cause bleeding and/or a sudden fall in lead over a long period of time to cancer of the continue to be involved in the national vaccine blood pressure (shock). Dengue can cause death cervix. If a woman is not infected by HPV, it is safety surveillance through the PAEDs program Associate Professor Peter Richmond in some cases, mainly in children. very unlikely that she will get cervical cancer. as well as the WA Vaccine Safety Surveillance Influenza is a viral infection that frequently There are no vaccines and no specific treatments Two types of HPV, called HPV-16 and HPV-18, System. Ensuring vaccines remain safe in those causes severe disease. The disease can presently available against the disease. cause about 70 percent of the cases of cervical who use them continues to have a high priority cause sudden onset of general and breathing cancer in the world. Consequently, a vaccine in our research activities. The purpose of this research study is to see symptoms (for example headache, muscle pain, able to prevent HPV infections would be of great if four different batches of the study vaccine It has been an exciting year in the respiratory chills, fever, shortness of breath, sore throat, value in the protection against cervical cancer. produce a similar antibody response and to infectious disease group with several new cough and runny nose).

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 105 GSK Biologicals has developed a vaccine the efficacy of the vaccine in older women vaccine administered intramuscularly that prevent infection of some HPV types: against HPV types 16 and 18. This HPV which can then be used for cost effectiveness according to a 0, 1, 6-month schedule 1. GARDASIL® a vaccine developed by Merck vaccine has been tested in thousands of modelling. in healthy female subjects who Sharp & Dohme (Australia) Pty. Ltd. and young women in different countries, and the received the placebo control in the Funders of the project – GlaxoSmithKline manufactured by CSL. This vaccine provides reactions observed with the injection of the GSK HPV-015 study. protection against HPV types 6, 11, 16 & 18 vaccine to date have been similar to those and is currently available free for girls and seen after vaccination with other common Dr Tanya Stoney and Associate Professor A phase IIIb, open, multi centre women aged 9 to 26 years. GARDASIL® will be vaccines. These studies have also shown Rachel Skinner gynaecological extension study for used as the ‘Control’ vaccine in this study. that the vaccine stimulates defences against follow-up of a subset of 580299/008 This study is an extension of the HPV-015 the viruses, e.g. production of antibodies 2. Cervarix*, developed by GlaxoSmithKline, study subjects who were either research study with GlaxoSmithKline (GSK) (substances made by your body to prevent provides protection against the infection of cervical cytology negative and Biologicals’ human papillomavirus (HPV) infections). It has also been shown that the HPV types 16 & 18. oncogenic HPV positive or pregnant at vaccine for healthy females over 26 years vaccine prevents persistent infections with their final 580299/008 study visit (Visit of age. Currently the HPV-16/18 vaccine Merck Sharp & Dohme (Australia) Pty. Ltd. has HPV-16 or -18 and associated pre-cancerous 10 at Month 48). (Cervarix) is licensed in over 100 countries developed a new vaccine called V505 which is abnormalities (this is called vaccine “efficacy”). world wide, and is offered free to young designed to protect against 9 different types of Although pre-teen and adolescent girls Associate Professor Rachel Skinner women in HPV vaccination programs in the UK HPV infection with are responsible for about represent an important target population for and some other European countries. Cervarix This study is an extension of the HPV-008 90 per cent of cervical cancers and 90 percent preventive HPV vaccination, vaccination should was licensed in Australia in May 2007 for research study with GlaxoSmithKline (GSK) of genital warts. This vaccine is similar to the also be made available to adult women. This women up to the age of 45 years. This study Biologicals’ human papillomavirus (HPV) GARDASIL® in that it contains proteins called study is therefore designed to evaluate the allows women over the age of 45 years, who vaccine for healthy females 15 – 25 years of VLPs that resemble different types of HPV immune responses, safety and efficacy of the have participated in the HPV 015 study, to age. This study offered women additional to the body’s immune system, but are not investigational HPV vaccine in women who are have access to the vaccine if they have not gynaecological follow-up if they were shown actually viruses. This is the first time this study 26 years of age or older. already had it during the course of the study. to have a positive oncogenic HPV infection vaccine (V505) has been tested in humans, This study is ongoing. The sixth year of the Cervarix HPV vaccine trial although their cervical cytology test was however a vaccine with eight (8) of the VLPs for women aged over 26 years commenced normal at their last HPV-008 study visit. In Funders of the project - GlaxoSmithKline has been tested in people and found to be in 2011. One hundred and fifty women were addition, a woman who was pregnant at her generally well tolerated. recruited into this study at VTG. The purpose last HPV-008 study visit and no cervical sample This study has been ongoing since 2007 and 25 of this study is to determine the efficacy, was taken, was also eligible to enter. Nineteen A Phase IIa Randomized, Double Blind, subjects were recruited at this site. This study safety and immunogenicity of Cervarix in older women were eligible to participate in this Controlled with GARDASIL™ Clinical was completed in 2011. women. Currently the HPV-16/18 vaccine study which began in 2009. Trial to Study the Tolerability and (Cervarix) is licensed in over 100 countries Immunogenicity of V505 (a multivalent Funders of the project. Merck Sharp and Funders of the project - GlaxoSmithKline world wide, and is offered free to young Human papillomavirus [HPV] L1 Virus- Dohme women in HPV vaccination programs in the Like Particle [VLP] Vaccine) in Healthy 16 UK and some other European countries. to 26 year old women A phase IIIb, open-label, multi-centre Cervarix was licensed in Australia in May A Phase 1 Trial to Evaluate the Safety, immunization study to evaluate 2007; however it is still important that the Associate Professor Peter Richmond Tolerability and Immunogenicity of 3 the safety of GlaxoSmithKline (GSK) current studies are completed to determine Ascending Dose Levels of a 3- Antigen Biologicals’ HPV-16/18 L1 VLP ASO4 Currently there are two HPV vaccines available

