Students in Health and Medical Research Conference 2015

SHMRC

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Students in Health and Medical Research Conference

2015

Conference Program

Sponsors

Platinum Sponsors

Gold Sponsors

School of Medicine and Pharmacology

2 Silver Sponsors

School of Pathology and Laboratory Medicine

Bronze Sponsors

School of Psychiatry and Clinical Neurosciences School of Population Health

Door Prize

Judges

Professor Sean Hood MBBS, MSc, FRANZCP

Professor Sean Hood undertook his undergraduate medical degree at the University of Western Australia before completing formal postgraduate training in Psychiatry in Perth (Australia) and Bristol (United Kingdom) in 2003. Prof Hood completed his Masters’ Degree in Affective Neuroscience (University of Maastricht, Netherlands, 2003). Subsequently, he returned to Perth setting up a Clinical Psychopharmacology laboratory as a clinical academic in the University of Western Australia’s Psychiatry & Clinical Neurosciences Unit. Prof Hood is Chair of the Australian Pristiq Advisory Board and a member of the Australian Cymbalta & Vortioxetine Advisory Boards. He is a psychiatrist in academic (UWA), public (SCGH) and private practice (Hollywood Medical Centre). Prof Hood currently runs the 6th year Psychiatry MBBS program at UWA and chaired the Systems’ Committee of the new UWA MD Program. Professor Hood is currently head of the UWA School of Psychiatry & Clinical Neurosciences.

Professor Neil Boudville MBBS, MMedSc, FRACP, FASN

Neil Boudville is Professor of Renal Medicine and Sub-Dean for the Faculty of Medicine, Dentistry and Health Sciences at the University of Western Australia. He is also the Head of Department of the Renal Unit at Sir Charles Gairdner Hospital and the Medical Director of the WA Home Dialysis Program. He has 4 current NHMRC Project grants and is the Chair of the Scientific Committee for the Australasian Kidney Trials Network.

Professor Fiona Lake MBBS, MD, FRACP

Professor Fiona Lake holds the Eric Saint Chair of Medicine at the University of Western Australia and is a Respiratory Physician at Sir Charles Gairdner Hospital, Perth. Her clinical work is based around inpatient and outpatient care, in particular, caring for patients with chronic underlying diseases (such as chronic obstructive pulmonary disease and interstitial lung disease). With colleagues, Prof Lake established a community-based service for patients with COPD, with the aim of reducing admissions and improving quality of life. In her academic practice, she has had extensive involvement in medical education, both in training health professionals through curriculum development, implementation and accreditation, and in training the supervisors.

Professor Mariapia Degli-Esposti BSc, PhD

Professor Mariapia Degli-Esposti is a NHMRC Principal Research Fellow at the University of Western Australia and heads the Experimental Immunology Group at the Centre for Ophthalmology and Visual Sciences. Professor Degli-Esposti is also the Head of the Immunology Division and was appointed Head of Research at the Lions Eye Institute in 2009. She has achieved international recognition as a viral immunologist with her research in the interactions between innate and adaptive immune responses being widely cited.

Professor Rodney Dilley BSc, PhD

Rod Dilley is at the Ear Science Institute Australia in Perth where he heads Molecular and Cellular Otolaryngology research. He is also an Associate Professor at the School of Surgery, University of Western Australia and Member of the UWA Centre for Cell Therapy and Regenerative Medicine. Since gaining his PhD at UWA and postdoctoral study in Seattle USA, he worked at Baker and O’Brien Research Institutes in Melbourne and Melbourne University on biology of cardiovascular disease and regenerative medicine. He developed a novel human cardiac tissue engineering method using vascularised chambers and stem cells from fat or pluripotent stem cells. Returning to Perth in 2011 his work at Ear Sciences Centre has focused on novel materials and stem cells for tissue engineering in relation to ear and hearing disorders. The work of his multidisciplinary team also includes development of devices for tissue engineering and reconstructive ear surgery. In addition, Rod has graduate and undergraduate teaching roles at UWA, Curtin, Murdoch and the University of Notre Dame and is a member of Research Committee Executive at University of Notre Dame Medical School.

