New Horizons 2015 - NSLHD Home

Transcription

Dr Chau Chak Wing Building, University of Technology Sydney
23 – 25 November 2015
NEW HORIZONS2015
32nd Combined Health Science Conference
Building Bridges between Basic Science and the Clinic; Academia and
the Medical Industry; Creative Education and Innovative Research
FINAL PROGRAM & ABSTRACT BOOK
Gold Sponsor:
www.newhorizons2015.org
NewHorizons2015 | Building Bridges 0
ACKNOWLEDGEMENTS
The New Horizons 2015 Program Committee would like to thank the following, who at the time of printing
had given their support to this conference:
INSTITUTIONS
GOLD SPONSOR
EXHIBITORS & OTHER SPONSORS (in alphabetical order)
TABLE OF CONTENTS
TABLE OF CONTENTS
TABLE OF CONTENTS.......................................................................................................................................... 1
WELCOME .......................................................................................................................................................... 2
PROGRAM AT A GLANCE .................................................................................................................................... 3
ORGANISING COMMITTEE ................................................................................................................................. 4
KEYNOTE SPEAKERS ........................................................................................................................................... 5
PLENARY SPEAKERS & PANELISTS ...................................................................................................................... 6
FULL PROGRAM – Day 1 – Monday 23rd November 2015 ............................................................................... 10
FULL PROGRAM – Day 2 – Tuesday 24th November 2015 ............................................................................... 12
FULL PROGRAM – Day 3 – Wednesday 25th November 2015 ......................................................................... 14
SPEAKER ABSTRACTS........................................................................................................................................ 17
POSTER ABSTRACTS ......................................................................................................................................... 45
GENERAL INFORMATION ................................................................................................................................. 51
DR CHAU CHAK WING BUILDING FLOOR PLANS .............................................................................................. 52
SPONSOR & EXHIBITOR INFORMATION ........................................................................................................... 53
WELCOME
On behalf of the Organising Committee we would like to extend a very
warm welcome to delegates and invited guests of New Horizons 2015.
This is the 32nd Combined Health Science Conference built on a history of
conferences hosted by University of Technology Sydney (UTS) and the
Kolling Institute (Northern Clinical School, The University of Sydney and
Royal North Shore Hospital, Northern Sydney Local Health District
(NSLHD).
Professor Michael Wallach,
Parasitology,
The ithree Institute,
University of Technology Sydney
It is an exciting time as this conference is now the centre-piece for the
Northern Sydney Academic Health Science Centre with UTS, The
University of Sydney, Macquarie University and the NSLHD our founding
partners.
Our location within the newly constructed Dr Chau Chak Wing Building,
designed by architect Frank Gehry, is the ideal place to showcase our
joint strategy and commitment to improving healthcare in the
community through “Building Bridges between Basic Science and the
Clinic; Academia and the Medical Industry; Creative Education and
Innovative Research”.
New Horizons 2015 features keynote presentations from Martin Bowles,
PSM Secretary Department of Health, Australian Government and Prof J
Robin Warren AC Nobel Prize Laureate. On Day 1 we will also hear from
each of the Vice Chancellor’s for our university partners about their
strategic plans to support improving healthcare, and from industry
partners about how they build bridges and how this presents
opportunities for early career researchers.
Professor Jonathan Morris AM,
Obstetrics and Gynaecology,
Director, Division of Research,
NSLHD (Kolling Institute),
Director, Biomedical and Health
Informatics, Sydney Medical
School
Day 2 and 3 is filled with presentations from our health and medical
research community in combination with a breakfast education session
on “Science Communication”.
We acknowledge and sincerely thank all of those who have committed
time and effort into the organising of this conference, as well as our
academic and health sponsors.
We hope that you find this meeting productive and informative, and take
the opportunity to form new cross-institutional and inter-disciplinary
collaborative and personal relationships.
Sincerely,
Professor Michael Wallach and Professor Jonathan Morris AM,
Co-chairs, New Horizons 2015 Organising Committee
PROGRAM AT A GLANCE
Monday 23rd November
Tuesday 24th November
0800
0830
0900
0930
1000
1030
Welcome and Keynote 1:
Understanding Health as a
System
0830-0930
Auditorium
Plenary 1.1: Understanding the
Academic Commitment to
Health
0930-1030
Auditorium
Science Communication Workshop
0800-0930
Collaborative Theatre
Chronic Injury &
Disease
0930-1032
Auditorium
Cancer:
Consumer to
Cure
0930-1032
Collaborative
Theatre
Morning Tea, Posters,
Exhibitors
Morning Tea, Posters, Exhibitors
Q&A: What Does it Take to
Build a Bridge?
1100-1230
Auditorium
Plenary 2.1: Bridging Cancer
Genetics and Immunology
1400-1230
Auditorium
1100
1130
1200
1230
1300
Lunch, Posters, Exhibitors
1230-1400
1330
1500
1530
1600
1630
1700
1730
Accugen Systems Presentation
1245-1315, Oval Room
1800
Plenary 1.2: Building Bridges
with Industry
1400-1515
Auditorium
Plenary 2.2: Integrating Research in
to a Healthy Lifestyle
1400-1530
Auditorium
Afternoon Tea,
Posters, Exhibitors
Afternoon Tea, Posters, Exhibitors
Plenary 1.3: Collaboration
Builds the Stronger, Most
Effective Bridges and Gets
Results
1545-1715
Auditorium
Post-Doctoral Prize
1600-1724
Auditorium
UTS Data Science Centre
Demonstration
1730-1830
Plenary 3.1: Technology and
Innovation in Health
0800-0900
John Hambley,
Douglas Piper,
and Macquarie
University Prize
0910-1058
Auditorium
Novel
Therapeutics &
Delivery Systems
0910-1058
Collaborative
Theatre
Morning Tea, Posters, Exhibitors
Young Investigators Prize
1100-1244
Auditorium
1230-1400
1400
1430
Wednesday 25th November
1244-1400
Keynote 2: The Ease and Difficulty of
a New Discovery
1400-1500
Auditorium
Afternoon Tea, Posters, Exhibitors
Improving
Healthcare
1530-1630
Collaborative
Theatre
Wrap Up & Prizes
1630 1700
Auditorium
Bridging the
Lifespan
1530-1630
Auditorium
Closing Drinks
1700-1800
1830
ORGANISING COMMITTEE
The Organising Committee of the New Horizons 2015 Conference includes (in alphabetical order):

A/Prof Beata Bajorek, Graduate School of Health, UTS and Academic Pharmacist, Royal North Shore
Hospital, NSLHD

Dr Hui Chen, Senior Lecturer, School of life Sciences, UTS

Dr Emily Colvin, Post-doctoral Research Fellow, Bill Walsh Cancer Research, Kolling Institute

Dr Deborah Debono, Post-doctoral Research Fellow, Centre for Healthcare Resilience and
Implementation Science, Australian Institute of Health Innovation, Macquarie University

Dr Amanda Hudson, Post-doctoral Fellow, Sydney Neuro-Oncology Group, Kolling Institute

Ms Karyn Joyner, Chief Operating Officer Research, Kolling Institute

A/Prof Sara Lal, School of Life Sciences, UTS

Dr Kelly McKelvey, Post-doctoral Fellow, Division of Perinatal Research, Kolling Institute
 Prof Jonathan Morris AM, Obstetrics and Gynaecology; Director of Division of Research, NSLHD
(Kolling Institute); Director of Biomedical and Health Informatics, Sydney Medical School

A/Prof Ken Rodgers, School of Life Sciences, UTS

Dr Sonia Saad, Senior Research Fellow, Kolling Institute and School of Life Sciences, UTS

Dr Nham Tran, Head of ncRNA Cancer Group, Centre for Health Technologies, School of Life
Sciences, UTS

A/Prof Stella Valenzuela, Centre for Health Technologies, School of Life Sciences, UTS

