melbourne health research week · master of ceremonies (mc) professor ingrid winship, executive...

Melbourne Health Research Week

26 May – 2 June 2011

1 1

Melbourne Health Research Week 2011

Research Week is an opportunity to share, be proud and celebrate research. Only through research can we afford to effect change that improves health care in our community. Showcasing a cross-section of disciplines during the week-long events – from research in neurosciences to research in genetics, cancer to colorectal medicine, clinical practice to infection, etc – Research Week 2011 promises to be all-encompassing and relevant. This year we received 185 abstracts and from these we have selected many for oral and poster presentation. Between the Research Symposium, the Opening and Closing Ceremonies, the Surgical Research Forum and the Translating Research into Practice session, this year features 44 oral presentations. 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 program. Thank you to –

Dr Matthias Ernst Ms Marie Gerdtz Ms Carol Jewell Ms Catherine Lander Ms Angela Magira Ms Morag Morrison Professor Nick Santamaria Professor Terry O’Brien Dr Peter Revill Dr Clare Scott Ms Jessica Turner Dr Angela Watt Mr David Zerman

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

Melbourne Health Melbourne Health Melbourne Health Melbourne Health Research WeekResearch WeekResearch WeekResearch Week

2

DAY 1 – Thursday 26 May 2011

Opening Ceremony 1.00 pm – 1.45 pm, Charles La Trobe Lecture Theatre (12.30 Lunch)

Welcome and opening ceremony of Melbourne Health Research Week with the opening plenaries:

1. Professor Danny Liew - Translational Research – From efficacy to effectiveness and cost-effectiveness

2. Susie Bae - From toppling regimes to facilitating rare cancer research – the power of social media

DAY 2 – Friday 27 May 2011

Research Symposium 9.15 am – 10.15 am, FIRST CONCURRENT RESEARCH SESSIONS

Cancer Research Seminar Room 1

3. Kathryn Field - Using a comprehensive dataset to define features that impact the outcome of patients with Glioblastoma Multiforme

4. Tracy Putoczki - Using high resolution mouse endoscopy to study new therapeutic opportunities for colon cancer

5. Yuan Tian - Morbidity Experienced by Breast Cancer Survivors

6. Elizabeth Vincan - Functions of FZD in the intestine and colorectal cancer

Infection and Immunity Seminar Room 2

7. Gabrielle Josling - Characterisation of a novel bromodomain protein of the malaria parasite Plasmodium falciparum

8. Caroline Marshall - Do rapid detection and isolation of colonised patients reduce MRSA spread in the intensive care unit?

9. Janet Fyfe - Identification and Molecular Characterisation of Oryx Bacillus Isolates Causing Disease in Human Patients

10. Bob Anderson - A Phase I study to determine safety, tolerability and bioactivity of Nexvax2® in HLA DQ2+ volunteers with celiac disease following a long-term, strict gluten-free diet

10.30 am – 11.30 am, SECOND CONCURRENT RESEARCH SESSIONS

Translational Research Seminar Room 1

11. Shlomo Cohney - Outcomes after transplanting kidneys from ‘Expanded Criteria Donors'

12. Hans Tu - Stroke patients with atrial fibrillation have frequent early cardiac complications and require more intense cardiac monitoring

13. Samuel Wright - Reducing door to reperfusion time in ST elevation myocardial infarct (STEMI) by catheter laboratory activation from the field

14. James Tatoulis - The right internal thoracic artery: The forgotten conduit. Clinical and angiographic results over 20 years

Basic Science Research Seminar Room 2

15. Michael Cangkrama - Identification of Target Genes of Grainyhead-like Family Transcription Factors in Epidermal Morphogenesis

16. Smitha Rose Georgy - Tissue-Specific Transcriptional Activation of PTEN by GRHL3 is critical for prevention of skin cancer

17. Maybelline Giam - Characterisation of novel Bcl-2 family member, Bcl-G

18. Nhu-Y Nguyen - The stem cell leukemia transcription factors SCL and LYL1 regulate the proliferative state of hematopoietic stem cells by repression of the cell cycle inhibitor p21.

26 May 26 May 26 May 26 May –––– 2 June 2011 2 June 2011 2 June 2011 2 June 2011

3

Lunch and Poster Viewing 11.30 am – 12.30 pm

Function and Convention Centre, Ground Floor, Royal Melbourne Hospital

This year’s Melbourne Health Research Week will display over 120 posters showcasing research in areas of Infectious Diseases, Immunology, Renal, Cardio-respiratory, Gastroenetrology, Neurosciences, Mental Health, Quality of Care, Endocrinology, Musculoskeletal, Emergency, Genetics and Cancer. Presenters will be on-hand to answer your questions.

The Great Debate 12.30 pm – 1.30 pm, Charles La Trobe Lecture Theatre

Tweeting improves the power of your research. The social media are essential

communication tools in research In the 2011 era of “e-everything”, social media such as Twitter and Facebook are part of the fabric of 21st century life. As Melbourne Health strives to further strengthen its position as a research leader can we trust the tools that have captivated the youth of today to maintain the integrity of our research endeavours? Are the social media the next communication panacea or are they the devil in disguise?

Melbourne Health has called together some of the greatest minds of our eminent Parkville Precinct to use their collective intellect to tackle this most challenging issue in this year’s Great Debate.

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 Linda Sorrell, Chief Executive, Melbourne Health.

Ms Sharon McGowan, Executive Director Communications and Community Relations, Melbourne Health (to be confirmed).

Professor Michael Richards, Director, Victorian Infectious Diseases Service, Melbourne Health.

Team for the Affirmative – “Team Twitter”

Professor Danny Liew, Clinical Epidemiology and health Services Evaluation Unit, Melbourne Health

Dr Emma McBryde, VIDS, Melbourne Health

Dr Ashley, Ng, Clinical Haematology, Melbourne Health and WEHI

Team for the Negative – “Team Tried and True”

Dr Ben Cowie, Victorian Infectious Diseases Service, Melbourne Health.

Dr Rosemary Masterson, Nephrology, Melbourne Health.

Dr Damon Eisen, Victorian Infectious Diseases Service, Melbourne Health.

Melbourne Health Melbourne Health Melbourne Health Melbourne Health Research WeekResearch WeekResearch WeekResearch Week

4

Research Symposium 1.45 pm – 2.45 pm, THIRD CONCURRENT RESEARCH SESSIONS

Quality of Care Research Seminar Room 1

19. Kunal Verma - Addressing shortfalls in experience levels and proficiency of medical students performing sensitive male examinations

20. Catherine Jones - Implementation of a framework for learning from mortality audit and review

21. Belinda Gout - Malnutrition across The Royal Melbourne Hospital goes undiagnosed - what is the impact?

22. Elizabeth Moore - The incidence and implications of Acute Kidney Injury in patients with Traumatic Brain injury

Genetic Research Seminar Room 2

23. Slave Petrovski - Investigating Genome-wide, Multigenic, Classifiers for Initial Anti-Epileptic Drug Response in Newly Treated Epilepsy

24. Gerry Zhi-Ming Ma - Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with multiple sclerosis susceptibility

25. Rachel Burt - Identifying drug targets for prevention and treatment of hearing loss

26. Andrew Bjorksten - Mutation Detection for Malignant Hyperthermia

2.50 pm – 3.50 pm, FOURTH CONCURRENT RESEARCH SESSIONS

Mental Health Research Seminar Room 1

29. G. Paul Amminger - Fatty acid metabolism and the onset of psychotic disorder in young people at ultra high-risk of psychosis

30. Cali Bartholomeusz - Orbitofrontal cortex sulcogyral patterns in first episode psychosis

28. Suresh Sundram - Investigating the role of the epidermal growth factor system in clozapine treated subjects with schizophrenia

27. Candice Boyd - Networks, resources and agencies: On the role of enabling places in facilitating young people's recovery from mental illness

Neuroscience Research Seminar Room 2

31. Daniel Chan - Effect of haloperidol on potassium currents in hippocampal CA1 neurons

32. Stella Hughes - The Kurtzke EDSS rank stability increases 4 years after onset of Multiple Sclerosis: results from the MSBase Registry

33. Amelia Koe - The enduring effects of early-life stress on limbic epileptogenesis are mediated by HPA axis hyper-reactivity

34. Sarah Miller - Carbamazepine Decreases Outward K+ Currents in Calvarial Osteoblasts

DAY 3 – Saturday 28 May 2011

Surgical Research Forum

Chair: Dr Anita Skandarajah

8.30 am – 9.30 am, Ewing Lecture Theatre, Level 5, Clinical Sciences Building

35. James Dimou - The gliomasphere as a platform for exploring novel therapies targeting the Pi3-kinase pathway

36. Brad Moffat - Radiological features correlating with tumour associated epilepsy in patients with supratentorial gliomas

37. Andrew Nichols - MRI biomarkers in patients with pituitary tumours

38. Adam Cichowitz - Effects of nutritional intervention in patients undergoing chemoradiotherapy for oesophageal cancer

39. Matthew Hong - Gene expression profiling in prostate cancer: Defining the lethal phenotype

40. Anton Lambers - How accurately is the hip arthroplasty patient positioned prior to surgery?


5 5

DAY 4 – Mondy 30 May 2011

Translating Research into Practice

Chair: Associate Professor Caroline Brand

1.00 pm – 2.00 pm, Lovell Lecture Theatre, Clinical School, Ground Floor, Royal Melbourne Hospital

This session will focus on how discoveries in research, whether they be at a research institute bench top or at a hospital bedside, can be turned into clinical outcomes leading to improved health for patients and the wider community. The session will focus on the concept of translational research and describe its wide spectrum from bench top to bedside. The ultimate aim of all medical research is better health outcomes. An expert panel of senior researchers will oversee the presentation of three quite different papers listed below, all of which illustrate valid and important aspects of translational research, and facilitate discussion with the researchers and members of the audience to maximise the benefit of this session to all participants.

41. Jonathan Knott - Mandatory pain scoring reduces time to analgesia

Vazirani J, KNOTT J.

Emergency Department, The Royal Melbourne Hospital; Medical Education Unit, The University of Melbourne.

42. Jun Hoe Tay - Study of radial EBUS in determining relationship between radiological findings (size of peripheral and location of lesion in lung fields) of lung lesion versus diagnostic yield and visualization yield.

TAY JH, Antippa P, Steinfort D.

The University of Melbourne; The Royal Melbourne Hospital

43. Anneke van der Walt - Botulinum Toxin Type A (Botox) for the treatment of disabling tremor in Multiple Sclerosis: a double-blind, randomized controlled study.

VAN DER WALT A1,3,4, Sung S1,2, Spelman T1, Marriott M1,4, Kolbe S3, Mitchell P1, Evans A1,2, Butzkueven H1,2,4.

1. Royal Melbourne Hospital; 2. Faculty of Medicine, The University of Melbourne; 3. Centre for Neuroscience, The University of Melbourne; 4. Box Hill Hospital.

DAY 5 – Tuesday 31 May 2011

From clinical inquiry to rigorous research practice

Shaping preliminary research ideas into viable research projects in Nursing and Allied Health

Chair: Professor Danny Liew

1.00 pm – 3.00 pm, Ewing Lecture Theatre, Level 5, Clinical Sciences Building, RMH City Campus

High calibre clinical research is essential in all aspects of health care. However, initiating and integrating relevant clinical research into everyday practice is a well-known challenge.

A series of research ideas that have been drawn from routine clinical practice will be showcased in this session, covering the backgrounds, rationale and preliminary work undertaken thus far. Discussion will be facilitated to utilise the skills and experience of the audience for further development and refinement of these preliminary ideas towards viable research projects.

Participants from all disciplines who have an interest in the topics being presented and an interest in building research capacity in Nursing and Allied Health are welcome to attend.

Melbourne Health Melbourne Health Melbourne Health Melbourne Health Research WeResearch WeResearch WeResearch Weekekekek

6

DAY 6 – Wednesday 1 June 2011

Introduction to Clinical Research Presenters: Ms Alex Gorelik and Professor Danny Liew

9.00 am – 12.30 pm, IT Training Room, Basement, Royal Melbourne Hospital

The Melbourne EpiCentre (Centre for Clinical Epidemiology, Biostatistics and Health Services Research) is pleased to offer this free, interactive teaching workshop covering topics such as:

Study Design

Data Collection and Management

Basic Statistics.

The workshop will involve practical exercises using mock data. Places are limited and to attend you will need to register with Wendy Lemaire, email at: [email protected] or telephone 93428772.

For questions or comments, please contact: Professor Danny Liew, Director at [email protected] or Alexandra Gorelik, Senior Statistician at [email protected].

DAY 6 – Wednesday evening

Community Lecture

“Rescuing Acute Stroke” Presenter: Professor Stephen Davis

5.30 pm – 6.30 pm, Charles La Trobe Lecture Theatre

This year's Community Lecture will be presented by leading expert on stroke and stroke research, Professor Stephen Davis, Divisional Director Neurosciences, Director of Neurology at Melbourne Health.

DAY 7 – Thursday 2 June 2011

Closing Ceremony Chair: Professor Ingrid Winship

1.00 pm – 2.00 pm, Charles La Trobe Lecture Theatre

Final plenary presentation by Professor Peter Colman 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.

44. Peter Colman - Autoantibodies to the Beta Cell-Specific Zinc Transporter 8: Prevalence in INIT II screenees

COLMAN PG1, Gellert S2, Andaloro E2, McManus F3, Breen C3, Harrison LC3 4

1 Diabetes and Endocrinology, The Royal Melbourne Hospital; 2 Pathology, The Royal Melbourne Hospital; 3 Burnet Clinical Research Unit, The Royal Melbourne Hospital; 4 The Walter and Eliza Hall Institute of Medical Research


7

ABSTRACTS ABSTRACTS ABSTRACTS ABSTRACTS ---- ORAL PRESENTATIONS 2011ORAL PRESENTATIONS 2011ORAL PRESENTATIONS 2011ORAL PRESENTATIONS 2011 1. Professor Danny Liew

Translational Research – From efficacy to effectiveness and cost-effectiveness

LIEW D.

Melbourne Health

Clinical trials provide the most reliable data about the efficacy of healthcare interventions but generally do not provide sufficient information in themselves to dictate clinical practice. The temptation to 'blindly' accept the results of clinical trials should be resisted, as the potential long-term effectiveness of any intervention is also reliant on many external factors, such as compliance, competing mortality and morbidity risks, demographic change and disease trends. Cost-effectiveness also takes costs into consideration, and is a major determinant of whether or not a healthcare intervention can feasibly be delivered. There is often a large gap between efficacy and (cost-) effectiveness. In this presentation, we will discuss 'translational' research that helps fill this gap.

2. Susie Bae

From toppling regimes to facilitating rare cancer research – the power of social media

Kosmider S, BAE S, Graenz J, Newman J, Scott C.

BioGrid Australia; The Walter and Eliza Hall Institute of Medical Research; The Royal Melbourne Hospital.

Background: Effective research into rare tumours is often challenging due to the small number of patients and subsequent difficulty in accruing adequate cases for analysis. Despite the rarity of each individual tumour type, in Australia all rare tumours combined represent up to 20 percent of cancers diagnosed each year and 31 percent of cancer-related mortality. In order to improve these outcomes, the paucity of data collected in this area must be addressed.

Methods: People are known to utilize a wide variety of resources in their search for health-related information and numerous studies have shown that the internet is a popular means of doing this. The Melbourne Health HREC approved CART-WHEEL website (www.cart-wheel.org), collects clinical information through the internet directly from people affected by rare cancers. All consumers contributing information to CART-WHEEL complete information consent forms determining how they will allow their data to be used. This ranges from using entered information to obtaining tumour samples and direct contact for participation in ethically approved research projects such as clinical trials. As the site is accessible via the world wide, it allows information to be collected from a greater number of patients than has previously been possible. It also provides people anywhere in the world the opportunity to offer their experience with rare tumours as a resource for clinical research. The potential of CART-WHEEL will largely be determined by the amount of data it collects and raising public awareness of the site is vital. How best to do this remains a challenge. Social Networking websites continue to grow on a huge scale with Facebook announcing in 2010 over 400 million worldwide users and Twitter reaching the benchmark of 50 million tweets per day. Social networking accounts for 11% of all time spent online. Many organizations now employ social networking as a marketing tool to create brand awareness and promote their business. CART-WHEEL has taken this initiative and established Facebook and Twitter accounts.

Conclusion: By harnessing the global power of the internet and social media, we will raise CART-WHEEL’s presence, increase consumer participation and ultimately enhance its clinical utility to the research community.

3. Kathryn Field

Using a comprehensive dataset to define features that impact the outcome of patients with Glioblastoma Multiforme

FIELD K, Rosenthal M, Yilmaz M, Gibbs P, Drummond K.

Departments of Medical Oncology and Neurosurgery, The Royal Melbourne Hospital; Ludwig Institute for Cancer Research; The University of Melbourne.

Background: Glioblastoma multiforme (GBM) is the most common malignant adult brain tumour. While the impact of variables such as age and performance status on outcome is well known, the potential impact of other variables such as socio-econonomic status and clinical trial participation to date have not been well explored.

Methods: Data on patients (pts) with GBM were accessed from a prospective neuro-oncology dataset collected over 12 years (1998-2010) at two institutions (one public, one private). Death data were obtained from the state Cancer Registry. Data linkage and analyses were performed by BioGrid Australia.

Results: In total 541 pts were evaluated; the median age was 60 years. 12% (n=65) were enrolled on to a clinical trial. In univariable analysis, positive predictors for longer survival were: clinical trial participation (median survival 18.7m on trial versus 7.4m not on trial, p<0.0001), higher IRSAD score (socioeconomically advantaged) (HR 0.85, 95% CI 0.8-0.95, p=0.0093), macroscopic resection versus biopsy alone (HR 0.5, 95% CI 0.4-0.6, p<0.001), and more than one operation (HR 0.5, 95% CI 0.4-0.6). Older age (HR 3.0, 95% CI 2.4-3.7, p<0.0001) and worse ECOG performance status (HR 1.5, 95% CI 1.3-1.7, p <0.0001) and multifocal disease (HR 1.5, 95% CI 1.2-1.97, p=0.001) were significantly associated with inferior overall survival. Gender, country of birth, smoking status and diabetes did not significantly impact on survival. Multivariate analysis will be presented.

Conclusions: This is the first study to demonstrate a profound effect of clinical trial participation and socio-economic status on survival in patients with GBM. These are novel findings that require further exploration and could be used to help inform best clinical management of patients with GBM.


8

4. Tracy Putoczki

Using high resolution mouse endoscopy to study new therapeutic opportunities for colon cancer

PUTOCZKI T1, Edwards K 2, Mckenzie B2, Ernst M1.