106 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Staphylococcus aureus Vaccine (SA3Ag) months. Virus vaccine in Healthy male & female against respiratory syncytical virus in Healthy Adults subjects 16yrs of age and older. (RSV) and parainfluenza virus type 3 (PIV This study aims to randomly assign a group of 3), in healthy 6 - <24 month-old children newborn infants to birth acellular Pertussis (Pa) Associate Professor Peter Richmond Associate Professor Peter Richmond in and 2 month old infants vaccine versus current standard practice. Infants Staphylococcus aureus (Staph) is a bacterium Ross River virus is a mosquito-borne virus will either receive a Pa-containing vaccine at Assoc/Prof Peter Richmond, Dr Tanya Stoney (germ) that inhabits the skin and mucous birth and then 6 weeks, four and six months that causes Ross River Virus Disease (RRVD) in membranes throughout life. Staph infection can of age or the standard schedule with the first humans. Ross River is endemic and enzootic RSV and PIV3 are important causes of cause pneumonia, skin and wound infections. dose given at 6 rather than 8 weeks. Antibody in Australia, Papua New Guinea, adjacent bronchiolitis (inflammation of the small airways The success of antibiotics in the prevention and responses in the blood, which are believed to Indonesia and the Solomon Islands. In the past in the lungs) and pneumonia in infants and treatment of staph infection has been limited correlate with protection, will be compared at 10 years RRVD has been most prevalent among young children. The purpose of this study by the rapid and widespread emergence of 6 weeks, 10 weeks, 6 months and 8 months of adults aged 25 and 39 and does not display a is to describe the safety, immune response antibiotic-resistant strains. age. clear sex effect. (ability of the body to fight infection), and virus shedding (virus that can be found in the The study is evaluating three different dose Subjects were divided into two age strata; This study aims to show whether earlier nose after vaccination) of an experimental live levels of the study vaccine in healthy adults aged Stratum A -1800 subjects aged 16 to 59 yrs vaccination gives better protection from PIV3 and RSV nasal vaccine called MEDI 534 in 18 to 85 years. A placebo was given to some and stratum B - 210 subjects aged 60 and over. Pertussis at the time when babies are most likely comparison to a placebo (an inactive sugar and participants to obtain safety data. A subset of approximately 1140 subjects in to die from this infection. salt solution that does not contain the vaccine, stratum A and all subject in stratum B were Data was collected on how well and how soon MEDI-534). MEDI -534 or placebo is given as This study is also being conducted in Adelaide, included in the immunogenicity evaluation. the vaccine offers protection against Staph Melbourne and Sydney and is funded by the nose drops in this study. infection. The study involves six clinic visits with three National Health and Medical Research Council Recruitment for this study was completed vaccinations and 2 follow phone calls. Those All per protocol visits have been completed. (NHMRC). in 2011, all subjects have received there last subjects in the immunogenicity group have a A final study report and the unblinding of dose of Investigational Product. The study is in The 440 babies required nationally were blood draws at each visit. Subjects complete treatment groups is expected mid 2012. phone call follow up of which the last calls will enrolled by the end of February 2012. Our site diary cards to capture injection site reactions, take place in October 2012. The Vaccines Trials Funders of the project. - Wyeth Pharmaceuticals, completed recruitment at the beginning of systemic adverse events and other AE’s. Group recruited 4 participants to this study. All Inc/Pfizer November 2011.Over half of the babies have completed all the study visits. There have been Recruitment for this study commenced in April visits and phone call follow ups were completed no serious adverse events causally related to the 2011with 114 subjects recruited at this site. in January 2012. There are a total of six sites in Australia. Immunogenicity and Safety of Acellular study vaccine and there have been no concerns Funders of the project - MedImmune Pertussis vaccine given at birth in with solicited and unsolicited adverse events Funders of the project - Baxter healthy infants. after subsequent vaccines. Funders of the Project - MHMRC A Prospective Study to Evaluate Associate Professor Peter Richmond, Dr Tanya A phase 1/2a, Randomised, double- the Immunogenicity of Trivalent Stoney blinded, placebo-controlled, dose- Inactivated Influenza Vaccine in Currently, vaccines to protect against A phase 3 study to assess the escalation study to evaluate the safety, Children (> 6 months to < 18 years of age) Pertussis (whooping cough) are given from 2 immunogenicity, safety and consistency tolerability, Immunogenicity and who are on Cancer Therapy months of age, but almost one third of infant of lot manufacture of Ross River vaccine-like viral shedding of MEDI-534, Dr Ushma Wadia, Dr Rishi Kotecha, Dr Nick hospitalisations for Pertussis occur prior to 2 a live, attenuated intranasal vaccine

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 107 Gottardo, Dr Angela Alessandri, Prof. Catherine Different Sites, in Healthy Adolescents administered with GSK Biologicals’ Meningococcal B Vaccine Study in 11 to Cole, Assoc/Prof Peter Richmond Aged 11-17 Years measles-mumps-rubella vaccine, 18 year olds: Study Protocol 6108A1- Priorix™, versus MenC-CRM197 2001. WW Influenza (the Flu) is an easily spread Associate Professor Peter Richmond conjugate vaccine co-administered disease caused by a virus, which most with GSK Biologicals’ Hib vaccine, Associate Professor Peter Richmond commonly causes fever, cough, breathing The meningococcal B vaccine study was Hiberix™ and Priorix™ in 12- to problems, runny/blocked nose, tiredness conducted in Australia and internationally Pfizer Australia Pty Ltd (formerly Wyeth 18-month-old toddlers primed in or irritability. Young children, elderly, and to compare 2 batches of the same vaccine Australia Pty Ltd) Vaccines Research has infancy with a Hib vaccine but not those on chemotherapy are more likely to manufactured at 2 different sites. The study developed an investigational vaccine (rLP2086) with a meningococcal serogroup C be infected, and are more likely to develop was conducted to see if the Men B vaccines against Meningococcal B infection. The study vaccine; and to evaluate the long term serious complications, which may require are safe and effective in adolescents. It is commenced at VTG with the first subject visit antibody persistence up to 5 years hospitalisation, and even in rare cases death. hoped that the vaccines produced at two on 09 February 2009. after the administration of the Hib- Those on cancer therapy should be given the different manufacturing sites will produce MenC vaccine No 106445 (primary phase) Stage 1: Stage 1 was designed to assess flu vaccination every year. You can still get a the same antibody responses in the study 106446,106449,106450,106452,106454 (long the safety and immunogenicity of the cold despite being vaccinated as a result of participants. term follow up) Meningococcal B vaccine and to provide the infection with either a different strain not The Vaccine Trials Group has enrolled 12 basis for the dose selection for stage 2. covered by the vaccine, or not being able to participants into the study. Participants Associate Professor Peter Richmond The Meningococcal B vaccine was evaluated produce protective antibodies to the three attended Vaccine Trials Group for 3 visits over This trial commenced in 2006 with 49 toddlers at three dose levels (60 micrograms, 120 stains in the vaccine. 