Prof Michael Wallach, Parasitology, The ithree Institute, UTS

Dr Jon Wardle, Chancellor’s Research Fellow, Faculty of Nursing Midwifery and Health, Australian
Research Centre in Complementary and Integrative Medicine, Health Services and Practice Research
Strength, UTS
KEYNOTE SPEAKERS
Martin Bowles PSM, Secretary of the Federal Department of Health
Mr Bowles has a Bachelor of Business degree and a Graduate Certificate of Public
Sector Management (Griffith University) and is a Fellow of the Australian Society
of Certified Practicing Accountants.
He has held a number of positions within the Australian
Public Service including appointment as Deputy Secretary of
the Department of Defense (2002), Deputy Secretary of the
Energy, Safety and Corporate Group at the Department of
Climate Change and Energy Efficiency (2010), Secretary of the Department of
Immigration and Citizenship (2011), and Department of Immigration and Border
Protection (2012). Mr Bowles is currently the Secretary of the Department of Health, a
position he has held since 2014.
On 26th January 2012 he was awarded the Public Service Medal (PSM) for
“outstanding public service in delivering highly the Home Insulation and Green Loans
programs”.
Public Service Medal
Prof J Robin Warren AC, Nobel Prize Laureate
Emeritus Professor Warren has a Bachelor of Medicine, Bachelor of Surgery
(MBBS; University of Adelaide).
After becoming a Registrar in Clinical Pathology he was elected to the Royal
College of Pathologists of Australasia (1967) and worked as a senior
pathologist at the Royal Perth Hospital.
Along with colleague Barry J Marshall at the University of Western Australia, Professor Warren was
awarded the 2005 Nobel Prize in Physiology or Medicine for “their discovery of the bacterium Helicobacter
pylori (H. pylori) and its role in gastritis and peptic ulcer
disease”. He also assisted in the development of the
14
C-urea breath-test for the diagnostic detection of
H. pylori in patients.
On 26th January 2007 he was awarded the Companion of
the Order of Australia (AC) for “service to medicine and to
medical research, particularly through the discovery of
the bacterium Helicobacter Pylori and its role in gastritis
and peptic ulcer disease”.
Interesting Fact: Australia has produced 15 Nobel Prize
winners.
Order of Australia Medal
Prof Warren (R) and Barry
Marshall (L) with their Nobel
Prize.
PLENARY SPEAKERS & PANELISTS
Plenary Speakers and Panelists of the New Horizons 2015 Conference include (in alphabetical order):
Prof Shirley Alexander, Deputy Vice-Chancellor and Vice-President of Education and
Students, UTS
Professor Alexander is involved in the learning design of subjects and courses that are
delivered via the internet and other information technologies. Her former positions include
Director of the Institute for Interactive Media and Learning, and Dean of the Faculty of
Education.
Prof Attila Brungs, Vice-Chancellor and President, UTS
Professor Brungs has been a researcher in Academia and Industry and was previously a
Senior Manager at global management consultancy firm McKinsey and Company, and the
General Manager of Science Investment, Strategy Performance at CSIRO.
Prof Enrico Coiera, Director, Centre of Health Informatics, Macquarie University
Professor Coiera has a broad interest in the application of information and communication
technologies (e-Health) to solve health service delivery problems, including patient safety
informatics, consumer e-Health and translational bioinformatics. He is a Fellow of the
American and Australian Colleges of Health/Medical Informatics.
Prof Aaron Coutts, Centre for Health Technologies, Faculty of Health, UTS
Professor Coutts is a Director of Exercise and Sport Science Australia (ESSA) and his research
focusses on developing methods for quantifying training, managing fatigue/recovery and
improving performance in team sport athletes.
Prof Henry Cutler, Director, Macquarie University Centre for the Health Economy (MUCHE)
Professor Cutler is a health economist and has evaluated a range of health care topics for
government, non-for-profit and private organisations. He was previously the Head of Health
Economics at KPMG Advisory, Head of the Sydney Health Economics and Social Policy at
Deloitte Access Economics, and Senior Economist at the Centre for International Economics.
Dr Tim Dean, Section Editor – Science and Technology, The Conversation
Dr Dean has been a science and technology writer and editor for over 15 years. His work has
appeared in print and online in various outlets around the world. Previously he was the
Editor of Cosmos, Australian Life Sciences, and PC & Tech Authority magazines.
Prof S Bruce Dowton, Vice-Chancellor, Macquarie University
Professor Dowton is a pediatrician, clinical geneticist, molecular biologist, researcher and
academic who has served as a Senior Medical Executive at a number of universities,
healthcare institutions and consulting organisations including Harvard Medical School and
the Massachusetts General Hospital for Children.
Dr Hugh Durrant-Whyte, ARC Federation Fellow, The University of Sydney
Dr Durrant-Whyte is recognised for his work on probabilistic methods for robotics. He was
previously the Director of the Australian Centre for Field Robotics, and Research Director of
the Australian Research Council Centre of Excellence for Autonomous Systems. In 2013 he
was named Professional Engineer of the Year.
Dr Dale Garsed, Peter MacCallum Cancer Centre
Dr Garsed is a Research Fellow in the David Bowtell: Cancer Genetics and Genomics
laboratory. His research focusses on whole-genome characterisation of chemo-resistant
ovarian cancer.
Prof David Gillat, Macquarie University
Professor Gillat is a consultant urologist specialising in surgery for prostate and bladder
cancer. His innovative research includes surgical clinical trials and recovery. He was integral
in the introduction and delivery of the Enhance Recovery Program for cystectomy and a
robotic pelvic surgery program at the Bristol Urological Institute in the United Kingdom.
Dr Dayong Jin, UTS; Macquarie University; ARC Centre for Nanoscale Biophotonics
Dr Jin is an ARC Future Fellow in biophotonics, nanotechnology and medical biotechnology.
In 2015 he was awarded the UNSW Eureka Prize for Excellence in Interdisciplinary Scientific
Research as an inventor of “Super Dots®” for rapid diagnostics and molecular imaging.
Mr Mitch Kirkman, Development Quality Assurance Manager, Novarits; Representative of
the Pharmaceutical Industry Council Research and Development (PIC R&D) Task Force
Mr Kirkman is interested in quality, training and improving the speed and efficiency of the
conduct of clinical trials.
A/Prof Valarie Gay and Dr Peter Leijdekkers, Co-directors, mhealth, UTS
Their collective research focusses on e-health and health informatics. They develop health
and fitness mobile apps and are the founders of www.myFitnessCompanion.com which
focusses on aggregating health and fitness data to empower users.
Mr Paul X McCarthy, Author; CEO of Online Gravity Consulting
Mr McCarthy is an author, speaker and observer of technology and its global impacts. He is
the author of “Online Gravity” and an adjunct Professor of Computer Science and
Engineering at UNSW. He was previously Executive Director of Strategy and Innovation at
Sirca, and is a co-founder of several innovative enterprises for IBM, NSW Government and
CSIRO.
Prof Jonathan Morris AM, Director Kolling Institute, Director of Research NSLHD (Kolling
Institute), Director of Biomedical and Health Informatics, Sydney Medical School
Professor Morris is an Academic Obstetrician and Maternal-Fetal medicine specialist. He has
held a number of leadership positions including Chair of the Maternal-Fetal Medicine
Subspecialty Committee of RANCOG, Chair of IMPACT, Chair of the High Risk Advisory Group
of NSW Perinatal Service Network and Head of the Northern Clinical School, The University
of Sydney.
Dr Justine Rogers, Lecturer, UNSW
Dr Rodgers’ research focuses on lawyers’ identities and wellbeing, legal ethics and ethical
decision-making, and the changes to the legal professions. She is the Chair of the Faculty's
Legal Education Research Cluster. Justine also produces pop academic events, including
Nerd Nite.
Ms Annette Schmeide, Executive Leader BUPA Health Foundation
Ms Schmeide’s career includes health services research, health service planning, governance
and policy development. She is a board member of the NSLHD and an adjunct Associate
Professor at the Menzies Centre for Health Policy, School of Public Health, at The University
of Sydney.
Ms Sophie Scott, ABC News Medical Reporter
Ms Scott is a reporter, public speaker, author, and ambassador for Bowel Cancer Australia.
In 2004 she won the Australian Museum Eureka Prize for medical reporting, and in 2005 she
received the Health Research in the Media Award.
Prof Michael Spence, Vice-Chancellor and Principal, The University of Sydney
Professor Spence is a leader in the field of intellectual property theory. In addition he
championed the development of the new multidisciplinary centres; the Charles Perkins
Centre, the China Studies Centre, the Sydney Southeast Asia Centre, the Australian Institute
of Nanoscale Science and Technology and the Brain and Mind Centre.
Mr Jake Sturmer, ABC News Environment and Science Reporter
Mr Sturmer is an ABC reporter who previously covered National Science and Technology. In
2012 he was awarded the Walkley Foundation Young Australian Journalist of the Year, and
in 2013 the European Union-QANTAS Journalism Award.
Dr Alan Taylor, Executive Chairman, Clarity Pharmaceuticals
Dr Taylor has 10 years’ investment Banking experience and a PhD in Medicine (Garvan
Institute of Medical Research). His experience includes capital raisings, mergers and
acquisitions, and general corporate advisory in a range of industries including healthcare
and life sciences, technology, and resources. Until recently he was an Executive Director and
shareholder of Inteq Limited.
