Melbourne Health Research Week 2012 24 – 31 May Melbourne Health Research Week 2012
Research Week is one of the highlights of the Melbourne Health Calendar. It provides a focus on research, where all members of our staff and the community can reflect on the value of research, and celebrate the advances in medical science. The week long programme varies in format from a formal symposium, plenary talks, and interactive research education. Light relief comes in the form of the Annual Great Research Debate. A new innovation this year is the Community engagement booth in the hospital foyer, to share research with people visiting the hospital.
I would like to thank the Research Week Committee who comprise of people from all different RMH departments and include members from Ludwig Institute for Cancer Research; The Walter & Eliza Hall Institute and The University of Melbourne. This hard working team have managed to pull together a wonderful programme.
Thank you to –
Prof Danny Liew Dr Angela Watt A/Prof Marie Gerdtz Prof Nick Santamaria Prof Terry O’Brien Dr Clare Scott Ms Michelle Eunson Ms Catherine Lander Ms Morag Morrison Ms Carol Jewell Dr Nadia Warner Dr Matthias Ernst Ms Jessica Turner Ms Louise Berns Dr Nitya Jani
In addition, the efforts of those involved in selecting the suitable abstracts and in the adjudication of the Awards and those coordinating and chairing sessions during Research Week are greatly appreciated.
Melbourne Health Research Week is successful because of the generous contributions of time, energy and expertise by so many people – thank you.
Professor Ingrid Winship Executive Director of Research
Research Week 2012 24 – 31 May 2012 Page 1
DAY 1 – Thursday 24 May 2012 Opening Ceremony
1.00 pm – 1.45 pm, Charles La Trobe Lecture Theatre
Welcome and opening ceremony of Melbourne Health Research Week with the opening plenary: 1. Professor Doug Hilton, Director Walter and Eliza Hall Research Institute "Melbourne Health: The Heart of Australia's Premier Medical Research Precinct" 2. Dr Peter Revill, Dept of Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne Health “Increased abundance of hepatitis B virus defective DNA in serum of patients with hepatocellular carcinoma”
DAY 2 – Friday 25 May 2012 Research Symposium
9.15 am – 10.15 am, FIRST CONCURRENT RESEARCH SESSIONS Cancer Research Emergency and Critical Care Seminar Room 1 (Chair: Prof Mark Rosenthal) Seminar Room 2 (Chair: Dr Jonathan Knott) 3. Jeffrey Kam - A 5-year analysis of 7. Kate Fetterplace - Improving the Practice magnetic resonance imaging as a screening tool in of Nutrition Therapy in the Critically Ill: women at hereditary risk of breast cancer International Nutrition Survey 2011 4. Elizabeth Vincan - Frizzled7 functions as a 8. Wayne Hoskins - A ten year analysis of Wnt receptor in intestinal epithelium stem cells splenic injury and trauma management at a rural hospital 5. Matthew Hong - A Program to Obtain Metastatic Tissue Samples from Prostate Cancer 9. Michael Gilbertson - Urgent vitamin K Patients antagonist reversal and outcomes - implications for novel anticoagulants 6. Stephanie Amiridis - Targeting Dynamin to Treat Malignant Brain Tumours 10. Rebbecca Waite - Developing and implementing a quality improvement framework for emergency department triage
10.30 am – 11.30 am, SECOND CONCURRENT RESEARCH SESSIONS Cardio-Respiratory Musculoskeletal & Seminar Room 1 (Chair: A/Prof Abe Rubinfeld) Gastro-intestinal Research 11. Elsa Gladigau - Prevalence of Seminar Room 2 (Chair: A/Prof Geoff Hebbard) Cardiovascular Risk Factors in Patients with Serious Mental Illness Attending Psychiatric 15. John Moi - The prevalence of gout in a Rehabilitation Services in Melbourne's Inner-West large tertiary hospital and the impact of in- hospital attacks of acute gout on patient outcomes 12. John Wentworth - Body mass index and health resource utilization - a nested case- correlates with ischemic heart disease and control study albuminuria in long-standing type 2 diabetes 16. Gene Ngian - Arterial stiffness is increased 13. Sky Chew - Moderate microvascular in systemic sclerosis: a cross-sectional comparison retinopathy predicts future cardiac events in a with matched controls population of patients with chronic obstructive pulmonary disease 17. Ilana Ackerman - The impact of severe hip and knee joint disease on work status and health 14. Peter Wallbridge - The utility of serial care utilisation and costs: Results from a national venous blood gases to assess ventilatory status in Australian survey patients undergoing flexible bronchoscopy. 18. Christopher Leung - Breaking the biopsy barrier in Barrett's: The use of Confocal Endomicroscopy to target oesophageal biopsies
Research Week 2012 24 – 31 May 2012 Page 2 Lunch and Poster Viewing 12 – 12.45 pm Function and Convention Centre, Ground Floor, Royal Melbourne Hospital
This year’s Melbourne Health Research Week will display 84 posters showcasing research under the themes of • Aged Care; • Blood; • Cancer; • Cardio-respiratory; • Emergency/Critical Care; • Endocrinology, Immunology & Allergy; • Gastro-intestinal; • Genetics; • Infectious Diseases; • Musculoskeletal; • Neurosciences; • Quality of Care; • Rehabilitation and Surgery.
Presenters will be on-hand to answer your questions.
The Great Debate
1.00 pm – 2.00 pm, Charles La Trobe Lecture Theatre “Ethics Schmethics” The requirements for ethical approval of research in 2012 are way over the top The need for diligent and rigorous ethical review of human research is indisputable. Everyone involved in human research has a responsibility to facilitate ethically good research that protects the rights and well being of the people who place their trust in the researchers and volunteer to participate in that research. We have come a long way since the world first cried out for ethical oversight of human research following World War 2 and the horrific Nazi war experiments, the notorious human radiation experiments conducted by the US army in the 1940s, the Thalidomide disaster of the 1950s and the US Syphilis Study of 1972, to name a few. Ethical milestones such as the Nuremberg Code of 1947 and the Declaration of Helsinki, which was first issued in 1964, were created in response to demands from people around the world for research to be regulated and researchers to be held accountable and to ensure that any research that was conducted was ethical and worthwhile. But have we now gone too far? In Australia, we are bound by the National Statement on Ethical Conduct in Human Research as well as no less than six other codes or regulations, a raft of legislation (both Commonwealth and State) governing privacy, guardianship and consent, genetics, radiation, ART and IVF, to name a few. On top of all the Australian laws and guidelines, we also have countless international guidelines and codes. And on top of all the ethical and good clinical practice guidelines, we now have a new “buzz” term to contend with - research governance! Institutions conducting research and the bodies that they are accountable to, their lawyers and the various levels of governments all resolved that research projects had to be governed! Researchers suddenly were faced with the challenges of finance and budgets, contract law, indemnities and insurance, joint appointments and rules of collaboration, clinical trials registries, version control of just about anything one can think of, and the list goes on… Is this modern day regulation of research truly a reassuring safety net or has it become a straight jacket of the most stifling proportions? Or perhaps this regulation is the life raft that has saved research, protecting it from greenies and scientologists and other crazed crusaders who view modern medicine as the greatest evil of our time? The Melbourne Health Research Week Committee has called together some of the greatest minds of our institution to use their collective intellect to tackle this most challenging issue in the form of a Great Debate.
Research Week 2012 24 – 31 May 2012 Page 3 Master of Ceremonies (MC) Professor Ingrid Winship, Executive Director of Research, Melbourne Health
The proceedings will be presided over by this panel of distinguished judges: Ms Christine Fitzherbert, Executive Director HR & Workplace Development, Melbourne Health. Ms Genevieve Juj, Director Allied Health, Melbourne Health (to be confirmed). Professor Bruce Mann, Director Cancer and Infection Medicine, Melbourne Health.
Team for the Affirmative – “Team Get me out of this regulatory straight-jacket” Professor Peter Morley Ms Sharon McGowan, Executive Director Communications and Community Relations, Melbourne Health Mr Paul Anderson, MH Urologist and member of the MH HREC
Team for the Negative – “Team We must proceed with every possible precaution” Dr Jayesh Desai, Oncologist, Melbourne Health. Ms Marian Lieschke, Nurse Unit Manager, Cancer Clinical Trials, Melbourne Health. Ms Sarah Bascomb, Cancer Trials Australia
Research Symposium 2.30 pm – 4.00 pm, THIRD CONCURRENT RESEARCH SESSIONS Infectious Diseases Mind and Brain Seminar Room 1 (Chair: A/Prof Damon Eisen) Seminar Room 2 (Chair: Prof Terry O’Brien) 19. Phillipe Boeuf - Placental adhesion of 24. Iwan Bennett - Perfusion MRI predicts malaria-infected erythrocytes: more than just levels of circulating endothelial progenitor cells in VAR2CSA/CSA interaction? glioblastoma multiforme 20. Shamista Selverajah - The novel histone 25. Sinnatamby Sujeevan- Investigating the variant H2Bv in the malaria parasite P. falciparum role of epidermal growth factor system in cooperates with H2A.Z in gene promoter clozapine treated subjects with schizophrenia nucleosomes 26. Simon Jones - Medical Emergencies in 21. Sook Kwan (Leah) Leang - Influenza Psychiatric Inpatient Units Antiviral Resistance in the Asia-Pacific region 27. Anneke van der Walt - Optic nerve axial during 2011 diffusivity predicts axonal loss but not clinical 22. Jeff Butler - Assessing the fitness of drug- outcome after acute demyelinating optic neuritis. resistant influenza viruses from a cluster of 28. Nigel Jones - Targeting community cases in Newcastle, NSW, in 2011 hyperphosphorylated tau with sodium selenate 23. Teagan Guarnaccia - Antigenic drift of the suppresses seizures in rodent models A(H1N1)pdm virus in the ferret model of vaccination
Research Week 2012 24 – 31 May 2012 Page 4 DAY 3 – Saturday 26 May 2012 Surgical Research Forum
Chair: Dr Anita Skandarajah 8.30 am – 9.30 am, Ewing Lecture Theatre, Level 5, Clinical Sciences Building
29. Wayne Hoskins - A ten year 32. Matthew Hong - A Program to Obtain analysis of splenic injury and trauma Metastatic Tissue Samples from Prostate management at a rural hospital Cancer Patients
33. Simon Liubinas - Radiological and 30. Iwan Bennett - Perfusion MRI molecular features correlating with seizures in predicts levels of circulating endothelial patients with supratentorial gliomas progenitor cells in glioblastoma multiforme
31. Andrew Nichols - Functional MRI of the visual pathway in patients with brain tumours causing optic chiasm compression
DAY 4 – Monday 28 May 2012 Clinical Research Skills Workshop “How to design clinical studies (and facilitate rapid HREC approval)”
9.30 am – 12.30 pm, Seminar Room 1, RMH Function & Convention Centre Hosted by the Melbourne Epicentre
Many research projects submitted for HREC approval are not well-designed for the research questions being posed. The main purpose of this interactive workshop is to introduce researchers to key concepts in study design and execution. Topics covered will be: study design, sample size calculation and data collection, management and analysis.
DAY 5 – Tuesday 29 May 2012 Clinical Research Skills Workshop “Data processing and simple analyses using Excel”
9.30 am – 12.30 pm, Seminar Room 1, RMH Function & Convention Centre Hosted by the Melbourne Epicentre
The major hindrance to data analysis is poor data quality. In this session, we will demonstrate simple techniques for accurate data collection and cleaning. We also will show how you can undertake simple statistical analyses in Microsoft Excel, and generate graphs. You’ll be surprised by what can be done in Excel!
Research Week 2012 24 – 31 May 2012 Page 5 DAY 6 – Wednesday 30 May 2012 Allied Health / Nursing Forum “Activating Accessible Pathways to Clinical and Translational Research in Nursing and Allied Health”
1.00 pm – 3.00 pm, Seminar Room 1, RMH Function & Convention Centre
This will be an interactive workshop led by Prof Danny Liew (Director, Melbourne EpiCentre) and Prof Ingrid Winship (Executive Director, Research). The workshop will include a representative group of novice clinician researchers, seasoned researchers, Nursing and Allied Health Managers, academics and other relevant stakeholders.
The aim is to identify the main challenges we face in undertaking research, especially in a busy clinical setting, and identify ways in which these can be overcome in a collaborative manner.
DAY 7 – Thursday 31 May 2012 RMH Academic Research Centre Symposium “Outcomes Research” 9.30 am – 12.30 pm, Charles La Trobe Lecture Theatre This year, for the first time, sees the inclusion of the RMH Academic Research Centre’s research symposium. Prof Graham Brown from the Nossal Institute for Global Health will present the keynote lecture. This will be followed by sessions in the fields of Radiology; Psychiatry; Surgery and Medicine.
Closing Ceremony Chair: Professor Ingrid Winship 1.00 pm – 2.00 pm, Charles La Trobe Lecture Theatre Final plenary presentation by Dr Jonathan Knott and the annual awarding of the Research Week prizes including best oral presenters, poster presentations and we announce the winner of this year’s Cleveland Young Investigator Award.
40. Jonathan Knott - Intravenous droperidol or olanzapine as adjuncts to midazolam for the acutely agitated patient: a multi-centre, randomised, double-blind, placebo- controlled clinical trial KNOTT J, Chan E W , Taylor D, Kong D, Castle D and Phillips G Emergency Departments of the Austin hospital, Royal Melbourne hospital and St Vincent's Health
Research Week 2012 24 – 31 May 2012 Page 6
ORAL PRESENTATIONS
1. Professor Doug Hilton, Director Walter and Eliza Hall Research Institute
2. Peter Revill Increased abundance of hepatitis B virus defective DNA in serum of patients with hepatocellular carcinoma Bayliss J1,2, Sozzi V1, Littlejohn M1, Preiss S1, Locarnini S1, REVILL P1 1Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria 3051 2Department of Medicine, Monash University, Alfred Hospital, Melbourne, Victoria 3004, Australia Background. The mechanisms through which chronic hepatitis B virus (HBV) causes hepatocellular carcinoma (HCC) are unknown. Recent evidence suggests that splicing of the HBV pregenome, resulting in the generation of spliced HBV transcripts including Sp1, may facilitate viral integration, in turn promoting tumourigenesis. This study aimed to compare the relative proportions of Sp1 DNA in patients with and without HCC. Methods. Wild type (wt) and Sp1 HBV DNA loads were determined by quantitative real time PCR in the serum of 220 patients with chronic HBV monoinfection. This included 29 patients with diagnosis of primary HCC. The ratio of Sp1/wt HBV DNA was the preferred measure to allow for use of total HBV DNA as a loading and purification control. In all cases quantification above 30 copies of wt HBV DNA per well was accepted as valid. Results. The ratio of Sp1/wt HBV DNA ranged from 0% to 26%. The relative abundance of HBV Sp1 was significantly higher in the serum of patients with HCC as compared to those with chronic HBV infection alone, independent of wt HBV DNA levels (5.19% ± 0.94% HCC. vs 3.03% ± 0.04% chronic HBV; p= 0.002). This result was also reflected in the median Sp1/wt HBV ratios with HCC patients having 2.86% (0- 21%) and chronic HBV alone having 0.66% (0- 26%). Conclusions. The results of this study demonstrate that pregenomic splicing of the HBV genome may contribute to the development of HCC. Further studies delineating the mechanisms involved are currently underway.