2 months. They were vaccinated at visits 1 at this site. The children received either a micrograms, and 200 micrograms, and and 2, and blood sample was collected at This study recruited 130 participants and the combined Hib and MenC (HibMenC) vaccine placebo. VTG enrolled 77 participants in stage visits 1 and 3. A diary card was completed by last samples were collected in November 2011. with the MMR vaccine at 12 months of age or 1. participants after each vaccination. Currently the statistics are being prepared the regular scheduled vaccines. The aim of Stage 2: Commenced with the first subject so that an article can be written up for a The active part of the meningococcal B vaccine this study is to demonstrate that the combined visit on 26 February 2010. Participation in journal submission. The PHAA 13th National study has closed in February 2012 and we are HibMenC vaccine produces as good as or Stage 2 will last up to 3 ½ years. Subjects in Immunisation conference to be held in currently waiting for the results. a better immune response than the same cohorts 2, 3 and 4 who received dose levels Darwin between 19th and 21st June 2012, has components when given separately. accepted our abstract as a poster presentation. Funders of the project - Novartis Vaccines and 120 micrograms, 200 micrograms and placebo Diagnostics We are currently completing the final visit in were invited to participate in stage 2. Funders of the project - PMH Foundation the fifth year of long term follow up for these Stage 2 will continue to evaluate the vaccine’s Grant children. The children have come in for annual ability to produce long term protection to A phase III, open randomized, visits for blood samples taken to measure their Meningococcal B disease. VTG enrolled controlled, multi-centre study to long term immunity to the Hib bacteria. Of 33 participants in stage 2, with no subject A Phase 3, Randomized, Comparative, demonstrate the non-inferiority the 49 subjects that were initially enrolled, 37 withdrawals to date. Multicenter Observer-Blind of the meningococcal serogroup subjects are still involved in this study after 5 Study Evaluating the Safety and C and the Haemophilus Influenza years. Funders of the project - Pfizer Australia Pty Ltd Immunogenicity of Novartis type b immune response of Funders of the project - GlaxoSmithKline rMenB+OMV NZ Vaccine Formulated GlaxoSmithKline(GSK) Biologicals’ with OMV Manufactured at Two conjugate Hib-MenC vaccine co- Meningococcal antibody levels in

108 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 11 – 15 years olds who received a single adverse events. The three conditions currently included as Margaret Hospital for Children Emergency ‘catch up’ dose of MenC vaccine in 2003/4 surveillance studies are: Acute Flacid Paralysis Department & hospital inpatients with an In 2011 399 children were recruited. Significant (AFP), Intussusception (IS) and Severe Varicella influenza like illness(ILI) adverse-events including fever following TIV Associate Professor Peter Richmond (VZV) were not observed in children who received the • During the 2011 influenza season we This study recruited 240 Australian children and 2011 formulation of Vaxigrip and overall rates of Cases screened and recruited at PMH from recruited a total number of 637 subjects. teenagers in Melbourne (160 participants) and any reaction were low. 1.1.2011 – 31.12.2011 Of these, 517 children presented to the Perth (80 participants), aged between 11 and Emergency Department, and 120 were Funders of the project - Communicable Disease AFP - 191 cases of AFP screened and 8 recruited 15 years, who received a single dose of MenC admitted to hospital. vaccine during a national ‘catch-up’ campaign in Control Directorate, Health Protection Group, with 100% stool sample collection Western Australian Department of Health (WA • Even though the recruitment numbers 2003/4. IS - 918 cases of IS screened and 18 recruited DoH) were high for 2011, uptake of the influenza We want to measure each child’s antibodies to VZV (Severe hospitalised) - 208 cases screened vaccine for under five year olds was very MenC, to see if they still have levels thought to and 7 recruited low (15% fully vaccinated for PMH hospital be protective. This information is vital to help Paediatric Active Enhanced Disease inpatients and only 5% for PMH Emergency Funders of the project - Commonwealth Dept of the Australian Government work out whether Surveillance - PAEDS Department recruitments). This was likely Health & Ageing an extra dose of MenC vaccine will need to be to be due to the adverse events associated included in the Australian National Immunisation Associate Professor Peter Richmond, Associate with the CSL Fluvax brand influenza vaccine Program Professor Christopher Blyth The Children’s Western Australian given in 2010 which caused an increase in Funders of the project - Novartis vaccines PAEDS is coordinated by the Australian Influenza Vaccine Effectiveness (WAIVE) high fever and febrile convulsions. Paediatric Surveillance Unit (APSU) and Study • Of the 633 subjects recruited with nasal the National Centre for Immunisation and swab/PNA results, there were a total of 69 Associate Professor Peter Richmond, Associate Surveillance of Vaccine-Preventable Diseases positive Influenza results. Surveillance (NCIRS). There are currently four sites involved Professor Dr Christopher Blyth, Dr Dale Carcione, Funders of the project - Communicable Disease The Western Australian Children’s across Australia: Dr Gabriela Dixon, Dr Paul Effler, Associate Professor Gary Geelhoed, Dr Anthony Keil, Dr Control Directorate, Department of Health WA Follow up and Active Surveillance of • Princess Margaret Hospital for Children Heath Kelly, Dr Alan Leeb, Dr Hannah Moore, Dr Trivalent influenza vaccine (FAST) Study (PMH), Perth David Smith, Dr Paul Van Buynder, Avram Levy, A/Prof. Peter Richmond, A/Prof. Christopher • Women’s and Children’s Hospital, Adelaide Peter Jacoby Rotavirus and Gastroenteritis Blyth, Dr Nicholas Conway, Dr Tracy Markus Surveillance Study (RAGS) • Royal Children’s Hospital, Melbourne The main objectives of the WIAVE study are: To detect any significant increase in seasonal Associate Professor Peter Richmond, Dr Paul • The Children’s Hospital at Westmead, NSW • To assess the effectiveness of the trivalent trivalent inactivated influenza vaccine (TIV) Effler, Dr Dale Carcione, Professor David Forbes, influenza vaccine in young children (full related febrile reactions and/or any other PAEDS objective is to test the value of hospital- Associate Professor Gary Geelhoed, Dr Gerald and partially vaccinated) and to assess the adverse events following immunisation based active surveillance for identifying and Harnett, Dr Anthony Keil, Associate Professor burden of influenza in young children and (AEFI) with seasonal TIV and to provide investigating childhood conditions of public Carl Kirkwood, Professor Tom Riley, Dr David their families active surveillance of seasonal TIV associated health importance which are difficult to Smith, Dr Michael Watson, Simon Williams adverse events and provide timely feedback to adequately capture through other surveillance • We recruit children aged between 7mths RAGS aims to assess the effectiveness of healthcare consumers re: rate of TIV associated mechanisms. and 5years who present to Princess Rotavirus vaccine on community acquired