Ms Susi Tegen, Chief Executive, Medical Technology Association of Australia (MTAA)
Ms Tegen has over 20 years’ experience in the medical and health sector. Her former
leadership positions include Chief Executive of the Royal Australian and New Zealand College
of Ophthalmologists and Chief Executive of Limestone Coast Division of General Practice in
South Australia.
Prof Bryan Williams, Director, Hudson Institute of Medical Research
Professor Williams is an immunologist and cancer biologist. He is Chair of the
Biopharmaceuticals, Biomaterials and Medical Devices Advisory Committee for Therapeutic
Innovation Australia and Chair of the Board of BioGrid Australia Ltd, a data sharing platform
for collaborative translational health and medical research. In 2013, he was elected as a
Fellow of the Australian Academy of Science and the American Academy of Microbiology.
FULL PROGRAM – Day 1 – Monday 23rd November 2015
Building a Better Healthcare System through Understanding
0800 – 1700
Registration Desk Open
WELCOME, KEYNOTE 1: Understanding the Landscape – Federal, State and Local
0830 – 0930
Session Chair: Prof Jonathan Morris AM
Auditorium
0830 – 0845 Welcome to Country
Aunty Joan Tranter, UTS Indigenous Elder in Residence
0845 – 0900 Welcome and Introduction to the Conference
Professor Attila Brungs, Vice-Chancellor and President, UTS
0900 – 0930
KEYNOTE: Understanding Health as a System
Mr Martin Bowles, Secretary, Department of Health, Australian Government
PLENARY SESSION 1.1: Understanding the Academic Commitment to Health
0930 – 1030
Auditorium
NSLHD Perspective:
0930 – 0945
Prof Jonathan Morris, Director Research NSLHD
0945 – 1000
1000 – 1015
1015 – 1030
Academic Strategic Commitment to Health:
Prof Attila Brungs, Vice-Chancellor and President, UTS
Prof Michael Spence, Vice-Chancellor and Principal, The University of Sydney
1030 – 1100
Morning Tea, Poster Presentations and Sponsored Table Displays
Q&A: What Does it Take to Build a Bridge?
1100 – 1230
Moderator: Ms Sophie Scott (ABC News)
Auditorium
Q&A Panel Members include:
Mr Martin Bowles, Secretary of the Federal Department of Health
Mr Mitch Kirkman, Novartis & Representative of the Pharmaceutical Industry Council Research &
Development Task Force
Ms Annette Schmeide, Executive Leader, BUPA Foundation
Prof Shirley Alexander, Deputy Vice-Chancellor and Vice-President of Education and Students, UTS
1230 – 1400
Lunch, Poster Presentations and Sponsored Table Displays
PLENARY SESSION 1.2: Building Bridges with Industry
1400 – 1515
Session Chair: Ms Karyn Joyner
Auditorium
1400 – 1425 Pharmaceutical Industry
Mr Mitch Kirkman, Novartis & Representative of the Pharmaceutical Industry Council Research & Development
Task Force
1425 – 1450 Medical Technology Industry
Ms Susi Tegen, Chief Executive, Medical Technology Association of Australia
1450 – 1515 Biotechnology Industry
1515– 1545
Afternoon Tea, Poster Presentations and Sponsored Table Displays
The Twits Twitter
#NewH2015
FULL PROGRAM – Day 1- Monday 23rd November 2015
PLENARY SESSION 1.3: Collaboration Builds the Stronger, Most Effective Bridges and gets Results
1545 – 1715
Auditorium
Health Informatics – How Data and Systems Thinking can Improve Health Care
1545 – 1600
1600 – 1625
1625 – 1650
1650 – 1715
1730 – 1830
The Potential for Health and Biomedical Informatics to Improve Health
Prof Jonathan Morris, Director, Health and Biomedical Informatics, Sydney Medical School
The Rhythms of the Hospital - Harnessing Temporal Patterns in Clinical Analytics
Prof Enrico Coiera, Director, Centre of Health Informatics, Macquarie University
The Potential of Computer Science: Insights from Other Domains
Prof Hugh Durrant-Whyte, ARC Federation Fellow, The University of Sydney
How do we Evaluate Systems within Health?
Dr Henry Cutler, Director, Macquarie University Centre for the Health Economy (MUCHE)
Demonstration of the UTS Data Science Centre
The Twits Twitter
#NewH2015
FULL PROGRAM – Day 2 – Tuesday 24th November 2015
Bridging the Gap: Forging the Paths to Cure Chronic Injury, Disease and Cancer
0745 – 1700 hours
Science and Communication Workshop
0800 – 0930
Moderator: Dr Tim Dean (The Conversation)
Workshop panel members include:
Ms Sophie Scott, ABC News Medical Reporter
Mr Jake Sturmer, ABC News Environment and Science Reporter
- Mr Paul X. McCarthy, Online Gravity Consulting
- Prof Bryan Williams, Director, Hudson Institute of Medical Research
- Dr Justine Rogers, Lecturer, UNSW
ABSTRACT SESSION 2.1:
0930 – 1032
Chronic Injury and Disease: Auditorium
Cancer: Consumer to Cure: Collaborative Theatre
Session Chair: Dr Sonia Saad
Session Chair: Dr Amanda Hudson
0930 – 0942 Cortical Reorganisation of Transtibial Amputees
Enriching Cancer Research with Consumer Dialogue
undertaking Prosthetic Rehabilitation
Janet Long, Macquarie University
Lynley Bradnam, UTS
0942 – 0956 Stromal Cells Isolated from Subchondral Bone Vary
Long Non-Coding RNAs are Differentially Expressed
between Patients in Multipotency and Therapeutic
in Ovarian Cancer-Associated Fibroblasts Compared
Potential to Ameliorate Tendon Pathology
to Normal Ovarian Fibroblasts
Margaret Smith, Kolling Institute
Emily Colvin, Kolling Institute
0956 – 1008 The Impact of Maternal Smoking on Childhood
Cancer and Chromatin: A New Therapeutic
Asthma in Mice
Opportunities Targeting the COMPLEX Landscape
Razia Zakarya, UTS and Woolcock Institute
Deborah Marsh, Kolling Institute
1008 – 1020 Comprehensive Mutation Analysis of Known and
Adaptive Radiotherapy for Bladder Cancer Patients
Candidate Motor Neuron Disease Genes
using Interpolation between Empty and Full Bladder
Emily McCann, Macquarie University
Imaging
Prabhjot Juneja, The University of Sydney, NSLHD, &
Kolling Institute
1020 – 1032 Maternal Obesity Exacerbates Chronic Kidney
The LIGHT SABR Clinical Trial: Tumour Tracking
Disease in Offspring with Diabetes
Radiotherapy for Superior Lung Cancer Outcomes
Sarah Glastras, Kolling Institute
Jeremy Booth, Kolling Institute
1032 – 1100
PLENARY SESSION 2.1: Bridging Cancer Genetics and Immunology
1100 – 1230
Session Chair: Prof Deborah Marsh
Auditorium
1100 – 1145
PLENARY: Innate Immunity and Cancer
Prof Bryan Williams, Director, Hudson Institute of Medical Research
1145 – 1230
PLENARY: Genome Characterisation of Chemo-resistant Ovarian Tumours
Dr Dale Garsed, Peter MacCallum Cancer Centre
1230 – 1400
™
AccuCal , A Simple, Unbiased Method For Absolute Quantification Using qPCR
Accugen Systems, 1245-1315, Oval Room (max. 50 people)
The Twits Twitter
#NewH2015
FULL PROGAM – DAY 2 – Tuesday 24th November 2015
PLENARY SESSION 2.2: Integrating Research into a Healthy Lifestyle
1400 – 1530
Session Chair: A/Prof Ken Rodgers
Auditorium
1400 - 1445
PLENARY: Mobile Health Technology
A/Prof Valarie Gay and Dr Peter Leijdekkers, Faculty of Information Technology, Computer Systems, UTS
1445 - 1530
PLENARY: From Research To Practice: Improving Athlete Preparation through Integrating Research in
Professional Sports
Prof Aaron Coutts, Centre for Health Technologies, Faculty of Health, UTS
1530 – 1600
POSTDOCTORAL PRIZE SESSION:
1600 – 1724
Session Chair: A/Prof Stella Valenzuela
Auditorium
1600 – 1612
Bone Marrow Derived Mesenchymal Stem Cells Alleviate Pain Response in Surgically Induced Osteoarthritis
in Mice
Cindy Shu, Kolling Institute
1612 – 1624 Motor Neuron Disease and Frontotemporal Dementia: Defining the Effects of Pathological Proteins using
New Transgenic Mouse Models
Adam Walker, Macquarie University
1624 – 1636 Intratumoral Heterogeneity of DNA Repair Pathways in Glioblastoma
Amanda Hudson, Kolling Institute
1636 – 1648 The Evidence of Anti-IgD mAb as a Novel Treatment for Autoimmune and Inflammatory Conditions: From an
Unconventional Perspective
Tommie Nguyen, Kolling Institute
1648 – 1700 Characterisation of the DBA/2J-Mated CBA/CaH Female Murine Model of IUGR and Perinatal Mortality
Kelly McKelvey, Kolling Institute
1700 – 1712 Genome-Wide and Targeted Analysis of DNA Methylation in Disease Discordant MND/FTD Cohorts
Kelly Williams, Macquarie University
1712 – 1724 FhHDM-1, a Peptide Secreted by the Helminth Fasciola hepatica, prevents Autoimmune Diabetes and
Reduces Disease Severity in Multiple Sclerosis in Two Murine Models
Maria Lund, UTS
The Twits Twitter
#NewH2015
FULL PROGRAM – Day 3 – Wednesday 25th November 2015
DAY 3 – Building Bridges: Research Innovation and the Current Healthcare Landscape
0745 – 1700
PLENARY SESSION 3.1: Technology and Innovation in Science and Health
0800 – 0900
Session Chair: Dr Deborah Debono
Auditorium
0800 - 0830
PLENARY: τ-Dots: Nanophotonics for Rapid Diagnostics and Drug Identification
Dr Dayong Jin, UTS, Macquarie University & ARC Centre for Nanoscale Biophotonics)
0830 - 0900
PLENARY: Surgical Innovation and Robotics: Research Network
Prof David Gillat, Macquarie University
0910-1058
John Hambley, Douglas Piper, and Macquarie
Novel Therapeutics and Delivery Systems:
University Prize: Auditorium
Session Chair: Dr Nham Tran
Session Chair: Dr Hui Chen
0910 – 0922 Novel Drug Treatments in Mild Traumatic Brain
Pancreatic Transdifferentiation in the Livers of a
Injury
Humanised Mouse Engineered to Express Insulin
Claire Linnane, UTS
Que La, UTS
0922 – 0934 Investigating the Effects of Manuka Honey on
Protein Cargo of Plasma Microparticles Released
Bacterial Growth using Model Organism
during Experimental Cerebral Malaria: Source of
Pseudomonas aeruginosa
Biomarkers and Role in Disease Pathogenesis?
Daniel Bouzo, UTS
Natalia Tiberti, UTS
0934 - 0946
Role of the TXA2 Receptor in the Development and
The Effect of Metformin on Inflammatory and
Host Response to Melanoma
Fibrotic Responses in Renal Tubular Cells
Yunjia ‘Carmen’ Zhang, UTS
Hao Yi, The University of Sydney
0946 – 0958 RET-Altered Non-Coding RNA in Medullary Thyroid
Plasma Levels of Endothelial and B Cell-Derived
Cancer
Microparticles Restored by Fingolimod Treatment in
Jin Suk ‘Lauren’ Joo, The University of Sydney
Multiple Sclerosis
Anna Zinger, The University of Sydney