Professor George Yeoh Bsc, PhD

Professor George Yeoh received his PhD in Biochemistry from UWA in 1972. Shortly after he was awarded the CJ Martin Overseas Research Fellow (NHMRC) and studied at the University of Pennsylvania USA and the Beatson Institute for Cancer Research, Glasgow, Scotland. He filled many roles as Visiting Scientist at a number of prestigious universities in the USA and in Europe. Following his return to Australia he was successful in obtaining an NHMRC Fellowship and achieved successive renewals to the level of Principal Research Fellow. He is currently the Associate Dean of Research in the UWA Faculty of Medicine, Dentistry and Health Sciences, as well as a Professor of Biochemistry & Molecular Biology. Professor Yeoh is the Head of the Liver Disease and Carcinogenesis Laboratory of the Centre for Medical Research at The Perkins Institute of Medical Research, and was appointed by the University of Western Australia as its representative on the Board and brings his knowledge of stem cell biology and tissue repair to the Institute.

Career Development Speaker

Robert Henderson MBBS, BMedSci (Hons),

STUDENT INFO NIGHT

21 August, 2015 Find more information 5:00pm – 7pm on our facebook page Lions Eye Institute In the Foyer, Harry Perkins Institute Student Information Night 6 Verdun St, Nedlands

Research opportunities available www.lei.org.au

Prizes

First Place Oral Presentation $1000

Second Place Oral Presentation $250

Third Place Oral Presentation $100

Most Engaging Speaker $100

Best Poster Presentation $250

Door Prize AMA Voucher worth $200

Best Question Copy of Clinical Examination, 7th Edition: A Systematic Guide to Physical Diagnosis By Talley and O’Connor

SHMRC

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The impact of risk taking behaviour in adolescence on future executive and cognitive function, psychomotor function, attention and associative memory.

Wendy Lim: UWA School of Paediatrics and Child Health

Background: Risk-taking behaviour during adolescence is a major public health concern. Reduced executive cognitive function (ECF) may result in the tendency to perform impulsive actions such as risk-taking behaviours. Further neurocognitive deficits may also result from neurotoxic effects of the misused substances This study aims to investigate the relationship between risk-taking behaviours and neurocognitive function, focusing particularly on ECF, psychomotor function, attention/vigilance and associative memory.

Methods: This cross-sectional study examined data from the Raine Study 16-18 year old follow up. Seven hundred and eight (n=708) participants underwent computerised cognitive testing using the CogState Battery, including the Groton Maze Learning Task (GML), Detection Task (DET), Identification Task (IDN) and Continuous Paired Associate Learning Task (CPAL). Information regarding sexual, marijuana and alcohol risk-taking behaviours were taken from self-reported questionnaires.

Results: Adolescents with early sexual debut, multiple sexual partners and frequent marijuana use made more errors on tasks assessing ECF (GML) and associative memory (CPAL). They also had a slower response speed on tasks assessing attention function (IDN), but showed no difference compared to peers on tasks assessing psychomotor function (DET). Compared to their peers, adolescents with binge-drinking behaviours showed worse performance on tasks assessing associative memory (CPAL), but displayed no difference on other tasks.

Conclusion: Risk-taking behaviours, such as early sexual debut, multiple sexual partners and frequent marijuana use were associated with reduced ECF, visual attention and associative memory, but not with psychomotor speed. Adolescents with binge-drinking behaviours demonstrated reduced associative memory compared to their peers, but otherwise had no significant association with other neurocognitive capacities.

11 Early Development and medical co-morbidity in rare genetic disorder: MECP2 Duplication Syndrome

Zhan Lim: Telethon Kids Institute / UWA

Background: Micro-duplications involving the MECP2 gene have been established as a form of X- linked neurodevelopmental disorder known as the MECP2 duplication syndrome (MDS). Cardinal features include global developmental delay, infantile hypotonia and facial anomalies. Epilepsy and recurrent respiratory infections appear to be common. However, there have been no large-scale studies describing the phenotype of this disorder. The aim is to provide exploratory analysis on the acquisition of gross motor milestones, functional abilities and comorbidities in MDS.

Methods: Questionnaire data provided by parents were obtained from the International Rett Syndrome Database (InterRett).

Results: Data were collected from 56 cases (48 males) with MDS. Mean age of diagnosis was 6 years, with MDS the initial diagnosis in only 11% of cases. Delayed milestones were commonly reported (47/56, 84%) by 10 months of life. Speech regression had occurred in 19 (43%) of the 44 cases who had attained babble or words for communication. Limited non-verbal communication was observed in more than 50%. The majority (71%) did not acquire independent ambulation, with mean age of acquisition of walking at 3.1 years. Common co-morbidities include gastrointestinal problems (90%), respiratory infections (71%) and epilepsy (45%). Behavioural abnormalities such as stereotypic hand movements and teeth grinding were observed in more than half of the sample.