3. Jeffrey Kam A 5-year analysis of magnetic resonance imaging as a screening tool in women at hereditary risk of breast cancer Kam JKP, Naidu P, Rose AK, Mann GB The Royal Melbourne Hospital Background: Women at very high risk of breast cancer due to mutations in breast cancer susceptibility genes or a strong family history are recommended to undertake enhanced surveillance with annual Magnetic resonance imaging (MRI) in addition to mammography. Adding MRI to mammographic screening increases detection sensitivity but reduces specificity. MRI surveillance of high risk women began at the Royal Melbourne Hospital in 2007. We aimed to review the performance of breast MRI as a screening modality over its first 5 years. Methods: Retrospective review using prospectively collected data from a consecutive series of women at high-risk of developing breast cancer undergoing surveillance MRI at the Royal Melbourne Hospital between 2007 and 2011. Results: 223 women had at least one screening MRI from January 2007 to November 2011. The number of women undergoing screening increased each year, from 5 in 2007 to 126 in 2011. The mean age of the cohort was 42 years old. 71 (31.8%) were confirmed genetic mutation carriers. The remaining 152 (68.2%) women were classified as high risk based on family history, without a confirmed genetic mutation. 340 screening MRI studies performed over 5 years. From these screens, 69 patients (20.3%) were recalled for further assessment. There was a significant reduction in the recall rate throughout the study for first time screens, from 50% (17/34) in 2008 to 14% (9/54) in 2011 (p=0.004). 271 of 340 (79.7%) episodes of imaging resulted in an all-clear result. Biopsy was performed in 39/59 of those attending the recall. The overall biopsy rate was 39 in 340 screens (11.5%). 4 in 340 (1.2%) screening MRIs identified a cancer. Three (75.0%) were in confirmed BRCA1/BRCA2 mutation carriers, and 1 (25%) was unconfirmed. All 4 were identified as suspicious on MRI, with 2 having benign mammography. The cancer detection rate of MRI was 11.76 per 1000 screens. The PPV was 7.0% for all rounds, 6.7% for first time screens and 7.1% for subsequent screens. Conclusion: Breast MRI as a screening modality for malignant lesions in women with high hereditary risk is valuable. The predictive value improved with more experience
Research Week 2012 24 – 31 May 2012 Page 7 4. Elizabeth Vincan Frizzled7 functions as a Wnt receptor in intestinal epithelium stem cells. VINCAN E, Amin N, Flanagan DJ, Phesse TJ, Malaterre J, Mao CD, Dworkin S, Nowell CJ, Ramsay RG, Ernst MRW, Barker N, Clevers H. University of Melbourne, Victorian Infectious Diseases Reference Laboratory, Ludwig Institute for Cancer Research, Peter McCallum Cancer Centre, University of Kentucky, KY, USA, Institute of Medical Biology, Immunos, Singapore and Hubrecht Institute of Developmental Biology and Stem Cell Research, Utrecht, The Netherlands The intestinal epithelium is a self-renewing tissue with a high turnover rate that is maintained by intestinal stem cells which reside at the base of glads (called crypts) in the epithelium. LGR5, a Wnt/β-catenin target gene, specifically marks the long-lived crypt based columnar (CBC) stem cells in the mouse and human intestine. Wnt/β-catenin signalling is crucial for normal CBC stem cell function, while aberrant activation of Wnt/β-catenin signalling in the CBC stem cells leads to the initiation of colorectal cancer. More specifically, Wnt3 signalling is necessary for the maintenance and function of CBC; intriguingly, this critical Wnt3 signal is provided by flanking Paneth cells. The Wnt3 signal emanating from the Paneth cells is augmented by R-spondin signalling through LGR. R-spondins are incorporated into complexes that contain LRP, LGR and FZD; this complex facilitates FZD-coupled Wnt3 signalling. Although FZD is involved in transmitting the Wnt3 signal in intestinal stem cells, the function of FZD has not been investigated in the intestine. Of the ten mammalian FZD family members, one FZD, Fz7, is frequently up regulated in stem cells and cancers from divers tissues. Here we show that in the intestinal epithelium, expression of Fzd7 is confined to LGR5+ CBC stem cells. Crypt cells isolated from the small intestine of LGR5-EGFP-Cre mice were sorted by FACS based on EGFP expression. Quantitative RT-PCR performed on mRNA extracted from EGFP+ and EGFP negative cells showed Fzd7 was primarily expressed by the EGFP+ (LGR5+) cells. To investigate the function of Fzd7 in the intestinal crypt, we generated floxed Fzd7 mice and crossed them to the AhCre mouse to allow inducible deletion of Fzd7 in the intestinal epithelium. We observed a transient loss of CBC stem cells from the intestinal. Linage tracing experiments using the LacZ reporter were consistent with a loss of long lived CBC stem cells from the crypts of induced Fzd7fl/fl;AhCre;LacZ mice. To further investigate the function of Fzd7, we established organoid cultures from crypts isolated from the proximal small intestine of Fzd7fl/fl;AhCre.LacZ mice. After Cre induction (Fzd7 deletion), the crypts of the organoids atrophy and die. Moreover, the Cre-induced cultures fail to regenerate organoids upon passage. Activation of the Wnt pathway downstream of the receptor rescues this phenotype. Co- immunoprecipitation experiments of epitope tagged Fzd7 and Wnt3 proteins in HEK293 cells confirmed interaction between Fzd7 and Wnt3. Taken together; our data indicate Fzd7 transmits the critical Wnt3 signal in intestinal stem cells
5. Matthew Hong A Program to Obtain Metastatic Tissue Samples from Prostate Cancer Patients HONG MKH, Pedersen J*, Sapre N, Costello AJ, Phal P+, Corcoran NM, Hovens CM Division of Urology, Department of Surgery, University of Melbourne, Royal Melbourne Hospital and the Australian Prostate Cancer Research Centre, VIC * Tissupath Specialist Pathology, Mount Waverley, VIC + Department of Radiology, Royal Melbourne Hospital Introduction To explore the biology of cancer metastases and their response to treatment, a molecular comparison between metastasis and matched primary tumour from the same patient is highly desirable. Studies of cancer metastases have commonly sourced tissues from rapid autopsy programs, but the logistical demands by these programs are prohibitive and response to treatment cannot be determined through serial sampling. We aimed to establish the feasibility of a program to procure fresh frozen samples of distant metastases from live patients who have previously undergone radical prostatectomy for prostate cancer. Methods Between 2006 and 2011 over 700 patients underwent radical prostatectomy for prostate cancer at our associated institutions, and had samples of their primary tumours archived for research. Several of these patients have subsequently developed metastatic disease. Ethical approval was obtained for a program to procure tissue samples for research. Patients with radiologically confirmed osseous metastases were invited to donate tissue. Under sedation, patients underwent image-guided biopsy of metastases with ultrasound or computed tomography as appropriate. Tissue samples were flash frozen then stored in liquid nitrogen. Results In five months, four patients had prostate cancer metastases sampled with no complications. Vertebral metastases were sampled in two patients, whilst scapular, sacral, and iliac crest metastases were obtained between the other two patients. One patient has undergone serial metastasis sampling: before and after the commencement of hormonal therapy. Conclusions The procurement of cancer metastasis samples from live patients in a tissuebanking program for research is feasible. This is a valuable tissue resource for research into late stage cancer.
Research Week 2012 24 – 31 May 2012 Page 8 6. Stephanie Amiridis Targeting Dynamin to Treat Malignant Brain Tumours Lau H*, AMIRIDIS S*, D’Abaco G M., Kountouri N, O’Brien T J., Robinson P, McCluskey A, Kaye A H., Drummond K, Morokoff A, Jones N, Chircop M. *Joint first author University of Melbourne, Royal Melbourne Hospital, University of Newcastle, Children's Medical Research Institute Brain tumours are one of most lethal and difficult to treat forms of cancer. In the case of the most aggressive form of brain cancer, glioblastoma multiforme (GBM) the median survival rate after surgical resection and therapy is only 40-60 weeks. Recently, we have investigated the potential of the intracellular brain protein, dynamin II, as a novel target for therapy of GBM. Dynamin II is a protein which is involved in membrane abscission - the final stage of cytokinesis which separates dividing cells into two daughter cells. A small molecule inhibitor of this protein, dynole 34-2, halts this process which causes these cells to remain multinucleated and results in targetted apoptosis. We employed both in vitro and in vivo experiments to determine anti-cancer effects of dynole 34-2. Firstly, we have assessed cell growth using the MTT assay, on a mouse glioma cell line (SMA560) and two human glioma cell lines (u87 and u251) after treatment with dynole 34-2. The results showed a marked inhibition of growth in all cells lines when compared to the non-treated, with 100µM dose resulting in an inhibition of 47.7% (± 0.63), 76.38% (± 4.12) and 61.48% (± 1.35) in SMA560, U87 and U251 cells respectively. We then performed the LDH cytotoxicity assay on two glioma stem cell (GSC) lines following a 100µM dose and found between 54% and 64% cell death as compared to the non-treated cells. GSC are a minority of cells within a GBM tumour, are resistant to standard chemo/radio therapy, and are thought to be the cause of recurrent tumours. Following this, we examined the in vivo effect of dynamin inhibitors in a model of mouse GBM (anti- tumour effect). In this model, SMA560 cells are injected into the amygdala of mice and following a recovery period, the mice were treated with either dynole 34-2 or vehicle twice daily. After 10 days, the tumour volumes were analysed. The results showed that mice treated with 60mg/kg twice daily of dynole 34-2 had significantly reduced tumour volumes as compared to the vehicle treated mice. This data suggests that the dynamin inhibitor, dynole 34-2, induces cell death in glioma cell lines and glioma stem cells, and provides proof of concept for dynamin II inhibition as an effective novel target for the treatment of GBM.
7. Kate Fetterplace Improving the Practice of Nutrition Therapy in the Critically Ill: International Nutrition Survey 2011 FETTERPLACE K, Royal Melbourne Hospital (RMH), Clinical Nutrition Department Background: In 2011 the ICU at RMH participated in the international nutrition survey, which is part of ongoing research activities at the Clinical Evaluation Research Unit (CERU) at Kingston General Hospital in Canada, that aims to improve the practice of nutrition therapy in the critical care setting. Nutrition therapy can prevent complications associated with malnutrition and when used appropriately has a positive influence on clinical outcomes including length of stay, morbidity and mortality. Making decisions regarding the most effective and safe nutrition strategy can be challenging. The Canadian Critical Care Nutrition Clinical Practice Guidelines published in 2003 and updated in 2009 sought to improve nutrition practices in ICUs across Canada and worldwide by providing 17 recommendations to assist health practitioners to select and deliver the most appropriate nutrition therapy. Methods: This study involves a period prevalence survey of nutrition therapies in critically ill patients in ICUs across the world. On 11 May 2011 data collection commenced, this included hospital and ICU characteristics, patient demographics and APACHE II score. Data on nutrition practices such as route of nutrition, kilocalorie and protein levels prescribed and received, feeding interruptions, blood sugars and insulin were collected on 20 consecutive patients on a daily basis from ICU admission, for a maximum of 12 days or until death or discharge. Data on clinical outcomes were collected 60 days after admission. Results: RMH was one of 183 ICUs who participated. We received an honorable mention for the Best of the Best award for achieving results in line with best practice guidelines. By day 6 patients received 100% of prescribed energy, which was 20% more than sister sites. On average patients received 77% of prescribed calories, compared to 66% for sister sites. 52% of patients were fed within 24hours and 31% of patients were fed between 24-48hrs. The median time of feeding interruptions was 5hrs compared to 6hrs for sister sites. On no occasions were small bowel feeding tubes trialled before changing to parenteral nutrition at RMH. Conclusion: RMH has achieved good compliance with the Canadian best practice guidelines and compared to sister sites and on average we achieved greater adequacy of nutrition support. However in order to achieve the best of the best we need to improve on time to initiate feeding, achieving nutritional adequacy sooner, decreasing the length of time of feeding interruptions and trial small bowel feeding before moving to parenteral nutrition.
8. Wayne Hoskins A ten year analysis of splenic injury and trauma management at a rural hospital HOSKINS W, Jacob A, Wijeratne S, Campbell I, Taylor P
Research Week 2012 24 – 31 May 2012 Page 9 The Royal Melbourne Hospital and Wimmera Health Care Group: Horsham Campus Background: There is paucity of research documenting the management of splenic injury in rural Australia. No data exists for Rural, Remote and Metroploitan Area (RRMA) 4 locations. Methods: A retrospective review of prospectively collected data for patients coded with injury of spleen or excision procedure on spleen, at Wimmera Health Care Group (WHCG): Horsham Campus, a RRMA 4, Level 3 trauma hospital between January 2000 and July 2011. Records were additionally sought from General Practitioner run transfer hospitals in the Wimmera region. Demographic details, method of presentation, mechanism of injury, injury severity, concurrent injuries, time to theatre, ASA score, operative details, complications, management and length of stay were recorded. A qualitative assessment of trauma management in the Wimmera Region was also performed. Results: Nineteen patients were included (mean age 27.8, range 8-54), 74% were from towns surrounding Horsham. Most injuries were due to sporting trauma / falls (53%) and MVA’s (37%). One patient died in theatre from massive trauma. Eleven patients were managed non-operatively. Seven patients had splenectomy performed. Four of these had delay in CT scanning, delay to theatre and suffered major post-operative complication. The age (mean 39.9 vs. 20.8) and Injury Severity Score (ISS) (mean 21.9 vs. 13.8) of patients requiring splenectomy was higher than those managed non-operatively. Six of the splenic injury admissions (32%) were transferred from surrounding Level 4-5 trauma, RRMA 5 hospitals. All of these patients met trauma call or alert criteria at the intial hospital of presentation with four having an ISS >15. Despite this, there was an approximate four hour delay in transfer of these patients, with transfer occurring when further clinical deterioration occurred. Conclusions: Although splenic injury is uncommon in the Wimmera region, improved triaging is required, with early transfer of unstable patients and high energy trauma mechanisms. A trauma call or trauma alert should be considered a trauma team activation and result in early transfer to a Level 3 trauma hospital at a minimum. These changes have the potential for improvement on a public health level. Early transfer to a Level 1 trauma centre for spleen preserving procedures should also be considered if the patient is stable.