0958 – 1010 Comorbidities in Patients with Psoriatic Arthritis
LOXL2 Inhibition Reduces Glomerulosclerosis and
(PsA): Analysis from the Australian Rheumatology
Albuminuria in a Mouse Model of Diabetic
Association Database (ARAD)
Nephropathy
Premarani Sinnathurai, NSLHD
Stefanie Stangenberg, Kolling Institute
1010 – 1022 Novel Interaction Between Succinate
Exploring Phenotypic Changes in Differentiating
Dehydrogenase Subunit B and Assembly Factor 3
Adult Stem cells for use in Regenerative Medicine
Associated with Phaeochromocytoma and
Jerran Santos, UTS
Paraganglioma Syndromes
Edward Kim, Kolling Institute
1022 – 1034 Psychophysical Placebo Responses in Patients
Systemic Delivery of a Connexin43 Mimetic Peptide
Receiving a Mock Laser (ML) Intervention: An
in Rats Improves Hindlimb Locomotor Function
Interoceptive Perspective
following Spinal Cord Injury
Shohreh Razavy, UTS
Yilin Mao, UTS
1034 – 1046 Text Classifiers for Automated Encoding of Surgeries Efficacy of Species-Specific Protein Antibiotics in a
Georgina Kennedy, Macquarie University
Model of Acute Pseudomonas aeruginosa Lung
Infection
Laura McCaughey, UTS
1046 – 1058 Defining Naivety: Human Peripheral Blood Naïve T
The Impact of L-Carnitine on Brain Mitophagy in
Cells as Defined by 13-Parameter Multi-Colour Flow
Male Offspring of Smoking Dams
Cytometry, Molecular Analysis and Illumina
Yik Lung Chan, UTS
Sequencing
Nicoleen Gasparillo, Macquarie University
1058 – 1130
FULL PROGRAM – Day 3 – Wednesday 25th November 2015
YOUNG INVESTIGATORS PRIZE SESSION:
1130 – 1230
Session Chair: Dr Emily Colvin
Auditorium
1130 – 1142 A Qualitative In-Vitro Test for the Detection of Six High-Risk Oral Cancer Markers in Human Serum
Samantha Khoury, UTS
1142 – 1156 Post-Traumatic Osteoarthritis: The Role of Joint Trauma versus Instability
Carina Blaker, Kolling Institute
1156 – 1208 Prediction of Osteoporotic Fracture by Genetic Profiling
Thao Ho-Le, UTS
1208 – 1220 The Long Non-coding RNA - PRINS as a Novel Recurrence Biomarker and Tumour Suppressor for
Adrenocortical Carcinoma
Anthony Glover, Kolling Institute
1220 – 1232 Gross Motor Performance in Primary School Aged Children Living in High-Risk Drinking Communities in
Remote Australia -the Lililwan Project
Barbara Lucas, NSLHD
1232 – 1244 Identification of Novel Gene Mutations causing Amyotrophic Lateral Sclerosis in Australian Families
Jennifer Fifita, Macquarie University
1244 – 1400
KEYNOTE 2: The Ease and Difficulty of a New Discovery
1400 – 1500
Session Chair: Prof Michael Wallach
Auditorium
1400 – 1500 KEYNOTE 2: Helicobacter pylori – The Ease and Difficulty of a New Discovery
Prof J Robin Warren, Nobel Prize Laureate
1500 – 1530
1530 – 1630
1530 – 1542
Bridging the Lifespan: Auditorium
Session Chair: Dr Kelly McKelvey
Placental Exosomes: A New Mechanism to Improve
Intrauterine Growth Restriction
Gaayathri Ariyakumar, Kolling Institute
Improving Healthcare: Collaborative Theatre
Session Chair: A/Prof Beata Bajorek
Bridging Pragmatic Gaps: Strategies to Inform
Feedback on Communicative Practice for Medical
Educators and Internationally Trained Doctor
Maria Dahm, Macquarie University
A Systematic Review of Interventions to Deprescribe
Benzodiazepines and Other Hypnotics among Older
People
Emily Reeve, Kolling Institute
Breathlessness in Individuals with Chronic Heart
Failure and Associated Outcomes
Gursharan Singh, UTS
1542 – 1554
Maternal Obesity Suppressed SIRT1 Signalling and
Related Autophagy in Offspring Kidney at Weaning
Long Nguyen, Kolling Institute
1554 – 1606
When Young People have a Parent Living with
Dementia: A Social Model Perspective
Karen Hutchinson, The University of Sydney
1606 – 1618
Hospital Pharmacists’ Perspectives in Optimising
Statin Therapy in Older Inpatients
Angela Wu, Kolling Institute
1618 – 1630
Ageing and Drug Induced Liver Injury: Insights from
Animal Studies
John Mach, Kolling Institute
1630 – 1700
Wrap Up and Presentation of Conference Prizes; Auditorium
1700 – 1800
Closing Drinks
Venous Thromboprophylaxis following Caesarean
Section: Current Clinical Practice in Four Tertiary
Hospitals in New South Wales
Kata Kraljevic, The University of Sydney
Developing a Logic Model to Evaluate Accreditation
in Acute Care Hospitals
Virginia Mumford, Macquarie University
SPEAKER ABSTRACTS
Speaker abstracts are provided in Presentation Order:
TUESDAY 24TH NOVEMBER 2015
CONCURRENT ABSTRACT SESSION 2.1: CHRONIC INJURY AND DISEASE
Cortical Reorganisation of Transtibial Amputees Undertaking Prosthetic Rehabilitation
1
2
Lynley Bradnam , Brenton Hordacre
1 University of Technology Sydney, Ultimo, NSW, Australia
2 University of Adelaide, Adelaide, SA, Australia
Background: Reorganisation of primary motor cortex (M1) is well described in chronic lower-limb amputees. Cortical
reorganisation in the sub-acute rehabilitation period after amputation has not been described, nor is it clear whether M1
reorganisation occurs bilaterally or is related to functional recovery.
Methods: Thirteen transtibial amputees (10 male, mean age 61.1 years) and thirteen age-gender matched control participants
were recruited. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of the M1
bilaterally. Neurophysiological assessments were conducted at admission, prosthetic casting, first walk and discharge. Gait
variability at discharge was assessed as a marker of functional recovery.
Results: There was no difference in corticomotor or intracortical excitability between controls and amputees at discharge. In the
amputees, short-latency intracortical inhibition was reduced for the contralateral M1 at walk compared to discharge (p=0.003).
Short-latency intracortical inhibition in ipsilateral M1 was reduced at admission (p=0.01) and casting (p=0.01) compared to
discharge. Long-latency intracortical inhibition was reduced at admission (p=0.05) and casting (p=0.02) compared to walk.
Bilateral corticomotor excitability, assessed as a laterality index, did not change significantly across rehabilitation. There were
relationships identified between intracortical excitability over rehabilitation and gait variability at discharge. For the
contralateral M1, reduced inhibition at admission (p=0.04) and walk (p=0.05) was associated with better gait function (i.e. lower
gait variability) at discharge. For the ipsilateral M1, reduced inhibition at discharge (p=0.05) was associated with poorer gait
function (i.e. higher gait variability).
Conclusion: This study characterised bilateral modulation of intracortical excitability during prosthetic rehabilitation. A
dichotomous relationship between intracortical inhibition for each M1 and gait function was observed. Intracortical inhibition
may be an appropriate cortical biomarker of functional recovery in lower limb amputees.
Stromal Cells Isolated from Subchondral Bone Vary Between Patients in Multipotency and Therapeutic Potential to
Ameliorate Tendon Pathology
1,2
2
1
2
Margaret M Smith , Varshini Ravi , David H Sonnabend , Christopher B Little
1 Department of Orthopaedics and Traumatic Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia
2 Raymond Purves Research Laboratories, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of
Sydney, St Leonards, NSW, Australia
Background: Rotator cuff tendinopathy is a major cause of morbidity in our ageing population. No effective drug therapies are
available so an urgent need exists for regenerative repair strategies to prevent further tendon degeneration and ameliorate
existing pathology. Mesenchymal stem/stromal cells (MSCs) are touted as an effective therapy in a plethora of chronic diseases
including tendinopathy, although robust evidence is lacking. MSC preparations isolated from various tissue sources by different
methods are extremely heterogeneous by both cell surface markers and functional assays.
Aim: In order to progress to a rational therapy of patients with rotator cuff injury, we sought to isolate stromal cells from a
clinically applicable autologous source, and compare their functionality between individual patients by colony formation, trilineage differentiation potential and determine whether these outcomes were related to their therapeutic action in an in vitro
model of tendon pathology induced by stress-deprivation.
Methods: Viable non-contaminated human stromal/stem cell preparations (hMSCs) were isolated from bone removed from
consented patients (n=13) with average age 77 years (range 48–90 years; 6 male/7female; 4 hip/9 knee) undergoing joint
replacement. hMSCs were expanded in culture to the 3rd or 4th passage, when cells were tested for colony-formation and
ability to undergo osteogenic, adipogenic and chondrogenic differentiation (histology and gene expression of differentiation
markers). To test for trophic ability to modulate tendon pathology, the same cell preparations were co-cultured with freshly
harvested sheep infraspinatus tendon explants (n=5 per cell line) for 24 hours. Tendon explant gene expression was determined
by real time RT-PCR.
Results: hMSCs exhibited diverse abilities to form colonies and to differentiate into fat, bone and cartilage. Chondrogenic (but
not adipogenic or osteogenic) differentiation declined significantly with decreasing ability to form colonies (P=0.002). Expression
markers of adipogenic differentiation (PPARG, r=0.61, P=0.034; ADIPOQ, r=0.64; P=0.034) correlated with increasing Oil red O
staining, however the correlations between histology and gene expression markers were not significant for osteogenesis or
chondrogenesis. Trophic effects of cells on tendon explant gene expression varied markedly between preparations and did not
correlate with patient donor age or osteogenic differentiation ability. Stimulation of tendon COL2A1 expression positively
correlated with the cells' chondrogenic ability (r=0.585; P=0.014). Increasing adipogenic capacity was associated with increased
stimulation of tendon ADAMTS4 (r=0.518; P=0.040) expression, and decreased MMP13 (r=0.536; P=0.027) and COL2A1
expression (r=0.551; P=0.022).