1 Ludwig Institute for Cancer Research; 2 CSL Ltd.

Interleukin (IL)-11, a member of the IL-6 family of cytokines, is readily detected in various inflammation-associated pathologies including cancers of the gastrointestinal tract. Similar to IL-6, IL-11 mediates pleiotropic activities via a multimeric receptor comprising its ligand binding α subunit (IL-11Rα), and the ubiquitously expressed gp130 β subunit which together trigger intracellular signaling. The shared use of gp130 by the IL-6 family of cytokines has previously made it difficult to dissect the contribution of individual cytokines to specific pathologies. However, by breeding the gp130Y757F mouse, which carries a mutation that results in ligand dependent hyper-activation of the Stat3 molecule, onto either an IL-6 or IL-11Rα – null background we have established that IL-11 mediated Stat3 signaling is required for colitis-associated cancer (CAC). Furthermore, pharmacological inhibition of IL-11 signalling in gp130Y757F mice reduces CAC tumour burden. In order to monitor the efficacy of our novel pharmacological antagonists we have employed high resolution mouse endoscopy, which allows us to follow the progression of individual tumors over time in live animals. Since both increased IL-11 mRNA and STAT3 activation are associated with colon cancers, our results demonstrate that inhibition of IL-11 signaling may represent a novel therapeutic opportunity for the treatment of inflammation-associated cancers.

5. Yuan Tian

Morbidity Experienced by Breast Cancer Survivors

TIAN Y ^, Schofield P *, Gough K *, Mann, B # ^.

Department of Surgery, The University of Melbourne ^; The Royal Melbourne and Royal Women’s Hospitals #; Peter MacCallum Cancer Centre *

Background: The cancer experience does not end upon the completion of cancer treatment. Side effects of treatment can have a considerable impact on patients’ quality of life. While medium- to long-term adverse effects of breast cancer treatment (BCT) were generally believed to be minimal in most cases, there is evidence of a substantial amount of underappreciated long-term morbidity associated with breast cancer treatment. This study aims to determine the medium to long term health-related quality of life (HRQoL) for breast cancer survivors who have undergone BCT and identify demographic, clinical, pathological and treatment factors associated with impaired HRQoL.

Methods: 400 English-speaking women treated for DCIS or stage I-III breast cancer between 1999 and 2009 and currently disease free were randomly selected and invited to participate in the study. Clinical details collected in this survey included date of surgery; pathology; TNM staging; surgery; and adjuvant treatments. A study questionnaire that included the Breast Cancer Treatment Outcome Scale (BCTOS) was sent to the women between September and November 2010. Statistical methods were used to examine the effects of different therapeutic schemes and analyze the relationship between this HRQoL measure and a number of key factors such as age, cancer staging and months since surgery.

Results: The BCTOS was completed by 253 eligible respondents (of 333) who had undergone breast conserving treatment. Over half (50.8%) of the respondents reported some difference in the functional status of the treated and untreated sides of the body. In addition, an overwhelming majority (95.2%) reported some difference in the physical appearance between the treated and untreated breast and 74.1% reported experiencing breast specific pain. The results revealed strong associations (all p<0.05) between age-based subgroups and all three subscales (Functional Status, Cosmetic Status and Breast Specific Pain). Interestingly, there was no significant association between months since surgery and responses to the BCTOS (all p>0.05). The important finding in this study is that different therapeutic schemes have significant influence on the participants’ HRQoL. Patients who had undergone surgery with axillary dissection reported poorer functional and cosmetic status when compared to those who had surgery alone (p<0.05).

Conclusion: A significant proportion of breast cancer survivors have long term physical and psychological morbidity. Disease and treatment related factors are associated with differences in the range and severity of these effects. This information may help clinicians and patients in treatment decisions and is important when planning breast cancer follow-up.

6. Elizabeth Vincan

Functions of FZD in the intestine and colorectal cancer

VINCAN E1, Flanagan DJ1, Amin N1, Phesse T2, Malaterre J3, Dworkin S4, DeIongh R1, Clevers H5, Barker N6.

1 The University of Melbourne and Victorian Infectious Diseases Reference Laboratories; 2 Ludwig Institute for Cancer Research, 3 Peter MacCallum, 4 Bone Marrow Institute, 5 Hubrecht Institute; 6 Institute of Medical Biology.

The signalling pathways that are initiated at the cell surface by Wnt and FZD molecules are critical for stem/progenitor cell and Paneth cell function in the intestinal crypt. Constitutive activation of the stem/progenitor cell gene program drives the initiation of colorectal cancer [Clevers, Cell (2006), while the progression of colorectal cancer is characterised by the simultaneous activation of stem/progenitor cell and Paneth cell gene programs in migrating cancer cells [van Es et al., et al., Nat Cell Biol (2005)]. However, the FZD receptor/s that transmits these Wnt signals is not known. Our studies strongly implicate FZD7. RNA in situ hybridisation revealed that FZD7 expression is confined to the stem/progenitor compartment of developing and adult intestine [Gregorieff et al., Gastroenterology (2005)]. Furthermore, FZD7 is over-expressed in colorectal cancer [Vincan et al., Oncogene (2007)] and has important, necessary roles during tumour formation [Vincan et al., Differentiation (2005)] and tumour morphogenesis [Vincan et al., Oncogene (2007)]. Based on these findings, we hypothesise that FZD7 transmits Wnt signals in the intestine. To test this hypothesis directly, we have generated mouse models that allow specific and inducible deletion of FZD7 (Fzd7LoxP/LoxP) in the intestinal epithelium (AhCre), where the various Wnt-driven programs are represented, or specifically in the intestinal stem cells (LGR5-


9

EGFP-Cre), using the LoxP/Cre-recombinase system. In the intestinal crypt, LGR5 is expressed exclusively by long-lived stem cells, while AhCre targets all the epithelial cells [Barker et al., Nature (2007)]. Our findings to date indicate alterations in stem and Paneth cell numbers 1 day after Fzd7 deletion with AhCre recombinase. The intestine is phenotypically normal 4, 7 and 14 days after Fzd7 deletion, indicating rapid recovery of the intestine in vivo. This finding is being investigated further by deleting Fzd7 exclusively in the stem cells (LGR5GFP-Cre) and by determining the effect Fzd7 deletion has on the regeneration of the intestine after irradiation challenge. These powerful mouse model systems allow us to directly probe the function of FZD7 in the gene programs that drive colorectal cancer and may offer novel avenues to stop the Wnt-driven stem cell behaviour of cancer cells.

7. Gabrielle Josling

Characterisation of a novel bromodomain protein of the malaria parasite Plasmodium falciparum

JOSLING G, Petter M, Lim M, Boysen K, Voss T, Bozdech Z, Brown GV, Duffy MF.

The University of Melbourne

The most severe form of malaria is caused by Plasmodium falciparum, an apicomplexan parasite. Epigenetic regulation has been shown to be extremely important for crucial pathogenic processes such as cytoadhesion, immune evasion, and red blood cell invasion. Among the various epigenetic mechanisms that P. falciparum utilises, post-translational modification of histone tails is perhaps the best studied. Many such modifications have been identified, but to date very little is known about the proteins that recognise these modifications.

In light of this, we are characterising a novel bromodomain-containing protein we have called Bromodomain Protein 1 (BDP1). The protein contains a bromodomain, which is a domain that specifically recognises acetylated lysine residues in histone tails. Acetylated histones are generally associated with active genes, so BDP1 is potentially important in transcription activation. It also has an ankyrin domain; ankyrin domains are generally involved in protein-protein interactions. This combination of domains is unique to apicomplexan parasites, indicating that the protein may be involved in a novel epigenetic pathway.

We have generated GFP- and HA-tagged parasite lines in order to investigate BDP1. Cellular fractionation revealed that BDP1 is primarily found in the nucleus, and this has been confirmed by direct fluorescence and immunofluorescence assays. IFA also showed that BDP1 colocalises with histone modifications associated with active genes, but not with those associated with repressed genes. We have also used these tagged lines for chromatin immunoprecipitation followed by real time PCR to investigate BDP1 distribution in genes affected by BDP1 over-expression. In addition, the recombinant bromodomain of BDP1 was shown to bind to histones, recognising histones 3 and 4 as well as the histone variant H2AZ. This supports BDP1’s role as a novel factor involved in epigenetic processes in the malaria parasite.

8. Caroline Marshall

Do rapid detection and isolation of colonised patients reduce MRSA spread in the intensive care unit?

MARSHALL C1,2, McBryde E1, Richards M1.

1. Victorian Infectious Diseases Service, Royal Melbourne Hospital 2. Department of Medicine, The University of Melbourne

Background: Although numerous studies suggest that active surveillance for MRSA in the intensive care unit accompanied by contact precautions reduce MRSA transmission, there have been few planned prospective studies addressing this as a single intervention in the endemic setting. In this study, we compared whether active surveillance using rapid detection methods accompanied by use of contact precautions reduced MRSA transmission compared with standard precautions for MRSA colonised patients. This study collected and analysed data to avoid confounding (of MRSA acquisition with length of stay) and serial dependence in the data due to colonisation pressure in accordance with ORION guidelines.

Methods: This was a planned prospective interrupted time series in the intensive care unit at Royal Melbourne Hospital. During the control period, patients were screened for MRSA colonisation on admission, discharge and twice weekly and were cared for using standard precautions only. During the intervention period, rapid PCR was used to detect MRSA colonised patients, who were then cared for in single rooms using gloves and long sleeved gowns. Data were collected on co-morbidities, sex and age. Daily (time dependent) data were collected on antibiotic usage, compliance with hand hygiene and infection control precautions and colonisation pressure. We used a generalised estimating equation (GEE) with each patient-day being the unit of interest. The outcome variable is MRSA acquisition. The predictor variables were both time-dependent and time-invariant covariates described above, and intra-individual risk correlation was adjusted for using the GEE framework.

Results: The primary outcome measure was the effect of the intervention phase, adjusting for colonisation pressure and individual and ward covariates. The relative risk of MRSA acquisition was 0.40 (95%CI 0.24-0.65). Secondary measures include the effect of colonised patients in the ward (RR 4.38; 95% CI 1.00-19.21) and the phase-colonised patient interaction, with a reduced risk from colonised patients in the intervention phase to 0.41 (95% CI 0.14-1.18) compared with phase 1.

Conclusion: We demonstrated a clinically significant effect of isolation on MRSA transmission. Our planned single intervention study is unique because of near-complete observations due to short intervals between swabs & full documentation of colonisation pressure and time varying risk factors.


10

9. Janet Fyfe

Identification and Molecular Characterisation of Oryx Bacillus Isolates Causing Disease in Human Patients

FYFE J, Globan M, Sievers A.

Mycobacterium Reference Laboratory, Victorian Infectious Diseases Reference Laboratory

Background: The Victorian Mycobacterium Reference Laboratory is responsible for the identification and molecular typing of all Mycobacterium tuberculosis complex (MTBC) isolates from tuberculosis (TB) patients in the state of Victoria. As the majority of these patients are born overseas, the 250 to 350 new MTBC isolates per year represent most of the major genetic lineages so far described on the basis of genomic deletions and single-nucleotide polymorphisms (SNPs).

Methods: Routine mycobacterial interspersed repetitive unit (MIRU) typing has been performed on all new isolates since 2003, and the data stored and analysed using Bionumerics v5.0. Prior to 2003, IS6110 RFLP was the typing method performed and records are available from the early 1990’s.

Results: Interrogation of the database and RFLP records has identified 15 MTBC strains with profiles significantly different from the other strains causing human disease in Victoria. Several of the isolates had been designated as Mycobacterium africanum based on phenotypic characteristics. An additional 8 isolates with similar MIRU profiles were identified from patients diagnosed with TB in New South Wales and South Australia. All 22 patients infected with these strains were born in India and 18 were females. The sites of isolation included pulmonary (7 cases), lymph node (7 cases), an abscess, ascitic fluid, peritoneal fluid, bone and urine. Further molecular characterisation of 9 of the isolates revealed that they all shared the spoligotyping profile ST587, described in the SpolDB4 database as a profile shared by 8 MTBC isolates from various countries, and presumed to be M. africanum. All the Australian isolates had similar (but not identical) IS6110 RFLP profiles with 21 to 26 copies of the IS, and had genomic deletions and SNPs recently described for the “oryx bacillus”, of which only two isolates (from oryxes) have been fully characterised. However, similar isolates have been identified from additional animal sources including deer, camels, dairy cattle and monkeys.

Conclusion: This study supports the proposal that the oryx bacillus is a potentially important phylogenetic linker specieswithin the MTBC, which unlike the predominantly human pathogen, M. tuberculosis, may be transmissible within and between a range of different mammalian hosts.

10. Bob Anderson

A Phase I study to determine safety, tolerability and bioactivity of Nexvax2® in HLA DQ2+ volunteers with celiac disease following a long-term, strict gluten-free diet

Brown GJ1, Daveson J2, Marjason J3, French RA4, Smith D5, Sullivan M5, Tye-Din JA6,7,8, ANDERSON RP1,6,7,8.

1 Gastroenterology, Alfred Hospital; 2 Gastroenterology, Princess Alexandra Hospital; 3 QPharm; 4 Burnet Institute; 5 Medicines Developments Ltd.; 6 Gastroenterology, The Royal Melbourne Hospital; 7 Immunology, The Walter and Eliza Hall Institute; 8 ImmusanT Inc. (USA)

Celiac disease affects 0.5 to 2% of the population. Currently, the only treatment for celiac disease is strict life-long gluten free diet, but it is potentially suited to peptide-based immunotherapy designed to restore immune tolerance to gluten. Nexvax2®, which is being developed as an immunotherapeutic and prophylactic for HLA DQ2-associated celiac disease, is an equimolar mixture of three 15-16mer peptides in saline manufactured to current Good Manufacturing Practice (cGMP) standards. The peptides in Nexvax2® encompass immunodominant HLA DQ2-restricted epitopes from wheat, barley or rye gluten. AIM: To evaluate the safety and tolerability of weekly intradermal (i.d.) injections of Nexvax2®, and to compare the bioactivity of Nexvax2® through the measurement of T-cell response.

METHODS: Thirty four healthy HLA DQ2+(DQ8-) adults with celiac disease on gluten free diet (GFD) were sequentially randomized to receive 9µg (n=6), 30µg (n=6), 60µg (n=6) or 90µg (n=7) of Nexvax2® or placebo (n=9) i.d. weekly for 3 weeks. The double blind study was undertaken in two dedicated Phase I clinical trial centres and conducted to Good Clinical Practice standards. Serial interferon-gamma (IFN-γ) ELISpot assays were used to enumerate peripheral blood T-cells specific for Nexvax2®.

RESULTS: Nexvax2® was well tolerated. Gastrointestinal adverse events were more commonly observed in subjects receiving 60µg and 90µg of Nexvax2® compared with 9 µg or 30 µg of Nexvax2® or placebo: 7/19 subjects administered 30µg, 60µg or 90µg of Nexvax2® (compared to 1/9 administered placebo and none receiving 9µg of Nexvax2®) reported nausea including two who were administered anti-emetics and two who vomited (at approximately 2h or 5.5h after the initial dose). The incidence of abdominal pain, diarrhoea and abnormal faeces was similar in the Nexvax2®-treated and placebo groups. One subject in the 90µg cohort withdrew due to gastrointestinal symptoms graded severe. There were no other clinically relevant adverse events, no deaths or serious adverse events. There were no clinically relevant changes in safety laboratory parameters or vital signs. Nexvax2®-specific T cells were detected most commonly on day-6, in four volunteers who had received 30µg (n=1), 60µg (n=2) or 90µg (n=1) Nexvax2®.

CONCLUSION: These data are supportive of further clinical evaluation of Nexvax2. The time course of symptoms and mobilization of gluten-specific T cells observed after administration of Nexvax2® were similar to those triggered by acute oral gluten exposure in HLA DQ2+ patients with celiac disease on GFD, suggesting a further potential role for Nexvax2® as a functional diagnostic.


11

11. Shlomo Cohney

Outcomes after transplanting kidneys from ‘Expanded Criteria Donors'

LIU D1, Lee M2, Clark B3, Suh N1, Walker R2, Opdam H3, Robertson A1, Millar R1, Yip D2, Cohney S2.

1 General and Transplant Surgery Unit, Department of General Surgery, The Royal Melbourne Hospital; 2 Department of Nephrology, The Royal Melbourne Hospital; 3 Donate Life, Organ and Tissue Authority

Background: Transplanting kidneys from Expanded Criteria Donors (ECD) increases available organs, but may be associated with reduced long-term graft survival. This single centre study evaluated the outcomes of transplanting ECD grafts, and identified the principle donor and recipient factors that influenced graft survival.

Methods: Retrospective analysis of 336 consecutive cadaveric transplants between January 2000 and April 2010. There were 112 ECD grafts and 224 standard grafts.

Results: Compared with standard grafts, ECD grafts had an increased rate of delayed graft function (35.9% vs. 23.9%, p=0.035), lower serial eGFR (p<0.001), longer length of stay (10.2±0.5 vs. 9.5±0.5 days, p=0.007), and more biopsies (2.9±0.2 vs. 2.4±0.1, p=0.009) and re-admissions (2.8±0.3 vs. 2.4±0.3, p=0.016) within the first three months after transplantation. Overall graft loss were similar between ECD and standard grafts, however, graft loss was higher in the ECD group after accounting for death with a functioning graft (HR: 2.70, 95% CI: 1.18 – 6.19, p=0.019). Multivariate analysis identified donor hypertension, pre-terminal creatinine >150µmol/L, severe graft atheroma, multiple graft vessels and recipient renal failure secondary to structural abnormalities as independent predictors of poor graft survival. The presence of three or more of risk factors predicted higher overall (HR: 3.1, 95% CI: 1.2 – 8.1, p=0.021) and death-censored (HR: 17.4, 95% CI: 4.6 – 65.9, p<0.001) graft loss.

Conclusion: Although ECD grafts had worse function and utilised more resources, overall graft survival was comparable to standard grafts. Graft atheroma, multiple graft vessels and recipient renal system structural abnormalities additively increases the risk of graft loss.

12. Hans Tu

Stroke patients with atrial fibrillation have frequent early cardiac complications and require more intense cardiac monitoring

TU H1, Campbell B1, Churilov L2, Kalman J3, Lees K4, Lyden P5, Shuaib A6, Donnan G2, Davis S1, on behalf of the VISTA collaborators

1 Department of Neurology, The Royal Melbourne Hospital, The University of Melbourne; 2 Florey Neuroscience Institutes; 3 Department of Cardiology, The Royal Melbourne Hospital; 4 University of Glasgow, UK; 5 Cedars-Sinai Medical Centre, USA; 6 University of Alberta, Canada

Background: Atrial Fibrillation (AF) is associated with worse outcomes following stroke that has chiefly been linked to greater baseline stroke size and severity. However, AF is also associated with more frequent cardiac complications in the general population. We aimed to establish the contribution of early cardiac complications to the poorer stroke outcomes in AF patients, independent of baseline stroke severity and cardiovascular risk factors. This might have important implications for acute stroke management in patients with AF, particularly regarding the need for continuous cardiac monitoring and more intensive clinical surveillance for cardiac complications.