9. Michael Gilbertson Urgent vitamin K antagonist reversal and outcomes - implications for novel anticoagulants. Michael GILBERTSON, Caitlin Cheshire and Huy Tran. Department of diagnostic haematology, The Royal Melbourne Hospital (MG, CC, HT); Centre for Blood Diseases, Monash University/Alfred Hospital (HT) INTRODUCTION: Many patients present to our institution requiring urgent reversal of systemic anticoagulation with warfarin sodium due to either bleeding complications or requiring urgent invasive procedures. AIMS: To determine the INR at which Prothrombin complex concentrates (PCC) were administered in acutely bleeding patients and in patients requiring prophylaxis. To determine the likely impact of the use of Direct thrombin inhibitors (DTI) rather than Vitamin K antagonists (VKA) on our patient population in respect to urgent reversal of oral anticoagulation. DESIGN: Single centre retrospective audit. METHODS: Data extraction of pathology laboratory system for two year period, with correlation with medical record coding database. Demographic data, indication for anticoagulation, mechanism of bleeding event, initial haematological parameters including International normalised ratio (INR), presence of acute or chronic renal failure, blood product use and 30 day mortality were recorded. RESULTS: 393 evaluable patients received 433 Prothrombinex-VF doses at our institution over a two year period. The median age was 74.2 years (range 15.5 to 99). Atrial fibrillation was the most common indication for anticoagulation (65%). Acute renal failure (eGFR <60mL/min) was present in 43% of patients at the time of administration of Prothrombinex-VF. A total of 212 patients (53%, 232 infusions) received Prothrombinex-VF for acute bleeding events. Intracranial bleeding was the most common bleeding site (43.5%). Spontaneous bleeding was the most common mechanism for bleeding events (63.5%). According to indication for anticoagulation in this group at the time of Prothrombinex-VF administration, most patients had a therapeutic or sub-therapeutic INR (sub-therapeutic 16.8%, therapeutic 40.5%, supra-therapeutic 42.7%). There was a trend towards higher red cell usage in the bleeding patients with supra-therapeutic INRs, but no statistically significant difference in 30 day mortality between the therapeutic and supra-therapeutic INRs. CONCLUSION: The majority of patients at our institution receive Prothrombinex-VF for therapeutic or sub- therapeutic INRs. A significant number of these patients have acute renal failure which would prolong the anticoagulant effects of DTIs. There is no difference in 30 day mortality in acutely bleeding patients stratified by the INR at time of PCC administration.
10. Rebbecca Waite Developing and implementing a quality improvement framework for emergency department triage. WAITE R, GERDTZ M F, Virtue, E, Vassiliou T, Garbutt B, Beardsmore M and McGurgan C The Royal Melbourne Hospital, The University of Melbourne BACKGROUND: The Australasian Triage Scale was adopted for standard use across Australian and New Zealand in the early 1990s. Clinical Guidelines and training programs have been implemented optimise the Research Week 2012 24 – 31 May 2012 Page 10 reliability of the scale. Currently there is no established quality improvement method for evaluating triage processes and outcomes at a hospital level. OBJECTIVE: To develop and evaluate a sustainable method for monitoring quality of triage processes and outcomes in one metropolitan emergency and trauma centre. METHODS: We used a pre-posttest design to measure the effect of an evidence-informed intervention on the quality of triage documentation. At three monthly intervals, (Baseline, Phase One and Phase Two) we audited a consecutive sample of one month of triage assessments to assess documentation rates and guideline adherence. In the first stage of the intervention audit results were used to make changes to the electronic interface utilized by triage nurses to record their assessments (Ascribe Symphony). In the second stage of the intervention feedback was given to triage nurses on their baseline documentation rates. A targeted 45 minute educational program for triage nurses was then developed and delivered to promote application of clinical criteria included in the national triage guideline. Data was downloaded from the electronic system for analysis and checked in Excel 2003 (Microsoft Corporation Redmond USA). Differences in documentation rates pre and posttest were assessed using a two proportion z-test. FINDINGS: The intervention occurred from March to December 2011. We audited a total of 15035 visits (15035/44216, 34%). There was a significant increase in the proportion of episodes of triage where any vital signs were documented (32.40% pre-test and 60.4% posttest, P<0.00). Rates of documentation for respiratory rate and heart rate and conscious state also increased (18.10% pre-test to 38.64% posttest, P<0.00; and 21.52% pre-test to 43.38% posttest P<0.00). CONCLUSIONS: A continued process for monitoring and improving rates of documentation was achieved over a 9 month period. The changes made to the electronic system for recording triage assessment and informing staff of baseline rates of documentation at triage accounted for most of the improvement that was observed. A sustained method for optimising documentation rates at the study site was established.
11. Elsa Gladigau Prevalence of Cardiovascular Risk Factors in Patients with Serious Mental Illness Attending Psychiatric Rehabilitation Services in Melbourne’s Inner-West GLADIGAU EL, Mee JB, Dawson L, Jones SG. Inner West Adult Mental Health Service and Royal Melbourne Hospital BACKGROUND: The life expectancy of people with a serious mental illness in Australia is 10-25 years less than the general population. The primary cause of premature mortality is cardiovascular disease. It has been reported that people with serious mental illness have higher rates of cardiovascular risk factors. This study measured the prevalence of major cardiovascular risk factors in a group of patients with serious mental illness. METHODS: An audit was conducted on patients who receive care from the Inner West Mobile Support and Treatment Team (MSTT) and Community Care Unit (CCU). The smoking status, body mass index (BMI), blood pressure (BP), diabetic status and lipid profile were collected and compared to the general Australian adult population, as reported by the Australian Bureau of Statistics and the Australian Institute for Health and Welfare. RESULTS: Complete data was available for 54 of a total of 66 current patients. All patients had a diagnosis of serious mental illness (a majority had schizophrenia). The mean age was 39 (range 20 – 56). Most patients (66.7%, n=36) were smokers, compared with 20.1% in the general population. Over half the cohort (53.7%, n=29) was obese (BMI ≥30), compared to one quarter (24.8%) of the general population. A further 31.5% (n=17) were overweight (BMI 25–<30). Whilst 29.7% of the general population has hypertension, only 18.5% (n=10) of this cohort was hypertensive (systolic BP ≥140mmHg OR diastolic BP ≥90mmHg OR taking antihypertensive medication). One in five patients had diabetes (20.4%, n=11), compared to only 4.0% of the general population. Furthermore, 7.4% (n=4) had impaired glucose tolerance and 11.1% (n=6) had impaired fasting glucose. Rates of hyperlipidaemia (defined as total cholesterol >5.5mmol/L OR on lipid-lowering therapy) were similar (53.7% [n=29], compared with 51.5% in the general population) and 14 patients were on lipid-lowering therapy. More importantly, 32.7% (n=16/49) of the population had hypertriglyceridaemia (>2.0mmol/L) and 46.8% (n=22/47) had low HDL-cholesterol (≤1.2mmol/L in women and ≤1.0mmol/L in men). This combination is a more sensitive predictor of cardiovascular disease. CONCLUSION: This audit strongly supports the notion that patients with serious mental illness have increased rates of cardiovascular risk factors. Very high rates of smoking, obesity and diabetes were observed in this population - well above the current prevalence rates in the Australian general adult population. These results highlight the importance of regular metabolic monitoring and subsequent intervention for physical health comorbidities in people with serious mental illness.
12. John Wentworth Body mass index correlates with ischemic heart disease and albuminuria in long-standing type 2 diabetes WENTWORTH JM, Fourlanos S and Colman PG. Royal Melbourne Hospital
Research Week 2012 24 – 31 May 2012 Page 11 Aims: Comprehensive data describing the effect of obesity on type 2 diabetes outcomes is lacking. We sought to address this by analyzing our hospital clinical database. Methods: We extracted clinical and biochemical data for patients who attended Royal Melbourne Hospital diabetes clinic between 1998 and 2011 and were aged less than 65 years. Body mass index (BMI) was correlated with the prevalence of vascular complications and with cardio- vascular risk factors. Results: The means of age and duration of diabetes for the 711 patients (392 men and 319 women) were 53 and 11 years respectively. BMI correlated with the prevalence of ischemic heart disease and, to a lesser degree, albuminuria, but not with the prevalence of cerebro- vascular disease, neuropathy, retinopathy or renal function. BMI did not correlate with glycosylated hemoglobin, although obese patients used insulin both more frequently and at higher doses. Conclusions: In people with long-standing type 2 diabetes who attend a tertiary hospital outpatient clinic, ischemic heart disease, in contrast to other vascular complications, correlates robustly with BMI. These findings indicate that clinical trials of weight loss in type 2 diabetes should use cardiac endpoints as their primary outcomes.
13. Sky Chew Moderate microvascular retinopathy predicts future cardiac events in a population of patients with chronic obstructive pulmonary disease CHEW S, Hutchinson A, Colville D, Savige J. The Royal Melbourne Hospital, The Northern Hospital Background: Patients with chronic obstructive pulmonary disease (COPD) are at an increased risk of cardiac disease. Identifying patients at highest risk improves management and reduces morbidity and mortality. Retinal photography allows non-invasive visualization of the microvasculature and may represent a surrogate for demonstrating cumulative damage to the cardiac vessels. Methods: One hundred and fifty one patients with COPD were examined. COPD was diagnosed if a patient met the GOLD criteria on spirometry. The mean age of participants was 69 + 9.7 years with 80 (53%) being male. Participants provided a medical history and underwent retinal photography. These photographs were graded by the primary researcher and an ophthalmologist. Participants were then followed up over a two-year period for a cardiac event defined as occurrence of acute coronary syndrome, increase in troponin (> 0.04), arrhythmias, abnormal coronary angiogram or new onset heart failure. Results: Moderate microvascular retinopathy was associated with a cardiac event over the following two years after adjusting for established cardiac risk factors such as age, gender, hypertension, diabetes, hypercholesterolaemia and severe pulmonary hypertension, (OR 2.32, 95% CI 1.16-5.1, p=0.04). Conclusion: Microvascular changes in the eye reflect damage to the vasculature and predict an increased risk of cardiac disease in patients with COPD within a two-year period. Further research is warranted to validate these results and to determine if early intervention improves patient outcomes.
14. Peter Wallbridge The utility of serial venous blood gases to assess ventilatory status in patients undergoing flexible bronchoscopy. WALLBRIDGE P, Hannan LM, Joosten SA, Irving LB, Steinfort DD. The Royal Melbourne Hospital Introduction: Venous blood gases are commonly utilised, particularly in the emergency setting, to assess and monitor patients at risk of ventilatory failure. The aim of this study was to evaluate the utility of serial venous blood gas analysis to assess ventilatory status in patients undergoing flexible bronchoscopy. Methods: This prospective study enrolled 30 patients undergoing flexible bronchoscopy under conscious sedation. Paired arterial and venous samples were taken before and after the procedure and results were analysed utilising descriptive statistics and bias plot (Bland-Altman) analysis to assess limits of agreement. Results: Post bronchoscopy, arterial and venous blood gases showed a reduced pH (-0.05 +/-0.05 and - 0.04 +/-0.04, respectively) and an increased arterial and venous pCO2 (5.9 +/-6.7 and 3.5 +/-5.5 respectively). The change in arterial pCO2 was significantly larger than the change in venous pCO2 (p = 0.035). Although there was statistical agreement between arterial and venous blood gas parameters, the 95% limits of agreement were wide at rest and, with regard to pCO2, widened post bronchoscopy. Conclusion: Serial venous blood gases provide a variable and unpredictable means for assessing pCO2 in patients undergoing flexible bronchoscopy. Venous blood gas analysis appears to have limited utility as a means of assessing changes in ventilatory status in patients at risk of acute ventilatory failure.
15. John Moi The prevalence of gout in a large tertiary hospital and the impact of in-hospital attacks of acute gout on patient outcomes and health resource utilization - a nested case-control study MOI JHY1, Tacey M1, Roberts C1, Brand C1,2, Gorelik A1, Van Doornum S1,2 1The Royal Melbourne Hospital, 2The University of Melbourne Aim: To investigate the prevalence of gout in a hospitalized population and to assess the impact of experiencing an in-hospital attack of acute gout on patient outcomes and health resource utilization. Research Week 2012 24 – 31 May 2012 Page 12 Methods: The study utilized hospital administrative data from The Royal Melbourne Hospital, Victoria over a ten year period (1 January 2001 to 31 December 2010). Gout episodes were defined according to ICD- 10-AM codes and were subdivided into three categories: ‘P-gout’ (gout was the primary reason for admission), ‘C-gout’ (gout occurred as a complication during hospitalization) or ‘A-gout’ (gout was an associated diagnosis and did not require specific treatment). All three categories of gout episodes during the study period were analyzed by calendar year in order to identify trends over time in the overall burden of gout. The impact of in-hospital attacks of acute gout was measured by determining the prevalence of ‘C-gout’ diagnoses in all hospital admissions (excluding day case admissions) over the study period. The effect of in-hospital attacks of acute gout on patient outcomes and health resource allocation was measured in a nested case control study with matching of ‘C-gout’ patients to controls (ratio of 1:5) by age, gender, and principal diagnosis. Results: There were 277,091 multi-day hospital admission episodes during the 10-year study period. Of these, 1,399 (0.5%) had an ICD-10-AM code for gout (‘P-gout’=1,058, ‘C-gout’=311, and ‘A-gout’=39). A steady increase in the annual burden of ‘P-gout’ and ‘C-gout’ over time was noted. Patients who experienced an in-hospital attack of acute gout had a substantially longer length of stay (LOS) than the controls (median (IQR) LOS in days 13 (7-25) vs. 5 (2-11), p<0.001) and also had higher 28-day readmission rates. Conclusion: Our study demonstrated a steady rise in the annual burden of gout in hospitalized patients over the past decade. It also highlighted the increased health resource utilization that occurs in patients who experience an in-hospital attack of acute gout. It was not possible from the design of our study to exclude other potential confounding factors which may have contributed to the observed increased hospital LOS in patients who experienced acute gout as a complication of their hospital stay.