Conclusion: Investigations for MDS should be considered in children (particularly boys) who present with severe developmental delay especially in the presence of respiratory infections. Data collected from this study will inform a better understanding of this condition.

12 Investigation of the cellular immune response in peripheral blood samples for children suffering an acute asthmatic episode

Anya Jones: UWA / Telethon Kids Institute

Background: Human rhinovirus and respiratory syncytial virus cause acute viral bronchiolitis in infancy and are a major risk factor for the development of asthma during childhood. At birth, the immune and respiratory systems are in a temporary state of functional immaturity, and the delayed postnatal maturation of immunological function is associated with increased risk for severe respiratory infections and development of persistent asthma. Our current understanding of how host immune responses to virus change from infancy to older children is limited. Hence, a systematic investigation is required of cellular and molecular mechanisms underlying acute viral respiratory illnesses from infants with bronchiolitis through to school age children with asthma. Here, the cellular mechanisms in older children with an asthma exacerbation are presented. The objective of this study is to investigate cellular immune responses in peripheral blood samples collected from children during an acute episode of asthma.

Methods: Peripheral blood mononuclear cells (PBMC) were collected from school age children (6-15 years of age) during an asthma exacerbation (acute visit) and at 6-8 weeks follow-up (convalescent visit). Multiparametric flow cytometry (12-colours) was employed to quantify myeloid and lymphoid cell subsets.

Results: The data showed a significant decrease in inflammatory cell subsets in PBMC during an acute episode of asthma, including pDCs (p<0.0001), cDCs (p=0.0101), basophils (p=0.0004) and T cells (p=0.0004). High affinity IgE receptor was significantly lower during the acute episode in DC subsets.

Conclusion: An asthma flare-up is associated with significant modulation of immune cell populations in peripheral blood.

13 An evaluation of the antibody response to the respiratory pathogens non-typeable haemophilus influenzae, streproccocus pneumoniae and Group A streptococcus in children

Tulia Mateus: UWA School of Paediatrics and Child Health

Background: Obstructive sleep apnoea (OSA) affects 2-3% of children under 10 years of age. The pathogenesis of OSA is not well understood but correlates with an increase in allergic disease. We hypothesize that OSA is driven by an enhanced allergic response to persistent respiratory bacteria. This study aimed to evaluate the antibody response to the respiratory pathogens nontypeable Haemophilus influenzae (NTHi), Streptococcus pneumoniae and Group A streptococcus (GAS).

Methods: Serum IgG and IgA to vaccine candidate proteins from NTHi (P4, P6 and PD), S. pneumoniae (Ply, PspA1, PspA2 and CbpA) and GAS (ScpA) were assessed in children with OSA (n=40), recurrent tonsillitis (RT, n=21), OSA+recurrent tonsillitis (OSA+RT, n=14) and healthy controls (n=55) using a multiplex bead based assay. Atopic status was assessed using total IgE and parental questionnaire.

Results: IgG titers against proteins PD from NTHi in OSA (M = 12.6x104 AU/ml), RT (M = 12.9x104 AU/ml) and OSA+RT (M = 6.9 x104 AU/ml) were significantly lower (p ≤ 0.003) than healthy controls (M = 44.3x104 AU/ml). IgG titers against P6 from NTHi in OSA (M = 23.6x105 AU/ml) and RT (M = 21.4x105 AU/ml) were significantly higher (p ≤ 0.004) than healthy controls (M = 7.3x105 AU/ml). There were no significant differences in antibody titers between the 3 clinical groups. IgG and IgA titers against S pneumoniae were not significantly different between the 4 groups, except for IgA titers for PspA1 and PspA2, which were significantly higher (p ≤ 0.04) in OSA (M = 58.6x103 AU/ml and M = 31.1x103 AU/ml, respectively) compared to RT (M = 33.7x103 AU/ml and M = 10.3x103 AU/ml, respectively). Antibody titers against SCPA protein from GAS and total IgE were not significantly different between the 4 groups.