Methods: We searched VISTA-Acute, an academic database containing standardized data for 28,131 patients from randomized-controlled acute stroke trials and registries, for placebo-treated patients with complete documentation of baseline demographics, cardiovascular risk factors, presence/absence of AF, neurologic impairment assessed using the National Institute of Health Stroke Scale (NIHSS), cardiac complications and 3-month outcome quantified using the modified Rankin Scale (mRS). Multivariate modeling was used to test the association between AF, stroke outcome and serious cardiac adverse events (SCAEs), a composite endpoint including acute coronary syndrome, symptomatic heart failure, cardiopulmonary arrest, VT, VF and cardiac mortality.

Results: In VISTA-Acute, 2865 patients from 6 randomized controlled trials met the selection criteria, of whom 819 (28.6%) had AF. All patients were enrolled into the source trials within 24 hours of stroke onset. At baseline, patients with AF were older (mean 75 vs 67 years, p<0.001) and had greater neurologic impairment (median NIHSS 15 vs 13, p<0.001). A total of 502 cardiac adverse events occurred in 428 (15%) patients within 3 months of stroke onset. The median time to the first cardiac adverse event was 3 days for both patients with and without AF. SCAEs occurred more frequently in patients with AF (14.2 vs 6%, OR 2.58, 95%CI1.97-3.37), including cardiac mortality (4.9% vs 2.6%, OR 1.89, 95%CI1.25-2.88), symptomatic heart failure (6.5% vs 2.2%, OR 3.01, 95%CI2.01-4.50), and ventricular tachycardia and/or fibrillation (2.4% vs 0.8%, OR 3.18, 95%CI1.64-6.16). At 3 months, AF was independently associated with SCAEs (OR2.16, 95%CI1.62-2.89) and mortality (OR1.44, 95%CI1.14-1.81) after adjusting for all baseline imbalances.

Conclusion: Early cardiac complications are common after stroke and are independently associated with AF. These results highlight the need for continuous cardiac monitoring and more rigorous clinical surveillance for cardiac complications in acute ischemic stroke patients with AF, as many cardiac complications are potentially remediable if detected early.


12

13. Samuel Wright

Reducing door to reperfusion time in ST elevation myocardial infarct (STEMI) by catheter laboratory activation from the field

WRIGHT S, Wong M, Grigg L.

The Royal Melbourne Hospital

Background: Total ischemic time in STEMI patients affects mortality and morbidity. Prior studies have demonstrated improvement in door to reperfusion (D2R) time with pre-hospital 12-lead ECG triage of STEMI and early activation of PCI resources.

Aim and Methods: We evaluated the reduction in D2R time with a strategy of pre-hospital catheter laboratory activation. Prospective analysis of all patients presenting to Royal Melbourne Hospital with STEMI in a 12-month period was undertaken. Two cohorts were compared. Group 1 - patients diagnosed with STEMI by Mobile Intensive Care Ambulance (MICA) paramedics with ECG faxed to the emergency admitting officer for activation of the catheter laboratory team prior to patient arrival (MICA activated Acute Myocardial Infarction [MAMI] group). Group 2 - Patients in whom STEMI was diagnosed on arrival to hospital. (CODE-AMI group).

Results: 110 STEMI were evaluated, of which 35 were MAMI. 14 patients did not require acute revascularisation. D2R times in the CODE-AMI group were comparable to contemporary cohorts. A significant reduction in median D2R time was observed in the MAMI group (42 v 96 minutes; p<0.01) compared to the CODE-AMI group. Both in hours (33 v 50; p<0.01) and out of hours (68 v 107; p<0.01) MAMI showed significant reduction.

Conclusion: D2R time in STEMI was significantly reduced with activation of the catheter laboratory from field 12 lead ECG, prior to arrival at hospital. Out of hours STEMI had most benefit. Although D2R improvement needs to be confirmed by analysis of time for first medical contact to reperfusion, it is likely treatment for STEMI could be improved with increased availability of field 12-lead ECG.

14. James Tatoulis

The right internal thoracic artery: The forgotten conduit. Clinical and angiographic results over 20 years

TATOULIS J, MD, Buxton BF, Fuller JA.

The Royal Melbourne Hospital; Austin Hospital; Epworth Hospital; The University of Melbourne

BACKGROUND: The right internal thoracic artery (RITA) is biologically identical to the left ITA, yet is rarely used in coronary artery bypass graft surgery (CABG). We examined the results and long term patency of RITA grafts.

METHODS: 991 consecutive RITA graft angiograms, between 1986 and 2008 for postoperative cardiac symptoms were evaluated by two independent observers. Grafts were considered non patent if they had a > 80% stenosis, string sign, or total occlusion. Patency was examined over time, by coronary territory, whether in-situ or free RITA, and compared to other conduits. Clinical results were collected prospectively and by the National Death Index.

RESULTS: 5766 patients had an RITA graft, as part of a bilateral ITA CABG procedure. Operative mortality was 1.1%, deep sternal infection 1.5%. Of 7780 coronary conduits studied, 991 RITA conduits were examined, a mean of 100 +/- 60 months postop (1-288 months). Overall 10 yr RITA patency was 90%. RITA graft patency to the left anterior descending artery (LAD), n=149, was 95% at 10 yrs and 90% at 15 yrs. 10 yr RITA patency to the circumflex marginal (CX), n=436, was 91%; right coronary artery (RCA), n=199, 84% (p<0.001); and posterior descending artery (PDA), n=207, 86%. 10 yr RITA and LITA patencies to the LAD were identical, 95% vs 96%, and to the CX, 91% vs 89% respectively. In-situ RITA (n=451) and free RITA (n=540) had similar 10 yr patencies, 89% vs 91% (pns). RITA patency was always better than radial artery (RA) (p<0.01) and saphenous vein grafts (SVG) (p<0.001). Atheromatous changes were not seen in the RITA angiograms. 10 yr survival of patients with RITA and LITA for triple vessel coronary disease was 89%.

CONCLUSION: Late patencies of RITA are excellent, equivalent to the LITA for identical territories, and always better than RA and SVG, and remain free of atheroma. Use of RITA in addition to LITA is associated with excellent survival in triple vessel coronary disease. More extensive use of the RITA in CABG is recommended.

15. Michael Cangkrama

Identification of Target Genes of Grainyhead-like Family Transcription Factors in Epidermal Morphogenesis

CANGKRAMA M, Darido C, Dworkin S, Jane SM.

The Royal Melbourne Hospital, Bone Marrow Research Laboratories

The grainy head (grh) transcription factor is a critical regulator of diverse aspects of Drosophila development. It is expressed predominantly in the surface ectoderm, where it is responsible for the formation and maintenance of the integument. Grh mutants exhibit grainy and discontinuous head skeletons and flimsy cuticles. Due to perturbed planar cell polarity signaling, grh mutants also exhibit several morphogenetic defects in epidermal wound repair, wing hair and eye ommatidial orientation.

Previous work in our laboratory have identified and characterised three mammalian homologues of grh. These genes, known as Grainy head-like (Grhl) 1, -2, and -3, demonstrate remarkable conservation of sequence, expression and function across more than 700 million years of evolution. Grhl1 knock-out mice display delay in hair coat growth and defects in epidermal desmosome formation with loss of cellular adhesion. Grhl2 deficient mice exhibit head skeleton abnormalities and cranial neural tube defects. Grhl3 is essential for epidermal morphogenesis in the setting of spinal neural tube closure, skin barrier formation, wound repair and epidermal eyelid migration. Recently, our laboratory has also identified a role for Grhl3 in maintaining skin homeostasis.


13

Central to the effects of GRHL factors are target genes that are transcriptionally regulated by the GRHL family. In this study, the phylogenetically conserved DNA binding site (AACCGGTT) has formed the cornerstone for identifying novel GRHL target genes. By employing a multifaceted approach incorporating bioinformatic analysis, gene profiling in knock-out mice and chromatin immunoprecipitation assays as well as gene knock-down strategies, we have discovered 22 previously unreported key target genes. These findings may provide new insights into developmental processes and homeostasis governed by the GRHL family.

16. Smitha Rose Georgy

Tissue-Specific Transcriptional Activation of PTEN by GRHL3 is critical for prevention of skin cancer

GEORGY SR1, Darido C1, Wilanowski T2, Dworkin S1, Papenfuss TA3, Pearson RB4, and Jane SM1 5.

1 Rotary Bone Marrow Research Laboratories, The Royal Melbourne Hospital; 2 Laboratory of Signal Transduction, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Poland; 3 Division of Bioinformatics, The Walter and Eliza Hall Institute; 4 Growth Control and Differentiation Program, Peter MacCallum Cancer Centre; 5 Department of Medicine, University of Melbourne

The molecular pathogenesis of squamous cell carcinoma (SCC) of the skin is poorly understood. The epithelial-specific transcription factor grainy head-like 3 (Grhl3) is essential for epidermal differentiation and regulates the balance between keratinocyte proliferation and differentiation during embryonic development. Primary keratinocytes from Grhl3-null embryos express high levels of proliferative markers, and display lack of cell-cell contact inhibition forming heaped up "pseudo-tumours" in the culture dish.

To examine the role of Grhl3 in tumorigenesis in adult skin, we have utilized a two-stage model of initiating and promoting skin carcinogenesis in conditional mice lacking Grhl3 expression in the epidermis (Grhl3Flox/-/K14Cre+). We report that loss of Grhl3 in adult epidermis provides potent stimulus for development of chemical-induced and spontaneous SCC, which exhibit marked activation of the PI3K/AKT pathway, and concomitant repression of Ras/MAPK/ERK signalling. Phylogenetic, biochemical and expression analysis identify PTEN as a direct transcriptional target of GRHL3, and the two genes interact epistatically, with compound heterozygous mice developing aggressive SCC. Consistent with this, knockdown of GRHL3 in human keratinocytes induces loss of PTEN expression, with resultant activation of PI3K/AKT signalling and hyperproliferation, which are rescued by lentiviral-mediated re-expression of wild-type, but not a phosphatase-dead mutant of PTEN. Expression of both GRHL3 and PTEN in human skin SCC is markedly reduced. Our findings delineate the GRHL3-PTEN axis as a critical pathway for suppression of SCC in the mammalian epidermis.

17. Maybelline Giam

Characterisation of novel Bcl-2 family member, Bcl-G

GIAM M1 2, Putoczki T3, Ernst M3, Strasser A1, Bouillet P1.

1 The Walter and Eliza Hall Institute of Medical Research; 2 The University of Melbourne; 3 Ludwig Institute for Cancer Research

Apoptosis is a form of programmed cell death important in the removal of damaged, infected or superfluous cells. Defects in the apoptotic pathway play an important role in tumorigenesis. The Bcl-2 family members are the main regulators of the intrinsic pathway of apoptosis. They are characterized by the presence of Bcl-2 homology (BH) domains and can be classed into the pro-survival proteins, the multidomain pro-apoptotic proteins and the BH3-only proteins. Bcl-G (Gonad) is a novel Bcl-2 family member with two major isoforms in humans. Bcl-GL has both the BH2 and BH3 while Bcl-GS contains only the BH3 domain and is testis-specific. In vitro over-expression studies suggest that Bcl-GS is a pro-apoptotic BH3-only protein. The mouse Bcl-G gene only produces one isoform which contains both the BH2 and BH3 domains. To study the functions of Bcl-G, we generated knockout mice by removing ATG-containing exon 3. Bcl-G-/- mice are viable and develop normally. We also produced monoclonal antibodies specific for Bcl-G and used these to study its tissue distribution and subcellular localization. Using immunofluorescence on transiently transfected HeLa cells, Bcl-G was found to be diffuse throughout cytoplasm. Immunohistochemistry revealed that Bcl-G is expressed highly in some dendritic cells and certain epithelial cell types including those lining the gastrointestinal tract and ducts of the mammary gland. Analysis of these cell types in the knockout mice is underway. We have found that Bcl- G deficiency confers resistance to DSS-induced acute colitis, a model of inflammatory bowel disease (IBD). Using our antibodies, we have used an IP-mass spectrometry approach to pull-down and identify Bcl-G interacting partners to further gain clues on its function and pathways it is involved in. Studying the Bcl-2 family will shed light into the intricacies of the pathway and give insight of important drug targets for the treatment of cancer and other diseases.

18. Nhu-Y Nguyen

The stem cell leukemia transcription factors SCL and LYL1 regulate the proliferative state of hematopoietic stem cells by repression of the cell cycle inhibitor p21.

NGUYEN NN, Salmon JM, Jane SM, Curtis DJ.

Bone Marrow Research Laboratories, Melbourne Health

Hematopoietic stem cells (HSCs), rare cells found in bone marrow, have the ability to self-renew as well as give rise to all the mature blood cells of the hematopoietic system. Critical to their regulation are a number of transcription factors, disruptions of which are often associated with leukemia. Scl and Lyl1 encode two related basic-helix-loop-helix (bHLH) transcription factors implicated in T-cell acute lymphoblastic leukemia.

At present, the target genes of Scl and Lyl1 that regulate hematopoiesis remain unclear. Mice lacking either Scl or Lyl1 exhibit no major HSC defect. However, work by our group using a conditional Scl/Lyl1 double knockout has shown HSCs lacking both Scl and Lyl1 are unable to grow in vitro or in vivo. Gene expression analysis of bone marrow cells from these mice revealed a 10-50 fold increase in expression of the cell cycle inhibitor p21. Furthermore, Scl-null HSCs have been shown to be more quiescent. Therefore, we hypothesized that double knockout HSCs cannot grow due to very high levels of p21.


14

To address this hypothesis, we generated triple knockout mice and performed comparative analyses. HSCs isolated from triple knockout mice were able to grow in vitro as ascertained by myeloid progenitor assays. In addition, these cells when used in bone marrow transplant assays were able to engraft and reconstitute hematopoiesis normally. These results show for the first time that p21 is a target gene of Scl and Lyl1. This effect is likely to be direct because Scl has been shown to bind to the p21 promoter.

19. Kunal Verma

Addressing shortfalls in experience levels and proficiency of medical students performing sensitive male examinations

VERMA K, Lo J, Turner R, Zimitat C, Sefton N.


Background: Sensitive male examinations (SME) are essential skills for all medical students to acquire; they can aid in the early detection of genitorectal cancers and in identifying other abnormalities. Current literature suggests graduates are qualifying with deficiencies in their clinical skills and confidence in performing DRE. The University of Tasmania is introducing a structured Men’s health curriculum that aims to improve student learning of SME and establish greater awareness of men’s health. We evaluated the experience, attitudes and skill acquisition of final year students (FYS) in performing SME. This research aims to inform teaching and curriculum development within the School of Medicine.

Method: An anonymous questionnaire was given to FYS studying at the University of Tasmania in 2010. SME were defined as testicular (TE), inguinal (IE) and digital rectal examinations (DRE).

Results: 90 of 104 FYS students responded (86%), of which 96% felt new graduates should be competent in performing SME. The median number of TE, IE and DRE performed by FYS in their clinical training was 3, 8 and 8 respectively. 9% of FYS had no clinical experience performing DRE. 73% of FYS had encountered limitations to performing SME; lack of opportunity and low confidence were the most common limitations identified.

Only 46% and 66% of FYS felt they were reasonably or very confident at identifying abnormal clinical signs in TE and DRE respectively. Significant results regarding factors that positively impacted the ability of FYS to identify abnormal clinical signs were confirmation by a doctor most or every time (TE: p=.04, DRE: p<.01), and bedside teaching (DRE p=.05, IE =.03). Discussion and conclusions: Although perceived importance and self-reported knowledge of male cancers is high, many FYS are graduating with insufficient experience and confidence in performing SME. Our findings build upon the conclusions of previous research, and may reflect shortcomings within existing teaching methods. The proposed Men’s Health curriculum at the University of Tasmania will incorporate a diverse range of teaching modalities, including supervised examination of trained patients. This should help remediate the shortfall in the interpretation and performance of SME by FYS.

20. Catherine Jones

Implementation of a framework for learning from mortality audit and review

JONES C1, Denahy A1, Walsh S1, McKenzie L1, Gorelik A1, Hayes I1, Tacey M1, Brand C1 2.

1 Melbourne Health; 2 The University of Melbourne

Objectives: Preventing avoidable in-hospital deaths must begin with the collection and analysis of data. This presentation will describe implementation and evaluation of a consistent organisation wide approach to mortality audit at Melbourne Health which aims to ensure that all preventable deaths are systematically reviewed and opportunities for improvement identified and addressed.

Methods: Phase 1: a) A review of current practice through revision of mortality audit policies and practices, analysis of mortality audit data and a survey of clinical leaders; b) establishment of best practice though a literature review and benchmarking with like organisations. Phase 2: Based upon the findings of phase 1, the development of a centralised web based electronic mortality audit tool the key features of which include: a) linkages with the patient administration system (iPM); and b) incorporation of a structured review process based upon a previously published structured review tool which identifies factors which may have contributed to the patient’s death. Analysis of data from the review process may identify possible clusters or trends in quality of care issues that can then be targeted for improvement.

Results: The electronic mortality audit tool has undergone useability and acceptability testing which indicated it is easy to navigate and does not require training. Between July 2009 and Feb 2010, there were 681 in-hospital deaths. For this period: a) the mean mortality audit rate (i.e. the number of in-hospital deaths that undergo audit) was 87%; b) the proportion of cases categorised as being associated with a possible quality of care issue was 3.7% (25/681 cases); and the proportion of these that underwent a review was 96% (24/25 cases).

Some of the quality of care issues identified include communication problems between staff members (including handover issues), no ICU beds being available and medical equipment being unavailable.

Conclusions: Identification of quality of care issues and opportunities for improvement will be an ongoing process. A robust mortality audit and review process is an important clinical governance activity and has potential to identify and address system or process issues related to quality of care.


15

21. Belinda Gout

Malnutrition across The Royal Melbourne Hospital goes undiagnosed - what is the impact?

Gout B, FETTERPLACE K, Garth A, Barker L, Crowe T.


Malnutrition is highly prevalent in the acute hospital setting and is associated with numerous negative clinical outcomes including poor wound healing, increased risk of infections and higher mortality rates. Despite the serious nature of this condition, referral rates for dietetic intervention are poor and malnutrition often goes undiagnosed. Misdiagnosed malnutrition can potentially result in significant financial reimbursement shortfalls to the hospital. A study conducted at The Royal Melbourne Hospital in 2008 found malnutrition prevalence to be 23% among recently admitted patients. Malnutrition identification and documentation in the medical histories was poor as were dietetic referral rates. It was estimated that there was a shortfall of AU$1,850 540 in entitled financial reimbursements over the financial year as a result of undiagnosed malnutrition.