16. Gene Ngian Arterial stiffness is increased in systemic sclerosis: A cross-sectional comparison with matched controls NGIAN GS1,2, Sahhar J3, Wicks IP1,2, Van Doornum S1,2 1 – The Royal Melbourne Hospital 2 – The University of Melbourne 3 – Monash Medical Centre BACKGROUND: Atherosclerosis may be increased in systemic sclerosis (SSc) patients. Increased arterial stiffness is a predictor of cardiovascular and all-cause mortality across a wide range of patient populations. We evaluated arterial stiffness in SSc patients and age- and gender-matched controls. METHODS: We compared arterial stiffness in 40 SSc patients and 40 matched controls, all of whom were free from clinically evident cardiovascular disease. Arterial stiffness was measured using augmentation index (AI) and carotid-femoral pulse wave velocity (PWV), both of which increase with increasing arterial stiffness. Descriptive data are presented as mean+SD or percentage, as appropriate. The independent sample t-test was used to compare arterial stiffness measurements between SSc patients and controls. RESULTS: The groups were well matched with no significant differences in age (52.2+12.0 years in SSc patients vs 49.8+12.6 years in controls, p=0.3941) or gender (80% female in both groups, p=1.000). There were no significant differences in the numbers of patients with hypertension, hypercholesterolaemia, diabetes mellitus or smoking between the two groups. SSc patients had significantly higher AI than the controls (31.2+8.4% vs 20.9+12.5% respectively, p<0.0001), with a non- significant increase in PWV (7.32+1.8 m/s vs 6.8+1.1 m/s respectively, p=0.1095). Both measures of arterial stiffness correlated positively with each other as well as with age and SSc disease duration. CONCLUSION: Compared with healthy controls, SSc patients had increased arterial stiffness, with significantly higher AI and non-significantly higher PWV. This suggests that patients with SSc may have an increased prevalence of subclinical atherosclerosis. Studies of arterial stiffness in larger cohorts of patients are warranted to elucidate other determinants of arterial stiffness in SSc.
17. Ilana Ackerman The impact of severe hip and knee joint disease on work status and health care utilisation and costs: Results from a national Australian survey. ACKERMAN IN, Ademi Z, Osborne RH and Liew D The Royal Melbourne Hospital, The University of Melbourne and Deakin University Background: Severe hip and knee joint disease is common, disabling and represents a growing public health burden for many countries. Using a national approach, this study aimed to evaluate paid and unpaid work status, health service utilisation and related prevalent costs according to severity of hip and knee joint disease. Methods: A sample of 5000 Australians was randomly selected from the federal electoral roll and invited to complete a questionnaire to screen for doctor-diagnosed hip arthritis, hip osteoarthritis (OA), knee arthritis and knee OA. Joint disease severity was classified using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (range 0-100): <7=asymptomatic, 7-38=mild- moderate, ≥39=severe. Self-reported data on employment status and health service utilisation were also collected, with healthcare costs estimated using Australian government data. Results: Data were available for 1157 participants, with 237 (20%) reporting hip or knee joint disease. Of these, 16% (n=37) were classified as asymptomatic, 51% (n=120) as mild-moderate and 27% (n=64) as severe. Only 25% of the severe group was in paid employment (vs 40% and 54% of the mild to moderate and asymptomatic groups, respectively) and 9% of the severe group had stopped work due to Research Week 2012 24 – 31 May 2012 Page 13 their hip or knee (vs 0% each for mild to moderate and asymptomatic groups). After adjustment for age and gender, the severe group was over 3 times less likely to be in paid employment (adjusted odds ratio (AOR) 0.28, 95%CI 0.09-0.88) and over 4 times less likely to undertake unpaid work (AOR 0.24, 95%CI 0.10-0.62), compared with the asymptomatic group. Mild to moderate joint disease was not associated with a reduced likelihood of being in paid employment or of undertaking unpaid work. The proportion of participants reporting need to change the way they worked was also associated with disease severity (59%, 20% and 5% for severe, mild to moderate and asymptomatic groups, respectively; p<0.01), as was changes to the number of hours worked (33%, 15% and 3%, p<0.01). Utilisation of primary care and orthopaedic consultations and related costs increased with greater severity of joint disease (mean total costs for previous month $AUD53.22, $12.76 and $10.37 for severe, mild to moderate and asymptomatic groups, respectively; p<0.01). No differences in hip and knee surgery costs were observed (p=0.71). Conclusion: The health and economic burden of hip and knee joint disease is significant in Australia, with evidence of a graded relationship according to disease severity.
18. Christopher Leung Breaking the biopsy barrier in Barrett's: The use of confocal endomicroscopy to target oesophogeal biopsies LEUNG C(1)(4), Lim EJ(1), Allen P(2), Delaney P(3), Murr E(3), Bhathal P(4), Marion K(5), Macrae F(1). (1) Royal Melbourne Hospital, Parkville, Victoria (2) St Vincent’s Hospital, Fitzroy, Victoria (3) Optiscan, Notting Hill, Victoria (4) University of Melbourne, Parkville, Victoria (5) Royal Melbourne Institute of Technology, Melbourne, Victoria Dysplasia in Barrett’s is usually flat, inconspicuous and patchy in extent and severity. Current guidelines recommending routine random biopsy sampling at four quadrants every two centimetres is time consuming and can miss dysplastic areas due to sampling error. We aim to study the accuracy of confocal endomicrosopy (CFE) in targeting biopsies. Methods: Confocal images were taken at 27 consecutive gastroscopies with macroscopic Barrett’s oesophagus. Corresponding tissue biopsies were taken at these sites. The confocal images were examined independently by four readers blinded to the patient’s clinical, endoscopic and histopathological findings. A consensus confocal diagnosis at each site was then made and a decision regarding whether to biopsy was made. These findings were then correlated with tissue biopsies to determine the accuracy of the confocal diagnosis and to measure any yield advantage and time efficiencies offered by CFE. Results: 25 gastroscopies were performed on 12 patients aged between 51 to 80 (mean 67), with 58% being male. 92 biopsies were taken with corresponding confocal images. Of the confocal images, it appeared that 22% of sites had high grade dysplasia (HGD) and/or cancer. Confocal images were 70% sensitive and 85% specific in discriminating HGD or cancer from non-dysplastic intestinal type Barrett’s, gastric or squamous epithelia. This gave a negative predictive value of 91%, a positive predictive value of 56% and an overall accuracy of 81%. If biopsies were targeted based on the CFE, the number of biopsies required would decrease by 54% and the biopsy yield would increase from 24% to 37% in detecting HGD or cancer. With this approach, no patients with HGD or cancer would have been missed. However, in two procedures, low grade dysplasia would not have been detected. The time required to perform confocal was on average 85 seconds per confocal site compared with 45 seconds per biopsy site. By decreasing the number of biopsies required, CFE guided biopsies had comparable procedure times to routine random biopsies. Conclusions: CFE is useful in targeting biopsies in Barrett’s oesophagus without compromising overall detection of HGD or cancer. Its utility is in offering a high negative predictive value so that non-dysplastic mucosa need not be biopsied. Consequently, the number of biopsies can be decreased by 54% and procedure times can become quite comparable.
19. Phillip Beouf Placental adhesion of malaria-infected erythrocytes: more than just VAR2CSA/CSA interaction? PHILIPPE BOEUF 1,2, Charanya Lakshmanan 1, Wina Hasang 1,2, Ali Salanti 3, Graham Brown 1,4, Stephen Rogerson1,2. 1Department of Medicine, University of Melbourne, Australia 2Victorian Infectious Diseases Services 3Centre for Medical Parasitology, University of Copenhagen, Denmark 4The Nossal Institute for Global Health, Melbourne, Australia In placental malaria, the adhesion of infected erythrocytes (IE) to placental tissue triggers local inflammation leading to placental functional impairment and poor pregnancy outcomes. There is indisputable evidence that the parasite-encoded protein VAR2CSA expressed at the surface of IE binds to the placental receptor chondroitin sulfate A (CSA). Anti-adhesion interventions, such as an anti-VAR2CSA vaccine, would improve outcomes but need to be based on a complete and relevant understanding of the mechanisms involved. However, most currently available adhesion assays lack relevance, mainly because the adhesion matrix they use does not encompass the complexity of the in vivo matrix: the syncytiotrophoblast microvillous membrane. We recently developed a flow cytometry-based adhesion assay that utilizes vesicles of the syncytiotrophoblast microvillous membrane as adhesion matrix. As such, this assay is ideal to investigate relevant mechanisms of IE placental adhesion.
Research Week 2012 24 – 31 May 2012 Page 14 Using this assay, we showed that var2csaKO IE can adhere to placental tissue at levels similar to wild type IE in a CSA-independent manner and investigated whether a ligand/receptor couple other than VAR2CSA/CSA could mediate placental adhesion. The var expression profile of var2csaKO IE able to adhere to placental tissue at high levels included one dominant var gene, which was only expressed at low levels in IE unable to adhere to placental tissue. This dominant var gene or other non-var genes may support the placental adhesion of var2csaKO IE. Also, preliminary data suggest that a CD36-related molecule may be involved as a placental receptor of these var2csaKO IE. If confirmed, these findings would have major implications for the design of a vaccine against placental malaria since an anti-VAR2CSA vaccine may select for this very efficient alternative adhesion mechanism against which a VAR2CSA-only vaccine would not offer protection.
20. Shamista Shelverajah The novel histone variant H2Bv in the malaria parasite P. falciparum cooperates with H2A.Z in gene promoter nucleosomes SELVARAJAH S1, Lee C1, Brown G. V1, Duffy M. F1, Petter M1 1 Department of Medicine, University of Melbourne, Australia Plasmodium falciparum is responsible for the severe form of malaria. This parasite utilizes epigenetic mechanisms to control fundamental processes of pathogenesis including red blood cell invasion, cytoadhesion and immune evasion. One of these epigenetic mechanisms is the exchange of canonical histones with alternative histone variants, which leads to changes in chromatin architecture and can affect gene regulation. We have shown previously that enrichment of the histone variant PfH2A.Z at transcriptional start sites (TSSs) of genes is independent of gene activity. Recently a novel H2B variant, H2Bv, has been identified in certain protozoan parasites, including P. falciparum. Importantly, novel and unique parasite specific proteins such as PfH2Bv may represent promising future drug targets. Here, we explore the possible interaction of the histone variants PfH2A.Z and PfH2Bv and their role in gene regulation of Plasmodium falciparum. We generated a parasite line expressing a HA tagged version of PfH2Bv. We found that PfH2Bv colocalizes perfectly with PfH2A.Z throughout blood stage differentiation of the parasite. Indeed, PfH2Bv exclusively associates with PfH2A.Z within the same nucleosomes, confirming the direct interaction of these two histone variants. PfH2Bv and PfH2A.Z containing nucleosomes are also characterized by histone modifications that are associated with transcriptionally competent genes. Chromatin immunoprecipitation showed that PfH2Bv enrichment correlates with PfH2A.Z enrichment near the TSS of stage specific genes, independent of gene activity. This suggests that PfH2Bv interacts with PfH2A.Z to define the promoter architecture of genes. Interestingly with genes of the var multi-gene family, which encode the major virulence factor, PfH2Bv enrichment, similar to PfH2A.Z enrichment, is restricted to the TSS of the actively transcribed var gene. This indicates that PfH2A.Z and PfH2Bv possibly play a role in regulating var gene expression and therefore cytoadhesion and immune evasion in Plasmodium falciparum.
21. Sook Kwan (Leah) Leang Influenza Antiviral Resistance in the Asia-Pacific region during 2011 SK LEANG, YM Deng, N Caldwell, IG Barr, A Kelso, AC Hurt WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, 10 Wreckyn St, North Melbourne, 3051 Victoria, Australia Background: Two classes of antiviral drugs are available for the treatment and chemoprophylaxis of influenza, the adamantanes (amantadine and rimantadine) and the neuraminidase (NA) inhibitors (oseltamivir [Tamiflu] and zanamivir [Relenza]). As part of the WHO Global Influenza Surveillance and Response System, influenza viruses received at the WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, during 2011 were tested for sensitivity to these drugs. Methods: Influenza viruses were analyzed using Sanger sequencing or pyrosequencing for the presence of key amino acid mutations known to confer resistance, and a fluorescence-based NA inhibition assay to determine NA inhibitor (NAI) sensitivity. During 2011, a total of 2152 influenza A viruses (1364 A(H1N1)pdm09 and 788 A(H3N2) viruses) and 1215 influenza B viruses from the Asia-Pacific region were analyzed for NAI sensitivity and 304 influenza A viruses for adamantane sensitivity (the adamantanes are not effective at inhibiting influenza B viruses therefore testing was not conducted on these). Results: All but one of the influenza A viruses (A(H1N1)pdm09 and A(H3N2)) (99.7%) were found to be resistant to the adamantanes due to a S31N mutation in the M2 gene, rendering these drugs ineffective in treating currently circulating influenza strains. In contrast, all influenza viruses were sensitive to the NAI zanamivir, while a low frequency of resistance to oseltamivir, the most commonly used influenza antiviral, was observed. 3.1% (42/1364) of A(H1N1)pdm09 viruses tested were found to have a mean 600-fold reduction in oseltamivir-sensitivity due to a H275Y NA mutation. The majority of these viruses were detected between June and August 2011, in the Hunter New England region of NSW, where 29 (16%) out of 186 specimens tested from that region, were found to be oseltamivir-resistant. Molecular analysis revealed that all of these were genetically similar, suggesting they originated from a single source. Research Week 2012 24 – 31 May 2012 Page 15 Notably, all but one were from community patients who had not been treated with oseltamivir. Other genetically related oseltamivir-resistant strains were also detected in Sydney and Perth, indicating significant spread of this resistant strain. No resistance was detected in A(H3N2) viruses, while one influenza B virus had a 16-fold reduction in oseltamivir-sensitivity due to a novel A245T NA mutation. Conclusion: The adamantanes drugs should no longer be used to treat currently circulating influenza viruses. Community-wide spread of oseltamivir-resistant viruses is of significant public health concern and highlights the importance of continuous monitoring to ensure the appropriate choice of drug for the treatment of influenza.