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 109 Rotavirus presenting to ED and hospital critically reliant on the innate immune system, by nontypeable Haemophilus influenzae contribute to advanced prevention and inpatients and also to assess the impact of detailed comparison of preterm and term (NTHi). Aboriginal children have the highest treatment strategies for OM. the infant rotavirus immunisation program infant responses to various microorganisms NTHi OM rates in the world. A vaccine has Funder of the project - National Health and on rotavirus genotypes circulating in the will allow characterisation of the key innate been introduced to Australia to reduce NTHi Medical Research Council (NHMRC). community. responses that normally recognise and control carriage and OM. H. haemolyticus(Hh) both commensals and pathogens in healthy masquerades as NTHi leading to inaccurate We recruit children presenting to the Princess infants and children. We have established a surveillance of NTHi carriage. Margaret Hospital for Children (PMH) Role of bacterial biofilm and number of clinical studies which give us unique emergency department or admitted to the This project will document true NTHi and Hh intracellular infection in chronic and access to preterm and term infant samples, medical ward with acute gastroenteritis under carriage rates in OM-prone children, to guide recurrent otitis media both at birth (cord blood) and during early life the age of 5 years and who have a history of at national vaccine policy and set a benchmark and childhood, when the risk of infection is least 3 episodes of diarrhoea within 24 hour for assessing the impact of OM-targeted Associate Professor Peter Richmond, H. highest. Using these cohorts we are trying to: period. vaccines in Australian children. Coates, S. Vijayasekaran and R. Thornton 1) Identify critical innate immune pathways In 2011 there were a total of 52 subjects Funder of the project - National Health and While more than 80% of children will of newborn commensal and pathogen recruited. Of these 60% of children were Medical Research Council (NHMRC). experience at least one ear infection (OM) recognition vaccinated for Rotavirus. Out of the 48 stool episode by three years of age, 33% will samples collected, only one child tested 2) Study the development of the innate experience three or more episodes by this positive for rotavirus and this child had not immune system in infancy and early childhood Evaluation of antibody levels and same age. Increases in children who suffer received a rotavirus vaccine. function in otitis-prone and healthy from recurrent OM have been observed and 3) Examine the impact of antenatal factors Australian children antibiotic treatment in these children is often Funders of the project - Department of Health (such placental inflammation) on innate ineffective. Our work has shown that the WA immune function Dr Selma Wiertsema and Dr Lea-Ann Kirkham bacteria which cause these infections can be found in a ‘slime’ or biofilm on the skin in the 4) Determine if innate responses in the We and others have shown that children with middle ears of children. When bacteria are in newborn are epigenetically regulated ear infections (OM) have a good immune this slime they are seen to be up to 1000 times Infectious Disease response against the pneumococcus which Funders of the project - Health and Medical more resistant to antibiotics than the ‘free causes OM, however, these children still get Newborn infection and immunity Research Council (NHMRC)., BrightSpark floating’ bacteria which make the children sick. sick. This raises two important questions: Foundation Inc, PMH Foundation, European They also allow the bacteria to be shielded Dr Andrew Currie Society of Infectious Diseases 1) is the immune response actually doing what from the body’s own response meaning that Preterm infants (>22,000/year in Australia) it is meant to do and when the antibiotics are finished the bacteria are particularly prone to infections with can again become free floating and cause an Dynamics of Haemophilus 2) is the immune system doing this at the right commensal microorganisms, such as coagulase infection. haemolyticus and nontypeable site, i.e. in the middle ear negative staphylococci, which rapidly colonise We have also shown that as well as been in Haemophilus influenzae colonisation To answer these questions we will use blood, all newborns after birth. Additionally, preterm slime, these bacteria can live inside the cells in otitis-prone children saliva and middle ear fluid samples that we infants have worse outcomes from infections of the middle ear, the problem with this being collected from children with OM. This work with more pathogenic organisms such as Dr Selma Wiertsema and Dr Lea-Ann Kirkham that when they survive inside the cell they are will give insight into the role of the immune Escherichia coli and Candida albicans. As again largely protected from the antibiotics Ear infections (OM) are predominantly caused system in the development of OM and will defence against infection in the newborn is that are commonly used to treat this infection

110 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 as well as the body’s own immune response. the immune system known as neutrophils. This patients with COPD. infections. This study will confirm whether Whether is biofilm or intracellularly, these is similar to what is seen in the lung fluid from bacteria survive in biofilms in the lungs of bacteria represent an infectious reservoir from patients with cystic fibrosis. P. Richmond, R. Thornton, S. Wiertsema and L. patients with COPD and which species are which they can cause reinfection giving rise to Kirkham. involved. By understanding how bacteria persist We believe that these DNA nets form the “glue” what we see in some children who always seem in the lung of these patients we will be able to in the middle ear and behave like the sticky fluid Chronic obstructive pulmonary disease (COPD) to have glue ear or infections. investigate alternative treatments, such as anti- in the lungs of children with cystic fibrosis. This is a broad term used to describe chronic lung biofilm agents that allow antibiotics to eradicate These findings are very important as it leads stops the body from getting rid of the bacteria disease that includes bronchiectasis, chronic the released bacteria. We will also measure us to explore new treatment options that will and acts as a site where bacteria are able to bronchitis, chronic asthma and emphysema. the immune response of patients with COPD to hopefully be more effective at targeting these grow and reinfect the ear. We believe that COPD is the fourth most common global cause investigate whether they are likely to benefit infectious reservoirs and preventing chronic and these DNA nets represent a treatment target of adult death with symptoms including a from new and developing protein vaccines that recurrent infections in the future. to reduce the number of complications and ear chronic productive cough, shortness of breath, could reduce the incidence of lung infections. infections following grommet surgery. Breaking wheezing and frequent acute infectious Funder of the project - PMH Seeding grant, down this glue will also make the bacteria more exacerbations. Acute exacerbations of COPD Funder of the project - Westcare. Garnett Passe and Rodney Williams Foundation. susceptible to the body’s protective responses. have been clearly associated with isolation of respiratory