Conclusions: IgG and IgA responses to bacterial vaccine candidates were similar between the three groups of children with adenotonsillar diseases, but different to healthy controls. Whilst overall atopy appears similar across the cohort, differences in pathogen specific IgE responses may still exist, resulting in the pathology observed. The IgE pathogen specific responses are the source of ongoing study.

15 Validating optical coherence tomography use for diabetic retinal screening in an Aboriginal population

Richard O’Halloran: Lions Eye Institute / UWA Centre for Ophthalmology and Visual Science

Background: The rise of diabetic retinopathy (DR) has precipitated growth in validated telehealth screening programs. Optical coherence tomography (OCT) is more able to detect DR than conventional screening methods. However, OCT use for screening has limited evidence and is rarely done. The aim is to evaluate the introduction of OCT into a pre-existing screening program for Indigenous Australians with diabetes.

Methods: A retrospective audit of screening reports from the Lions Outback Vision DR Screening Program was undertaken at two Aboriginal Medical Services. Reports were accessed from April- October in both 2014 (prior to OCT introduction) and 2015 (following OCT introduction). Reports were included for all patients with diabetes, unless a patient was receiving other ophthalmology or optometry care or necessary data was unavailable. The primary outcome was how management changed with OCT use. Secondary outcomes include rates of referral, adequate photos, DR prevalence and severity and the overall system coverage.

Results: Preliminary results show 65 included results in 2015 compared with 57 in 2014. Referral rates to ophthalmology were 34.3% (2014) and 26.1% (2015). 2015 results showed that 70.8% of fundus photos were adequate for grading, with 69.6% of these showing no DR. Of the 27 requiring referral to ophthalmology on fundus photo alone, 10 could be followed-up in one year following OCT review.

Conclusion: The results suggest that OCT reduces ophthalmology referrals and clinic burden. Further research is needed to ascertain the cost-effectiveness of its widespread use.

16 An exploration of the Epigenetic profile of megakaryocytes in human MPN

Jacques Malherbe: School of Pathology & Laboratory Medicine

Background: Myeloproliferative neoplasms (MPN) are a heterogenous group of clonal proliferative bone marrow diseases characterised by megakaryocyte hyperplasia and morphological atypia. Proliferative and apoptotic signalling disturbances, in conjunction with JAK2V617F and CALR mutations, promote megakaryocyte expansion in the MPN. However, mutations in several epigenetic regulators (e.g. EZH2, SUZ12, Ikaros) are implicated in the myelofibrotic (MF) transformation of MPN. Despite this knowledge, the epigenetic pathology of myeloproliferative megakaryocytes remains poorly defined. We have explored the epigenetic profile of megakaryocytes in human MPN.

Methods: Immunohistochemical staining was performed on bone marrow trephine biopsies of 81 MPN (with and without MF transformation) and 15 normal controls to assess the megakaryocytic expression of select epigenetic biomarkers (i.e. EZH2, SUZ12, Ikaros).

Results: Myeloproliferative megakaryocytes showed significantly greater expression of SUZ12 than controls, but not for EZH2. Moreover, MF cases had significantly fewer SUZ12-expressing megakaryocytes than non-MF trephines. Ikaros was not expressed by megakaryocytes in MPN or control trephines.

Conclusions: Defective epigenetic regulation contributes towards the uncontrolled expansion of megakaryocytes in MPN. The overexpression of SUZ12 may act to silence “hyperactivated,” proliferation-inducing genes in MPN. However, the attenuation of megakaryocytic SUZ12 expression among transforming MPN towards MF implicates a loss of epigenetic control that may exacerbate acquired megakaryocyte abnormalities and promote adverse thrombotic events. EZH2 and Ikaros do not appear to play a role in the megakaryocyte pathology of MPN.

Master of Surgery

School of Surgery Medicine, Dentistry and Health Sciences

The course is facilitated by CTEC, the Clinical

Training and Evaluation Centre. CTEC is a designated surgical training facility at UWA specialising in the teaching of surgical skills outside the operating theatre. In addition to academic competencies, students gain practical experience by participating in advanced surgical skills workshops at CTEC.

The UWA Master of Surgery (MS) course is a For further information contact Shauna Budd unique and innovative program for junior doctors CTEC who are pursuing a career in Surgery. T +61 8 6488 8044 The course aims to develop technical skills in E [email protected] surgical procedures and provide students with the W ctec.uwa.edu.au skills to initiate and progress research effectively and independently. Students will expand their knowledge and learn how to design, conduct, For information about other workshops we analyse and evaluate surgical research. offer at CTEC, please visit our website.