The current study aimed to reassess the prevalence of malnutrition and to determine if the provision of training in a nutrition assessment tool (Subjective Global Assessment) to dieticians improved their documentation of malnutrition. It also aimed to determine potential shortfalls in financial reimbursements as a result of malnutrition misdiagnosis.

The Subjective Global Assessment (SGA) tool was used to assess the nutritional status of 239 inpatients across all acute care wards of The Royal Melbourne Hospital. A retrospective audit of the medical histories of the 109 patients assessed as malnourished is being performed to determine diagnosis, documentation and dietetic referral rates for malnutrition. Where malnutrition has not been coded for, the admission will undergo a hypothetical recode to determine whether it changes the Diagnosis Related Group and payment allocated for that admission.

Hospital-wide malnutrition prevalence was 43%, with 35% of patients mildly or moderately malnourished and 8% severely malnourished. The units with the highest rates of malnutrition included gastroenterology and gastrointestinal surgery (60%), medical oncology, bone marrow transplant and haematology (60%) and general medicine (55%). It is hypothesised that SGA training will have improved malnutrition documentation but that dietetic referral rates remain poor and that financial shortfalls are continuing as a result of undiagnosed malnutrition.

The results of this study highlight that malnutrition continues to be a major burden in the acute hospital setting. Malnourished patients are shown to have poorer clinical outcomes and increased lengths of stay and are largely remaining unrecognized and untreated. These results affirm that routine nutrition screening should be implemented to ensure timely diagnosis of malnutrition for optimal patient outcomes and accurate financial reimbursements to the hospital.

22. Elizabeth Moore

The incidence and implications of Acute Kidney Injury in patients with Traumatic Brain injury

MOORE EM1 2, Bellomo R1, Nichol AD1 3, Harley N2, MacIsaac C2, Cooper DJ1 3.

1 ANZIC Research Centre, Department of Epidemiology and Preventive Medicine, Monash University; 2 Intensive Care Unit, The Royal Melbourne Hospital; 3 Intensive Care Unit, The Alfred Hospital.

Background: Information on the incidence of acute kidney injury in patients with traumatic brain injury is very limited, although acute kidney injury contributes to morbidity, mortality and resource use. We performed the first dedicated investigation of the incidence of acute kidney injury in patients with moderate and severe traumatic brain injury, and assessed the association of acute kidney injury with risk factors and outcomes in these patients.

Materials and methods: We studied all traumatic brain injury patients over 16 years of age admitted to the Royal Melbourne and Alfred hospitals in Melbourne from January 1 to December 31, 2008. Patients were included if they had head trauma and presented with a Glasgow Coma Score < 13. Prospectively collected data from the hospital trauma registries, intensive care units and pathology databases were analysed retrospectively. The extensively validated RIFLE criteria were used to categorise renal function.

Results: The incidence of acute kidney injury was 9.2% (19/207). Patients who developed acute kidney injury were older, had higher severity of illness scores, and a lower Glasgow Coma Score. Overall 42.1% of these patients died in hospital compared with 18.1% in patients without acute kidney injury. In univariable linear regression analysis, age, severity of illness and admitting hospital were associated with acute kidney injury. After multivariable logistic regression, the occurrence of acute kidney injury was associated with age (p<0.001) and higher APACHE III scores (p=0.016).

Conclusion: Acute kidney injury is relatively common even in patients with traumatic brain injury. Its association with age and APACHE III scores helps identify patients at higher risk of acute kidney injury. The presence of acute kidney injury in over 9% of patients with traumatic brain injury, and its association with increased mortality allows the identification of whether interventions which appear to be beneficial in neurotrauma can simultaneously protect brain and kidney and decrease the incidence of AKI. Erythropoietin and prophylactic hypothermia are 2 such treatments. Indeed, the multi-centre randomised controlled EPO-TBI and POLAR trials to respectively investigate the benefit of erythropoietin, and early and sustained hypothermia for neurological outcomes, also assess the effect of these interventions on the kidneys. These trials have recently commenced recruitment in Australia.


16

23. Slave Petrovski

Investigating Genome-wide, Multigenic, Classifiers for Initial Anti-Epileptic Drug Response in Newly Treated Epilepsy

PETROVSKI S1 2 3, Miller H4, Hickey PF5, Isaac A6, Lonie A6, Smith KR5, Reumann M7, Rodrigues S4, Marson A8, Sills GJ8, Bahlo M4 5, Huggins RM4, Johnson M9, O’Brien TJ1 2 3.

1 Department of Medicine (RMH/WH), The University of Melbourne; 2 Department of Neurology, The Royal Melbourne Hospital; 3 BioGrid Australia; 4 The Department of Mathematics and Statistics, The University of Melbourne; 5 The Walter and Eliza Hall Institute of Medicine; 6 Life Science Computation Centre (LSCC), Victorian Life Sciences Computation Initiative; 7 IBM Research Collaboratory for Life Sciences, Victorian Life Sciences Computation Initiative; 8University of Liverpool, UK; 9 Department of Medicine, Imperial College London, UK.

Genome-wide association studies (GWAS) were developed to be unbiased scans across the entire genome reflecting their hypothesis-generating rather than hypothesis-testing nature. Two main approaches to investigating GWAS data exist. The ‘causative gene identification’ approach identifies trait-causing genomic variants, and therefore, generally investigates individual, single nucleotide polymorphisms (SNPs). This approach focuses on identifying allele/genotype frequency differences between two groups, and a SNPs relevance generally depends on significance from a logistic regression model. When a positive association is identified, there is generally no direct clinical consequence without additional investigation, including resequencing of candidate regions to identify the causative variant(s) or functional investigations to prove the mutations relevance.

A less pursued approach has been ‘risk prediction modeling’. Here, the primary aim is developing a model that best predicts the trait based on a set of SNPs. If the SNPs predict the trait with high accuracy then their functionality is generally less relevant. Risk prediction models are evaluated based on diagnostic measures, such as sensitivity and specificity. A limitation of risk prediction modeling is the dependence on a clinically homogeneous cohort, one that is representative of the clinical population that will benefit from the resulting model(s).

Current treatment for epilepsy is less than satisfactory, with approximately 40% of newly-treated patients failing to achieve seizure control with the first anti-epileptic drug (AED). Failure to achieve seizure control is associated with increased physical and psychosocial morbidity. Predicting the biological chance of seizure control with AED treatment will have clinical and socioeconomic value.

We will present results from a unique dataset of approximately 1,500 patients from Australia and the English newly-treated epilepsy cohorts—genotyped on the Illumina 670K-QuadCustom™ platform. We are investigating both ‘causative gene identification’ and ‘risk prediction modeling’ approaches. Success with our risk prediction modeling will have important prognostic value.

We are expanding the in-house developed kNN approach and exploring other machine learning models, including ‘wrapper’ approaches, in which recursive multivariate analyses are applied to identify and model groups of interacting SNPs, and lasso-penalised and ridge regression models. Careful validation design is established to ensure predictions are reliable when applied to new patients.

Finally, model robustness for clinical practice will be tested on additional cohorts, including the ongoing Australian newly treated and the Glasgow epilepsy cohorts. These previously AED-naïve patients will be genotyped for relevant SNPs and are prospectively recruited to represent the population that will benefit from predictive models regarding initial AED response.

24. Gerry Zhi-Ming Ma

Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with multiple sclerosis susceptibility

MA GZM1 2, Stankovich J3, ANZgene4, Kilpatrick TJ1 2, Binder MD1 2, Field J1 2.

1 Florey Neuroscience Institutes, The University of Melbourne;2 Centre for Neuroscience, The University of Melbourne; 3 Menzies Research Institute, University of Tasmania; 4 Members of the ANZgene Consortium.

Background: Multiple sclerosis (MS) is a debilitating, chronic demyelinating disease of the central nervous system affecting over 2 million people worldwide. The TAM family of receptor tyrosine kinases (Tyro3, Axl and MerTK) have been implicated as important players during demyelination in both animal models of MS and in the human disease. We therefore conducted an association study to identify single nucleotide polymorphisms (SNPs) within genes encoding the TAM receptors and their ligands associated with MS.

Methods: Analysis of genotype data from a genome-wide association study which consisted of 1618 MS cases and 3413 healthy controls conducted by the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) revealed several SNPs within the MERTK gene (Entrez Gene ID: 10461) that showed suggestive association with MS. We therefore interrogated 28 SNPs in MERTK in an independent replication cohort of 1140 MS cases and 1140 healthy controls.

Results: We found 12 SNPs that replicated, with 7 SNPs showing p-values of <10-5

when the discovery and replication cohorts were combined. All 12 replicated SNPs were in strong linkage disequilibrium with each other.

Conclusion: In combination, these data suggest the MERTK gene is a novel risk gene for MS susceptibility.


17

25. Rachel Burt

Identifying drug targets for prevention and treatment of hearing loss

BURT RA1 2 3, Carpinelli MR1 2 3, Manning MG1 2 3, Cooray A 1 3, Hilton DJ1 2 3.

1 Walter and Eliza Hall Institute; 2 Department of Medical Biology, The University of Melbourne; 3 Hearing CRC

Background: Age-related hearing loss (presbycusis) is a significant public health issue and is predicted to become increasingly so given the aging population. Noise, and drug-induced hearing-loss are also common. The molecular mechanisms resulting in these conditions are poorly understood. However, it is clear that apoptosis of cells within the cochlear is often involved. Through better understanding of the genetics of hearing loss it is hoped that we will identify therapeutic targets for prevention and treatment of presbycusis and environmentally-induced hearing loss.

Objectives: To understand the molecular basis of hearing loss so as to identify drug targets for prevention and treatment of deafness.

Method: A combination of reverse and forward genetic approaches to studying hearing loss in mouse models, have been used to characterise the genetic and molecular variation underlying hearing loss. Two major streams of work are underway. Firstly, Ethyl Nitrosourea (ENU) mutagenesis screens are being conducted to identify genes involved in progressive forms of hearing loss. Secondly, a panel of engineered mouse strains harbouring mutations in apoptotic regulators is being assessed for hearing loss, to better understand the role of cell death in the auditory system.

Results: Mutations at particular points of the intrinsic pathway of apoptosis have a profound effect on the auditory system. In addition, genome-wide ENU mutagenesis screens have generated a number of mutant mouse strains with subtle and progressive forms of hearing loss. Several interesting mutations are currently being mapped and characterised.

Conclusion: Our work suggests that tightly regulated apoptosis is required for both development and maintenance of hearing. Targeting of apoptotic regulators may prove useful in prevention of cell death and resultant hearing loss in the ear. Future work is planned to test this hypothesis.

26. Andrew Bjorksten

Mutation Detection for Malignant Hyperthermia

Gillies R, Hockey B, BJORKSTEN A.


Malignant hyperthermia (MH) is a pharmacogenetic condition affecting calcium homeostasis of skeletal muscle with known causative mutations in the ryanodine receptor gene (RYR1) and alpha1 subunit gene (CACNA1S) of the skeletal muscle calcium channel. While generally asymptomatic, it can cause a severe life-threatening hypermetabolic state when triggered by several commonly used anaesthetic drugs.

After informed consent, RNAlater stabilized muscle samples from 41 unrelated individuals with in-vitro contracture test (IVCT) confirmed malignant hyperthermia susceptible (MHS) status were extracted for RNA. RNA was immediately reverse-transcribed to copy DNA (cDNA) and the DNA sequence of the entire RYR1 gene determined. In individuals without a potentially causative DNA variant in RYR1, the CACNA1S) was also sequenced. All observed variants were confirmed from genomic DNA in the same patient from a separate blood sample.

Known MHS causative mutations in RYR1 were found in 10 families (24%) with potentially causative variants in a further 6 families (total of 39% of families). In addition to the families with variants in RYR1, a further 14 individuals had potentially MHS causative variants in CACNA1S (total of 73% of families) although none of these are currently definitely known to be causative.

While many DNA variants have been determined we are in a position to move to cascade predictive testing in only the 24% of families with known causative mutations at this stage. Further testing of family members will be required to determine whether the potentially causative variants in the other 49% of families are concordant with MHS phenotype, and can be used for future predictive testing.

27. Candice Boyd

Networks, resources and agencies: On the role of enabling places in facilitating young people's recovery from mental illness

DUFF C, Boyd C.

Social Sciences and Health Research Unit, Monash University

This paper presents select findings derived from a series of studies completed in Melbourne, Australia and Vancouver, Canada exploring the role of “enabling places” in facilitating young people’s recovery from mental illness. Research in each city aimed to explore and elaborate the distinctive role local community settings play in facilitating recovery and promoting social inclusion, health and wellbeing for youth aged 15 - 30 years living with a mental illness.

These studies examined the characteristic dynamics of enabling places in an attempt to clarify the links between these places or environments and the development of protective factors that might promote recovery while buffering the severity of the symptoms and sequelae associated with mental illnesses like bi-polar disorder, schizophrenia and schizo-affective disorder. Drawing on various ethnographic, film and qualitative methods, studies in Melbourne and Vancouver documented an array of enabling places ranging from schools, libraries, community services and parks to less familiar sites such as cemeteries, street-scapes, opportunity shops, cafes and hair-dressing salons. In each city, the protective or therapeutic value of local enabling places was found to derive from the distinctive “enabling resources” that such settings provided for young people. Three categories of enabling resources were identified: social, affective and material resources. It was found that young people draw on these resources in support of various developmental and therapeutic


18

processes central to the experience of recovery, and the wider goals of social inclusion, health and wellbeing. These social, affective and material resources were found to include the development of community and a sense of personal “belonging”; the extension of social networks and social connectedness; the development of personal competencies and the promotion of autonomy; as well as improved access to services and community supports. In each instance, the social, affective and material resources available in local enabling places facilitate the experience of recovery by providing young people with tangible support, encouragement and motivation. The paper closes with a discussion of the ways these enabling resources might be mobilised in the delivery of novel community based mental health promotion initiatives in youth populations.

28. Suresh Sundram

Investigating the role of the epidermal growth factor system in clozapine treated subjects with schizophrenia

Sujeevan S, Pereira A, SUNDRAM S.

Molecular Psychopharmacology, Mental Health Research Institute, Northern Psychiatry Research Centre, Department of Psychiatry, The University of Melbourne

Background: Schizophrenia is a major mental illness with significant disability. Even with novel antipsychotic drugs (APD), 45% are left with little improvement. Clozapine is the only APD that is superior in treatment resistant schizophrenia but is plagued by toxic side effects limiting its usage. Ability to predict response can facilitate early introduction and reduce unnecessary exposure to its side effects. So far genetic, biochemical and clinical studies have failed to identify useful markers that could predict response.

Study objectives: Our in vitro and in vivo evidence support a mechanism of action of clozapine involving the epidermal growth factor (EGF) receptor. This study aims to examine 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 42 patients have been recruited and 38 have completed the study. Six patients discontinued medication. Of those who completed, 5 were females, and the age range was from 20 to 65.

Mean reduction in PANSS score was 6.97 and CGI-S was 1.79. Thirteen patients showed > 20% reduction in PANSS.

Our initial analysis (n=10) demonstrated that clozapine treatment in schizophrenia elevated serum EGF levels in some but not all patients and that post-treatment serum EGF levels significantly correlated (r2=0.39; p=0.05) with post-treatment PANSS (Positive and Negative Syndrome Scale) total scores. Of note was the even stronger relationship (r2=0.70; p<0.04) in those who increased EGF levels post-treatment (n=6).

Conclusions: The overall response rate in out study population is similar to other studies. Initial biochemical studies are in keeping with our hypothesis, in that for those in whom clozapine is effective it augments EGF system signalling in exerting its therapeutic effectiveness. The information from this study can help facilitate safe and early introduction of clozapine and inform research in to new APD development.

29. G. Paul Amminger

Fatty acid metabolism and the onset of psychotic disorder in young people at ultra high-risk of psychosis

AMMINGER GP 1 2, Lavoie S1 3, Schäfer M R1 2, Berk M1 4, Whitford T1 5.

(1) Orygen Research Centre, The University of Melbourne; (2) Department of Child and Adolescent Psychiatry, Medical University of Vienna, Austria; (3) Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland; (4) Department of Clinical and Biomedical Sciences-Barwon Health, The University of Melbourne; (5) Melbourne Neuropsychiatry Centre, The University of Melbourne

Potentially chronic diseases often have a critical point in their course beyond which treatment becomes less effective. In support of this, early treatment in schizophrenia and other psychoses has been linked to better outcome. Intervention prior to the first episode therefore holds the promise of even better outcomes, with the potential to prevent psychotic disorders. In the 1990s, criteria were developed and tested in a series of prospective naturalistic studies which identify a clinical population with subthreshold symptoms at ultra-high-risk for psychosis. The emergence of simultaneous brain volume changes in those ultra high-risk individuals who develop psychosis indicate an active biological process, and underline the importance of pre-onset treatment.

However, pre-psychotic intervention has also been questioned as, using current criteria, only 20-50% of individuals classified as prodromal develop a psychotic disorder within a 1-2 years period. Treatment agents in the pre-psychotic phase should, therefore, not have major side effects. Bioactive lipids are molecules that have both intra- and intercellular roles, including mediation, modulation and control of neurobiological processes, such as ion channel and receptor activity, neurotransmitter release, synaptic plasticity, second messenger pathways and neuronal gene expression. Long-chain omega-3 polyunsaturated fatty acids (PUFAs) have been shown effective for both, mood and psychotic symptoms, and they have neuroprotective properties. Because of the controversy concerned with the extent to which an intervention may produce harm which outweighs its benefits, omega-3 PUFAs are prime candidates for evaluation in putatively prodromal individuals.

We report on the first randomized, placebo-controlled trial on the preventive use of omega-3 fatty acids in 81 ultra-high-risk individuals (Amminger et al., 2010). Supplementation with long-chain omega-3 PUFAs reduces the risk of progression to psychotic disorder, and offers a safe and efficacious strategy for indicated prevention in individuals at ultra high-risk of developing a psychotic illness. Extending this evidence, we also address if baseline erythrocyte membrane fatty acids: (1) predict transition to psychotic disorder; (2) predict response to treatment with omega-3s; (3) correlate with resting state electroencephalographic activity.


19

30. Cali Bartholomeusz

Orbitofrontal cortex sulcogyral patterns in first episode psychosis

BARTHOLOMEUSZ C1, Whittle S1,2, McGorry P2, Velakoulis D1, Pantelis C1, Wood S3.