bacteria, particularly nontypeable In the laboratory we have shown that in a test Haemophilus influenzae, Streptococcus An open-label, multi-centre, single Dissolving the glue in glue ear: tube, a treatment commonly used in cystic pneumoniae, Moraxella catarrhalis and arm study to evaluate the safety and Assessment of the use of Dornase alfa fibrosis treatment (Pulmozyme® or Dornase Pseudomonas aeruginosa, from sputa at tolerability of intravenous zanamivir as an adjunct therapy to ventilation alfa) is able to break down the sticky “glue” from the time of exacerbation. These recurrent in the treatment of hospitalised adults, tube insertion. the ears of children with chronic and recurrent exacerbations result in a worsening of the adolescents and paediatric subjects middle ear infections. We believe that this has patient’s condition, which usually requires R. Thornton, P. Richmond, H. Coates, S. with confirmed influenza infection practical applications in treating middle ear additional treatment and significantly increases Vijayasekaran and P. Jacoby. infections and lowering the rate of infection mortality rates. Associate Professor Chris Blyth and Associate Grommet insertions for middle ear infections recurrence following grommet insertion. Professor Peter Richmond We propose that the cause of recurring bacterial are the second most common reason for In this study we will trial the use of Dornase alfa infection in patients with chronic lung disease There are currently no intravenous influenza preschool children to undergo surgery. Up to at the time of grommet insertion to break down (COPD) is that bacteria are not cleared from (flu) antiviral agents approved for use in patients one third of these children will need to have the “glue” in the middle ear to allow for more the lung, either by antibiotics or by the host’s with severe flu. The purpose of this study is repeat surgeries due to infection recurrence. effective clearance of bacteria from this site and immune system. We have preliminary evidence to test the safety and effectiveness of a new We believe the recurrence of otitis media is due to increase the effectiveness of the antibiotic that the bacteria survive and persist in the lung intravenous form of zanamivir in adults and to the presence of bacteria in “slime” which drops which are commonly used. in superstructures known as biofilms, which are children with severe flu. Zanamivir is usually is known as biofilm. Biofilm protects bacteria made up of bacteria surrounded by host and given to patients who have the flu, using a from the body’s immune responses and makes Funders of the project - Western Australian bacterial DNA and proteins. Bacteria residing in puffer. The study commenced in 2010 and due bacteria up to 1000 times more resistant to Government State Health Research Advisory a biofilm are resistant to antibiotics and cannot to quieter than usual flu seasons we have not antibiotics. These biofilm structures need to be Council and PMH Foundation. be eliminated by the immune system. When enrolled anyone into the study. The study will be broken down to make treatments work. We have conditions for the bacteria become favourable ongoing in 2012. shown that biofilms can be found within DNA they can be released from the biofilm and net-like structures in the middle ear fluid. These Mechanisms of bacterial persistence Funder of the project – GlaxoSmith Kline replicate, thereby causing recurring acute DNA structures are largely produced by cells of and potential for vaccination in

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 111 Laboratory cells (PBMCs) for the GSK Antigen Specific Network, Child and Adolescent Health Service Jennifer Kent DipN Cancer Immunotherapeutic (ASCI) project Head, Department of Clinical Research and Lea-Ann Kirkham PhD BSc (Hons) Generic Bank for Peripheral Blood NYES01-AS15-MEL-001/112406. This study Education, Child and Adolescent Health Mononuclear Cell (PBMC) and serum explores the immune responses and holistic Services Kiara Kinder Medical student to look at Immunology Responses outcomes of immunotherapy on 8 cancer Honorary Research Fellow and Director, Timothy Loy Medical student to Allergens, Bacteria and Vaccine patients. The patients are followed up with 12 Vaccine Trials Group, Telethon Institute for Antigens visits over a 5 year period. The clinical side to Child Health Research Justine Mackie Medical student the study takes place at the Princess Alexandra Deputy Chair, Australian Technical Advisory Fiona MacDonald BSc RM RGN Associate Professor Peter Richmond Hospital in Queensland and the Cancer Clinical Group on Immunization, Commonwealth This study seeks to establish a bank of Trials Centre in Victoria. Blood is then flown to Department of Health and Aging Lisa Montgomery peripheral blood mononuclear cells (PBMC’s), the VTG in Perth for processing where PBMCs Samantha Moore Medical student plasma and serum for the in vitro analysis of are frozen and sent on to GSK for final analysis. Research Staff Jennifer Morrison RN RM adult immunology responses to allergens, VTG had to meet a variety of ‘minimum quality bacterial, viral and vaccine antigens. The Annemarie Naylor Grad Cert CTM assurance requirements’ that GSK set to Sanela Bilic MBA BSc samples are obtained from healthy volunteers. become a certified lab. In addition to this four Amy Prosser BSc (Hons) To date there are 97 study participants laboratory personnel completed a ‘dry run’ Associate Professor Christopher Blyth MBBS enrolled. Throughout the year we replenish where samples were processed and the PBMCs (Hons) DCH FRACP FRCPA Alison Roberts Post Grad Dip Health stocks of existing participants. Promotions BSc Dip Health Sci were sent to GSK for analysis, to determine Karli Corscadden BSc (Hons) Recruitment is ongoing. if the operators and the methods used were Christine Robins EN Nicholas Conway MBChB MRCPCH MPH adequate for the study. All personnel obtained Funders of the Project - Investigator Initiated Chantelle Ruoss Medical student their certification in November 2011. VTG was Andrew Currie PhD BSc (Hons) ready to receive samples in 2011 however no Gabrielle Sicari Medical student Helen Currie Medical student samples were sent. PBMC Preparation for CMI Testing Zakary Snelson Medical student Samantha Curtis BSc (Hons) in GSK Antigen Specific Cancer Funders of the project: GlaxoSmithKline Tanya Stoney MBBS Dip Child Health Immunotherapeutic (ASCI) Projects Jennifer Ebsary DipN RM Rachel Skinner MBBS PhD FRACP (NYES01-AS15-MEL-001/112406) OR Camille Gibson BSc Environmental Health RM Peripheral Blood Mononuclear Staff and Students BSc Nursing Nichola Taylor Dip HE BSc (Hons) Cell Preparation for Cell Mediated Immunity Testing in GSK Antigen Head of Division Julie Hibbert BSc (Hons) MSc Patrick Thornton Medical student Specific Cancer Immunotherapeutic Jessica Hillwood Medical student Ruth Thornton PhD BSc (Hons) Projects (NYES01-AS15-MEL-001/112406) Peter Richmond MB BS MRCP FRACP Associate Professor, School of Paediatrics and Julia Inman Medical student Selma Wiertsema PhD MScBSc Associate Professor Peter Richmond Child Health, University of Western Australia Matthew James Medical student Ushma Wadia MBBS Consultant Paediatrician and Paediatric Late 2011 the Vaccine Trials Group (VTG) Immunologist, Princess Margaret Hospital for Jane Jones BSc (Hons) BScN DipHealth Sc Verity Watt Medical student became a certified laboratory for the Children processing of peripheral blood mononuclear Jan Jones BSc (Hons) DipEd Caroline Wharton EN Director, Child and Adolescent Health Research