Discussion: Stromal cells isolated from bone of patients undergoing joint replacement provided access to a clinically relevant
autologous MSC source. This study demonstrates the marked inter-patient variability in MSCs and therefore the clinical
therapeutic utility of autologous cells. Our results suggest that cells with increased chondrogenic capacity may enhance
chondroid differentiation in tendon that would be detrimental in tendinopathy. Greater adipogenic differentiation, on the other
hand, may be an indicator of therapeutic potential, being associated with modulation of pathological expression changes
induced by stress-deprivation in our in vitro assay, that would reduce chondroid metaplasia, a classical feature of tendinopathy.
The Impact of Maternal Smoking on the Development of Childhood Asthma in Mice
2, 1
1
2, 1
Razia Zakarya , Hui Chen , Brian G. G. Oliver
1 School of Life Sciences, University of Technology Sydney, Ultimo, NSW, Australia
2 Molecular Pathogenesis Group, Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia
Objective: In Australia, 13% of the population smoke daily and it has been noted that 15% of women have smoked tobacco
during pregnancy (AIHW, 2013). Asthma impacts on the quality of life of many individuals across the world. Australian youth
have some of the highest rates of asthma worldwide, with 32.4% of 13-14 year olds within Australia and NZ experiencing
symptoms of asthma, compared to the global average of 13.8% (Uphoff et al, 2014). Epidemiological evidence has implicated the
role of smoke exposure (SE) in the development of childhood asthma; however the distinction between the effects of
intrauterine and environmental tobacco smoke (ETS) remains to be elucidated (Jaakkola & Gissler, 2004). We thus hypothesised
that that maternal smoking increases the susceptibility of offspring to asthma. This project aimed to use both in vivo and in vitro
methods to investigate the impact of intrauterine cigarette smoke exposure on the susceptibility of asthma development in the
mice offspring.
Methods: The in vitro study measured the effect of cigarette smoke extract (CSE) on phenotypic changes seen in asthma,
namely airway smooth muscle (ASM) hyperplasia and inflammatory reaction. In the in vivo study, female BALB/c mice were
exposed to cigarette smoke 7 days a week for six weeks before mating, during gestation and lactation. The offspring were
sensitised to chicken-egg ovalbumin (OVA), with a final allergic challenge taking place a day prior to sample collection.
Results: In the in vitro study, combined CSE and Th2 cytokine treatment showed no synergistic or additive difference in
inflammatory cytokine levels. However, cell viability was significantly decreased when cells pre-treated with CSE were treated
with Th2 cytokines. In the in vivo study, serum anti-OVA IgG1 level was significantly higher in the SE offspring compared with the
Sham offspring. However, there was no significant difference in inflammatory cytokine levels in the lung lavage.
Conclusion: CSE pre-treatment negatively impacts cell viability when ASM cells are placed in an asthmatic environment; whilst
maternal smoke exposure increases the likelihood of offspring responding to antigen.
Comprehensive Mutation Analysis of Known and Candidate Motor Neuron Disease Genes
1
1
1
1
1
1
Emily P McCann , Kelly L Williams , Jennifer A Fifita , Lorel Adams , Dominic Rowe , Ian P Blair
1 Macquarie University, North Ryde, NSW, Australia
Background: Motor neuron disease (MND) is a debilitating and ultimately fatal disease, caused by progressive degeneration and
elimination of upper and lower motor neurons. Roughly 10% of cases are hereditary (familial MND), with the remainder
occurring sporadically. The only known causes of MND are gene mutations. Together, hexanucleotide repeat expansions in
C9ORF72 and missense mutations in SOD1 account for the cause of disease for more than 50% of familial MND cases.
Aims: To implement a detailed genetic analysis pipeline to streamline investigations into the molecular basis of MND. This
includes the screening of known MND genes for mutations, as well as identifying novel MND genes.
Methods: To determine the frequency of mutations in C9ORF72 and SOD1 in Australian familial MND cases, we have optimised
the gene screening protocols. For C9ORF72, we combine repeat primed PCR for the repeat expansion and TaqMan genotyping
for the SNP in linkage disequilibrium with the pathogenic expansion. For SOD1, we have modified current PCR protocols for
successful direct Sanger sequencing of all five coding exons. Familial MND cases (n=31) were screened for the repeat expansion
in C9ORF72 and mutations in SOD1. Sporadic MND cases (n=111) were screened for the repeat expansion in C9ORF72. Familial
MND patients found to not harbour a gene mutation in SOD1 or C9ORF72 were subsequently exome sequenced. Resultant
variant files from exome data were parsed for all genes known to cause, or be associated with, MND (n= 43), using in-house
bash scripts. Candidate gene mutations identified by exome sequencing were validated by PCR and sequencing, followed by
TaqMan SNP genotyping through large cohorts of non-related controls.
Results: We have identified three MND families (11.1%) and two sporadic MND cases (1.8%) as harbouring a C9ORF72
hexanucleotide repeat expansion. Five MND families (18.5%) harbour a SOD1 missense mutation. Bioinformatic analysis of
exome sequencing data successfully parsed 152 patients for known MND genes. Several novel candidate genes identified from
exome sequencing data have withstood validation and may be potential novel MND genes.
Conclusion: We have implemented our genetic analysis pipeline to successfully identify the cause of disease in eight MND
families and two sporadic MND cases. Surprisingly, we observed lower proportions of patients presenting with C9ORF72
mutations compared with the frequencies reported in the literature (9.6% familial and 0.18% sporadic compared to 38.5% and
3.5%, respectively, in Australian MND cases).
Maternal Obesity Exacerbates Chronic Kidney Disease in Offspring with Diabetes
1,2
1
3
1,2
1
3
1
1
Sarah Glastras , Rachel Teh , Michael Tsang , Rachel McGrath , Amgad Zaky , Hui Chen , Carol Pollock , Sonia Saad
1 Department of Medicine, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St Leonards,
NSW, Australia
2 Department of Endocrinology, Royal North Shore Hospital, St Leonards, NSW, Australia
3 School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia
Background: We have previously shown that maternal obesity is associated with adverse renal outcomes in offspring at an early
time point. We hypothesised that a second-hit such as diabetes may further exacerbate renal damage in offspring exposed to
maternal obesity.
Aim: To determine whether maternal obesity accelerates the development of chronic kidney disease (CKD) in offspring with
diabetes.
Methods: Female C57Bl6 mice were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy
and weaning, and their offspring were weaned to chow diet. At Week 8, the male offspring were randomized to streptozotocin
55mg/kg/day for five consecutive days (to induce type 1 diabetes), strepotozotocin 100 mg once only (to induce type 2 diabetes)
or placebo. Weight and glucose levels were tested fortnightly. 24 h urine collection was performed at Week 20 and 30. The
kidneys were harvested at Week 32 and renal structure was observed. Gene expression levels of proinflammatory, oxidative
stress and profibrotic markers were measured by real time PCR and confirmed with western blot and/or immunohistochemistry.
Results: Offspring of obese mothers had increased epididymal and retroperitoneal fat deposition. Diabetic offspring had
reduced weight gain, hyperglycaemia and microalbuminuria. Urinary albumin measurements were highest in diabetic offspring
of obese mothers. Furthermore, the kidneys of the offspring exposed to maternal obesity and induced with diabetes had
increased structural damage, heightened inflammatory changes and greater levels of oxidative stress markers when compared
to the kidneys of diabetic offspring of normal weight mothers. There was also evidence of renal fibrosis.
Conclusions: Offspring exposure to maternal obesity accelerates the severity of damage to the kidney caused by diabetes. Renal
inflammation and oxidative stress may be key pathways for this accelerated risk. Thus, maternal weight in pregnancy is an
important modifiable risk factor for CKD in offspring.
CONCURRENT ABSTRACT SESSION 2.1: CANCER: CONSUMER TO CURE
Enriching Cancer Research with Consumer Dialogue
1
1
1
2
1
Janet Long , Deborah Debono , Sharron O'Neill , Mary Potter , Natalie Taylor
2 Consumer Advisory Council, Translational Cancer Research Centre, Sydney, NSW, Australia
Working with consumers has sometimes been described as a “tick the box” exercise, complying with funding bodies’
requirements but not adding value to a project. We describe how we have worked productively with consumers in a study to
improve timely referral to genetic counseling.
Lynch syndrome (LS) is a genetic mutation that predisposes its carriers to a range of cancers, often occurring at a young age.
People identified as being at a high risk of having LS can be referred to a genetics service for diagnostic testing and for family
history mapping. Identification of people who carry the mutation enables them to undergo surveillance to detect cancers early
as well as extending this opportunity to inform and educate their relatives. While it is believed that tens of thousands of people
in Australia are affected by LS it is currently extremely under-diagnosed. In NSW less than half of colorectal cancer patients with
a high risk of LS are referred for genetic counseling and testing. The goal of the study is to increase timely and appropriate
referrals.
Multidisciplinary healthcare professionals and consumers have provided unique perspectives on potential barriers to referral
and appropriate strategies to target them. The research team has included health services researchers, oncologists, geneticists,