1 Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne; 2 Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne; 3 School of Psychology, University of Birmingham

Background: The orbitofrontal cortex (OFC) is a region known to be involved in various higher order cognitive processes, in particular those associated with reward/punishment, moral judgement/decision-making and social cognition. Three types of OFC sulcogyral patterns have been identified in the general population; Type I is most commonly found (56% of the time), Type II is less common (30%), while Type III is rare (14%) (Chiavaras and Petrides, 2000). Altered OFC sulcogyral patterns have been found in ultra-high risk, first episode psychosis and chronic schizophrenia patients, where Type I was less common and Type III was more common. The Type III pattern has also been associated with poorer outcome. The aim of the current study was to replicate and extend this research by investigating whether OFC sulcogyral patterns are altered in a large sample of first episode psychosis (FEP) patients.

Methods: 96 (71 male, 25 female) FEP patients (age M= 21.3, SD= 3.2; illness duration M= 66, SD= 107 days) were recruited from Orygen Youth Health. 85 (54 male, 31 female) healthy control participants were recruited from the general population. T1-weighted MR images were acquired with a 1.5T scanner. OFC pattern classifications were based on the method devised by Chaivaras and Petridies (2000). Chi square statistics were employed.

Results: Distribution of the three OFC Types differed significantly between groups for the right (p<.05) but not the left (p=.40) hemisphere. Specifically, patients were less likely to have Type I (44.8%) and more likely to have Type II (28.1%) in this hemisphere compared to controls (62.4% and 11.8% respectively). In addition, significantly fewer intermediate rostral sulci were observed in the left hemisphere of patients (p<.05).

Discussion: Our findings partially support previous research in that OFC pattern distribution differed significantly between patients and controls in the right hemisphere. We did not find Type III to be more common in FES patients as expected. Given that cortical folding pattern is determined by the 3rd trimester of gestation, Type I may be somewhat protective against the development of a psychotic disorder. The finding of fewer intermediate sulci in the left hemisphere may reflect underdevelopment of the neural system in that area. Further investigation into the relationship between OFC pattern Type and social functioning is needed and should encompass not only schizophrenia cohorts but other clinical populations as well.

31. Daniel Chan

Effect of haloperidol on potassium currents in hippocampal CA1 neurons

CHAN D1, French C1,2.

1 Department of Medicine, The University of Melbourne; 2 Department of Neurology, The Royal Melbourne Hospital

Introduction: Neuroleptics have been used to treat pyschosis since the first antipsychotic drug, chlorpromazine, was approved for clinical use in 1952. However, it is well documented that conventional and atypical antipsychotics can cause seizures as an adverse drug reaction, with prevalence figures ranging from 0.5% to more than 10% depending on various factors. Though it is generally thought that neuroleptics lower the seizure threshold, the exact mechanism by which this occurs has not been conclusively elucidated. This study investigates the hypothesis that the pro-seizure effect of haloperidol, a common antipsychotic, is mediated partly by its effect on potassium channels.

Methods: Single dissociated neurons were obtained from the CA1 region of 3 week old rat hippocampi. They were perfused with a control HEPES solution with 1 µM tetrodotoxin (TTX) added to abolish Na+ currents. Whole-cell patch voltage clamp recordings were performed on these neurons to examine the effects of 10 nM to 50 µM haloperidol on outward, or membrane stabilizing currents. Cells were kept at a holding potential of -100 mV and outward currents evoked by step commands of 10 mV between -100 mV to +40 mV. Cell recordings were obtained when varying concentrations of haloperidol were added to the perfusate, and washouts with the control solution were done between haloperidol infusions. These experiments were repeated with 0.2 mM cadmium added to the control solution to eliminate the Ca2+ & Ca2+-dependent currents, as well as at a -60 mV holding potential to eliminate transient outward currents.

Results: Current values from the haloperidol infusions and subsequent washouts were normalized against the largest current amplitude in the control solution. Current-Voltage (I-V) curves of the control, drug and washout were plotted at each concentration of haloperidol, for both the peak and steady state outward currents. We found that haloperidol reduced steady state current amplitudes ranging from a 10% decrease at 10 nM to 100% at 50 µM, with peak currents showing similar results. The experiments with cadmium added displayed essentially the same reductions in peak and steady state currents.

Conclusion: Haloperidol dose-dependently reduces potassium currents in rat hippocampal CA1 neurons. There is a prominent suppression of the steady state currents with a smaller decrease in the transient currents. The effect was most marked at higher concentrations but still noticeable at lower therapeutic concentrations. This suppression of repolarising potassium currents by haloperidol may cause decreased neuronal stability, leading to network hyperexcitability and an elevated risk of seizure generation.


20

32. Stella Hughes

The Kurtzke EDSS rank stability increases 4 years after onset of Multiple Sclerosis: results from the MSBase Registry

HUGHES SE1,2, Gray OM3, Spelman T1, Butzkueven H1,4, on behalf of the MSBase Registry1.

1 Queen’s University Belfast, Northern Ireland; 2 The Royal Melbourne Hospital; 3 Craigavon Area Hospital, Northern Ireland; 4 Department of Medicine, The University of Melbourne.

Background: Predicting disease severity in individuals with multiple sclerosis (MS) has become increasingly important with the development of therapeutic options. The Kurtzke Expanded Disability Status Scale (EDSS) is used in clinical and research settings to delineate an individual's disease progression. The Global Multiple Sclerosis Severity Score was devised to allow comparisons of disease severity at all EDSS levels for a given disease duration, using ranking of individual patients with the same disease duration by EDSS. We assess rank stability of EDSS in the MSBase dataset, a large multi-centre study of MS outcomes. Methods: Data was extracted on 17 May 2010 from centres with more than 20 cases. Cases fulfilled either Poser or McDonald criteria for MS and were within 16 years of disease onset. The EDSS was averaged in each individual over a 2-year period. We analysed the rank of each individual’s EDSS at beginning and end of each 5-year interval, change in rank and 5-year EDSS stability using Spearman Rank-sum correlations. Results: MSBase had 14062 patients enrolled from 67 centres in 26 countries at the time of data extraction. Data extracted for this study was taken from 42 centres in 19 countries with 91,730 complete EDSS calculations from 13,809 patients. The Spearman rank-sum correlation for rank of EDSS across the 5-year time interval year 1-6 was 0.55. Spearman rank-sum correlations consistently increased with time from onset with values of 0.74 across the interval years 4-9, 0.80 for years 7-12 and 0.83 for years 10-15. This indicates strong correlation between rank of EDSS at the beginning and end of 5-year intervals after 4 years since onset of MS.

Conclusion: EDSS rank stability increases with increasing disease duration, probably due to reduced influence of relapses and non-relapse fluctuations. EDSS at 4 years from diagnosis is already highly predictive of EDSS 5 years later. This may suggest a role for the EDSS as an outcome predictor in individual patients after at least 4 years disease duration.

33. Amelia Koe

The enduring effects of early-life stress on limbic epileptogenesis are mediated by HPA axis hyper-reactivity

KOE AS1, Salzberg MR1,2, O’Brien TJ1, Morris MJ3, Jones NC1.

1 Department of Medicine (RMH), The University of Melbourne; 2 Department of Psychiatry, St Vincent’s Hospital; 3 Department of Pharmacology, University of New South Wales

Background: Evidence suggests that the enduring effects of early-life stress on the brain may contribute to the development of limbic epilepsy later on in life. This process is possibly mediated by hyper-reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and concomitant increased corticosterone release. Using the maternal separation (MS) model of early-life stress in rats, this study was designed to assess whether inhibiting the synthesis of corticosterone could ameliorate the adverse effects of MS stress on kindling epileptogenesis.

Methods: On postnatal days 2-14, female Wistar rats were exposed to maternal separation stress for 3h/day (MS) or early-handled for 15min/day (EH). At 8 weeks of age, rats were assessed for seizure threshold via a bipolar electrode implanted in the left amygdala, and subsequently subjected to the electrical amygdala kindling model of limbic epileptogenesis. Throughout the kindling period, rats were administered with either metyrapone (corticosterone synthesis inhibitor, 50mg/kg, s.c) or vehicle 60 minutes prior to each stimulation.

Results: Vehicle-treated MS rats displayed reduced seizure threshold (p=0.03), and longer seizure duration (p=0.02) compared to EH rats. Metyrapone treatment in MS rats significantly increased seizure threshold (p=0.0001) and reduced seizure duration during kindling (p=0.018) to levels of EH rats. In MS rats only, metyrapone treatment delayed the progression of kindling, with rats requiring more stimulations to reach the fully-kindled state (p=0.03).

Groups: MS-MET: n=18 ; MS-VEH: n=19; EH-MET: n=17; EH-VEH: n=18.

Conclusion: The inhibition of corticosterone synthesis with metyrapone alleviated the enduring effects of MS stress on seizure threshold, seizure duration and kindling rate. This suggests that increased corticosterone release, associated with HPA axis hyper-reactivity, is critical to the effect of MS stress in increasing vulnerability to limbic epileptogenesis.

34. Sarah Miller

Carbamazepine Decreases Outward K+ Currents in Calvarial Osteoblasts

MILLER SE1, Todaro M1,2, Hill EL1, Wark JD1, O’Brien TJ1,2, Mackie EJ3, French CR1,2, Petty SJ1.

1 Department of Medicine, The University of Melbourne; 2 Department of Neurology, The Royal Melbourne Hospital; 3 Faculty of Veterinary Sciences, The University of Melbourne

Background: Epileptic patients on Anti-Epileptic Drug (AED) medication experience a higher risk of bone fracture compared to the general population. This increased risk may be a result of a direct effect of AEDs, such as carbamazepine (CBZ), on bone. This study examined the effect of CBZ on ion-selective channels in the cell membranes of primary calvarial osteoblast cultures to examine whether AEDs act on bone cells through ion channel targets similar to those in neurons.

Methods: Calvarial osteoblasts were isolated from neonatal C57B6 mice using a collagenase/ trypsin digest and cultured in DMEM supplemented with 10% FBS, L-glutamine, amphotericin B, and gentamicin, in a 5% CO2 incubator for 3-10 days. Osteoblasts cultured on microscope coverslips were placed on microscope slides in a HEPES solution for


21

baseline recording. Currents were recorded using electrodes (4-8MΩ) containing a KF intracellular solution. Test solutions were applied via a microperfusion system to enable direct application onto the osteoblast of interest. Currents were recorded from individual osteoblasts using a step voltage protocol in whole cell voltage clamp mode.

Results: Depolarising voltage commands from a holding potential of -80mV resulted in outward currents with kinetic properties similar to potassium channels seen in neurons. Application of the Ca2+ channel blocker Cd2+ (0.2mM ) reduced the amplitude of these currents by 25% (n=9), suggesting the presence of a calcium-activated potassium conductance component of the outward currents. In the presence of Cd2+ an additional outward current persisted, suggesting the presence of another type of potassium channel; the delayed rectifier. Application of 50µM CBZ reduced the outward current by 37% compared to baseline recordings (n=9), providing evidence that CBZ effects the potassium conductance in osteoblasts.

Conclusion: The observed decrease in outward K+ currents following CBZ application indicate modulation of channel excitability by this AED in primary calvarial osteoblasts. Altering membrane ion permeability influences intra and extracellular communication pathways, which control vital cell functions such as mechanotransduction and cell proliferation. This study provides a novel mechanism whereby CBZ may affect bone by direct effects on ion channels, analogous to its effect on central neurons.

Acknowledgements: Dr. Sandra Petty is supported by the DW Keir Fellowship, The Royal Melbourne Hospital.

35. James Dimou

The gliomasphere as a platform for exploring novel therapies targeting the Pi3-kinase pathway

DIMOU J1, D’Abaco G1, Burgess A2, Paradiso L1, Drummond K1, Kaye A1, Morokoff A1.

1 Departments of Surgery and Neurosurgery RMH/WH, The University of Melbourne; 2 Ludwig Institute for Cancer Research.

Receptor tyrosine kinase inhibitors have been clinically disappointing. New downstream pharmacotherapeutic targets need to be identified in high grade glioma. Alterations of phosphoinositide 3-hydroxykinase (Pi3k)/Akt pathway targets are critical for high grade gliomagenesis. Akt inhibition retards glioma stem cell proliferation. PTEN loss, a Pi3k tumor suppressor protein, is common in glioma, portending a poor clinical outcome.

Additionally, cell-line based models of glioma have a poor track record in delivering effective translational outcomes. Brain tumour stem cells represent a sub-population of cells resistant to therapy with recurrence potential, due to capacity for self-renewal. Glioma stem cells are more aggressive in recurrent rather than primary glioblastoma. High CD133/nestin positivity within glioma samples, along with successful in vitro gliomasphere formation, predict inferior outcome, highlighting the stem cell as the main target, and the gliomasphere as the ideal vehicle, for any advance in glioma therapeutics.

Aims and methods: 1) to establish a reproducible method for culturing gliomaspheres; 2) to confirm the presence of CD133 positivity (and thus tumour stem cells) within gliomaspheres; 3) to demonstrate stem cell differentiation along oligodendroglial, neuronal and glial lineages; 4) to determine glioma stem cell expression of key proteins of the Pi3k/Akt pathway (Western Blot analysis); 5) to determine sensitivity of glioma stem cells to novel small molecule inhibitors, testing for drug-induced cytotoxicity using colourimetric LDH assays

Results: 62 glioma specimens have been processed. 35 produce gliomaspheres able to be passaged successively. FACS analysis shows that gliomaspheres contain CD133+ cells. Gliomaspheres are verified to be pluripotential, with expression of 3-tubulin (neuronal differentiation marker) and glial fibrillary astrocytic protein (astrocyte marker) via immunofluorescence post-differentiation.

Sixteen tumour stem cell lines are investigated for expression of key Pi3k/Akt proteins (Western blot analysis). Akt phosphorylation is present in 13/16 lines; PTEN is lost in 9/16 clones. EGFR amplification and Akt phosphorylation do not correlate, confirming observed poor efficacy of EGFR inhibitors in high grade glioma treatment. Early data from LDH assays confirms the capacity for Akt inhibition (i.e. AktX, triciribine) to induce gliomasphere cytotoxicity.

Conclusions: We conclude that gliomaspheres exhibiting CD133+ positivity and multipotentiality express appropriate ‘stem cell’ properties, enabling a reliable, high throughput screening of target molecules, primarily including Pi3k/Akt axis inhibitors. We plan to transfect stem cells with fluorescent markers, enabling tracking of in vivo gliomagenesis using IVIS bioluminescence, pre- and post-drug therapy, further accelerating our capacity to move promising Pi3k/Akt inhibitors from pre-clinical evaluation to clinical testing.

36. Brad Moffat

Radiological features correlating with tumour associated epilepsy in patients with supratentorial gliomas

LIUBINAS S1,2, Moffat B3, O’Brien TJ4,5, Rosenthal M6, Kaye AH1,2, Morokoff A1,2, Drummond K1,2.

1 Department of Surgery, The University of Melbourne; 2 Department of Neurosurgery, The Royal Melbourne Hospital; 3 Department of Radiology, The University of Melbourne; 4 Department of Medicine, The University of Melbourne; 5 Department of Neurology, The Royal Melbourne Hospital; 6 Medical Oncology, The Royal Melbourne Hospital.

Background: Gliomas are the most common malignant brain tumours, with more than 1,500 new cases diagnosed in Australia each year. Epileptic seizures are a frequent presenting symptom of gliomas, and overall around 50% of patients suffer from one or more seizures (i.e. tumour associated epilepsy, TAE) during the course of their disease. TAE is often not effectively treated by removal of the tumour and difficult to control with current anti-epileptic drugs (AEDs). TAE contributes significantly to the morbidity and socioeconomic costs of gliomas. The molecular mechanisms of TAE are currently unknown, however one of the key factors implicated in the aetiology of TAE is elevation of the excitatory neurotransmitter glutamate. Magnetic resonance spectroscopy (MRS) provides a non-invasive method to measure metabolites in the brain, including glutamate. Here we investigated whether MRS, and volumetric measurements of cortical involvement by the tumour and oedema on anatomical MRI, can be used a biomarkers for the prediction and outcome of TAE in patients with gliomas.


22

Methods: All patients admitted to the Royal Melbourne Hospital from March 2010 with known or likely gliomas are invited to partake in this prospective study, and to date 140 patients have been enrolled. Routine preoperative anatomical MRI is performed on all patients, and a subset (n=44 to date) also undergo MRS. Tumour volume and cortical involvement by tumour and oedema on anatomical MRI are measured using the computer program Analyze™ and the glutamate, glutamine and creatine concentrations on MRS are measured using the computer program LCModel™.

Results: Preliminary data analysis shows that for Grade II gliomas (n=9), there was a trend towards significance when comparing MRS measured glutamate plus glutamine to creatine ratios (Glx/Cr) in the tumour and in the peritumoural brain for patients with TAE compared to those without TAE (p=0.16). For Grade IV gliomas (n=16) there was a significantly higher MRS measured Glx/Cr in the tumour than the peritumour for patients with TAE (p<0.01). In patients with grade IV gliomas (n=20), there is a trend for a higher area of involvement cortex by oedema (measured on FLAIR MRI sequences) for patients with TAE compared to those without (p=0.12).

Conclusion: Preliminary data analysis suggests that MRS glutamate measurements and volumetric MRI measurements are potential biomarkers for TAE. Further data analysis is needed to determine the sensitivity and specificity of these measures, and their relationship with outcome and response to treatment.

37. Andrew Nichols

MRI biomarkers in patients with pituitary tumours

NICHOLS A, Moffat B, Danesh-Meyer H, Kaye A.

The University of Melbourne; The Royal Melbourne Hospital; University of Auckland

Introduction: Pituitary adenomas represent 8-10% of all intracranial tumours. Growth of pituitary tumours superiorly may cause optic chiasm or optic nerve compression and lead to visual failure or visual field (VF) defects. Anatomical magnetic resonance imaging (MRI) to evaluate compression of the optic apparatus is part of standard pre-surgical care. Surgery to remove pituitary adenomas and decompress the optic apparatus may result in visual recovery in some patients. Previous studies have identified that retinal nerve fibre layer (RNFL) thickness on optical coherence tomography (OCT) predicts the likelihood of visual recovery following surgery for optic removal of pituitary tumours and decompression of the optic chiasm. This study investigates the role of functional magnetic resonance imaging (fMRI) and diffusion tractography biomarkers in patients with pituitary tumours in a clinical setting.

Methods: Patients who had undergone surgery for pituitary tumours at the Royal Melbourne Hospital or Melbourne Private Hospital were recruited to undergo a single additional MRI scan with anatomical, fMRI and diffusion weighted imaging protocols. MRI was performed on a Siemens Trio 3 Tesla full body MRI scanner equipped with a clinical fMRI system (MRIχ Technologies, Chicago, IL). This study has been approved by the Melbourne Health human research and ethics committee.