112 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Postgraduate Students 2010, Melbourne, Victoria, Australia. (Poster C Blyth, Data Safety and Monitoring Board, Margaret Hospital for Children Presentation - Best Poster Award) Bronchiectasis Exacerbation Study (BEST) Angela Fuery BSc (Hons) PhD Candidate C Blyth, Safe Design Advisory Committee. New R Thornton, S Wiertsema, L Kirkham, J Pickering Children’s Hospital, Perth Stephanie Trend BSc (Hons) PhD Candidate and K Corscadden. OMOZ 2012 Organising A Currie, Australasian Society for Immunology Committee. Janesssa Pickering (Hons) PhD Candidate External Committees (WA) Organising Committee P Richmond, Chair, ATAGI MMR-Varicella and Divya Muthiah Honours student International A Curie, PMH Ethics Scientific Advisory Sub- Herpes Zoster Vaccine Working Party, 2006 – Committee Gemma Mullaney Honours student C Blyth, Vaccines Working Group, International present Society of Chemotherapy P Richmond, WA Immunisation Scientific P Richmond, Member, ATAGI Pneumococcal Advisory Group 2006 – present C Blyth, Data Safety and Monitoring Board, Vaccine Working Party, 2007 – present Theses passed A study to determine the safety and P Richmond, Member, ATAGI Hib and immunogenicity of 10-valent and 13-valent R Thornton, PhD University of Western Australia, meningococcal C Vaccine Working Party, 2008 – pneumococcal conjugate vaccines in Papua New Invited Presentations Biofilm and intracellular infection: Persistence present Guinean children mechanisms of bacterial otopathogens in P Richmond, Member, ATAGI H1N1 Influenza A Currie. “To in utero and beyond” Australasian chronic and recurrent otitis media. Vaccine Working Party, 2009 – present Society for Immunology. ASM Adelaide, Dec G Mullaney, Hons (1st Class) University of National 2011 P Richmond, Member, ATAGI Influenza Vaccine Western Australia, No difference in the C Blyth. Combination antifungals in Aspergillosis. A Currie, Australasian Society for Immunology Adverse Event Working Party, 2010 – present functionality of anti-pneumolysin antibodies Mycology Masterclass V, Hamilton Island 2011 in the serum of children with and without Special Interest Group for Infection and P Richmond, Deputy Chairperson, Australian recurrent otitis media. Immunity (State representative) Technical Advisory Committee on Immunisation Numerous local presentations to doctors, community groups, medical students etc C Blyth, Local Organising Committee: WSPID (ATAGI), P Richmond, Commonwealth Dept. of Conference, World Society for Pediatric Health and Ageing 2010 to present R Thornton. Biofilms and intracellular infection Awards Infectious Diseases, Melbourne 2011 P Richmond, Member NHMRC Grant Review in OM and tonsillitis. Interamerican Pediatric Otorhinolaryngology’s (IAPO) 7th International C Blyth, Local Organising Committee: ASID Panel for Microbiology & Virology (GRP 2E) C Blyth, Research Travelling Award, European Symposium on Pediatric ENT in São Paulo, 18-20 Conference, Australian Society for Infectious August 2011 Society of Clinical Microbiology and Infectious November, 2011. (Invited Speaker - Workshop) Diseases, Perth 2012 Diseases, 2011 R Thornton, Chronic mucosal disease and the C Blyth, Australian and New Zealand Mycology C Blyth, Clinical Teacher of the Year, Princess Local role of intracellular infection and biofilms Interest Group Business Committee, Australasian Margaret Hospital for Children. 2011 Interamerican Pediatric Otorhinolaryngology’s Society for Infectious Diseases C Blyth, WA Tuberculosis Advisory Council, (IAPO) 7th International Symposium on Pediatric R Thornton, H Coates, P Rigby, S Vijayasekaran Health Department of Western Australia C Blyth, Australasian Stewardship of ENT in São Paulo, 18-20 November, 2011. & P Richmond, Chronic mucosal disease and Antimicrobials in Paediatrics Group, Australasian C Blyth, WA Tuberculosis Control Committee (Invited Speaker) the role of intracellular infection, biofilm and New Zealand Paediatric for Infectious Health Department of Western Australia and the pneumococcus. Frontiers 2010: The R Thornton, Why do children have more tonsillar Diseases Group Art,Science and Future of Otorhinolaryngology. C Blyth, Infection Control Committee, Princess hypertrophy accounting for most tonsillectomy

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 113 indications? Interamerican Pediatric P Richmond, Studies on the protection ACTIVE collaborations McKartney K, Wood N, Snelling T, Buttery J, Otorhinolaryngology’s (IAPO) 7th International of seasonal influenza vaccines against Crawford N, Gold M, Marshall H, Richmond P, Symposium on Pediatric ENT in São Paulo, 18- pandemic influenza. 7th Australian Influenza A/Prof Ofer Levy, Harvard Medical School, Blyth CC. Collaboration between Collaboration 20 November, 2011. (Invited Speaker) Symposium, Melbourne, October 2011. Boston, USA between University of Sydney, Children’s Hospital Westmead, Princess Margaret P Richmond, Impact influenza is having on P Richmond, Vaccinating children against Dr Donald Davidson, University of Edinburgh, Hospital, University of Western Australia, Royal the ATSI population. Influenza Specialist influenza: where to now? Roundtable Scotland, UK Children’s Hospital Melbourne, University of Group Annual Scientific Meeting, Melbourne, discussion. 7th Australian Influenza Robyn Marsh and Anne Chang, Menzies Melbourne, Women’s and Children’s Hospital, February 2011 Symposium, Melbourne, October 2011. School of Health Research, Northern Territory, Adelaide. University of Adelaide. P Richmond, Future of Paediatric influenza P Richmond, Meningococcal vaccines in use: Australia. Australian Encephalitis Study Group: Jones vaccination in Australia. Influenza Specialist what have we learned from the introduction of Heidi Smith-Vaughan and Michael Binks, C, Booy R, Elliot E, Durheim D, Marshall H, group Annual Scientific Meeting, Melbourne, meningococcal conjugate vaccines? Progress Menzies School of Health Research, Northern Dale R, Buttery J, Kesson A, Barton B, Blyth C. February 2011 towards control of meningococcal disease Territory, Australia. Collaboration between University of Sydney, NCIRS workshop, Melbourne, November 2011. P Richmond, Immunisation and Chronic Children’s Hospital Westmead, Princess Kirsty Short, University of Melbourne, Victoria, respiratory Disease: Who should we P Richmond, Impact of influenza: vaccination Margaret Hospital, University of Western Australia. immunise? Thoracic Society of Australia and in young children in Western Australia: the Australia, Royal Children’s Hospital Melbourne, New Zealand Annual Scientific Meeting, Perth, WAIVE study? 7th World Congress of the Kim Lema, Australian Institute of Marine University of Melbourne, University of WA, April 2011 World Society for Pediatric Infectious diseases, Science, Queensland, Australia. Adelaide. Melbourne, November 2011. P Richmond, Dogmas Regarding Natural Allan Cripps and Helen Massa, Griffith Febrile convulsion following influenza Vaccine Immunology of Pneumococcal Carriage: Where P Richmond, Burden of Invasive Meningococcal University, Queensland, Australia. Study Group: Blyth CC, Currie AJ, Wiertsema are we now? PneumoCarr Workshop Dogmas, Disease: Impact on Public Health. 