22. Jeff Butler Assessing the fitness of drug-resistant influenza viruses from a cluster of community cases in Newcastle, NSW, in 2011 BUTLER JM, McCaw J, Xue L, Guarnaccia T, Kelso A, Barr IG, and Hurt AC WHO Collaborating Centre for Reference and Research on Influenza – Victorian Infectious Diseases Reference Laboratory Background: Antimicrobial resistance poses a major challenge to the management of infectious diseases. Viruses, such as influenza, which spread rapidly throughout the community pose a significant threat when they acquire resistance to antiviral drugs. Oseltamivir (Tamiflu) is the drug most commonly prescribed for the treatment of human influenza infection. Prior to 2011, oseltamivir resistant pandemic 2009 H1N1 (A(H1N1)pdm09) influenza viruses were most commonly detected in oseltamivir treated patients, many of whom were immuno compromised. Spread of the resistant viruses to the community was thought to be unlikely as the mutation that caused resistance was also known to compromise the ‘fitness’ of the virus and reduce its ability to spread. However between June and September 2011, 16% of A(H1N1)pdm09 influenza viruses from Newcastle, NSW, were oseltamivir-resistant, and were detected in ‘community’ patients who had not been treated with oseltamivir. Hence we sought to assess the fitness of these viruses to determine whether they had enhanced transmissibility and may be capable of efficient spread both nationally and globally. Methods: Ferrets, which are a commonly used model of human influenza infection, were infected with a Newcastle 2011 oseltamivir resistant virus, an equivalent ‘sensitive’ (non-resistant) virus, or deliberately prepared mixtures of the two strains (20%:80%, 50%:50%, 80%:20%). Additional naive ferrets were placed in direct contact with the infected ferrets to monitor transmission of the viruses. Ferrets were nasal washed daily and samples analysed to determine the relative transmissibility and replication of the oseltamivir-resistant virus compared to the sensitive strain. Two different pairs of resistant/sensitive viruses were tested. Results: The first pair of oseltamivir-resistant and -sensitive viruses demonstrated an equivalent level of replication within ferrets and transmissibility between ferrets. In ferrets infected with the second pair of viruses however, the oseltamivir resistant virus replicated and transmitted more efficiently than its paired oseltamivir sensitive strain. These results demonstrated that the Newcastle oseltamivir resistant A(H1N1)pdm09 influenza viruses replicated as well as, if not better than, equivalent oseltamivir sensitive A(H1N1)pdm09 influenza viruses. Conclusion: The transmissibility and replication of two different Newcastle oseltamivir resistant A(H1N1)pdm09 viruses was not compromised, suggesting that other recent A(H1N1)pdm09 influenza viruses may have the capability to acquire oseltamivir resistance without affecting viral fitness. Further work is ongoing to investigate which molecular changes enable the oseltamivir resistant A(H1N1)pdm09 viruses to maintain fitness. Global spread of oseltamivir resistant A(H1N1)pdm09 influenza viruses is of significant concern as it would mean the most widely used influenza antiviral drug was no longer effective for the treatment of such viruses.
23. Teagan Guarnaccia Antigenic drift of the A(H1N1)pdm virus in the ferret model of vaccination. GUARNACCIA T1,2, Carolan L1, Kelso A1, Barr I1, Mosse J2, Laurie K1. WHO Collaborating Centre for Reference and Research on Influenza, VIDRL1 , Monash University, Gippsland Campus2 Background: The Melbourne WHO Collaborating Centre for Influenza at VIDRL is one of five centres worldwide responsible for monitoring changes in human influenza viruses. Viruses are analysed for changes (drift) in their surface protein structure (antigenic) and sequence (genetic). These data are used annually to determine if the human influenza vaccine requires updating. In April 2009 a new virus emerged from Mexico, resulting in a pandemic. A vaccine was available in November 2009. This virus (A(H1N1)pdm) continues to circulate and surveillance data demonstrates that the vaccine is still antigenically matched to the virus. Serological and epidemiological studies indicate up to 40% of Australian adults have neutralising antibodies to A(H1N1)pdm virus. Virus circulation in the presence of antibodies may drive changes in the surface protein sequence and structure, especially in the main influenza virus protein, haemagglutinin (HA). The aim of this project was to investigate how A(H1N1)pdm virus may drift, using an animal model of influenza. Method: A(H1N1)pdm virus was passaged through a series of ferrets that had been vaccinated with human pandemic influenza vaccine. Virus was collected from the animals, growth properties assessed and Research Week 2012 24 – 31 May 2012 Page 16 changes in HA sequence and protein structure analysed. Animals were also assessed for clinical symptoms. Results: No changes in clinical symptoms of the ferrets were identified over the passage series. However, a novel mutation was identified in the HA protein halfway through the series and this mutant virus was maintained until the last passage. The mutation is in a region of the HA protein known to influence antibody binding, suggesting the virus had changed to escape immunity from vaccination. Attempts to isolate a pure population of the HA mutant virus in conventional cell and egg culture techniques, and reverse genetics, were unsuccessful. The mutant virus can successfully transmit and replicate in naïve ferrets, demonstrating it is fit. Human clinical specimens with this mutation have also been detected in surveillance studies. Conclusion: A mutant A(H1N1)pdm virus that can escape immunity and transmit efficiently has been generated in the ferret model of human influenza infection. Difficulty in culturing this virus highlights a potential problem for future surveillance of human A(H1N1)pdm influenza viruses, and vaccine selection. Novel isolation techniques are under exploration. Overall, these data demonstrate the A(H1N1)pdm virus has potential to change as it circulates through the human population. Furthermore, this project demonstrates the usefulness of running complementary research and surveillance programs to better understand human influenza viruses.
24. Iwan Bennett Perfusion MRI predicts levels of circulating endothelial progenitor cells in glioblastoma multiforme. BENNETT I, Morokoff A, Hovens C, D'abaco G, Kountouri N, Moffat B, Guo S, Kaye A. University of Melbourne & Royal Melbourne Hospital. Background: Glioblastoma multiforme (GBM) is the most common & most aggressive form of primary brain tumour, & is a very formidable disease. Current first-line therapy includes maximal safe debulking surgery followed by radiotherapy with concomitant as well as adjuvant chemotherapy. Despite this it remains incurable with a median survival of little over a year. The outcomes are somewhat better for patients enrolling into research trials however, with median survivals of greater than 20 months being reported. Many of these trials, including studies conducted here in Melbourne, are investigating the effects of anti- angiogenic chemotherapeutic agents in GBM. As GBM is one of the most vascular tumours known & these agents target tumour vascularity, it seems intuitive that they may be of clinical use. Individual assessment of tumour vascularity is likely to be of benefit in determining which patients will respond most favourably to anti-angiogenic agents, & also as a means of monitoring response to treatment. Tumour vascularity is traditionally assessed histopathologically, but there are a number of problems with this technique, including the requirement of tissue via surgery & significant inter-observer error. The search for biomarkers which non-invasively reflect tumour vascularity stems from this current area of investigation. Two such vascular biomarkers are perfusion MR imaging (perfusion-weighted imaging or PWI), an advanced MRI technique measuring the amount of blood-flow to the tissues,7 & circulating endothelial progenitor cell (EPC) concentrations, identifying stem cells recruited from the bone marrow which facilitate the development of new blood vessels. In our institution we have developed protocols for the objective assessment of both these biomarkers, & have begun investigating their role in GBM. Methods: Pre-operative blood samples were collected prospectively from 13 patients with GBM & analysed for EPC levels using immunofluorescence staining (CD31+/CD133+) & flow cytometry. Objective analysis of pre-operative PWI for tumour relative cerebral blood volume (CBV) was also undertaken. A novel perfusion parameter - CBV load - was developed to provide a measure reflecting the overall vascularity of the tumour. Results: EPC levels ranged from 59 to 1647 cells/mL. CBV load correlated significantly with EPC levels (p = 0.0081). Conclusion: The correlation of CBV load with EPC levels suggests it may be a valid, non-invasive vascular biomarker. This study gives the first example of this novel PWI parameter, as well as a correlation between circulating & imaging vascular biomarkers.
25. Sinnatamby Sujeevan Investigating the role of the epidermal growth factor system in clozapine treated subjects with schizophrenia Sujeevan S, Sathiamoorthy S, Pereira A, Sundram S Molecular Psychopharmacology, Mental Health Research Institute, Northern Psychiatry Research Centre, Department of Psychiatry, University of Melbourne Background: Schizophrenia is chronic debilitating mental illness. Anti psychotic drugs (APD) are the main stay of treatment in schizophrenia, yet even with novel antipsychotic drugs (APD), significant proportion of patients, about 45% show little improvement. Clozapine is the only APD that is superior in treatment resistant schizophrenia but its use is restricted because of serious side effects. Ability to predict response to clozapine will allow early introduction and reduce unnecessary exposure to its side effects. To date genetic, biochemical and clinical studies have failed to identify useful markers that could predict response.
Research Week 2012 24 – 31 May 2012 Page 17 Study objectives: Our in vitro and in vivo evidence support a mechanism of action of clozapine involving the epidermal growth factor (EGF) receptor. Preliminary data have shown increase in EGF levels in some patients and significant correlation with symptom improvement. This study aims to further explore this correlation as well as EGF system markers as possible predictors for clozapine response. Methodology: Schizophrenia patients commencing on clozapine are clinically assessed before starting clozapine and 6 months later, and their blood samples collected for EGFR ligand assays and genetic analysis. Results: To date 60 patients have been recruited and 42 have completed the study. Nine patients discontinued medication. Of those who completed, 9 were females, and the age range was from 20 to 65. Mean reduction in PANSS score was 7.09 and CGI-S was 1.70. Twenty patients showed > 20% reduction in PANSS. Our analysis (n=20) demonstrated that clozapine treatment in schizophrenia elevated serum EGF levels in some patients (n=11). The post-treatment serum EGF levels of these patients significantly correlated (r = -0.61; p<0.05) with post-treatment PANSS total scores with post-treatment PANSS – General Scale scores showing even stronger relationship (r =-0.71; p=0.01). Conclusions: The overall response rate to clozapine in our study population is consistent with other studies. Our analysis so far supports our hypothesis, in that for those in whom clozapine is effective it augments EGF system signaling. We hope that the information from this study will help safe and early introduction of clozapine and development of new APD
26. Simon Jones Abstract Title: MEDICAL EMERGENCIES IN PSYCHIATRIC INPATIENT UNITS JONES SG, Velakoulis D Royal Melbourne Hospital - Inner West Area Mental Health Service; Department of Psychiatry, University of Melbourne Background: There are no known published audits or studies about medical emergencies in acute psychiatric inpatient units. Medical Emergency Team (MET) calls are designed to treat hospital inpatients early to prevent more serious medical deterioration. The aims of this audit were to measure the incidence of MET calls and cardiac arrest (CA) calls in three psychiatric inpatient units; to examine the reasons for MET/CA calls; and to examine the characteristics of patients who required a MET/CA call including what physical health assessment and monitoring occurred prior to the call. Methods: This study was a retrospective file review of all people who were subject to a MET or CA call while an inpatient in the general adult inpatient unit, the neuropsychiatry unit or the eating disorders unit at the Royal Melbourne Hospital between January 1st 2005 and December 31st 2010. Results: Over the 6-year period 72 inpatients were subject to 82 MET or CA calls. The incidence was 1 MET or CA call per 78 admissions. There were six patient deaths. 57% of MET/CA calls occurred within the first 72 hours of being admitted to the inpatient unit – of these, 60% had arrived on the psychiatry ward from the emergency department or from a hospital transfer. 62% of the total sample had no regular physical health monitoring prior to the MET/CA call. Conclusions: Physical health assessment and monitoring protocols on inpatient units should be reviewed and audited. This audit suggested that the first 72-hours, following ward or hospital transfer, and after medication changes are the most critical times for physical health monitoring.
27. Anneke van der Walt Optic nerve axial diffusivity predicts axonal loss but not clinical outcome after acute demyelinating optic neuritis. ANNEKE VAN DER WALT1,2,4, Scott Kolbe1,3, Y Wang1, Aleksandr Klistorner4, Neil Shuey5, Gelareh Ahmadi1, Mark Paine5, Stephanie Tsonis5, Mark Marriott2, Peter Mitchell2, Gary Egan1,3, Helmut Butzkueven2,6, Trevor Kilpatrick1,2. 1. Center for Neuroscience, University of Melbourne 2. Royal Melbourne Hospital, Melbourne 3. Monash University, Melbourne 4. Sydney Eye Hospital, Melbourne 5. Royal Victorian Eye and Ear Hospital, Melbourne 6. Department of Medicine, University of Melbourne Objective: 1. To evaluate optic nerve diffusion tensor imaging parameters in the first 12 months after demyelinating optic neuritis. 2. To determine if early changes in directional diffusivity in the optic nerve can predict axonal loss or clinical outcomes at 12 months. Methods: 40 patients presenting within 2 weeks with a first episode of acute unilateral optic neuritis and at high risk of developing Multiple Sclerosis based on MRI criteria were recruited. Patients were studied at baseline and at 1,3,6 and 12 months. 37 patients completed all testing. Eleven age and sex matched controls were recruited and tested twice, one month apart. Testing protocol included MRI (3T with 32- head coil), multi-focal visual evoked potentials and OCT (Stratus) to measure retinal nerve fiber layer thinning. Vision was assessed using high and low contrast letter acuity charts Sloan 100, 2.5 and 1.25) and Snellen charts. Results: Asymmetry in Axial diffusivity at 1 month correlated with RNFL thinning at 12 months (r=0.437, p=0.008) and with mfVEP amplitude at 6 (r=0.461, p=0.02) and 12 months (r=0.530, p=0.004). There was no correlation between axial diffusivity and mfVEP latency at any time point. Asymmetry in axial diffusivity at baseline correlated with high contrast letter acuity at baseline (r=0.493, p=0.002) but not
Research Week 2012 24 – 31 May 2012 Page 18 with visual outcomes at 6 or 12 months. Early asymmetry in radial diffusivity at baseline or 1 month did not correlate with clinical or paraclinical outcomes. Conclusions: Early decrease in optic nerve axial diffusivity after optic neuritis predicts axonal loss but not visual outcome. Early changes in axial diffusivity could be used to stratify patients when designing neuroprotective trials in MS.