Results: fMRI activation maps were obtained and tractography performed using a constrained spherical de-convolution (CSD) probabilistic tractography algorithm. Analysis of manually selected anatomically defined regions of interest (ROI) and seeding based on fMRI activation of the lateral geniculate nucleus (LGN) was performed. fMRI and diffusion tractography could be performed reliably in this patient population in a clinical environment.

Discussion: MRI offers an opportunity to further investigate the structure and function of the optic pathway in a non-invasive manor that would not otherwise be possible. Further studies are warranted to investigate the utility of fMRI and diffusion tractography as clinical biomarkers in patients with pituitary tumours. MRI biomarkers have the potential to improve and individualise the management of patients with pituitary tumours.

38. Adam Cichowitz

Effects of nutritional intervention in patients undergoing chemoradiotherapy for oesophageal cancer

CICHOWITZ A, Shakerian R, Spillane J, Duong C.

The Royal Melbourne Hospital; Peter MacCallum Cancer Centre.

Purpose: To analyze the nutritional outcomes and impact of supportive interventions in patients undergoing chemoradiotherapy for oesophageal carcinoma.

Methodology: A retrospective study was conducted involving 70 patients treated between 2005 and 2010 with either neoadjuvant or definitive chemoradiotherapy for non-metastatic oesophageal adenocarcinoma or squamous cell carcinoma. Patient characteristics were determined along with nutritional parameters before and after chemoradiotherapy. The effects of various enteral interventions were compared with those following best supportive care provided by dieticians. Interventions included the insertion of a nasogastric tube, PEG tube, laparoscopic jejunostomy or oesophageal stent.

Results: The overall percentage weight loss for all patients was 5.7% while the corresponding drop in albumin was 6 g/L. Neither of these nutritional parameters varied significantly with tumour type, degree of oesophageal stricturing or initial BMI. Complications during treatment were associated with a significantly greater percentage weight loss and drop in albumin. These patients were at greatest risk of malnutrition at the end of treatment along with those with a low initial BMI which was significantly associated with severe stricturing and squamous histology. Despite being a high risk group, patients who received prophylactic intervention pre-treatment experienced less complications, were better able to maintain weight and had a smaller drop in albumin during treatment compared with those who received no intervention or required intervention mid-treatment.

Conclusion: Patients at high risk of malnutrition following chemoradiotherapy for oesophageal carcinoma may benefit from prophylactic nutritional intervention.


23

39. Matthew Hong

Gene expression profiling in prostate cancer: Defining the lethal phenotype

HONG MKH1, Moore EK1, Amiry N1, Chin X1, Kerger M1, Haviv I2, Costello AJ1, Hovens CM1, Corcoran NM1.

1 Division of Urology, The Royal Melbourne Hospital; Department of Surgery, The University of Melbourne; Australian Prostate Cancer Research Centre, Epworth Hospital; 2 Baker IDI.

Introduction: Gene expression profiling of prostate cancer tissue by microarray promises to provide clinicians with an adjunct to help distinguish lethal from biologically indolent prostate cancer, and provides researchers with a powerful means to explore the complex molecular mechanisms underlying prostate cancer. In this study, we aimed to characterise gene expression signatures of prostate cancers with lethal tendencies in both malignant and matched non-malignant components from prospectively stored fresh frozen tissue.

Patients and Methods: This study involves patients from a radical prostatectomy series occurring at Epworth Hospital from 2006-2008. Samples of their prostate cancer tissue and adjacent non-malignant tissue had been fresh frozen and prospectively stored. Frozen sections were cut from selected cores of matched benign and malignant tissue and stained with haematoxylin and eosin for assessment in real time by a pathologist to confirm the presence or absence of tumour. Total RNA was extracted from the tissue by mechanical homogenisation and column chromatography (Qiagen Rneasy Minikit). The RNA was interrogated using the HumanHT-12 v4 BeadChip (Illumina) and read using a beadchip reader. Statistical analysis was performed on BeadStudio (Illumina).

Results: Preliminary results will be presented. The first part of the study involved six patients and compared malignant with matched benign tissue. A very clear distinction could be made between malignant and benign tissue. Genes such as PCA3 and AMACR overexpressed in cancer. However, a significant number of genes were associated with epithelium such as EPCAM in cancer and stromal genes in benign tissue. This suggests that varying epithelial content accounted for a significant proportion of the difference seen. The second part examined five patients with high grade prostate cancer and five with low grade cancer. Adjacent benign prostate tissues were compared to find preliminary evidence for field change effect occurring in prostate glands harbouring low versus high grade prostate tumours. Subtle differences were seen.

Conclusions: To accurately discriminate between biologically indolent and lethal prostate cancer, a thorough molecular interrogation of high quality tumour tissue is required. Clear differences are seen between cancer and benign tissue, and it may be possible to determine the nature of the cancer based on data from adjacent non-malignant portions of the prostate gland. However, the varying epithelial content in prostate should be taken into account in future expression profiling experiments.

40. Anton Lambers

How accurately is the hip arthroplasty patient positioned prior to surgery?

LAMBERS A, Jennings B, Bucknill A.

The Royal Melbourne Hospital; The University of Melbourne.

BACKGROUND: Patient malpositioning preceding total hip arthroplasty (THA) has the potential to cause implant mal-alignment and associated post-operative complications. When implanting the prosthetic cup during THA in the lateral decubitus position, the surgeon makes the assumption that the pelvis is perpendicular to the table. This study examines the actual positioning of the patient relative to the table prior to total hip replacement.

METHODS: A consecutive series of 36 patients undergoing total hip arthroplasty were included in the study. Following the usual positioning of the patient by the surgeon a lateral fluoroscopic image of the pelvis was taken. With the two acetabulae visible, the C-arm of the image intensifier was manipulated until a proper lateral view of the hip was obtained, defined as when the native cups overlapped.

The degrees deviation from the true lateral position was recorded from the graduations on the C-arm. Tilt in the axial plane was defined as rolling towards prone or supine. Tilt in the coronal plane was defined as the cranio-caudal movement of one acetabulum relative to the other. The number of degrees of pelvic tilt and BMI were recorded. Using this information the patient’s position was then corrected before the surgery began.

RESULTS: In the axial plane: The average deviation from a true lateral position in this plane was 2.9 degrees. 19 patients (52.8%) were malpositioned by more than 2 degrees following the surgeon’s positioning. A further 7 patients (19.4%) were tilted by 5 degrees or more. A statistically significant correlation was shown between BMI and the magnitude of pelvic tilt in this plane (R=.35, p-value=0.0343).

In the coronal plane: The average deviation from lateral positioning in this plane was 3.1 degrees. 20 patients (55.6%) were malpositioned by more than 2 degrees from true lateral. In addition, 14 patients (38.9% of entire group) were tilted by more than 5 degrees. A correlation was found between BMI and the magnitude of pelvic tilt in this plane (R=.32, p-value=0.0584).

CONCLUSIONS: This study demonstrates that there are often inaccuracies in pre-operative patient positioning prior to total hip arthroplasty, and these are somewhat related to patient size. The study describes a quick and easy method of improving this before the operation commences. It is important to note that a number of patients had a clinically significant amount of tilt on the table, which alone, or in combination with other random errors during cup impaction, could result in cup malpositioning.


24

41. Jonathan Knott

Mandatory pain scoring reduces time to analgesia

Vazirani J, KNOTT J.

Emergency Department, The Royal Melbourne Hospital; Medical Education Unit, The University of Melbourne.

Background: The management of pain in Emergency departments does not meet the expectations of patients or staff. This study sought to determine the effectiveness of mandatory pain scoring and subsequent provision of a staff educational package in reducing the time to initial analgesic delivery.

Methods: This two stage prospective interventional study was conducted in the Emergency Department of a tertiary referral hospital in Melbourne, Australia. Following an eight week observation of baseline performance, pain score collection at triage was made mandatory using the ED Information System and outcomes recorded for a further eight weeks. Finally, an educational package on the importance of timely analgesia was delivered to all staff. Data was collected again for eight weeks. The primary outcome was time to analgesia (the difference between time of patient first contact with staff) and time of dispensing the first dose of any defined analgesic. The time to analgesia was stratified by triage category, drug class and initial pain score.

Findings: 26 612 patients were analysed (8771, 8752 and 9089 in each phase) and 9788 patients received analgesics (3130, 3341 and 3317 in each phase). Median time to analgesia at baseline was 123 min. Following introduction of mandatory pain scoring, median time to initial analgesia dropped by 29 min to 94 min (23·5%, 95% CI; 22·9 – 24·2, p<0·0001). There was no clinical or statistical difference in time to analgesia following the further addition of an educational package. The findings were consistent across all sub-groups.

Conclusion: Mandatory pain scoring at triage greatly reduced time to initial analgesia in this Emergency Department, the effect was sustained in the medium term and occurred for all patients. Education offered no additional benefit.

42. Jun Hoe Tay

Study of radial EBUS in determining relationship between radiological findings (size of peripheral and location of lesion in lung fields) of lung lesion versus diagnostic yield and visualization yield.

TAY JH, Antippa P, Steinfort D.


Background and study objective: Endobronchial Ultrasound (EBUS) has increased the yield of bronchoscopic biopsy of peripheral pulmonary lesions (PPL). This study aims to evaluate those factors predicting peripheral diagnostic yield and also visualization yield of radial EBUS-guided bronchoscopy for investigations of PPL.

Methods: Retrospective analysis of 196 consecutive patients who underwent EBUS investigations from Feb 2008 – July 2010 in a tertiary teaching hospital. Size and distance of lesion from hilum and pleura were measured from patients’ CT scans. Diagnostic yield and visualization yield were obtained from EBUS bronchoscopy reports. Diagnosis not obtained through EBUS but through other modalities such as surgery, surveillance and biopsy were classified as negative diagnostic yield.

Results: A definitive diagnosis was established by combined brushing, washing and transbronchial biopsy (TBB) using EBUS in 109 PPL (56%). The diagnostic yield of PPL <20mm in mean diameter (31%) was significantly lower than that of PPL ≥20mm in mean diameter (64%; p= 0.0001). Visualised lesion by EBUS probe had a higher diagnostic yield (65%) than EBUS-invisible lesions (20%; p= 0.0001). Patients with malignancy also had a significantly higher diagnostic yield (67%) than patients with benign lesions (31%; p= 0.0001). Female patients had a higher diagnostic yield (67%) than their male counterparts (47%; p= 0.0061). PPL not adhering to adhering to the pleura (>0mm) had a significantly lower diagnostic yield (48%) compared to that of PPL adhering to the pleura (0mm) (66%; p- value= 0.0132). In multivariate analysis, only lesion size, visualization by EBUS probe, malignant lesion and gender were determined to be significant factors predicting diagnostic yield.

In multivariate analysis, lesion size, malignancy and distance from hilum to lesion were found to significantly affect visualization yield. Lesion of < 20mm had a significantly reduced visualization yield (63%) than lesions of ≥ 20mm (85%; p-value = 0.0022). Malignant lesions had a higher visualization rate (85%) than benign lesions (66%; p-value = 0.0025). Distance of hilum ≤50mm to PPL had a significantly higher visualization yield (91%) than lesions located >50mm from the hilum (66%; p-value= 0.0001).

Conclusions: Lesion size, visualization, final diagnosis and gender are significant variables in predicting EBUS diagnostic yield for investigations of PPL; while lesion size, final diagnosis and distance from hilum to lesion are significant predictors of EBUS visualization yield. Clinicians should review these factors in patients to guide choice of optimal investigation for diagnosis of PPL.

43. Anneke van der Walt

Botulinum Toxin Type A (Botox) for the treatment of disabling tremor in Multiple Sclerosis: a double-blind, randomized controlled study.

VAN DER WALT A1,3,4, Sung S1,2, Spelman T1, Marriott M1,4, Kolbe S3, Mitchell P1, Evans A1,2, Butzkueven H1,2,4.

1. Royal Melbourne Hospital; 2. Faculty of Medicine, The University of Melbourne; 3. Centre for Neuroscience, The University of Melbourne; 4. Box Hill Hospital.

Background: Upper limb tremor in MS patients is common but under recognized. Action tremor, in the form of postural (present whilst maintaining position against gravity), and intention tremor (increases during movement towards a target), are the most commonly described tremors in MS. Medical treatment of MS tremor is unrewarding and surgical


25

intervention is invasive with variable results. In this study, we examined the efficacy and side effects of Botox in the treatment of MS tremor.

Methods: 25 MS patients were recruited of which 11 had bilateral upper limb involvement resulting in a cohort of 36 limbs. After exclusions, 33 limbs were included in a cross-over study with each limb randomized to receive Botox or placebo at baseline and the reverse injection at 12 weeks. Both patients and treating physicians were blinded. Patients were assessed at 6 weekly intervals for 6 months. The main outcome was the change in the Bain score of tremor severity, writing and drawing from baseline to 6 and 12 weeks following Botox compared to placebo. Secondary outcomes included a change in different tremor components (rest, kinetic, postural, batswing and intention tremor) measured by components of the UTRA and CRST scores. Assessments were video-recorded and videos of each patient were randomized before being assessed by a blinded independent rater. The McNemar and Wilcoxon signed–ranks tests were used.

Results: Data is reported as median change at 6 and 12 weeks with interquartile (IQR) range in brackets. There was a significant improvement after Botox compared to placebo in all the main outcomes including Bain scores for tremor severity at 6 weeks (median change -2 (IQR -2,-1), p=0.0005) and 12 weeks (-2 (-2,-1), p=0.0001), writing at 6 (-1 (-1,0), p=0.0001) and 12 weeks (-1 (-1,0), p=0.0003) and drawing at 6 (-1 (-1,0), p=0.0006) and 12 weeks (-1 (-2,0), p=0.0002). Significant improvements after Botox were recorded at 6 and 12 weeks in postural, batswing and kinetic tremor using UTRA and CRST scores. Intention tremor improved following Botox at 6 weeks but not at 12 weeks. More patients developed weakness post Botox (42.2%) than after placebo (6.1%), p=0.0005. Weakness, when present, was mild (just detectable) to moderate (present but still able to use limb) and resolved within 2 weeks.

Conclusions: Botox injections significantly improves upper limb tremor in MS patients and offers a novel treatment for a disabling condition. Weakness, although a common side effect, is mild to moderate and rapidly improves.

44. Peter Colman

Autoantibodies to the Beta Cell-Specific Zinc Transporter 8: Prevalence in INIT II screenees

COLMAN PG1, Gellert S2, Andaloro E2, McManus F3, Breen C3, Harrison LC3 4.


Autoantibodies to islet proteins are predictors for increased risk of type 1 diabetes (T1D). First-degree relatives of T1D probands with autoantibodies to glutamic acid decarboxylase (GADAb), protein tyrosine phosphatase-like islet antigen 2 (IA2Ab) and insulin (IAA) have a 5-year risk of diabetes approaching 50%. Recently, autoantibodies to the cation efflux zinc transporter 8 (ZnT8Ab) have been described as a new marker of islet autoimmunity (1). Given the predictive significance of multiple islet autoantibodies, we measured ZnT8Ab in relatives who screened positive for one other islet autoantibody in the INIT II* T1D prevention trial.

ZnT8Ab were measured by precipitation of 35S-methionine-labelled recombinant ZnT8 generated by in vitro transcription-translation. The assay was included in the Diabetes Autoantibody Standardization Program (DASP) in 2009, in which it achieved a disease sensitivity of 64% and specificity of 100%.

Of 4280 relatives tested, 171 (4.0%) had a single autoantibody detected (GADAb 131, IA2Ab 16, IAA 24) and 90 (2.1%) had >2 antibodies detected. ZnT8Ab were detected in 12% of those with GADAb alone, 84% with IA2Ab alone and 0% of those with IAA alone.

Our findings demonstrate that a significant proportion of T1D relatives with only GADAb or IA2Ab, especially the latter, have ZnT8Ab. While only long-term follow up will determine the risk associated with ZnT8Ab in combination with other autoantibodies, it is likely that ZnT8Ab will increase the risk of progression to T1D.

*INIT II is supported by the NHMRC and JDRF through the Diabetes Vaccine Development Centre (DVDC) POSTER PRESENTATIONS 2011POSTER PRESENTATIONS 2011POSTER PRESENTATIONS 2011POSTER PRESENTATIONS 2011 (Refer to page 36 for Poster Locations)

45. Sinjini Biswas - Stent post-dilatation in ST-Elevation myocardial infarction – beneficial or detrimental? PODAMIS study

BISWAS S, Soon KH, Lim YL

Western Hospital

46. Danielle Schubiger - Melbourne Health multidisciplinary Tracheostomy Team 10 years on!

SCHUBIGER D, Lumsden J, Hedberg N.

The Royal Melbourne Hospital.

47. Samuel Wright - Functional testing in the prediction of cardiac events: A comparison of fractional flow reserve (FFR) and myocardial perfusion imaging (MPI).

WRIGHT S, Lefkovits J, Ajani A, Westcott J, Better N


48. Nadia Chaves - How well are antimicrobials prescribed in the ICU? A simple point prevalence survey of two Victorian intensive care units

CHAVES NJ 1, Truong NH 2, MacIsaac CM 1, McGain F 2, Buising KL 1.

1 The Royal Melbourne Hospital; 2 Western Hospital.


26

49. Nadia Chaves - What do doctors know about antibiotics? A knowledge and attitude survey of 74 doctors at an Australian tertiary hospital

CHAVES NJ, Buising KB.

Victorian Infectious Disease Service, The Royal Melbourne Hospital.

50. Nadia Chaves - Do doctors know how to prescribe antibiotics? A knowledge and attitude survey of 324 medical staff in three Australian tertiary hospitals

CHAVES NJ 1, Buising KL 1, Cotta O 2, Hewagama SS 3, Kirschner J 4, Lee T 4, Cheng AC 4.

Victorian Infectious Disease Service, The Royal Melbourne Hospital; Department of Pharmacy, St Vincent's Hospital; Infectious Diseases Unit, St Vincent's Hospital; Department of Epidemiology and Preventive Medicine, Monash University, Alfred Health.

51. Benjamin Cowie - Is it even more cost effective for well resourced, low hepatitis B prevalence countries to vaccinate infants in endemic regions than their own children?

COWIE B.

Victorian Infectious Diseases Reference Laboratory; The Royal Melbourne Hospital; The University of Melbourne.

52. Justin Denholm - TIRAP gene polymorphism and susceptibility to tuberculosis: a meta-analysis

DENHOLM JT, McBryde ES.

The Royal Melbourne Hospital; Department of Medicine RMH/WH, The University of Melbourne.