pathologists, surgeons and two consumers. The consumers have been a part of the research team since inception. One is a
cancer survivor and the other a person with LS. Both consumers are familiar with research processes: the former attended
training on consumer representation run by the TCRN; the other is an academic. Two separate meetings between the principal
investigator and the consumers early in project planning included their input in the study design and shaped the research
questions. Three subsequent meetings have allowed opportunities for consumers to raise additional issues as data is collected.
Our consumer representatives have informed study design by advising on the approach to take and making it more relevant to
consumers. They helped to design the lay-summary and later raised issues around: the cost of testing; knowledge of healthcare
professionals about LS, and ramifications of being diagnosed with LS. They brokered invitations to speak at a consumer forum
run by Lynch Syndrome Australia. This provided opportunities to present emerging study findings including concerns offered by
health professionals around referral for genetic counselling for LS.
Discussion points and questions raised by an audience of consumers, many with LS further moulded researchers' understanding
of the issues people with LS face. This two-way flow of information has informed new areas for research investigating the
patient’s experience of referral and diagnosis of LS. Being known to this group of engaged consumers will provide opportunities
for collaboration in future studies. Far from a “tick box” exercise, consumers make a valuable and unique contribution to the
entire research process, from study design to dissemination of results. Based on their experience with specific conditions, or
more generally being a patient, consumers are well placed to inform further research opportunities that can have a meaningful
impact for patients.
Long Non-coding RNAs are Differentially Expressed in Ovarian Cancer-associated Fibroblasts Compared to Normal Ovarian
Fibroblasts.
1
2
3
4
1
5
Emily K Colvin , Fatemeh Vafaee , Samuel C Mok , Michael J Birrer , Viive M Howell , Goli Samimi
1 Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St Leonards, NSW, Australia
2 Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
3 Department of Gynecologic Oncology and Reproductive Medicine Research, Division of Surgery, MD Anderson Cancer Centre,
The University of Texas, Houston, Texas, United States
4 Harvard Medical School, Massachusetts General Hospital Cancer Centre, Boston, Massachusetts, United States
5 The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
Background: Ovarian cancer is the most lethal gynaecological malignancy in women. Expression profiling of the high-grade
serous subtype has revealed that patients exhibiting a “stromal expression signature” demonstrate the poorest prognosis (Tothil
et al 2008). However, genetic aberrations in ovarian cancer-associated fibroblasts (CAFs) are extremely rare (Qiu et al, 2008),
raising the possibility that alternative mechanisms that regulate gene expression, such as long non-coding RNAs (lncRNAs), are
present in CAFs. LncRNAs are polyadenylated RNA transcripts that do not encode for protein, but have been shown to correlate
with cancer progression and outcome.
Aims: Our aim was to investigate the presence of differentially expressed lncRNAs in ovarian CAFs versus normal ovarian
fibroblasts.
Methods: CAFs were laser-capture microdissected from 51 advanced-stage high-grade serous ovarian cancers and 10 normal
ovaries removed from women for non-cancer reasons. RNA was extracted from the microdissected samples and expression
analysed using Affymetrix U133 Plus 2.0 Arrays. Probes previously identified as lncRNAs were used in this analysis (Zhang et al,
2012). Samples were normalised and background corrected using the robust multi-arrray average (RMA) method and expression
values were log2 transformed. Differentially expressed probes between cancer versus normal samples were calculated using
linear models for microarray data (limma) package from Bioconductor and a moderated t-statistic used to assess significance.
Results: Based on a significance cutoff of fold-change > 2 and a p-value < 0.05, 54 lncRNAs were identified as differentially
expressed in cancer versus normal fibroblasts. These included lncRNAs previously implicated in ovarian cancer such as XIST, as
well as several lncRNAs that are known to play a role in other cancer types such as NEAT1, GAS5 and CASC2. In addition, 16
lncRNAs were differentially expressed between patients with short (<15 months) versus long (>15 months) overall survival.
These included MALAT1, MEG3, TUG1, and CRNDE.
Conclusion: In summary, we have identified for the first time in any cancer type lncRNAs that are differentially expressed in CAFs
compared to normal fibroblasts, as well as lncRNAs that are differentially expressed based on survival. Given that CAFs are
known to promote tumour progression and metastasis, these lncRNAs present suitable candidates for their role in the tumourpromoting function of CAFs.
Cancer and Chromatin – New Therapeutic Opportunities Targeting the COMPLEX Landscape
1
Deborah J Marsh
1 Hormones and Cancer, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St Leonards,
NSW, Australia
Cancer can be described as a disease of aberrant transcription and faulty DNA repair mechanisms. Both processes are
inextricably linked to chromatin and its accessibility, defined by either a condensed, or alternatively open, structure. Histones
are the most abundant proteins bound to DNA in eukaryotic cells. Post-translational modifications (PTMs) of histones influence
accessibility to DNA of factors involved in DNA damage repair and transcription. Histone PTMs occur at specific amino acids on
histone tails and include acetylation, methylation, phosphorylation, monoubiquitination and sumoylation. They are tightly
regulated by specific factors functioning in complexes. These factors include chromatin “writers”, such as histone
methyltransferases (HMTs), and conversely “erasers”, including enzymes such as histone deacetyltransferases (HDACs) and
deubiquitinases (DUBs). The signals laid down by writers and erasers are interpreted and acted upon by chromatin “readers”,
including those important in histone cross-talk. Drugs functioning as HDAC inhibitors, such as Vorinostat® and Valproate®, are
already in clinical use.
Of all the histone PTMs, monoubiquitination, at 8.5 kDa, is one of the largest. We, and others, have shown that
monoubiquitination of histone H2B at lysine 120 (H2Bub1), a PTM associated with open and accessible chromatin, is lost in a
broad range of advanced malignancies, including ovarian, parathyroid (Hahn et al, 2012), breast, colon and lung cancers. H2Bub1
leads to physical separation of chromatin strands and active recruitment of factors involved in histone cross-talk, transcription
and repair of DNA damage that are dysregulated in advanced cancers. Manipulating the regulatory machinery of H2Bub1, either
alone or in combination with DNA damage based therapies including chemotherapeutics such as carboplatin, shows promise for
the treatment of malignancy (reviewed in Cole et al, 2015).
In the case of parathyroid cancer, we have shown that loss-of-function mutations of the tumour suppressor CDC73, a member of
the RNA polymerase II-associated factor 1 (PAF1) transcriptional complex that interacts with factors that regulate H2Bub1, leads
to H2Bub1 loss. Using models of high-grade serous ovarian cancer, we have shown that down-regulation or mutation of the
tumour suppressor E3 ubiquitin ligase BRCA1, leads to loss of H2Bub1 in vitro; however, other E3 ligases appear to compensate
for this function in vivo. A role for the most frequently mutated tumour suppressor protein, p53, in disrupting the chromatin
landscape has recently been reported (Zhu et al, 2015). The extent of physical interactions between wild-type or mutant p53
and chromatin writers, erasers and readers remains to be fully elucidated. An overview of our research investigating the role of
tumour suppressor genes in the regulation of H2Bub1 will be presented. Epigenomic-based drugs that are able to regulate
enzymes that modify histone PTMs demonstrate great promise for the treatment of cancer.
Adaptive Radiotherapy for Bladder Cancer Patients using Interpolation between Empty and Full Bladder Imaging
1,2,3
1
1
1,2
2
1
1
Prabhjot Juneja , Peter Hunt , Hannah Caine , Jeremy Booth , David Thwaites , Andrew Kneebone , Thomas Eade
1 Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW, Australia
2 School of Physics, The University of Sydney, Camperdown, NSW, Australia
Background: Bladder can undergo large deformations over the course of radiotherapy and therefore generous margins (up to 20
mm) for bladder radiotherapy are utilized. A common goal of various bladder adaptive radiotherapy (ART) methods is to reduce
irradiation of normal tissue while maintaining target coverage.
Aims: The goal of this retrospective study is to develop and evaluate bladder ART, based on interpolation of empty and full
bladder volumes, applicable from the first day of treatment.
Method: This retrospective study utilized information from 5 past bladder cancer patients (a total of 100 treatment fraction).
Deformations between empty and full bladder were used to construct bladder anisotropic planning target volumes (a-PTV)
through interpolation. For each patient, four a-PTVs were constructed such that a-PTV1 was the largest and a-PTV4 was the
smallest and the a-PTVs covered at least the bladder volume plus 5 mm margin. These a-PTVs were compared to the current
clinical standard (conv-PTV) of 10 mm uniform margins.
Results: The a-PTVs based on the empty and full bladder have been successfully constructed. Evaluation of the a-PTV found that
the smaller a-PTV, a-PTV4 and a-PTV3 were appropriate in 85% of the fractions, while a-PTV2 and a-PTV1 were required in 15%