Go further with a UWA postgraduate health degree Let us help you pursue your full potential as a health professional. Build on your skills, experience and qualifications and prepare yourself for a leadership role in the health system with a Master of Public Health, or get world-class research training in a field you’re passionate about with a MPhil or PhD with the School of Population Health. Find out more about these and other courses with us. Visit sph.uwa.edu.au

Samuel Taylor: UWA School of Pathology and Laboratory Medicine

Background: A major issue with current cancer treatment is myelosuppression, which is the harmful depletion of the haematopoietic system that occurs as a result of chemotherapy. We have previously identified that treatment with AC220 (quizartinib), a second-generation FLT3 inhibitor, induces a transient quiescence in early haematopoietic progenitor cells in a murine model. We investigated this phenomenon further to determine whether AC220-induced quiescence could protect wildtype (WT) progenitors from chemotherapy-induced death.

Methods: B6 mice were dosed via oral gavage with AC220, or vehicle, to determine quiescence (via flow cytometric Ki67 expression and cell cycle analysis) and the resultant sensitivity to the chemotherapeutic agent 5-FU (bone marrow and blood flow cytometry).

Results: B6 mice dosed with AC220 display a transient induction of quiescence in their hematopoietic progenitor cell compartment. This AC220-induced quiescence proved sufficient to induce protection from the cytotoxic actions of 5-FU such that pre-treatment with AC220 (2-18hr prior to 5-FU) led to a 10-fold increase in the number of hematopoietic multipotent progenitor cells surviving 2 days post injection. Furthermore, AC220-primed B6 mice displayed significantly higher survival and improved peripheral blood parameters after serial 5-FU treatment.

Conclusion: A priming dose of AC220 before 5-FU provides a simple and effective means to protect bone marrow progenitors from chemotherapy-induced death. This experimental protocol has the potential to drastically improve the quality of life of cancer patients and reduce costs associated with chemotherapy-induced myelosuppression.

19 A New Measure of Tibial Sesamoid Position in Hallux Valgus in Relation to the Coronal Rotation of the First Metatarsal in CT Scans

Yejeong DeGeer: UWA Podiatric Medicine Faculty, School of Surgery

Background: We aimed to find a new radiographic measurement for evaluating first metatarsal pronation and sesamoid position in hallux valgus (HV) deformity.

Methods: Data from a clinical study of 19 control patients (19 feet) with no HV deformity were compared with preoperative data of 138 patients (166 feet) with HV deformities. Using a weightbearing plain radiograph in anteroposterior (AP) view, the intermetatarsal angles (IMAs) and the hallux valgus angles (HVAs) of the control and study groups were measured. Using a semi- weightbearing coronal computed tomography (CT) axial view, the α angle was measured in the control and study groups. In addition, the tibial sesamoid grades in plain radiograph tangential view and the CT axial view were measured. The tibial sesamoid position in an AP view was checked preoperatively. Based on these measurements, 4 types of HV deformities were defined.

Results: The mean values of the α angle in the control and HV deformity groups (control group µ = 13.8 degrees, study group µ = 21.9 degrees) was significantly different. Among 166 HV feet, 145 feet (87.3%) had an α angle of more than 15.8 degrees, which is the upper value of the 95% confidence interval of the control group, indicating the existence of abnormal first metatarsal pronation in HV deformity. Four types of HV deformities were defined based on their α angles and tibial sesamoid grades in CT axial view (CT 4 position). Among 25.9% (43/166) of the study group, abnormal first metatarsal pronation with an absence of sesamoid deviation from its articular facet was observed. The prominent characteristic of this group was that they had high grades in the AP 7 position (≥5); however, in the CT 4 position, their grade was 0. This group was defined as the “pseudo-sesamoid subluxation” group.

Conclusions: Patients with HV deformities had a more pronated first metatarsal than the control group, with a greater α angle. Pseudo-subluxation of the sesamoids existed in 25.9% of our study group. From our results, we suggest that the use of the CT axial view in assessments of HV deformity may benefit surgeons when they make operative choices to correct these deformities. With regard to the pseudo-sesamoid subluxation group, the use of the distal soft tissue procedure is not surgically recommended.