53. Jonathan Knott - Pandemic influenza health literacy and the effect of the health department public campaign

*Jhummon-Mahadnac ND, *KNOTT JC, ~Marshall C.

*Emergency Department; ~Victorian Infectious Disease Services, The Royal Melbourne Hospital.

54. James Knox - Severe infection with hypervirulent Clostridium difficile acquired in Melbourne, Australia

Richards M 1, KNOX J 1, Elliott B 2, Mackin K 3, Lyras D 3, Waring L J 4, Riley TV 2 5

1 The Royal Melbourne Hospital; 2 University of Western Australia; 3 Monash University; 4 Melbourne Pathology; 5 PathWest

55. Margaret Littlejohn - Analysis of precore/core mutations associated with hepatitis B e antigen (HBeAg) seroconversion

LITTLEJOHN M, Edwards R, Jackson K, Lacey S, Yuen L, Locarnini S, Revill P.

Victorian Infectious Diseases Reference Laboratory

56. Irani Ratnam - Incidence and risk factors for acute respiratory infections (ARIs) and influenza virus infections in Australian travellers to Asia

RATNAM I 1 2 4, Black J 2, Leder K 1 3, Biggs BA 1 4, Matchett E 1, Padiglione A 6, Woolley I 3 6, Panagiotidis T 7, Gherardin T 8, Pollissard L 5, Luxemburger C 5, Demont C 5, Torresi J 4 9

1 The Royal Melbourne Hospital; 2 The Nossal Institute for Global Health; 3 Monash University; 4 The University of Melbourne; 5 Sanofi-Pasteur, France; 6 Monash Medical Centre; 7 Victorian Infectious Diseases Reference Laboratory; 8 The Travel Doctor/ TMVC; 9

57. Shamista Selvarajah - The histone variant H2Bv is enriched in gene promoters in the malaria parasite P. falciparum

SELVARAJAH S, Petter M, Lee C, Brown GV, Duffy MF.


58. Fiona Brown - Next Generation Sequencing of an ENU-mutant identifies a putative activating mutation in the K-Cl cotransporter, KCC1, with potential implications in the pathogenesis of sickle cell disease and human diseases of red cell hydration.

BROWN F1, Rank G1, Curtis D1, Ho S2, Wiley J3, Jeunemaitre X4, Hilton D2, Kile B2, Jane S5

1 Bone Marrow Research Laboratories, 2 Walter and Eliza Hall Institute of Medical Research, 3 Howard Florey Institute, 4 University of Paris-Descartes, 5 Department of Medicine, Monash University

59. Andrew Guirguis - BCL2-mediated apoptosis in myelodysplasia:- Key player or side-line spectator?

GUIRGUIS AA, Curtis DJ, Boyd J, Slape C.

Bone Marrow Research Laboratories, Melbourne Health

60. Mun Yoong Cheang - Is there an advantage in adopting an aggressive neurosurgical approach without staging the primary lung cancer first in lung cancer patients with symptomatic cerebral metastases?

CHEANG MY, Antippa P, Drummond K.



27

61. Yeomin Cho - The establishment of an evidence-based clinical practice guideline for the assessment, investigation and management of blunt abdominal trauma

CHO Y, Judson R.


62. Jade El-Mohamed - A detailed anatomical study of the marginal mandibular and cervical branches of the facial nerve.

EL-MOHAMED J, Le Roux M, O'Brian J, Ashton M.

The Jack Brockhoff Plastic Surgery Research Unit, Department of Anatomy and Cell Biology, The University of Melbourne

63. Mary Karavias - TUG Flap: A viable and effective option for reconstructive surgery

KARAVIAS M, Whitaker I, Le Roux CM, Hao Lie K, Ashton M

The Jack Brockhoff Reconstructive Plastic Surgery Research Unit; Taylor Lab, The University of Melbourne

64. Anton Lambers - The usefulness of computer navigation in leg length and offset restoration in total hip arthroplasty

LAMBERS A, Jennings B, Bucknill A


65. Anton Lambers - A prospective analysis of pin-site morbidity in patients undergoing navigated total hip replacement

LAMBERS A, Jennings B, Bucknill A.


66. Wei-Ren Pan - Lymphatic routes from the lateral heel to the inguinal lymph nodes

PAN WR, le Roux CM, Sidney ML.

The RPSR Unit, The Royal Melbourne Hospital; Department of Anatomy and Cell Biology, The University of Melbourne.

67. Kunal Verma - Student Demographics and Sensitive Male Examinations: Implications for Teaching Men’s Health

VERMA K, Lo J, Turner R, Zimitat C, Sefton N


68. Derek Weidner - Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) with alendronate

WEIDNER D, Crow M, Williams C.

Pharmacy Department, The Royal Melbourne Hospital

69. Jeong-Moh Yahng - Anatomic access to the petrous apex: comparing nasal and lateral approaches

YAHNG J, Iseli T.


70. Kiryu Yap - Liver tissue engineering using oval cell spheroids in a murine in vivo vascularised chamber model

YAP KK 1, Dingle AM 1, Palmer JA 1, Dhillon R 1, Yeoh GC 3, Penington AJ 1 2, Morrison WA 1 2, Mitchell GM 1 2.

1 O’Brien Institute; 2 The University of Melbourne, Department of Surgery, St Vincent’s Hospital; 3 Western Australian Institute for Medical Research

71. Brian Yue - The Arterial Supply of the Cervical and Thoracic Spinal Muscles and the Overlying Skin: Anatomical Study with Implications for Surgical Wound Complications

YUE BYT, Corlett RJ, De la Harpe D, Le Roux CM, Richardson MD, Ashton MW

Department of Anatomy and Cell Biology, The University of Melbourne

72. Ilana Ackerman - The impact of severe, doctor-diagnosed hip and knee osteoarthritis on the Health-Related Quality of Life of Australians

ACKERMAN IN, Osborne RH

The Royal Melbourne Hospital and The University of Melbourne; Deakin University

73. Louisa Chou - An analysis of the clinical utilisation of foot and ankle SPECT/CT at a tertiary referral centre

CHOU L 1, Liew D 1, Ngian G 1, Nadesapillai S 1 2.

1 Department of Rheumatology, The Royal Melbourne Hospital; 2 Department of Nuclear Medicine, The Royal Melbourne Hospital.


28

74. Christian Collopy - Comparing the blood supply of the scaphoid with the blood supply of the talus bone

COLLOPY C

The Taylor Lab, The University of Melbourne

75. Nancy Amin - Wnt/FZD signalling in colorectal cancer morphogenesis

AMIN N, Flanagan DJ, Schwab R, Maedler A, Vincan E.

The University of Melbourne and Victorian Infectious Diseases Reference Laboratories.

76. Susie Bae - Quality Assessment of Clinical Information Entered by Consumers on the CART-WHEEL.org rare tumour website

Scott C, Desai J, Kosmider S, BAE S.

The Royal Melbourne Hospital; Peter MacCallum Cancer Centre.

77. Yasmin Bylstra - Discussing familial cancer with the Chinese community: What are the barriers in accessing FCC services?

Bylstra Y, Kentwell M, Lindeman G, Winship I, Hodgkin L

Familial Cancer Centre, The Royal Melbourne Hospital

78. Ryan Farid - Understanding the Role of Interleukin-11 and MyD88 Signaling in Colon Cancer

FARID R, Loving A, Mckenzie B, Edwards K, Trinchieri G, Ernst M, Putoczki T.

Ludwig Institute for Cancer Research

79. Janice Lai - Nutrition screening in 5 West Day Centre to determine the risk of malnutrition amongst cancer patients

LAI J, Osborne J


80. Finlay Macrae - Comparison of screening outcomes in patients with a family or a personal history of colorectal neoplasia

MACRAE F, Good N, Young G, Bampton P, Lane J, St John J, Diehl R, O’Dwyer J, Slattery M.

The Royal Melbourne Hospital; Flinders Centre for Cancer Prevention and Control, Flinders University; CSIRO pHealth Flagship

81. Finlay Macrae - Both Parents affected with bowel cancer affords risk equivalent to early age onset colorectal Cancer

MACRAE F (1), Goood N (3), Young G (2), Bampton P (2), St John J (1), Diehl R (3), O’Dwyer J (3), Slattery M (1).

Colorectal Medicine and Genetics and The University of Melbourne Dept of Medicine, The Royal Melbourne Hospital (1); Flinders Medical Centre Dept of Gastroenterology, Flinders Centre for Cancer Prevention and Control, Flinders University (2); CSIRO pHealth Flagship (3).

82. Emma Moore - Analysis of TAG-72 expression in human prostate cancer

MOORE EK, Hong MKH, Corcoran NM, Pedersen J*, Costello AJ, Hovens CM.

Division of Urology, The Royal Melbourne Hospital; Department of Surgery, The University of Melbourne; Australian Prostate Cancer Research Centre, Epworth Hospital; *Tissupath Pty Ltd.

83. Emma Stuart - Curcumin elicits a chemotherapeutic effect in a Stat3-dependent model of Stomach cancer

STUART EC, Phesse, TJ, Ernst T

Ludwig Institute for Cancer Research; The Royal Melbourne Hospital

84. Stanley Stylli - The Tks5 adaptor protein – a regulator of invadopodium function and metastasis in cancer cells

STYLLI SS 1 2, Courtneidge SA 3, Kaye AH 1 2, Lock P 4.

1 Department of Surgery, The University of Melbourne; 2 Department of Neurosurgery, The Royal Melbourne Hospital; 3 Burnham Institute for Medical Research, US; 4 Department of Biochemistry, La Trobe University.

85. Stefan Thiem - Gastric Tumourigenesis requires Stat3 and mTor Signaling

THIEM S, Jarnicki A, Palmieri M, Putoczki TL, Ernst M.

Ludwig Institute for Cancer Research; The Royal Melbourne Hospital.

86. Monique Topp - Novel xenograft mouse model of high grade epithelial ovarian cancer

TOPP M, Cook M, Hartley L, Wakefield M, Bowtell D, McNally O, Scott C and the Australian Ovarian Cancer Study (AOCS).

The Walter and Eliza Hall Institute of Medical Researchp; Peter MacCallum Cancer Centre; The Royal Women’s Hospital; Australian Ovarian Cancer Study.


29

87. Vikki Dearie - The Management of Clinical Aggression - Rapid Emergency Department Intervention (MOCA-REDI), a Qualitative Evaluation of the Impact and Outcome

DEARIE V, Daniel C, Gerdtz M

The Royal Melbourne Hospital; The University of Melbourne; Emergency Care Improvement and Innovation Clinical Network

88. Jonathan Knott - Management of acute agitation in Australasian Emergency Departments: variations in practice

Chan EW*, Taylor DMcD~, KNOTT JC#, Kong DCM*.

*Monash University; ~Emergency Department, Austin Hospital; #Emergency Department, The Royal Melbourne Hospital.

89. Joanne Tropea - Patients who leave Victorian emergency departments before being seen: an analysis of predictive factors and outcomes using the Victorian Linked Dataset.

TROPEA J 1, Sundararajan V 2, Gorelik A 1, Kennedy M 3, Cameron P 4, and Brand C 1 4.

1 Centre for Clinical Epidemiology, Biostatistics and Health Services Research, The University of Melbourne and The Royal Melbourne Hospital; 2 Victorian Data Linkages, Department of Health; 3 DCEHP, Monash University and Adult Retrieval Victoria, Ambulance V

90. Zexi Allan - Auditory processing deficits in schizophrenia and their relationship to the symptoms of psychosis

ALLAN Z, Carter OL, Sundram S

The Mental Health Research Institute

91. Mario Alvarez-Jimenez - The Horyzons project: Online Recovery for Youth-Onset Psychosis

ALVAREZ-JIMENEZ M, Gleeson J, Lederman R, Wadley G, Bendall S, Larkin M, Killackey E, Yung A, McGorry PD.

Orygen Youth Health Research Centre, The University of Melbourne

92. Paul Amminger - Emotion recognition in individuals at clinical high-risk for schizophrenia

Amminger GP,1,2 Schäfer MR,1,2 Papageorgiou K,3 Klier CM,2 Schlögelhofer M,2 Mossaheb N,2 Werneck-Rohrer S,2 Nelson B,1 McGorry PD1

(1) Orygen Research Centre; (2) Department of Child and Adolescent Psychiatry, Medical University of Vienna, Austria; (3) Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.

93. Sarah Arnold - The visual integration deficit and its relationship to symptoms of schizophrenia

Arnold S L, Carter O L, Sundram S

Northern Psychiatry Research Centre; Melbourne Health; Northern Hospital, MHRI.

94. Michelle Blanchard - Navigating the Digital Disconnect: Understanding the use of information communication technologies by the youth health workforce to help improve young people’s mental health and wellbeing

BLANCHARD M, Herrman, H and Burns, J

Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne; Cooperative Research Centre for Young People, Technology and Wellbeing.

95. Fiona Blee - Do it your way! Student-devised mental health promotion in a university setting

BLEE F, Reavley N, McCann T, Jorm AF.

Orygen Youth Health Research Centre, The University of Melbourne.

96. Lydia Brown - Motion processing disturbances are independent of sustained attention in schizophrenia

BROWN LA, Carter OL, Sundram S

Melbourne Health, Northern Psychiatry Research Centre, MHRI, The University of Melbourne

97. Ho Nam Choi - The epidermal growth factor receptor (EGFR) expression in the Mouse CNS and its regulation by Clozapine

CHOI H, Malcolm P, Sundram S

The Mental Health Research Institute of Victoria

98. Zoe Collins - Results of a Randomized Controlled Trial of Individual Placement and Support for Vocational Rehabilitation in First Episode Psychosis

Killackey E 1 2, COLLINS Z 2, Jackson H 1 2, McGorry P 1 2.

1 Department of Psychology, The University of Melbourne; 2 ORYGEN Research Centre


30

99. Georgina Cox - E-based interventions targeting suicidal behaviour, self harm, depression and anxiety in young people: a systematic review and meta-analysis

1 COX GR, 1 Robinson J, 1 Hetrick S, 2 Owens C.

1 Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne; 2 Devon Partnership NHS Trust, Peninsula Medical School, University of Exeter.

100. Sarah Hetrick - How does real world clinical practice compare with ‘gold standard’ treatment for young people with depression?

HETRICK S, Thompson A, Willet M

Orygen Youth Health Research Centre

101. Barnaby Nelson - The Neurapro Study: A multicentre RCT of omega-3 fatty acids and cognitive-behavioural case management for patients at ultra-high risk of psychotic disorders. Background and Study Design

NELSON B, Yung AR, Amminger GP, Thompson A, McGorry PD

Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne

102. Alexandra Parker - Psychosocial assessment of young people: refining and evaluating a youth friendly assessment interview

PARKER A, Hetrick S, Purcell R

Orygen Youth Health Research Centre and headspace Centre of Excellence for Youth Mental Health, Centre for Youth Mental Health, The University of Melbourne

103. Mark Phelan - Evaluation of medium-term course, outcome and treatment of complex adolescent Major Depressive Disorder: study background, progress and preliminary data.

PHELAN M, Chanen A, Lau K-Y, Ko Y-K, Yuen K, Mackinnon A, Allen N, Perera S, McDougall E, Betts J.

Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne.

104. Jo Robinson - An e-health intervention for adolescents at risk of suicide: development of a randomised controlled trial

1 ROBINSON J, 1 Hetrick S, 2 Pirkis J, 1 O’Donnell M, 1 Yuen HP, 1 Yung A.

1 Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne; 2 Centre for Health Policy, Programs and Economics, The University of Melbourne.

105. Raja Sadhu - Neuropsychological and behavioural deficits in Indian children with specific developmental disorders of scholastic skills

SADHU R, Mehta M, Kalra V, Sagar R, Mongia M

All India Institute of Medical Sciences, India

106. Faye Scanlan - The role of ‘knowledge translation’ resources in improving responses to young people with mental health problems

SCANLAN F, Purcell R

Centre of Excellence in Youth Mental Health, Orygen Youth Health Research Centre

107. Faye Scanlan - Exploring the role of ‘knowledge-translation’ resources in supporting best-practice in the treatment of Borderline Personality Disorder (BPD) in adolescence

SCANLAN F, Purcell R

Centre of Excellence in Youth Mental Health, Orygen Youth Health Research Centre

108. Pamela Sun - Effects of stability of accommodation at discharge to readmissions over 12 months in first episode psychosis: A preliminary file audit study

Killackey E, SUN P, Creek R, Redlich C, Martin C.

Orygen Youth Health Research Centre, Centre for Youth Mental Health, The University of Melbourne

109. Vaidy Swaminathan - Investigating the mechanism of clozapine signaling to MAPK/ERK pathway via EGFR transactivation using H4 cells as an in vitro model

SWAMINATHAN V1, 2, 3, Pereira A1, 3, Sundram S1, 2, 3

1. Molecular Psychopharmacology, Mental Health Research Institute, 2. Northern Area Mental Health Service NorthWestern Mental Health, 3. Department of Psychiatry, The University of Melbourne

110. Annemarie Wright - Youth mental health: How can a label be good for you?

WRIGHT A 1, Jorm A 1, Mackinnon A 1, Allen N 12

1 Orygen Youth Health Research Centre, Centre for Youth Mental Health; 2 Department of Psychological Sciences, The University of Melbourne


31

111. Slave Petrovski - Attempted Replication of an Australian population derived, machine learning, multigenic classifier for seizure control in the newly-treated epilepsy populations from the UK.

PETROVSKI S, Shazadi K, Roten A, Huggins RM, Marson A, O’Brien TJ, Sills GJ

Department of Medicine (RMH/WH), The University of Melbourne; Department of Neurology, The Royal Melbourne Hospital; BioGrid Australia; University of Liverpool; Department of Mathematics and Statistics, The University of Melbourne

112. Idrish Ali - Enduring effects of early-life stress on neuronal firing patterns in thalamic reticular nucleus: implications for limbic epilepsy

ALI I1, Salzberg MR2, Jones NC1, O’brien P1, Pinault D3, French C1, Margaret JM4 and O’Brien TJ1

1Departments of Medicine, The University of Melbourne; 2 Department of Psychiatry, The University of Melbourne; 3 Université de Stausborg, FRANCE; 4 Department of Pharmacology, University of New South Wales.

113. Paul Anderson - Characterising the effects of anti-psychotic medications on gamma frequency oscillations in rodents

ANDERSON PM1, O’Brien TJ1, Pinault D2, Jones NC1

1Department of Medicine, The University of Melbourne; 2Faculté de Médecine, Université de Strasbourg.

114. Iwan Bennett - Vascular biomarkers in malignant glioma

BENNETT I

Department of Surgery, The University of Melbourne

115. Rasin Bhuiyan - Assessment of the effect of formal training on the clinical utility of transcranial Doppler ultrasound monitoring in aneurysmal subarachnoid haemorrhage patients.