of the fractions respectively. The use of the a-PTVs reduced the PTV volume by 34% (32-35%) as compared to conv-PTV.
Conclusions: The preliminary results indicate that the use of a-PTV could result in substantial decrease in the course averaged
planning target volume. This reduction in the PTV is likely to decrease the radiotoxicity and benefit bladder cancer patients. The
evaluation of more patients and dosimetric impact are currently underway.
The LIGHT SABR Clinical Trial: Tumour tracking radiotherapy for superior lung cancer outcomes
1,2
1,2
2
1
1
1
1
Jeremy Booth , Vincent Caillet , Ricky O’Brien , Nick Hardcastle , Kathryn Szymura , Charlene Crasta , Carol Haddad , Ben
1,2
1
1,2
2
Harris , Mark Stevens , Tom Eade , Paul Keall
1 Depts Radiation Oncology or Respiratory and Sleep Medicine, Royal North Shore Hospital, St Leonards, NSW, Australia
2 School of Physics, Central Clinical School or Radiation Physics Lab, Northern Clinical School, The University of Sydney, St
Leonards, NSW, Australia
Background: Lung cancer is the leading cause of cancer death worldwide. Radiotherapy is a core component of lung cancer
treatment and in Australia approximately 45% of all cancer patients will receive radiotherapy. An issue for lung cancer
radiotherapy is respiratory motion; as the tumours typically move 1 to 5cm with respiration. To ensure the tumour is irradiated
during treatment, an expanded volume of tissue is irradiated ensuring that the tumour is always covered by radiation during the
respiratory cycle, but necessarily increasing the dose to healthy tissues. This means that the tumour whilst the treatment beam
is on is static. We have clinically pioneered a method where the treatment beam is continuously aligned with and targeting the
tumour as it moves. This method is called real-time adaptation. In a world first clinical trial we will deliver real-time adaptive
treatments. A local planning study showed a 20% mean lung dose reduction with application of tumour tracking from a recent
cohort of 10 patients. The Lung Intensity Guided and Hypofractionated tumour Tracking with Stereotactic Ablative Body
Radiotherapy (LIGHT SABR) study aims to demonstrate the safe use of tumour tracking technology to deliver high doses to the
lung tumour and reduce collateral healthy lung dose. LIGHT SABR will be the first clinical application of tumour tracking on a
standard treatment unit for any tumour site affected by respiratory motion.
Methods: The LIGHT SABR clinical trial has full ethics approval through NSLHD HREC and will recruit 20 patients with stage 1 lung
cancer or metastasis in the lung. The patients will have 3 electromagnetic lung beacons implanted transbronchially. These
beacons will be tracked during radiotherapy treatment using the room mounted Calypso tracking station. TGA approval has
been granted to use software developed at The University of Sydney to drive the treatment unit to follow the moving tumour
with our radiotherapy treatment beam.
th
Results: The first two patients had Calypso beacons implanted on Monday 12 October and are scheduled to begin treatment
th
from 28 October. The beacon implantation process was well tolerated by both patients. Treatment planning 4DCT’s showed
the beacon movement is consistent with that of the tumour thus will be an accurate surrogate for tumour tracking.
Conclusions: The first tumour tracking radiotherapy clinical trial has full ethics approval and has recruited 2/20 patients to
demonstrate that this technology is safe, accurate and reduces collateral radiation dose.
POST-DOCTORAL PRIZE SESSION (<10 years post-PhD)
Bone Marrow Derived Mesenchymal Stem Cells Alleviate Pain Response in Surgically Induced Osteoarthritis in Mice
1,2
1,2
1,2
1,2
1,2
Cindy Shu , Varshini Ravi , Sanaa Zaki , Susan Smith , Christopher Little
2 Raymond Purves Bone and Joint Research Laboratories, The University of Sydney, St Leonards, NSW, Australia
Background: Osteoarthrits (OA) is the most prevalent of all joint diseases, and causes more mobility disability than any other
medical conditions. There are no current disease-modifying therapeutics, with only symptomatic management (pain relief) or
joint replacement (for end-stage disease) available. Intra-articular injection of mesenchymal stem cells (MSCs) has been
suggested as a potential OA treatment, however the utility and mechanisms of action remain unclear.
Aim: We used a well-characterised mouse model of post-traumatic OA to address this issue, and investigated the effects of
MSCs on progressive structural joint damage, synovial inflammation and pain.
Methods: 10 week-old male C57BL6 mice underwent surgical destabilisation of the medial meniscus (DMM) to induce OA. At 2
5
and 4 weeks post-surgery they received intra-articular saline (10µl) or heterologous marrow-derived MSC (2x10 cells/10µl), and
were sacrificed at 4/8/12 weeks post-DMM. Tactile allodynia (pain) was measured pre/post-surgery and pre/post-injection to
quantify pain threshold. Synovial tissue RNA was extracted for gene expression analyses. Cells from synovial tissue were
released by enzymatic digestion, evaluated by surface staining for flow cytometry to quantify inflammatory cell populations. The
remaining knee joint was processed for histology and analysed by histopathology scoring.
Results: Tactile allodynia was significantly increased post-DMM, and was alleviated (~50%) by MSC injection from 4 to 12 weeks
(P < 0.05). MSCs significantly reduced femoral (but not tibial) cartilage proteoglycan loss and structural damage at 12 weeks (but
not earlier), but had no effect on subchondral bone sclerosis or osteophyte development (size or maturation). Synovial Il6, Ccl3,
Col1a1, Adamts4, Adamts5, Mmp2, Mmp3 and Mmp13 all significantly decreased with time post-DMM. However, MSCs induced
a significantly greater reduction in Adamts5 (4 weeks) and Adamts4 (8 weeks) compared to saline. Flow cytometry
demonstrated a significant temporal change in both the absolute number and relative proportion of synovial inflammatory cells:
compared with saline MSCs significantly reduced macrophages (specifically M2a & M2c) and T-cells (both CD4+ & CD8+) at 4
weeks, but increased CD8+ T-cells at 8 weeks.
Discussion: Intra-articular injection of MSCs after an OA-inducing injury (DMM surgery) resulted in significant and prolonged
pain alleviation. However this was associated with only a minor reduction in structural pathology: the reduced cartilage
proteoglycan loss observed in late-stage disease potentially due to reduced synovial Adamts4/5 expression. Reduction in
allodynia/pain was temporally associated with changes in joint inflammation, more particularly synovial inflammatory cell influx.
The association between reduced allodynia by MSCs and modulation of synovial T-cells is consistent with recent evidence
implicating these cells in pain sensitisation. Future studies will target specific T-cell populations to identify their role in OA
pathophysiology.
Motor Neuron Disease and Frontotemporal Dementia: Defining the Effects of Pathological Proteins using New Transgenic
Mouse Models
1,2
2
2
2
Adam K Walker , Linda K Kwong , John Q Trojanowski , Virginia MY Lee
2 University of Pennsylvania, Philadelphia, PA, United States
Background: Motor neuron disease (MND) is a paralysing and inevitably fatal disease, and frontotemporal dementia (FTD) is a
progressive disease causing changes in behaviour, personality and/or language. Seemingly disparate, MND and FTD are however
both incurable neurodegenerative diseases defined pathologically as the ends of a spectrum: at autopsy, almost all patients with
MND and a majority of patients with FTD have accumulation of pathology in the brain and spinal cord containing the same
protein, TDP-43. TDP-43 is a DNA/RNA-binding protein with many diverse functions but in both MND and FTD, TDP-43 is cleared
from the nucleus and is phosphorylated, ubiquitinated, C-terminally cleaved, becomes detergent-insoluble, and forms large
cytoplasmic inclusions. The contributions of each of these pathological changes to disease remain unclear, due primarily to a
lack of valid in vivo models of MND/FTD.
Aims: The aim of these studies was to define the role of cytoplasmic pathological TDP-43 and its major disease-related fragment
in MND and FTD pathogenesis, by the development of new transgenic mouse models of disease.
Methods: New transgenic mouse lines with neurofilament heavy chain (NEFH) promoter-driven expression of tetracycline
transactivator protein (tTA) were crossed with tet-responsive ∆NLS-TDP-43 mice, to allow doxycycline-suppressible expression of
cytoplasmic human TDP-43 in neurons of the brain and spinal cord. Similarly, Camk2a-tTA mice were crossed with new tetresponsive 208-TDP-43 mice, to allow doxycycline-suppressible expression of an FTD-related C-terminal human TDP-43
fragment, comprising amino acids 208-414, in neurons of the brain. Mouse tissues were characterised biochemically and
immunohistologically at multiple time points to define pathology onset and progression. Motor behaviour, body and organ
mass, brain and muscle atrophy, neuromuscular junction (NMJ) innervation, and motor neuron number were similarly defined
over time.
Results: NEFH-tTA/tetO-∆NLS-TDP-43 mice accumulated detergent-insoluble pathological cytoplasmic TDP-43 and lost normal
nuclear TDP-43 in the brain and spinal cord, accompanied by progressive motor dysfunction, brain and muscle atrophy, NMJ
denervation, motor neuron loss, weight loss and decreased survival. Camk2a-tTA/tetO-208-TDP-43 mice accumulated
detergent-insoluble cytoplasmic C-terminal fragment TDP-43 in the brain and progressively lost neurons in the hippocampus,
but without loss of normal nuclear TDP-43 and without a motor phenotype. Suppression of either ∆NLS-TDP-43 or 208-TDP-43
expression allowed for clearance of pathological TDP-43 and ameliorated neuron loss, even after disease onset.