28. Nigel Jones Targeting hyperphosphorylated tau with sodium selenate suppresses seizures in rodent models. JONES NC, Nguyen T, Corcoran NM, Velakoulis N, Chen T, Grundye R, O’Brien TJ, Hovens CM. Departments of Medicine, Surgery and Psychiatry, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia; dNational Institutes of Health, National Institute of Neurological Disorders and Stroke, Rockville, MD, USA; Cerebricon Ltd. London BioScience Innovation Centre, London, United Kingdom Background: Tau hyperphosphorylation has been implicated in the pathogenesis of a variety of forms of human epilepsy. Here we investigated whether treatment with sodium selenate, a drug which reduces pathological hyperphosphorylated tau by enhancement of PP2A activity, would inhibit seizures in rodent models. Methods: In vitro, sodium selenate reduced tau phosphorylation in human neuroblastoma cells and reversed the increase in tau phosphorylation induced by the PP2A inhibitor, okadaic acid. Sodium selenate treatment was then tested against three different rodent seizure models. Firstly the propensity of 6-Hz electrical corneal stimulation to induce seizures in adult mice was assessed following acute treatment with different doses of sodium selenate. Secondly, effect of chronic treatment with sodium selenate in drinking water to rats on the number of seizures induced by pentylenetetrazole (PTZ) i.p. was quantified. Finally, fully amygdala kindled rats were chronically treated with sodium selenate in drinking water and the length and the severity of the seizures evoked by stimulation of the amygdala recorded. Results: A dose-dependent protection of sodium selenate against 6-Hz stimulation induced seizures, and significant reduction in the total number of seizures following PTZ injection, was seen. Amygdala kindled rats chronically treated with sodium selenate had significantly shorter seizure durations compared controls, with more pronounced effects observed as the duration of treatment increased. Conclusions: Targeting hyperphosphorylated tau by treatment with sodium selenate has anti-seizure effects in a broad range of rodent models, and may represent a novel approach to treatment of patients with epilepsy. Sodium selenate is currently being tested in a Phase IIa clinical trial for Alzheimer’s Disease.
29. Wayne Hoskins (see #8)
30. Iwan Bennett (see #24)
31. Andrew Nichols Functional MRI of the visual pathway in patients with brain tumours causing optic chiasm compression NICHOLS AD, Moffat BA, Danesh-Meyer HV, Kaye AH The University of Melbourne, The Royal Melbourne Hospital, The University of Auckland Background: Brain tumours such as pituitary adenomas and meningiomas can cause compression of the optic chiasm and lead to visual failure or visual field (VF) deficits. These tumours account for up to 10% of all brain tumours. Previous studies have shown that retinal nerve fibre layer (RNFL) thickness on optical coherence tomography (OCT) can predict visual recovery following surgery for optic chiasm compression, however no study to date has investigated the downstream changes in the visual pathway that occur from tumours causing optic chiasm compression. The advanced magnetic resonance imaging (MRI) technique of functional magnetic resonance imaging (fMRI) allows in-vivo, non-invasive investigation of the visual pathway posterior to the optic chiasm including measurement of activation of the lateral geniculate nucleus (LGN) and primary visual cortex (V1). This study aims to use fMRI to investigate changes in the LGN and V1 of patients with tumours causing optic chiasm compression. Mehtods: Patients were recruited to participate in the study at least one year following surgery to remove tumours causing optic chiasm compression and were divided into two groups based on their visual function. The normal vision group (n=9) had no VF deficit and normal RNFL thickness on OCT and the abnormal vision group (n=6) had persistent VF deficit and RNFL thinning on OCT at one year post-op. Patients had fMRI performed on a clinical 3-Tesla MRI scanner including acquisition of T1-weighted anatomical images and a clinical visual-guided saccade fMRI paradigm. The fMRI results for each patient were analysed to generate fMRI activation data for each voxel. Analysis of fMRI activation for bilateral LGN and V1 regions of interest based on the Jeulich histological atlas MRI dataset was performed for each patient group. Results: A significant decrease in bilateral V1 activation (p=0.02) was observed in the group of patients with abnormal vision. A non-significant decrease in V1 activation was also observed for each of left V1 (p=0.18) and right V1 (p=0.09). No difference in LGN activation was observed for bilateral LGN (p=0.54), left LGN (p=0.61) or right LGN (p-0.86). Conclusion: This study demonstrates decreased fMRI activation in the bilateral primary visual cortex of patients with persistent visual deficits following surgery for tumours causing optic chiasm compression. Research Week 2012 24 – 31 May 2012 Page 19 Additional studies are needed to further investigate the downstream effects of these tumours on the visual pathway and to investigate whether fMRI changes pre-op can predict visual recovery following surgery.
32. Matthew Hong (see #5)
33. Simon Liubinas Title: Radiological and molecular features correlating with seizures in patients with supratentorial gliomas. LIUBINAS SV (MBBS)1,2, Drummond KJ (MBBS, MD)1,2, D’Abaco G1, Desmond P (MBBS)3, Bjorksten A (PhD)4, Morokoff AP (MBBS, PhD)1,2, Kaye AH (MBBS, MD)1,2, O’Brien TJ (MBBS, MD)5,6, Moffat BA (PhD)3. 1Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne. 2Department of Neurosurgery, The Royal Melbourne Hospital. 3Department of Radiology, The Royal Melbourne Hospital, The University of Melbourne. 4Department of Anaesthesia, The Royal Melbourne Hospital. 5Department of Neurology, The Royal Melbourne Hospital. 6Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne. Gliomas are the most common malignant brain tumours, with more than 1,500 new cases diagnosed in Australia each year. Generalized or partial seizures are the presenting feature in up to 80% of low grade gliomas and up to 50% of gliomas overall, and overall around 50% of glioma patients suffer from one or more seizures (tumour associated epilepsy, TAE). The seizures are commonly difficult to control with current anti-epileptic drugs (AEDs) and may not be effectively treated by removal of the tumour. Glutamate is the major excitatory neurotransmitter in the mammalian CNS, and glutamate toxicity is now widely regarded as the initiator of excitotoxic neurodegeneration in stroke, CNS trauma and non-tumoural epilepsy. Previous research performed in the Department of Surgery (RMH/WH) has found that gliomas have much levels of glutamate compared to normal brain tissue. Magnetic resonance spectroscopy (MRS) provides a non-invasive measurement of brain metabolites, including glutamate. This project aims to further investigate the link between glutamate and TAE, and in particular whether non-invasive measurement of glutamate via MRS can act as a biomarker for TAE. This will allow therapy tailored to individual patient needs, reducing the use of, and side effects from, conventional AEDs. In a combined group of grade II, III and IV gliomas, ratios of glutamate+glutamine to creatine (Glx:Cr) are lower in both the tumour and peritumour (n=68, p=0.02; and n=73, p=0.01 respectively). In a subgroup of Grade II gliomas only, ratios of Glx:Cr and absolute levels of Glx were found to be lower in both the tumour and peritumour. Tumour Glx (n=17, p=0.0005), peritumour Glx (n=19, p=0.003), tumour Glx:Cr (n=30, p=0.08), peritumour Glx:Cr (n=31, p=0.07). Hyperpolarization-activated cationic (HCN) channels are found in the plasma membranes of neurons and contribute to resting membrane potential, to the shaping of synaptic inputs and to the generation of rhythmic and synchronized neuronal events. Previous work in the Departments of Surgery and Medicine (RMH/WH) has suggested that peritumoural HCN1 and HCN2 expression is reduced in glioma patients with TAE compared to those with no TAE. This is the first time that HCN channels have been analysed in gliomas, and we aim to extend these novel results with a further prospective cohort of glioma patients. There is a growing body of evidence that hyperphosphorylated tau may be involved in the pathogenesis of epilepsy. Glutamic acid decarboxylase (GAD) is the enzyme responsible for production of ϒ-aminobutyric acid (GABA) in the central nervous system. Alterations in the GABA-ergic system have been reported in both animal and human models of epilepsy. We aim to examine the role of hyperphosphorylated tau and GAD in glioma growth, and tumour associated epilepsy. This novel research may lead to potential drug therapy for TAE.
34. Jonathan Knott
Research Week 2012 24 – 31 May 2012 Page 20
AGED CARE AC01: Rachel Buckley Cognitive and affective predictors of subjective memory complaints in the Australian Imaging Biomarkers and Lifestyle (AIBL) study of aging: a cross-sectional analysis. RACHEL F. BUCKLEY1,3, Michael M. Saling1,2, Kathryn Ellis3,4, Nicola Lautenschlager5, Paul Maruff6,7, Ralph N. Martins8, Colin L. Masters3, Christopher C. Rowe9,10, Greg Savage11, Cassandra Szoeke12, David Ames13 and the AIBL Research Group 1 Department of Psychology, School of Behavioural Science, University of Melbourne, Victoria, Australia 2 Brain Research Institute, Florey Neuroscience Institutes (Austin Hospital), Melbourne, Australia 3 Mental Health Research Institute, University of Melbourne, Victoria, Australia 4 Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, St Vincent's Aged Psychiatry Service, St George's Hospital, Victoria, Australia 5 Department of Psychiatry, University of Melbourne, Victoria, Australia 6 Cogstate, Victoria, Australia 7 Centre for Neuroscience, University of Melbourne, Victoria, Australia 8 Centre of Excellence for Alzheimer's disease Research and Care, School of Exercise Biomedical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia 9 Department of Nuclear Medicine and Centre for PET, Austin Health, Victoria, Australia 10 Department of Medicine, Austin Health, Victoria, Australia 11 Macquarie Centre for Cognitive Science, Macquarie University, NSW, Australia 12 CSIRO, Parkville Building, Melbourne, Victoria 13 National Ageing Research Institute, Melbourne, Victoria
BLOOD B01: Sheila Dias Novel insights into the role of MYB in lymphocytes - an in vivo study DIAS S, D’Amico A, Wu L, Nutt S The Walter and Eliza Hall Institute of Medical Research
B02: Sarah Hanieh Determining the effect of different iron and multiple micronutrient supplementation regimes during pregnancy on maternal and infant health outcomes in Vietnam : a cluster randomised trial HANIEH S, Tran H, Casey G, J.Simpson, Tran T, Tran Th, Fisher J, Biggs B University of Melbourne, Research Training Centre for Community Development Vietnam, School of Population Health, Monash University
CANCER C01: Susie Bae Clinical Attributes of Common Types of Rare Cancers Entered on www.CART-WHEEL.org BAE S1,2, Kosmider S1,2, Scott C1-3 1 Royal Melbourne Hospital, 2 BioGrid Australia, 3 Walter and Eliza Hall Institute of Medical Research
C02: Susie Bae Quality Assessment of Consumer Entered Information on www.cart-wheel.org, the CART-WHEEL rare tumour database BAE S (1,2,4) Kosmider S (1,2), Desai J (1,2,4), Scott C (1-3) 1. Royal Melbourne Hospital, 2. BioGrid Australia, 3. Walter and Eliza Hall Institute of Medical Research, 4. Peter MacCallum Cancer Centre
C03: John Ciciulla An Audit of Tissue Procurement Methods and a Proposal for a Quality Assurance Program for Biobanks CICIULLA, J Royal Melbourne Hospital and Victorian Cancer Biobank, Parkville
C04: Kerry Drury Analysis of the Src Phosphorylation Sites Which Regulate the beta-catenin/E-cadherin Interaction in Colorectal Cancer DRURY, KE, Faux, MC, Catimel, B, Burgess, AW Epithelial Laboratory, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria 3050
Research Week 2012 24 – 31 May 2012 Page 21 C05: Dustin Flanagan LGR5 function in the regeneration of the intestinal epithelium Flanagan DJ1*, Phesse TJ2*, Barker N3, Amin N1, Nowell CJ2, Clevers H4, Ernst MRW2, Vincan E1 1University of Melbourne and Victorian Infectious Diseases Reference Laboratories, VIC, Australia. 2Ludwig Institute for Cancer Research, Melbourne, Australia. 3Institute of Medical Biology, Immunos, Singapore. 4Hubrecht Institute of Developmental Biology and Stem Cell Research, Utrecht, The Netherland
C06: Lily Lee C-KIT inhibitors: a new treatment for basal-like breast cancers? Lee L1,2, Vaillant F1, Lindeman GJ1,2, Visvader JE1,2 1Walter & Eliza Hall Institute, 1G Royal Parade, Parkville, Australia 2Department of Medical Biology, University of Melbourne, Parkville, Australia
C07: Wayne Ng Utilisation of Glioma Stem Cells to Investigate Novel Therapies NG W, Kaye A.H., Morokoff A, Drummond K, D'Abaco G, Pébay A, Kountouri N Department of Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville
C08: Stanley Stylli Prognostic significance of Tks5 expression in gliomas STYLLI SS1,2, I STT3, Kaye AH1,2, Lock P3 1 Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia, 2Department of Neurosurgery, Royal Melbourne Hospital, Parkville, VIC, Australia, 3Department of Biochemistry, La Trobe University, Bundoora, VIC, Australia.