BHUIYAN MR, Mitchell R, Deb S, Drummond K, Teddy PJ.

The Royal Melbourne Hospital; The University of Melbourne

116. Bruce Campbell - Validation of 24 hour multimodal MRI in assessing response to stroke thrombolysis

CAMPBELL BCV, Tu HT, Christensen S, Desmond PM, Levi CR, Bladin CF, Hjort N, Ashkanian M, Sølling C, Donnan GA, Davis SM, Østergaard L, Parsons MW.

Departments of Neurology and Radiology, The Royal Melbourne Hospital; Department of Medicine, The University of Melbourne; Hunter Medical Research Institute, John Hunter Hospital; University of Newcastle; Box Hill Hospital; Monash University; Florey Neuroscience Institutes; Center of Functionally Integrative Neuroscience; Århus University Hospital, Denmark.

117. Lisa Cardamone - Can structural or functional changes following traumatic brain injury in the rat predict the epileptic outcome?

CARDAMONE L 1, Bouilleret V 1 5, Liu YR 1, Gregoire MC 2, Hicks RJ 3 , Williams JP 4, Jones NC 1, Myers DE 1, O’Brien TJ 1

1 Department of Medicine (RMH), The University of Melbourne; 2 Australian Nuclear Science and Technology Organisation; 3 Centre for Molecular Imaging, Peter MacCallum Cancer Centre; 4 Small Animal MRI Facility, Florey Neurosciences Institute; 5 Department of Neurophysiology and Epilepsy, APHP, CHU Bicêtre, France

118. Gabi Dezsi - Ethosuximide treatment restricts epileptogenesis and alleviates behavioural co‑morbidities in the GAERS model of absence epilepsy

Dezsi G1, Blumenfeld H2, Salzberg M R1,3, O’Brien T J1,4, Jones N C1

1 The University of Melbourne; 2 Yale University School of Medicine, New Haven, Connecticut, USA; 3 St Vincent’s Hospital, Melbourne; 4 The Royal Melbourne Hospital.

119. Tahir Hakami - Effects of levetiracetam versus valproate or carbamazepine on bone health: a randomized trial

HAKAMI T, O’Brien TJ, Petty S, Sakellaridis M, Christie J, Kantor S, Todaro M, Wark JD

The University of Melbourne

120. Elisa Hill - NMDAR-mediated elevation in gamma power in a mouse model of autism.

HILL EL1, Rind G1, Argyropoulos A1, Anderson P1, O’Brien TJ1,2.

1. Department of Medicine, The University of Melbourne. 2. Department of Neurology, Royal Melbourne Hospital.

121. Katherine Holland - Clinical and molecular genetic factors determining recurrence and survival in glioblastoma multiforme

Holland K, Drummond K, Morokoff A, Dimou J, Kaye AH.

The Royal Melbourne Hospital; The University of Melbourne

122. Vilija Jokubaitis - Predictors of confirmed disability progression after a first demyelinating event

JOKUBAITIS V1, Spelman T1, Meyniel C1, Tanner M1, Rutherford M1 and Butzkueven H1,2 on behalf of the MSBASIS study group.

1Royal Melbourne Hospital; 2Department of Medicine, The University of Melbourne.


32

123. Prasanti Kotagiri - Changes in the human subventricular zone cyto-architecture in Autism

KOTAGIRI P 1 2 3, Chance S 1, Szele F 4, Esiri M 1

1 Department of Neuropathology, Radcliffe Infirmary, University of Oxford, UK; 2 Department of Medicine (Neuroscience), Monash University; 3 The Royal Melbourne Hospital; 4 Department of Physiology, Anatomy and Genetics, University of Oxford, UK

124. Lee Kai Lim - Can negative CT, CTA or MRA rule out aneurysmal subarachnoid haemorrhage in CT negative subarachnoid haemorrhage patients?

LIM LK, Dowling R, Yan B, Mitchell PJ.


125. Mithun Nambiar - Intradural Spinal Cord Tumours - Clinical Presentation and Outcome

NAMBIAR M, Kavar B


126. Slave Petrovski - Australian pharmacogenomics study: value of non-genomic variables in predicting drug response in newly treated epilepsy.

PETROVSKI S, Roten A, Germaine D, Hosking S, Todaro M, Huggins RM, O’Brien TJ

Department of Medicine (RMH/WH), The University of Melbourne; Department of Neurology, The Royal Melbourne Hospital; BioGrid Australia; The Department of Mathematics and Statistics, The University of Melbourne

127. Kim Powell - Linking the brain and heart: alterations in cardiac function and HCN channel expression in acquired and genetically epileptic rats

POWELL KL 1, Ng C 1, Urmaliya V 2, Kennard JTT 1, Ozturk E 1, Jones NC 1, Megatia I 1, Reid CA 3, Pinault D 4, White P 2, O’Brien TJ 1

1 Department of Medicine (RMH), The University of Melbourne; 2 Department of Pharmaceutical Biology, Monash University; 3 Howard Florey Institute, The University of Melbourne; 4 Inserm, Université de Strasbourg, FRANCE

128. Baemisla Shiek Ahmad - Prevalence of fractures and falls with antiepileptic drug (AED) use and patient awareness of the issue: survey findings

SHIEK AHMAD B 1, Hill KD 2 3, O’ Brien TJ 1 5, Wark JD 1 4

1 Department of Medicine (RMH) The University of Melbourne; 2 Musculoskeletal Research Centre and School of Physiotherapy, La Trobe University and Northern Health; 3 National Ageing Research Institute; 4 Bone and Mineral Service, The Royal Melbourne Hospital; 5 Department of Neurology, The Royal Melbourne Hospital.

129. Meng Tan - Safety of Inpatient Video-EEG Monitoring with Aggressive Withdrawal of Anti-Epileptic Drugs

TAN KM, Carino JM, Yerra SR, French CR, Matkovic Z, OBrien TJ.


130. Anneke van der Walt - Mutations in the Ciliary Neurotrophic Factor (CNTF) gene do not influence Multiple Sclerosis phenotype or disease outcome.

VAN DER WALT A1,2,3, Stankovich J4,5, Bahlo, M6, Taylor BV4, van der Mei I4, Foote S6, Rubio JP6, Kilpatrick T1,2, Butzkueven, H1,3,7

1. Royal Melbourne Hospital; 2. Centre for Neuroscience, The University of Melbourne; 3. Box Hill Hospital; 4. Menzies Institute, Hobart; 5. Walter and Eliza Hall Institute; 6. Howard Florey Neurosciences Institute; 7. The University of Melbourne, Department of Medicine.

131. Lucy Vivash - Localisation of the epileptogenic zone in patients with medically refractory focal epilepsy using [18F]-Flumazenil PET without need for arterial blood sampling: A pilot study

VIVASH L1, Gregoire MC2, Lau EW 3, Ware RE3, Roselt P3, Binns D3, Bouilleret V1, Katsifis A2, Myers DE1, Hicks RJ3, O’Brien TJ1

1 Department of Medicine (RMH), The University of Melbourne; 2 ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation; 3 The Centre for Molecular Imaging, Peter MacCallum Cancer Centre

132. Zhen Zeng - How does Anti-Epileptic Drug Phenytoin work?

ZENG Z1, French CR1,2.

1 Department of Medicine, The University of Melbourne; 2 Neurosciences, Royal Melbourne Hospital

133. Bob Anderson - A population study to optimize the role of serology and genetics in the diagnosis of celiac disease (CD)

Costa M 1, Henry M 2, Taylor R 3, Duncan E 4, Kotowicz M 2, Pasco J 2, Tye-Din JA 15, Pollock W 3, Toh BH 3, Brown MA 4, Nicholson G 2, ANDERSON RP 15

1 Immunology, The Walter & Eliza Hall Institute; 2 Clinical and Biomedical Sciences, Barwon Health; 3 Healthscope Pathology; 4 Diamantina Institute, Princess Alexandra Hospital, University of Queensland; 5 Gastroenterology, The Royal Melbourne Hospital

134. Seok Mei Lim - Confocal endomicroscopic characteristics of microscopic colitis.

LIM S M1, Leung C1, Delaney P2, Bhathal P3, Marion K4, Macrae F156.

1 Colorectal Medicine & Genetics and The University of Melbourne Department of Medicine, The Royal Melbourne Hospital ; 2 Optiscan Pty Ltd; 3 Melbourne Pathology; 4 School of Mathematics and Geospatial Sciences, RMIT; 5 Cabrini Medical Centre; 6 Department of Surgery, Monash.


33

135. Caroline Brand - High Performing Hospitals: What are the important healthcare service characteristics?

BRAND C*+, Barker A+, Morello R+, Vitale M+, Evans S+, Stoelwinder J+, Scott I+, Cameron P+.

*The Royal Melbourne Hospital; *The University of Melbourne; +Centre for Research Excellence in Patient Safety, Monash University

136. Caroline Brand - Screening and review of adverse events at Royal Melbourne Hospital

BRAND C* #, Walsh S*, Tacey M*, Winter E*, Cowie B*, McCormick A*, Jones C*.

* The Royal Melbourne Hospital; # The University of Melbourne

137. Zhongxiong Cai - Medical Emergency Team (MET) calls at Royal Melbourne Hospital: antecedents and outcomes in 225 patients

Morgan R2, CAI, Z2, Chen W2, Crawford, E2, Creelman A2, Bell J1, Morley P 1&2, Santamaria N1&2.

The Royal Melbourne Hospital 1; The University of Melbourne 2

138. Alan Gijsberts - Spirituality and addiction in the clinical encounter

139. Janice Lam - Satisfaction Study of Laser Therapy

LAM J 1 2, Paver R 1, Richards S 1, See A 1, Kalouche S 1 and Penas PF 1 3

1 Skin and Cancer Foundation Australia; 2 Faculty of Medicine, The University of Melbourne; 3 Discipline of Dermatology, Sydney Medical School, University of Sydney

140. Sunny Fan - Wound chart documentation adherence at Melbourne Health

FAN S 1, Mackay S 1, McKenzie K 1, Moral R 1, Petroff T 1, Sage S 2, Santamaria N 1 2

1 The University of Melbourne; 2 The Royal Melbourne Hospital

141. Marcel Mihulka - Intern eOrientation – Orientation from a different angle

MIHULKA M, Morley P, Reid E


142. Choon Ean Ooi - Improving Communication of Medication Changes through a Medication Management Summary (MMS) Prepared by Hospital Pharmacists

OOI CE, Elliott R, Rofe O, Vienet M.

The Royal Melbourne Hospital; Monash University.

143. Natasha Pasquier - Deteriorating patient simulation training

Morley P, PASQUIER N, Reid E

Melbourne Health

144. Marion Robertson - Management of medicines withheld peri-operatively.

Ankravs M, Crow M, French S, Griffiths E, Honson K, Kulman A, ROBERTSON M, Williams C.

The Royal Melbourne Hospital, Pharmacy Department

145. Jo-Anne Slee - Benchmarking person-centred care survey – Royal Melbourne Hospital results

SLEE J, Fearn M

The Royal Melbourne Hospital, National Ageing Research Institute

146. Tristan Vasquez - Cultural Change Through Lean Six Sigma Improvement Training

VASQUEZ T.


147. Sharon Walsh - The cost of implementing a robust adverse event screening and review process

WALSH S *, Jones C *, Tacey M *, Brand C * #

* The Royal Melbourne Hospital; # The University of Melbourne

148. Sharon Walsh - The global trigger tool adverse event screening program – understanding the nature of adverse events at the Royal Melbourne Hospital

WALSH S*, Jones C*, Tacey M*, Winter E*, Cowie B*#$, McCormick A*, Brand C*#

*The Royal Melbourne Hospital, #The University of Melbourne, $VIDRL

149. Jen Alviar - Do patient-reported measures used in assessing outcomes in rehabilitation after hip and knee arthroplasty capture issues relevant to patients?: Results of a systematic review and International Classification of Functioning, Disability and Health (ICF) linking process

ALVIAR MJ 1, Olver J 2, Brand C 1, Hale T 1, Khan F 1

1 The University of Melbourne -Royal Melbourne Hospital; 2 Monash University/ Epworth Rehabilitation


34

150. Bhasker Amatya - Rehabilitation for Cerebral Palsy: analysis of the Australian rehabilitation outcome dataset

AMATYA B, Khan F.


151. Bhasker Amatya - Rehabilitation for Parkinson’s disease: analysis of the Australian rehabilitation outcome dataset

Khan F, AMATYA B


152. Bhasker Amatya - Outcomes of high and low intensity rehabilitation programme for persons in chronic phase after Guillain-Barré Syndrome: a randomized controlled trial

Khan F 12, Pallant JF 2, AMATYA B 1 , Louisa Ng 12, Gorelik A 1, Brand C 123.

1 The Royal Melbourne Hospital; 2 The University of Melbourne; 3 Monash University

153. Shinay Mackey - Patient centered care: Incorporating the patient’s perspective in goal setting on the rehabilitation unit

Furlong H, Cowan C, Louie J, MACKEY S, Moore M, Ng L.


154. Louisa Ng - Motor Neurone Disease: Disability profile and service needs and gaps in an Australian cohort

NG L 1, Talman P 2, Khan F 1.

1 The Royal Melbourne Hospital; The University of Melbourne; 2 Barwon Health.

155. Louisa Ng - Neuropsychological sequelae in Motor Neurone Disease: outcomes of a peer support (Lifemoves) program

NG L 1, Talman P 2, Khan F 1.

1 The Royal Melbourne Hospital; The University of Melbourne; 2 Barwon Health.

156. Louisa Ng - Use of the International Classification of Functioning, Disability and Health to describe patient-reported disability: comparing Motor Neurone Disease, Guillain-Barré Syndrome and Multiple Sclerosis in an Australian cohort

NG L, Khan F.


157. Louisa Ng - Use of the International Classification of Functioning, Disability and Health: comparing the impact of motor neurone disease on patients and their caregivers

NG L, Khan F.


158. Tim Hewitson - Relationship Between Serum Phosphate and Age in a Haemodialysis Population

HEWITSON TD, Beavis J, Pedagogos E, Becker GJ.

North West Dialysis Service, The Royal Melbourne Hospital.

159. Sarah Livesey - Extended CMV prophylaxis with valganciclovir in renal transplantation reduces the incidence of CMV disease

LIVESEY S, Walker R, Toussaint N, Crosthwaite A, Ryan J, Yip D, Cohney S.

Nephrology Department, Royal Melbourne Hospital.

160. Jodie Morgan - Exploring new territory: Our experience with an on-line education module

MORGAN J, Beavis J, Pickering J.

North West Dialysis Service, The Royal Melbourne Hospital.

161. Anna Munasinghe - Metformin in the treatment of post-transplant diabetes

MUNASINGHE A, Cohney S, Teh P, Yates C.


162. Kathy Nicholls - Foot Screening in a Dialysis Unit: A Pilot Educational Project

Leo J , NICHOLLS K and Likouresis L

Department of Nephrology and North West Dialysis Service, The Royal Melbourne Hospital


35

163. Peggy Teh - Treatment of type 2 diabetes mellitus after renal transplantation

Munasinghe A, Cohney S, TEH P, Yates C.


164. Christopher Yates - Ninety-five percent of kidney transplant recipients have abnormal glucose metabolism early post-transplant

YATES CJ, Cohney S, Yip D, Walker RG, Colman PG, Fourlanos S.

Departments of Diabetes and Endocrinology and Nephrology, The Royal Melbourne Hospital.

165. Candice Breen - The Intranasal Insulin Vaccine Trial to Prevent Type 1 Diabetes: Identifying barriers to recruitment

BREEN CR 1, McLean CH 2, McManus FJ 1, Pawlak DB 3, Colman PG 4, Harrison LC 12.

1 Burnet Clinical Research Unit, The Royal Melbourne Hospital; 2 The Walter and Eliza Hall Institute of Medical Research; 3 Juvenile Diabetes Research Foundation; 4 Diabetes and Endocrinology, The Royal Melbourne Hospital

166. Cherie Chiang - Investigation of Methods to Remove Thyroglobulin Auto-antibodies Interference in Thyroglobulin Immunoassay

Herath T 1, Goodwin M 1, Lu Z 2, Mohr M 1, Colman P 1 3, CHIANG C 1 3.

Departments of Diabetes and Endocrinology and Pathology, The Royal Melbourne Hospital; Melbourne Pathology.

167. Nicholas Collins - Pathogenesis of Dermatitis Herpetiformis

COLLINS N 1, Carbone F 1, Anderson R 2, Varigos G 3

1 The University of Melbourne; 2 The Walter and Eliza Hall Institute of Medical Research; 3 The Royal Melbourne Hospital

168. Peter Colman - The Intranasal Insulin Trial (INIT II) - Update on screening progress

COLMAN PG 1, Gellert S 2, Andaloro E 2, McManus F 3, Breen C 3, Harrison LC 3 4.


169. Baemisla ShiekAhmad - Longitudinal studies of bone health during antiepileptic drug (AED) therapy

SHIEK AHMAD B 1, Petty SJ 1, Hill KD 2 3, O’ Brien TJ 1 5, Wark JD 1 4

1 Department of Medicine (RMH), The University of Melbourne; 2 Musculoskeletal Research Centre & School of Physiotherapy, La Trobe University & Northern Health; 3 National Ageing Research Institute; 4 Bone and Mineral Service, The Royal Melbourne Hospital; 5

170. Christina Woelwer - Potential role for T-or B-cells in promoting Stat3 dependent gastric tumourigenesis

WOELWER C1, Loving A1, McKenzie B2, Wilson N2, Hunter C3, Williams B1, Ernst M1, Putoczki T.1

1Ludwig Institute for Cancer Research; 2CSL Ltd; 3University of Pennsylvania, USA.

36 36

POSTER LOCATIONSPOSTER LOCATIONSPOSTER LOCATIONSPOSTER LOCATIONS FFooyyeerr

CClliinniiccaall SScchhooooll

Emergency (87-89) &

Mental Health (90-110)

Neurosciences (111-132) &

Gastrointestinal (133-134) Cancer (75-86)

Renal (158-164) &

Endocrinology, Immunology and Allergy (165-169)

Surgery (60-71) &

Musculoskeletal (72-74)

Quality of Care (135-148)

& Rehabilitation (149-157)

Infectious Diseases (48-57)

& Blood (58-59, 170) BBaarr AArreeaa

HHeeaalltthh PPrroommoottiioonnss AArreeaa,, FFooyyeerr,, MMaaiinn EEnnttrraannccee,,

RRooyyaall MMeellbboouurrnnee HHoossppiittaall

((nneeaarr CCaafféé ZZoouukkii)) Cardio-Respiratory (45 – 47)

melbourne health research week · master of ceremonies (mc) professor ingrid winship, executive...

Documents