7th World SP, Markus T, Conway N, Kirkham LAS, Fuery Phil Thompson, Lung Institute of Western Science and New Frontiers - Immunological Congress of the World Society for Pediatric A, Mascaro F, Geelhoed GC, Richmond PC Australia, Australia Determinants of Pneumococcal Carriage. Infectious diseases, Melbourne, November Armstrong PK, Dowse GK, Effler PV, Carcione Helsinki, Finland June 2011 2011. PNG Meningitis and Pneumonia Study group: D, Scully M, Weeramanthri TS. Collaboration Blyth C, Greenhill A, Kirkham LA, Lehmann D, between UWA, TICHR, PMH, CDCD (DoHWA) P Richmond, Carriage and immune responses P Richmond, Chairperson. The effect of Duke T, Tanumei J, Hwaihwanje. Collaboration to neonatal and early infant pneumococcal pneumococcal vaccines on disease worldwide: Acute lower respiratory tract infection and between PMH, UWA, TICHR and PNGIMR conjugate vaccination followed by assessing new data, estimating the impact database linkage: Moore H, Blyth CC, Effler P, pneumococcal polysaccharide vaccine booster and exploring global opportunities. 7th World Severe influenza coinfection Study group: Richmond PC, Lehmann D, de Klerk N, Smith in Papua New Guinea. PneumoCarr Workshop Congress of the World Society for Pediatric Blyth CC, Webb SAR, Kok J, Dwyer DE, van DW, Keil AD. Collaboration between UWA, Dogmas, Science and New Frontiers - Infectious diseases, Melbourne, November Hal SJ, Foo H, Ginn AN, Kesson AM, Seppelt I, TICHR, PMH, CDCD (DoHWA), PathWest Immunological Determinants of Pneumococcal 2011. Iredell JR. Collaboration between UWA, PMH, Australasian Infectious Diseases Physician Carriage. Helsinki, Finland June 2011 Royal Perth Hospital, University of Sydney, survey. Ingram P, Blyth C, Murray R, David J, Westmead Hospital, Liverpool Hospital, P Richmond, Pneumococcal vaccination for Cheng A. Collaboration between Royal Perth Children’s Hospital at Westmead Adults at High Risk for Pneumococcal Disease. Hospital, UWA, Sir Charles Gardner Hospital, Adult Pneumococcal vaccine workshop, Paediatric Active Enhanced Disease Menzies School of Health Research, Royal University of NSW, Sydney August 2011. Surveilance. Elliot E, McIntyre P, Booy R, Darwin Hospital, Alfred Hospital, Monash

114 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 University WAIVE: Dr Dale Carcione, Dr Gabriela Dixon, Dr Paul Effler (Public Health Physician), A/Prof Gary Geelhoed (Director, Emergency Dept PMH), Dr Anthony Keil (Microbiologist PMH), Dr Heath Kelly (Epidemiologist), Dr Alan Leeb (General Practitioner), Hannah Moore (Epidemiologist), Dr David Smith (Microbiologist QE11), Dr Paul Van Buynder (Public Health Physician), Simon Williams (Microbiologist QE11)

TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 115 publications

2011 Publications for annual report (236) PG, James AL, Jankovic S, Joubert BR, Karrasch disease. Hepatology. 2011;53(3):800-809. 14. Bertram C, Gottardo NG, Kees UR, S, Klopp N, Koch B, Kritchevsky SB, Launer LJ, 8. Bailey HD, Armstrong BK, De Klerk NH, Bhoola KD, Dallas P, B. Biological and Clinical Liu Y, Loehr LR, Lohman K, Loos RJF, Lumley Fritschi L, Attia J, Scott RJ, Smibert E, Milne Relevance of Neural Stem Cells in the 1. Allen KL, Byrne SM, Lampard A, Watson H, T, Al Balushi KA, Ang WQ, Barr RG, Beilby J, Pathogenesis of Childhood Medulloblastoma. Fursland A. Confirmatory factor analysis of the E. Exposure to professional pest control Blakey JD, Boban M, Boraska V, Brisman J, treatments and the risk of childhood acute In: Salvatti EK, editor. Brain Cancer, Tumor Eating Disorder Examination-Questionnaire Britton JR, Brusselle GG, Cooper C, Curjuric Targeting and Cervical Cancer. New York: Nova (EDE-Q). Eating Behaviors. 2011;12(2):143-151. lymphoblastic leukemia. International Journal I, Dahgam S, Deary IJ, Ebrahim S, Eijgelsheim of Cancer. 2011;129(7):1678-1688. Science; 2011. 75-162. 2. Allen KL, Fursland A, Raykos B, Steele A, M, Francks C, Gaysina D, Granell R, Gu X, 15. Bizzintino J, Lee WM, Laing IA, Vang F, Watson H, Byrne SM. Motivation-focused Hankinson JL, Hardy R, Harris SE, Henderson 9. Bailey HD, De Klerk NH, Fritschi L, Attia J, Daubenton JD, Armstrong BK, Milne E. Pappas T, Zhang G, Martin AC, Khoo SK, Cox Treatment for Eating Disorders: A Sequential J, Henry A, Hingorani AD, Hofman A, Holt DW, Geelhoed GC, McMinne PC, Goldblatt J, Trial of Enhanced Cognitive Behaviour Therapy PG, Hui J, Hunter ML, Imboden M, Jameson Refuelling of vehicles, the use of wood burners and the risk of acute lymphoblastic leukaemia Gern JE, Le Souëf PN. Association between with and without Preceding Motivation- KA, Kerr SM, Kolcic I, Kronenberg F, Liu JZ, human rhinovirus C and severity of acute Focused Therapy. European Eating Disorders Marchini J, McKeever T, Morris AD, Olin AC, in childhood. Paediatric and Perinatal Epidemiology. 2011;25(6):528-539. asthma in children. European Respiratory Review. 2011;online. Porteous DJ, Postma DS, Rich SS, Ring SM, Journal. 2011;37(5):1037-1042. Rivadeneira F, Rochat T, Sayer AA, Sayers I, Sly 3. Allen KL, Fursland A, Watson H, Byrne SM. 10. Bailey HD, Milne E, De Klerk NH, Fritschi PD, Smith GD, Sood A, Starr JM, Uitterlinden 16. Blair E. Rates of cerebral palsy. In: P. PC, Eating disorder diagnoses in general practice L, Attia J, Cole C, Armstrong BK. Exposure to AG, Vonk JM, Wannamethee SG, Whincup PH, editor. Cerebral Palsy - A multidisciplinary settings: Comparison with structured clinical house painting and the use of floor treatments Wijmenga C, Williams OD, Wong A, Mangino approach. Munich-Orlando: Dustri-Verlag Dr. interview and self-report questionnaires. and the risk of childhood acute lymphoblastic M, Marciante KD, McArdle WL, Meibohm B, Karl Feistle; 2011. 27-37. Journal of Mental Health. 2011;20(3):270-280. leukemia. International Journal of Cancer. Morrison AC, North KE, Omenaas E, Palmer 2011;128(10):2405-2414. 17. Blair E, Cans C, Pantedialis CP. The 4. Al-Tamimi M, Gardiner EE, Thom JY, Shen Y, LJ, Pietiläinen KH, Pin I, Polašek O, Pouta A, 11. Banerjee B, Ling KM, Sutanto EN, Musk definition of cerebral palsy. In: P. PC, editor. Cooper MN, Hankey GJ, Berndt MC, Baker RI, Psaty BM, Hartikainen AL, Rantanen T, Ripatti M, Yerkovich ST, Hopkins PMA, Stick SM, Kicic Cerebral Palsy - A Multidisciplinary Approach. Andrews RK. Soluble Glycoprotein VI Is Raised S, Rotter JI, Rudan I, Rudnicka AR, Schulz H, A, Chambers DC. 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116 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 N, Kirkham LAS, Fuery A, Mascaro F, Geelhoed G, Urbonaite B, Šipetić S, Schober E, Devoti G, women dispensed selective serotonin reuptake 41. Ehret GB, Munroe PB, Rice KM, Bochud M, GC, Richmond PC. Trivalent influenza vaccine Ionescu-Tirgoviste C, de Beaufort CE, Stoyanov inhibitors in pregnancy. Birth Defects Research Johnson AD, Chasman DI, Smith AV, Tobin MD, and febrile adverse events in australia, 2010: D, Buschard K, Radon K, Glatthaar C, Patterson Part A - Clinical and Molecular Teratology. Verwoert GC, Hwang S-J, Pihur V, Vollenweider P, Clinical features and potential mechanisms. CC. Birth order and childhood type 1 diabetes 2011;91(3):142-152. O’Reilly PF, Amin N, Bragg-Gresham JL, Teumer Vaccine. 2011;29(32):5107-5113. risk: A pooled analysis of 31 observational 35. Creaney J, Yeoman D, Musk AW, de Klerk N, A, Glazer NL, Launer L, Zhao JH, Aulchenko 22. Blyth CC, Markus TY, Effler PV, Richmond PC. studies. 