CARDIO-RESPIRATORY CR01: Maree Daly Telephone-delivered cognitive behaviour therapy for people with chronic obstructive pulmonary disease Doyle C 1, Antonopoulos S, DALY M, Irving L 2, Smallwood N, Thompson M 1 National Ageing Research Institute, 2 The Royal Melbourne Hospital
CR02: Meir Lichenstein Myocardial Perfusion Imaging (MPI) is Superior to the Demonstration of Collateral Arteries in the Prediction of Cardiac Events in Chronic Total Occlusion (CTO) Wright S, LICHTENSTEIN M, Grigg L, Sivaratnam D Departments of Nuclear Medicine and Cardiology, Royal Melbourne Hospital
CR03: Ai Vee Ng Hypoplastic Left Heart Syndrome:A Single Australian Centre Experience NG A, ZENTNER D, GRIGG L. The Royal Melbourne Hospital
CR04: Vara Perikala Implementing a Respiratory Education Module (REM), bedside assessments and competencies in ward based (5SW) Respiratory care unit and nursing staff experience PERIKALA V, Irving L, Vella D, Dodgson, K, Quade, K The Royal Melbourne Hospital
CR05: Eliza Teo Velocardiofacial Syndrome : Experience at An Adult Congenital Cardiac Centre Teo E, Zentner D, Grigg L The Royal Melbourne Hospital
Research Week 2012 24 – 31 May 2012 Page 22 EMERGENCY/CRITICAL CARE ED01: Graeme Baker The Volunteers in Emergency Department program: participant's perspectives of their role and implications for recruitment, retention and ongoing training of volunteers BAKER G, WONG S, GERDTZ M, VIRTUE E Royal Melbourne Emergency Department
ED02: Meredith Heily Intensive Care Unit Emergency ResuscitationTrolleys - how are they actually used? HEILY M, Hadley D, Hall P, Ross W Intensive Care Unit, The Royal Melbourne Hospital
ED03: Jonathan Knott Referral patterns by Emergency Department consultants for head and neck trauma: an Australian and New Zealand perspective A Bobinskas, A Nastri, J Knott The Royal Melbourne Hospital
ED04: Jonathan Knott Predicting patients at risk of early Emergency Department representations Tetcher L and Knott J The Royal Melbourne Hospital Emergency Department
ENDOCRINOLOGY, IMMUNOLOGY & ALLERGY EIA01: Julian Bosco Conditional CD52-deficient T cells display augmented proliferation in response to T-cell receptor activation JJ Bosco1,2, Y Zhang1, ME Bandala1, A Neale1 and LC Harrison1,2 1- Immunology Division, Walter & Eliza Hall Institute 2 - Dept of Clinical Immunology & Allergy, Royal Melbourne Hospital
EIA02: Peter Colman Abnormalities in glucose tolerance in the late pre-clinical stage of Type 1 Diabetes - metabolic staging in the Init II trial P. G. Colman (1), C. Breen (2), L. C. Harrison (3), I. Collaborators (4) 1 Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Australia 2 Burnet Clinical Research Unit, Royal Melbourne Hospital, Parkville, VIC, Australia 3 Walter and Eliza Hall Institute, Parkville, VIC, Australia 4 INIT II collaborators, Australia
EIA03: Candice Hall Facebook: A tool for clinical trial recruitment? C. R. Hall 1, R. K. Jones 2, F. J. McManus 1, P.G. Colman 3, L. C. Harrison 1,2 and the INIT II Collaborators 1 Burnet Clinical Research Unit, Royal Melbourne Hospital, VIC, Australia 2 Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia 3 Diabetes and Endocrinology, Royal Melbourne Hospital, VIC, Australia
EIA04: Christopher Yates Improving the detection and management of fragility fractures in ambulatory patients: the Fracture Capture Program YATES C.J.1,2, Bucknill A.T.3, Wark J.D. 1,2,4 1 Department of Diabetes and Endocrinology, Royal Melbourne Hospital 2 Department of Medicine, The University of Melbourne 3 Department of Orthopaedics, Royal Melbourne Hospital 4 Bone & Mineral Service, Royal Melbourne Hospital
EIA05: Christopher Yates Continuous Glucose Monitoring identifies reduced Hyperglycemia post Kidney Transplantation with Split Dose Prednisolone YATES C.J. 1,2, Cohney S.J. 2, Colman P.G. 1, McWhinney B.C. 3, Fullinfaw R 1, Fourlanos S 1 1. Diabetes and Endocrinology, Nephrology and Special Chemistry, Royal Melbourne Hospital 2. Medicine, University of Melbourne 3. Chemical Pathology, Pathology Queensland
EIA06: Christopher Yates
Research Week 2012 24 – 31 May 2012 Page 23 The ratio of insulin resistance to secretion is stable in the first month after kidney transplantation YATES C.J.1,2, Cohney S. 2, Pickering J. 3, Colman P.G. 1, Fourlanos S. 1 1 Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Australia, 2 Medicine, The University of Melbourne, Parkville, Australia, 3 Nephrology, Royal Melbourne Hospital, Parkville, Australia.
EI07: Christopher Yates Differential sensitivity of tests for hyperglycaemia after kidney transplantation YATES C.J.1,2, Cohney S. 2, Colman P.G. 1, Fourlanos S. 1 1 Diabetes and Endocrinology, and Nephrology, Royal Melbourne Hospital, Parkville, Australia, 2 Medicine, The University of Melbourne, Parkville, Australia.
GASTRO-INESTINAL GI01: Nancy Amin Wnt2b and Wnt11 in colorectal cancer morphogenesis AMIN N1, Schwab RHM1, Maedler A1, Beuchert E1, Flanagan DJ1, Barker N2, Vincan E1 1University of Melbourne and Victorian Infectious Diseases Reference Laboratories. 2. Institute of Medical Biology, Immunos, Singapore
GI02: Shakuntla Gondalia Molecular characterization of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings GONDALIA S.a, Palombo .E a,b, Cox S.d, and Austin D.a,c a Swinburne Autism Bio-Research Initiative (SABRI), b Environment and Biotechnology Centre, c Brain and Psycology Science Research Centre, Faculty of Life and Social Sciences, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia d Research and Testing Labs, Lubbock, Texas 79416
GI03: Christopher Leung Confocal Endomicroscopy Characteristics that Count: A Multivariate Analysis revealing Key Features in Diagnosing Dysplasia and Carcinoma in Barrett's Esophagus LEUNG C(1)(4), Lim EJ(1), Allen P(2), Delaney P(3), Murr E(3), Bhathal P(4), Marion K(5), Macrae F(1). (1) Royal Melbourne Hospital, Parkville, Victoria. (2) St Vincent's Hospital, Fitzroy, Victoria. (3) Optiscan, Notting Hill, Victoria. (4) University of Melbourne, Parkville, Victoria. (5) Royal Melbourne Institute of Technology, Melbourne, Victoria
GI04: Christopher Leung A NOVEL SIMULATION BASED METHOD OF DETECTING BARRETT'S DYSPLASIA: AN ANALYSIS OF THE INITIAL LEARNING CURVE IN CONFOCAL ENDOMICROSCOPY LEUNG C (1)(3), Delaney P (2), Bhathal P (3), Marion K (4), Tan A (1), Allen PB (5), Murr E (2), Macrae F (1)(3) (1) Department of Gastroenterology, Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, Victoria. (2) Optiscan Pty Ltd, Notting Hill, Victoria. (3) University of Melbourne, Parkville, Victoria. (4) Royal Melbourne Institute of Technology, Melbourne, Victoria. (5) Department of Gastroenterology, St Vincent's Hospital, Fitzroy, Victoria
GI05: Christopher Leung GASTROENTEROLOGY ADVANCED TRAINING - HOW MUCH IS ENOUGH? LEUNG C (1)(2), Jones A (2), Sliwka G (2), De Cruz P (2), Hebbard GS (1)(2) (1) The Royal Melbourne Hospital (2) The Royal Australasian College of Physicians
GI06: Eu Jin Lim CAPSULE ENDOSCOPY IN OROFACIAL GRANULOMATOSIS PATIENTS COMMONLY DIAGNOSES CROHN'S DISEASE LIM EJ(1), Cameron D(2), Wiesenfeld D(3), Brown G(1), Macrae F(1) Departments of Colorectal Medicine and Genetics (1) and Oral and Maxillofacial Surgery (3), The Royal Melbourne Hospital. Department of Gastroenterology (2), The Royal Children's Hospital
Research Week 2012 24 – 31 May 2012 Page 24 GI07: Paul Nguyen Understanding the role of epithelial Stat3 activation during chronic inflammation and cancer NGUYEN P, Preaudet A, Farid R, Loving A, Ernst M, and Putoczki T. Ludwig Institute for Cancer Research
GENETICS G01: Sarah Best Role of the Transcription Factors Id4 and Runx2 in Mammary Development BEST, S1,2, Fu N.Y.1,2, Lindeman G J1,3,4, Visvader J E1,2 1Walter and Eliza Hall Institute, 1G Royal Pde, Parkville 2Department of Medical Biology, University of Melbourne 3Royal Melbourne Hospital, Grattan Street, Parkville 4Department of Medicine, University of Melbourne
G02: Bianca Capaldo A genome-wide RNAi screen for novel regulators of the oncoprotein LMO4 BIANCA D CAPALDO1,2, Nai Yang Fu1,2, Kaylene J. Simpson4,5, Ekaterina Voronova1, Geoffrey J. 3. Lindeman1,3,4, Jane E. Visvader1,2 1 The Walter and Eliza Hall Institute of Medical Research 2 Department of Medical Biology, The University of Melbourne 3Department of Medical Oncology, The Royal Melbourne Hospital 4Department of Medicine, The University of Melbourne 5Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre 6 Sir Peter MacCallum Department of Pathology, University of Melbourne
INFECTIOUS DISEASES IF01: Louise Carolan Quantitation of cytokine mRNA levels in ferrets following influenza infection CAROLAN LA, Butler J, Reading P, Hurt AC, Kelso A, Barr IG and Laurie KL WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Victoria 3051, Australia
IF02: Upeksha Chandrasiri Glucose transport across the placenta disrupted in the presence of placental malaria with inflammation Upeksha P Chandrasiri1, Caroline L.L. Chua1, Alexandra J Umbers1, Paul R Sanders2, E. Chaluluka3, Jocelyn D. Glazier4, Stephen J Rogerson1, Philippe Boeuf1 1Department of Medicine, University of Melbourne, Parkville, VIC Australia, 2The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC Australia, 3College of Medicine, University of Malawi, Blantyre, Malawi, 4Maternal and Fetal Health Research Group, Research School of Clinical and Laboratory Sciences, Manchester Academic Health Sciences Centre, University of Manchester, St. Mary's Hospital, Manchester, UK
IF03: Caroline Chua The different uptake pathways of malaria-infected erythrocytes by macrophages result in distinct cytokine profiles CHUA C 1, Brown G 1,2, Hamilton J 1, Jaworowski A 3, Rogerson S 1, Boeuf P1 1Department of Medicine, University of Melbourne, Parkville, VIC, Australia 2Nossal Institute of Global Health, The University of Melbourne, Parkville, VIC, Australia 3The Macfarlane Burnet Institute for Medical Research and Public Health, VIC, Australia
IF04: Katherine Gibney Improving the health of international students in Victoria: Novel strategies to promote awareness of tuberculosis and travel related infections among a high-risk group GIBNEY KB, Brass A, Leder K Victorian Infectious Diseases Service, Royal Melbourne Hospital; Department of Epidemiology and Preventive Medicine, Monash University
IF05: Kristina Grant The effect of VZV vaccine on chickenpox and shingles Kelly H, GRANT K Victorian Infectious Disease Reference Laboratories, Melbourne Health
Research Week 2012 24 – 31 May 2012 Page 25 IF06: Wina Hasang HIV-1 infection decreases antibodies to merozoite antigens and antibodies that opsonise malaria infected erythrocytes in Malawian adults Hasang W.P12, Wijesinghe R 3, Dembo E 4, Kublin J 5, Molyneux M 6 and Rogerson S12 1Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Victoria; 2Victorian Infectious Diseases Service, Royal Melbourne Hospital, Victoria; 3School of Public Health, University of Queensland; 4Department of Experimental Medicine and Public Health, University of Camerino, Italy; 5Fred Hutchison Cancer Research Center, Seattle USA; 6Malawi-Liverpool- Wellcome Trust Clinical Research Programme and University of Liverpool, Liverpool UK
IF07: Marlena Kaczmarek Estimating the benefit and risk of influenza vaccination of children aged 6 months to 4 years Kelly H.A, KACZMAREK M.C, Moore H Victorian Infectious Diseases Reference Laboratory, Melbourne Health; Telethon Institute for Child Health Research, University of Western Australia
IF08: Margaret Littlejohn Molecular Epidemiology of Hepatitis B in Indigenous Australian Populations LITTLEJOHN M1, Edwards R1, Sozzi V1, Revill P1, Bowden S1, Cowie B 1,2, Davies J 3,4, Tong S 3,4, Anderson E5, Ho V6, Davis J 3,4, Locarnini S1. (1) Victorian Infectious Diseases Reference Laboratory, Melbourne (2) Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne (3) Menzies School of Health Research and Charles Darwin University, Darwin (4) Department of Infectious Diseases, Royal Darwin Hospital, Darwin (5) Cairns Base Hospital, The Esplanade, Cairns (6) School of Medicine, James Cook University
IF09: Louise Ludlow Investigating the role of cytokines and activated complement in peripheral blood cells from malaria-immune and non-immune pregnant women exposed to infected erythrocytes LUDLOW, L.E 1, Hasang W 1, Cutts J 2, Schofield L 2, Jaworowski A 3, Mueller I 2, Siba P 4, and Rogerson S.J 1 (1) Department of Medicine, Clinical Sciences Building, Royal Melbourne Hospital, University of Melbourne, Australia, (2) The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, (3) Centre for Virology, Burnet Institute, Melbourne, Australia and (4) Papua New Guinea Institute of Medical Research, Goroka, PNG
IF10: Tim Shaw Serum Guanase Activity as a Surrogate Marker for Hepatocyte Damage and Response to Interferon-alpha Treatment for Chronic Hepatitis C SHAW T, Zhang Y, Holmes J, Bowden DS Victorian Infectious Diseases Reference Laboratory, North Melbourne
IF11: Benjamin Teh Hepatitis B serological changes following allogeneic bone marrow transplantation TEH B1, 2, Slavin M1, 2, Szer J3, Sasadeusz J1, 4 1 Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria, Australia 2 Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia 3 Department of Clinical Haematology & Bone Marrow Transplant Service, Royal Melbourne Hospital, Parkville, Victoria, Australia 4 The Alfred Hospital, Centre for Clinical Research Excellence in Infectious Diseases, Prahran, Victoria, Australia.