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TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 119 84. Jayakumar A, Castilho TM, Park E, following receipt of seasonal influenza vaccine Lakhdar F, Mehta N, Liu Y, Devi BI, Sudhir BJ, 105. Lawrence D, Mitrou F, Zubrick SR. Goldsmith-Pestana K, Blackwell JM, McMahon- in 2009. Vaccine. 2011;29(37):6419-6426. Lund-Johansen M, Gjerris F, Cole CH, Gottardo Global research neglect of population-based Pratt D. TLR1/2 activation during Heterologous 91. King RHM, Chandler D, Lopaticki S, Huang NG. Meningiomas in children and adolescents: approaches to smoking cessation: Time for a prime-boost vaccination (DNA-MVA) enhances D, Blake J, Muddle JR, Kilpatrick T, Nourallah A meta-analysis of individual patient data. The more rigorous science of population health CD8+ T cell responses providing protection M, Miyata T, Okuda T, Carter KW, Hunter M, Lancet Oncology. 2011;12(13):1229-1239. interventions. Addiction. 2011;106(9):1549- against Leishmania (Viannia). 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120 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 112. Logie KM, Kusel MMH, Sly PD, Hall of CXCR1 and CXCR2 in susceptibility to visceral indigenous and non-Indigenous children. Journal and safety of an investigational combined GL. Exhaled breath temperature in healthy leishmaniasis in north-east India. BMC Medical of Epidemiology and Community Health. 2011. Haemophilus influenzae type B-Neisseria children is influenced by room temperature Genetics. 2011;12(1):162-169. 127. Mullin BH, Carter KW, Lewis JR, Ingley E, meningitidis serogroups C and Y-tetanus toxoid and lung volume. Pediatric Pulmonology. 120. Mehrotra S, Oommen J, Mishra A, Wilson SG, Prince RL. Significant Association conjugate vaccine. Pediatric Infectious Disease 2011;46(11):1062-1068. Sudharshan M, Tiwary P, Jamieson SE, Fakiola M, between Common Polymorphisms in the Journal. 2011;30(3):190-196. 113. 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Biochemical Journal. 2011 Mar depressive symptoms in adolescents. Depression 117. McIntyre S, Badawi N, Brown C, Blair E. Growth Characteristics in Different Trimesters. 15;434:399-413. and Anxiety. 2011;28(7):582-588. Population case-control study of cerebral palsy: Journal of Clinical Endocrinology & Metabolism 132. Noble PB, Jones RL, Needi ET, Cairncross 138. Oddy WH, Li J, Whitehouse AJO, Zubrick Neonatal predictors for low-risk term singletons. [Article]. 2011 May;96(5):E810-E815. A, Mitchell HW, James AL, McFawn PK. SR, Malacova E. Breastfeeding duration and Pediatrics. 2011;127(3):e667-e673. 125. Moore HC. Acute lower respiratory Responsiveness of the human airway in vitro academic achievement at 10 years. Pediatrics. 118. McKenzie A. Consumer stories about infections (ALRI) in Indigenous and during deep inspiration and tidal oscillation. 2011;127(1):e137-e145. labelling. Australian Prescriber. 2011;34(5):138. non-Indigenous children. 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TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 121 140. Oddy WH, Robinson M, Kendall GE, Li 147. Payne J, France K, Henley N, D’Antoine H, Wong G, Bateman ED. Global strategy for 413. J, Zubrick SR, Stanley FJ. Breastfeeding and Bartu A, O’Leary C, Elliott E, Bower C. Changes the diagnosis and management of asthma 159. Rees CS, Smith AJ, O’Sullivan PB, Kendall early child development: A prospective cohort in health professionals’ knowledge, attitudes in children 5 years and younger. Pediatric GE, Straker LM. Back and neck pain are related study. Acta Paediatrica, International Journal and practice following provision of educational Pulmonology. 2011;46(1):1-17. to mental health problems in adolescence. of Paediatrics. 2011;100(7):992-999. resources about prevention of prenatal alcohol 153. Pereira G, Nassar N, Cook A, Bower C. BMC Public Health. 2011;11. exposure and fetal alcohol spectrum disorder. 141. 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TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 123 Randomised controlled trials in cystic fibrosis: 188. Sobrin L, Green T, Sim X, Jensen RA, Tai wealthy countries. Acta Paediatrica, Australia. p. 1-8 What, when and how? European Respiratory ES, Tay WT, Wang JJ, Mitchell P, Sandholm N, International Journal of Paediatrics. 200. Sutanto EN, Kicic A, Foo CJ, Stevens Journal. 2011;37(5):991-993. Liu Y, Hietala K, Iyengar SK, Family Investigation 2011;100(1):26-28. PT, Mullane D, Knight DA, Stick SM. Innate 182. Smith AJ, O’Sullivan PB, Beales DJ, of N, Diabetes-Eye Research G, Brooks M, 192. Stanley FJ, Bower C. Commentary: inflammatory responses of pediatric cystic De Klerk N, Straker LM. 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124 • TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 Differences in innate immune function between 214. Whitehouse AJO, Hickey M, Ronald A. KJ, Mowe EN, Bowman JM, Jacoby P, Francis R, statement on Hip Surveillance for Children with allergic and nonallergic children: New insights Are Autistic traits in the general population Vijayasekaran S, Coates HL, Riley TV, Richmond Cerebral Palsy: Australian Standards of Care. into immune ontogeny. Journal of Allergy and stable across development? PLoS ONE. P. Predominance of nontypeable haemophilus Journal of pediatric rehabilitation medicine. Clinical Immunology. 2011;127(2):470-478.e1. 2011;6(8):e23029.1-8. influenzae in children with otitis media following 2011 2011-Jan-1;4(3):183-95. 208. Urbanowicz A, Downs J, Bebbington A, 215. Whitehouse AJO, Hickey M, Stanley introduction of a 3+0 pneumococcal conjugate 229. Yang X, McLaughlin RA, Lorenser D, Jacoby P, Girdler S, Leonard H. Use of equipment FJ, Newnham JP, Pennell CE. 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TELETHON INSTITUTE FOR CHILD HEALTH RESEARCH 2011 • 125 deficits in lung function and alters lung structure. American Journal of Respiratory and Critical Care Medicine. 2011;183(10):1336- 1343. 234. Zubrick SR, D’Antoine H, & WAACHS team. The Mental Health of Australian Aboriginal Children and Adolescents: Current Status and Future Prospects. In: Fitzgerald HE, Puura K, Tomlinson M, Paul C, editors. International Perspectives on Children and Mental Health. Volume 2 Prevention and Treatment. California: Praeger; 2011. 155-183. 235. Zubrick SR, Lawrence D, Mitrou F, Christensen D, Taylor CL. Early mental health morbidity and later smoking at age 17 years. Psychological Medicine. 2011 [cited 2011];FirstView:1-13. 236. Zubrick SR, Mitrou F, Lawrence D, Silburn SR. Maternal death and the onward psychosocial circumstances of Australian Aboriginal children and young people. Psychological Medicine. 2011;41(9):1971- 1980.

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The 2011 Annual Report was produced by the Public Relations Office of the Telethon Institute for Child Health Research. Published in May 2012. Project management, copywriting/editing and design - Tammy Gibbs. Copywriting/editing - Elizabeth Chester, Carole Kerr, Ebony Frost, Lesley Yuen. Children and researcher photography - Tony McDonough and Annaliese Frank (www.rawimage.com.au). Printing - Daniels Printing Craftsmen (www.danielspc.com.au). We wish to acknowledge the staff of the Telethon Institute for Child Health Research for their contributions to the 2011 Annual Report.