IF12: Nadia Warner Antiviral drugs can select resistant HBV variants that are directly cytopathic to the host cell Colledge D, Soppe S, Selleck L, Locarnini S and WARNER N Victorian Infectious Diseases Reference Laboratories, North Melbourne, Victoria, AUSTRALIA
MENTAL HEALTH MH01: Kelly Allot Improving functional outcome using compensatory strategies in comorbid intellectual disability and psychosis: A case study ALLOTT K., Francey SM, Velligan DI Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne, Australia; Orygen Youth Health, Melbourne, Australia; University of Texas Health Science Center, San Antonio, USA MH02: Daniel Bennett
Research Week 2012 24 – 31 May 2012 Page 26 The problem of integrating sensory information in schizophrenia Bennett, D ., Carter, O., Cropper, S., Sundram, S
MH03: Georgina Cox A Systematic Review of School Based Interventions Aimed at Preventing, Treating, and Responding to, Suicide-Related Behaviour in Young People Robinson J, COX G, Malone A, Williamson M, Baldwin G, Fletcher K and O'Brien M Orygen Youth Health Research Centre, University of Melbourne; headspace (Australia's Youth Mental Health Foundation)
MH04: Jonathan Knott Depression Symptoms and Risk Factors in Adult Emergency Department Patients: A Multi-site Cross-sectional Prevalence Survey Khav N, Weiland T, Jelinek G, Salzberg M and Knott J St Vincent's Hospital Emergency Practice and Innovation Centre Melbourne, St Vincent's Hospital Melbourne Mental Health Services, The Royal Melbourne Hospital Emergency Department
MH05: Carsten Schley ‘Time to Reflect’: An innovative partnership model between an educational and a clinical service to enhance the practice of secondary school wellbeing personnel in responding to mental health needs of students. SCHLEY C (1), Ring J (2), McKay-Brown L (2), Crothers L (1), Robinson J (3), Bruxner A (3), Cox G (3) (1) Orygen Youth Health - Training & Communications, (2) Department of Education and Early Childhood Development - Travancore School, (3) Orygen Youth Health - Research Centre
MH06: Vaidy Swaminathan Perceptual disturbance in Schizophrenia is related to differential EGFR mRNA expression in cortical layers in post mortem brain SWAMINATHAN V1, 2, 3, 4, Pereira A1, 2, Weickert CS4, 5, 6, Sundram S1, 2, 3 1: Mental Health Research Institute, Victoria, 2: University of Melbourne, 3: Northern Psychiatry Research Centre, Northern Area Mental Health Service, 4: Schizophrenia Research Institute, NSW, 5: Schizophrenia Research Laboratory, NeuRA, NSW, 6: University of NSW
MUSCULOSKELETAL MS01: Jemma Christie Emerging nutritional and lifestyle risk factors for bone heath in young women: a mixed longitudinal twin study CHRISTIE JJ, Nowson C, Garland SM, Wark JD University of Melbourne; Deakin University
NEUROSCIENCES N01: Idrish Ali Enduring effects of early-life stress on neuronal firing patterns in thalamic reticular nucleus and hippocampus: implications for limbic epilepsy ALI I.1, Salzberg M. R.2, Jones N. C.1, Pinault D.3, O'Brien P.1, French C.1, Morris M. J.4, O'Brien T. J.1 1Dept. of Medicine, Univ. of Melbourne, Melbourne, Australia; 2Dept. of Psychiatry, Univ. of Melbourne, Melbourne, Australia; 3Faculté de Médicine, Univ. de Strasbourg, Strasbourg, France; 4Dept. of Pharmacology,, Univ. of New South Wales, Sydney, Australia
N02: Ryan Atkins Regulation of GSK-3beta by the Akt pathway in gliomas RYAN ATKINS*, Andrew Morokoff*, Kate Drummond*, Andrew Kaye* *Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, Vic, Australia
N03: Christen Barras CT Angiographic 'Spot Sign' Predicts Intracerebral Hemorrhage Growth and Poor Outcome - A Prospective Study BARRAS C.D.J.,1 Tress B.M.,1 Christensen S.,1 Desmond P.M.,1 Salinas S.,1 Churilov L.,2 Davis S.M.2,3 1. Department of Radiology, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia 2. Melbourne Brain Centre, The University of Melbourne, Melbourne, Australia 3. Department of Neurology, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia
Research Week 2012 24 – 31 May 2012 Page 27 N04: Christen Barras CT Angiographic 'Spot Sign': Significance, Appearance, Mimics, and Unusual Cases BARRAS C.D.J.,1 Tress B.M.,1 Desmond P.M.,1 Davis S.M.2,3 1. Department of Radiology, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia 2. Melbourne Brain Centre, The University of Melbourne, Melbourne, Australia 3. Department of Neurology, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia
N05: Katherine Burn The effect of grandmothering on cognition in post-menopausal women: the Women's Healthy Aging Project (WHAP) Katherine Burn1, David Ames2, Lorraine Dennerstein3, Casssandra Szoeke1 1National Aging Research Institute, University of Melbourne 2National Aging Research Institute 3University of Melbourn
N06: Bruce Campbell Perfusion-diffusion mismatch reflects leptomeningeal collateral quality and changes in collateral flow are associated with infarct growth CAMPBELL BCV, Christensen S, Tress BM, Desmond PM, Parsons MW, Barber PA, Levi CR, Bladin CF, Donnan GA, Davis SM for the EPITHET Investigators Departments of Medicine and Neurology (B.C.V.C., S.M.D.), The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; the Department of Radiology (B.C.V.C., S.C., B.M.T., P.M.D.), Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; the Department of Neurology and Hunter Medical Research Institute (M.W.P., C.R.L.), John Hunter Hospital, University of Newcastle, Australia; the Centre for Brain Research (P.A.B.), University of Auckland, Auckland, New Zealand; the Department of Neurology (C.F.B.), Box Hill Hospital, Monash University, Melbourne, Australia, and the Florey Neuroscience Institutes (G.A.D.), Parkville, Australia
N07: Bruce Campbell CT perfusion improves diagnostic accuracy and confidence in acute ischemic stroke CAMPBELL BCV, Weir L, Desmond PM, Tu HTH, Hand P, Yan B, Donnan GA, Parsons MW, Davis SM Departments of Medicine and Neurology (BC, HT, PH, BY, SD), The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; the Department of Radiology (BC, PD), Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; the Department of Neurology and Hunter Medical Research Institute (MP), John Hunter Hospital, University of Newcastle, Australia, and the Florey Neuroscience Institutes (GD), Parkville, Australia
N08: Bruce Campbell Comparison of CT Perfusion Mismatch with Perfusion-Diffusion MRI in Ischemic Stroke - a Reliable Alternative? CAMPBELL BCV, Christensen S, Levi CR, Desmond PM, Donnan GA, Davis SM, Parsons MW Departments of Medicine and Neurology (BC, SD), The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; the Department of Radiology (BC, SC, PD), Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; the Department of Neurology and Hunter Medical Research Institute (CL, MP), John Hunter Hospital, University of Newcastle, Australia, and the Florey Neuroscience Institutes (GD), Parkville, Australia
N09: Mun Yoong Cheang Does recanalisation success correlate with good clinical outcome at 3 months in stroke patients treated with Solitaire FR? CHEANG MY, YAN B, MITCHELL P, DOWLING R The Royal Melbourne Hospital
N10: Judith Field Analysis of genotype-dependent CD40 expression in multiple sclerosis FIELD, J., Johnson, L.J., Butzkueven H., Kilpatrick, T.J., Australia and New Zealand Multiple Sclerosis Genetics Consortium Florey Neuroscience Institutes, University of Melbourne N11: Hui Lim Moving in time: the story of phenylketonuria, ophthalmic illustration and an asylum Lim H, Yeoh J, Kaufman D Department of Ophthalmology, Royal Melbourne Hospital
N12: Gerry Ma TAM receptor signalling in inflammatory demyelination MA GZM, Field J, Kilpatrick TJ and Binder MD Florey Neuroscience Institutes and Centre for Neuroscience, University of Melbourne Research Week 2012 24 – 31 May 2012 Page 28
N13: Avril Pereira Dopamine D1 receptor involvement in EGF receptor transactivation to ERK signaling induced by clozapine PEREIRA A, Zhou Y, Raaijmakers H, Sundram S. Mental Health Research Institute, The University of Melbourne, Parkville, Australia
N14: Jan Quiney Best Practice for Upper Limb Management for Neurological Patients Physiotherapy and Occupational Therapy Departments at the Royal Melbourne Hospital City Campus and Royal Park Campus Royal Melbourne Hospital, Physiotherapy and Occupational Therapy Departments
N15: Pragati Sharma Neuroanatomical Underpinnings To Interrelated Neurological Disorders Sharma P, Jones NC, O’ Brien T, Gilby K Melbourne Brain Centre, The Royal Melbourne Hospital, The University of Melbourne
N16: Baemisla Shiek Ahmad Chronic effects of antiepileptic drugs (AEDs) on balance function: a longitudinal twin and sibling pair study SHIEK AHMAD B 1, 6, Hill K D 2, 3, O’ Brien T J 1, 5, Gorelik A 7, Petty S J 1, Wark J D 1, 4 (1) Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, (2) School of Physiotherapy, Faculty of Health Sciences, Curtin University, WA, (3) National Ageing Research Institute, Parkville, VIC, (4) The Royal Melbourne Hospital Bone and Mineral Service, Parkville, VIC, (5) Department of Neurology, The Royal Melbourne Hospital, Parkville, VIC, (6) Department of Physiology, Faculty of Medicine, University of Malaya, MALAYSIA, (7) The Melbourne EpiCentre, The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC
N17: Lucy Vivash [18F]-Flumazenil: A novel PET radiotracer for the localisation of drug resistant focal epilepsy VIVASH L1, Gregoire MC2, Lau EW3, Ware RE3, Roselt P3, Binns D3, Bouilleret V1, Myers DE1, Hicks RJ3, O’Brien TJ1 1 Department of Medicine (RMH), University of Melbourne, Melbourne, Australia 2 ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Sydney, Australia 3 The Centre for Molecular Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia
N18: Paul Yates Incidence and associations of lobar microbleeds: results fro the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) Yates, P 1,2, Desmond, P 2,3, Raniga, P 4, Phal, P 3, Steward, C2, Salinas, S2, Salvado, O4, Martins, R5, Ellis, K 2,6, Szoeke, C7, Masters, C 2,6, Ames, D 7, Villemagne, V 1,2, and Rowe, C 1,2, for the AIBL Research Group. 1 Austin Health 2 University of Melbourne 3 Royal Melbourne Hospital 4 CSIRO, Brisbrane Australia 5 Edith Cowan University, Joondalup, Western Australia 6 Mental Health Research Institute, Parkville 7 National Ageing Research Institute, Parkville
QUALITY OF CARE Q01: Cathy Daniel Staff and public perceptions of the processes used to prevent aggression in emergency departments Cathy DANIEL 2, Marie Gerdtz 2, Jonathan Knott 2, Stephen Elsom 1 1. The University of Melbourne, Department of Nursing, Melbourne 3030 2. The Royal Melbourne Hospital, Grattan St, Parkville, 3053
Q02: Eugenia Hong The effects of clinical trials pharmacist counselling on participant compliance in clinical trials Hong E, Michael E Royal Melbourne Hospital, Clinical Trials Pharmacy
Research Week 2012 24 – 31 May 2012 Page 29 Q03: Suzanne Kosmider Filling the knowledge void- the BioGrid Facilitated Solution KOSMIDER S, Gibbs P, O'Brien T, Colman, P BioGrid Australia, Western Health, Royal Melbourne Hospital, Ludwig Institute Cancer Research, University of Melbourne
Q04: Nicole Lafontaine Chest-Tube Insertion: Improving Adherence to Consensus Guidelines Lafontaine N, Joosten S, Irving L, Hew M Respiratory & Sleep Medicine, Royal Melboure Hospital, Department of Medicine, University of Melbourne
Q05: Marcel Mihulka Developing a combined E-learning platform for a major Melbourne Hospital and University Clinical School MIHULKA M, Morley P, Reid E The Royal Melbourne Hospital
Q06: Laura Piu Electronic Handover Tool for Junior Doctors- An HMO Improvement Project Dr P Tescher, L PIU, J Harper, Dr P Bradford, Dr H Su, Dr A Altson The Royal Melbourne Hospital
Q07: Mark Tacey Predictors and costs of unplanned readmissions among general medical patients Tacey M*#, Jones C*, Liew D*#, Brand C*#, Jackson C*, Yew S*, Russell D*# * The Royal Melbourne Hospital, # The University of Melbourne
Q08: Tristan Vasquez Reducing Medication Errors in Mental Health Community Settings Vasquez, T. NorthWestern Mental Health
REHABILITATION R01: Maria Jenelyn Alviar Do patient-reported outcome measures in hip and knee arthroplasty rehabilitation have robust measurement attributes? a systematic review ALVIAR MJ, Olver J, Brand C, Tropea J, Hale T, Pirpiris M, Khan F University of Melbourne-Royal Melbourne Hospital; Epworth Rehabilitation
R02: Maria Jenelyn Alviar Can the World Health Organization-International Classification of Functioning, Disability and Health (WHO-ICF) Osteoarthritis (OA) core set represent a future clinical tool in measuring functioning in persons with OA undergoing hip and knee joint replacem ALVIARMJ, Olver J, Pallant J, Brand C, de Steiger R, Pirpiris M, Bucknill A, Khan F University of Melbourne-Royal Melbourne Hospital, Rural Health Academic Centre-University of Melbourne, Epworth Healthcare
SURGERY S01: Wayne Hoskins Elective and emergency colectomies performed at a rural Australian hospital: a seven year analysis HOSKINS W, Taylor P, Jacob A, Wijeratne S, Campbell I Royal Melbourne Hospital / Wimmera Health Care Group: Horsham Campus
Research Week 2012 24 – 31 May 2012 Page 30 RESEARCH WEEK 2012
POSTER DISPLAY MAP
Foyer Clinical School Infectious Diseases x12 (IF01 – IF12) Endo, Immunology & Allergy x7 (EIA01 – EIA07) Musculoskeletal x1 (MS01) ED/Critical Care x 4
Neurosciences x 18 (N01 – N18) Rehabilitation x2 (R01 – R02)
Quality of Care x8 (Q01 – Q08)
Aged Care x1 (AC01) Gastro‐intestinal x7 (GI01 – GI07)
Mental Health x6 (MH01 – MH06) Cardio‐respiratory x5 (CR01 – CR05) Surgery x1 (S01)
Cancer x8 (C01 – C09) Blood x2 (B01 – B02) Genetics x2 (G01 – G02)
Research Week 2012 24 – 31 May 2012 Page 31