Discussion: The NEFH-tTA/tetO-∆NLS-TDP-43 mice develop, for the first time, disease-like cytoplasmic TDP-43 pathology
accompanied by a progressive motor phenotype, and are therefore the most reliable in vivo model of MND. Likewise, the
Camk2a-tTA/tetO-208-TDP-43 indicate for the first time that neurodegeneration can be caused by an FTD-linked C-terminal TDP43 fragment even in the absence of loss of normal nuclear TDP-43, suggesting that TDP-43 fragments are involved in
pathogenesis of disease. The amelioration of neuron loss after disease progression by removal of TDP-43 pathology indicates
that future therapeutics targeting TDP-43 could be effective in patients even after symptom onset, and further studies in these
mice will allow investigation of disease-modulating pathways and testing of potential therapeutic agents.
Intratumoral Heterogeneity of DNA Repair Pathways in Glioblastoma
1,2,3
1,2,3
1,2,3
1,2,3
1,2,3
4,2
Nicole R Parker , Amanda L Hudson , Peter Khong , Jonathon F Parkinson , Rowan J Ikin , Ying Zhu , Zhangkai
5,6
6,7
8
1,2,3
1,2,3
Jason Cheng , Fatemeh Vafaee , Jason Chen , Helen R Wheeler , Viive M Howell .
1 Sydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards, NSW,
Australia
2 Northern Sydney Local Health District, St Leonards, NSW, Australia
3 Sydney Medical School Northern, The University of Sydney, St Leonards, NSW, Australia
4 Hunter New England Health, NSW, Australia
5 Department of Physics, The University of Sydney, Camperdown, NSW, Australia
6 Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
7 School of Mathematics and Statistics, The University of Sydney, Camperdown, NSW, Australia
8 Department of Anatomical Pathology, Northern Sydney Local Health District, St Leonards, NSW, Australia
Background: Glioblastoma, the most common and aggressive brain cancer in adults, has a very grim prognosis and a 5 year
survival rate of less than 10%.
6
Promoter methylation status of the DNA repair enzyme O -methylguanine DNA methyltransferase (MGMT) is the most
important clinical biomarker in glioblastoma, predicting for therapeutic response. However, it does not always correlate with
response. This may be due to significant intratumoral heterogeneity, with a single biopsy unlikely to represent the entire lesion.
Aberrations in the mismatch repair (MMR) and base excision repair (BER) pathways may also contribute to response.
Aims: To investigate intratumoral heterogeneity in key glioblastoma biomarkers in a cohort of glioblastoma tumours with a
particular focus on the DNA repair pathways.
Methods: We analysed a robust cohort of 57 individual tumour biopsy specimens taken from 14 patients. Classification of
transcriptional subtype was performed by gene expression profiling (Fluidigm, Taqman assays). Pyrosequencing was used to
identify MGMT promoter methylation. Expression of MMR and BER genes was determined using qRT-PCR and Taqman assays
and deep sequencing of these genes was performed using the MiSeq Illumina platform and Avadis NGS software.
Results: Transcriptional intratumoral heterogeneity, defined as biopsies from the same individual being classified into different
subtypes, was identified in 40% of cases. Variability in MGMT promoter methylation status was found in 14% of cases.
Intratumoral variation in the expression of the MMR and BER genes was identified in 15-30% of cases. Targeted next generation
sequencing of these genes identified intratumoral heterogeneity in 100% of cases. Eight novel predicted deleterious mutations
were identified that may contribute to therapeutic response. Of note, predicted deleterious mutations in the MMR gene MSH6
mutations were identified in all patients, independent of MGMT methylation status.
Discussion: Our results demonstrate intratumoral heterogeneity at the epigenetic level through MGMT status, the gene
expression level, and the DNA mutational level through sequence variation. The identified intratumoral heterogeneity highlights
the importance of taking multiple biopsies from the same tumour in order to correctly classify patients. This intratumoral
heterogeneity may be the reason for variations in treatment response and thus should be considered thoroughly when analysing
tumours to stratify patients. Caution must be taken when interpreting the results of a genomic biomarker from a single biopsy
specimen.
The Evidence of Anti-IgD mAb as a Novel Treatment for Autoimmune and Inflammatory Conditions - From an Unconventional
Perspective
1
1
Tommie Nguyen , Jonathan Morris
Background: Membrane IgD (mIgD) is expressed as a major component of B-cell receptor (BCR) complexes on maturing B cells.
Its wider role in the immune system has been enigmatic. Stimulation of B cells with an anti-IgD monoclonal antibody (mAb) can
activate B-cell and T-cell immune responses in vitro and in vivo. Given the role of B cells and T cells in autoimmune diseases, the
potential effects of anti-IgD mAb on autoimmune diseases and inflammatory conditions are intriguing and need to be
investigated.
Aim: Our study aimed to examine the effects of anti-IgD mAb treatment on autoimmune and inflammatory conditions in animal
models.
Methods: Collagen-induced arthritis (CIA) and chronic contact hypersensitivity (CHS) mouse models, animal models of human
autoimmune diseases and chronic allergic inflammatory conditions respectively, were used to investigate the effects of anti-IgD
mAb on the course of clinical diseases in vivo. Systematic reviews of available published literature were also performed to
highlight the corroborative evidence of our scientific findings.
Results: Therapeutic treatment with anti-IgD mAb at the onset of early clinical symptoms significantly ameliorates clinical
diseases and overt inflammations in both CIA (B cell-dependent diseases) and CHS (T cell-mediated conditions) mouse models.
Anti-IgD mAb treatment selectively depletes mature B cells while it augments regulatory B-cell and T-cell subsets in vivo. AntiIgD mAb treatment significantly reduces of autoantibody productions but does not affect vaccine antibody responses to foreign
antigens. Systematic review of recently published studies highlights the compelling evidence of pathological involvement of IgD+
mature B cells that are activated and expanded in human autoimmune and chronic inflammatory diseases, supporting the
rationale of targeting them for depletion as a novel treatment for human conditions.
Conclusion: Our research demonstrated the therapeutic potentials of anti-IgD mAb technology which represents as a more
specific and selective method of B-cell depletion and immune-modulation that promotes immune tolerance and antiinflammatory tendencies to treat human autoimmune and inflammatory conditions without compromising the host’s general
immune responses.
Disclosure: TN and JM both declare commercial interests and are named as inventors on granted patents related to anti-IgD
mAb.
Characterisation of the DBA/2J-mated CBA/CaH Female Murine Model of IUGR and Perinatal Mortality
1
1
1
1,2
1
Kelly J McKelvey , Vanessa Yenson , Anthony W Ashton , Jonathan M Morris , Sharon A McCracken
1 Division of Perinatal Medicine, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St
2 Department of Obstetrics and Gynaecology, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of
Background: Intrauterine growth restriction (IUGR) affects 14-20 million pregnancies each year and is the second leading cause
of perinatal mortality worldwide. However, there remains a paucity of clinically available therapeutic interventions. This is in
part due to a relative absence of robust animal models which mimic human disease for the evaluation of new therapeutics.
Aim: To characterise the CBA/J x CBA/CaH murine model of IUGR and perinatal mortality.
Methods: Twelve-week old CBA/CaH virgin females were mated with DBA/2J (high mortality), Balb/c (low mortality) and
CBA/CaH male mice (physiological control) in 4-6 independent experiments of 5 mice per mating group. Pregnant females were
sacrificed mid-gestation (14.5 days post coitum, dpc) and at term (18.5 dpc), and fetuses and placentae excised. Pregnancy
outcomes, fetal growth and placental pathology and maternal immunology were assessed by weight, measurement, histological,
immunohistochemistry and flow cytometry respectively.
Results: DBA/2J-mated pregnant females had significantly higher perinatal mortality (p=0.0063), smaller fetuses (crown-rump
length; p<0.0001), and greater prevalence of IUGR (<10th percentile; 47% vs 10%) than Balb/c-mated females. High perinatal
mortality in all mating groups was associated with an increase in maternal Th1 (CD4+/Tbet+) and reduced Th2 (CD4+/GATA3+)
cells in uterine-draining lymph nodes.
Placentae from IUGR fetuses from all mating groups were significantly smaller (dimensions and weight; both p<0.0001) and
showed abnormal placental morphology including thrombosis and fibrosis, when compared to normal-weight fetuses (>10th
percentile).
Despite bearing normal-weight fetuses, placentae from DBA/2J-mated females were significantly smaller (diameter and crosssectional area; p<0.0001 and p=0.0006 respectively) with a greater proportion of labyrinth area, the primary site of maternalfetal nutrient transport (p=0.0128) when compared to placentae of Balb/c matings. Placental efficiency and glycogen-storage
were not different, instead placental inflammatory infiltrate was a distinguishing factor, with an 11-fold increase in F4/80+
macrophages and 1.5-fold reduction in CD3+ T-lymphocytes in the DBA/2J-mated placenta (CD3+: 83% CD4+ and 17% CD8+).
Conclusion: Using clinically relevant measures and definitions, our data show that the DBA/2J-mated CBA/CaH female is a
mouse model of IUGR and perinatal mortality and demonstrates pathology consistent with human IUGR. Therein, this is a viable
animal model to study new therapeutic agents to prevent IUGR and perinatal mortality.
Genome-wide and Targeted Analysis of DNA Methylation in Disease Discordant MND/FTD Cohorts
1
2
1
2
2
1
1
Kelly L Williams , Beben Benyamin , Emily P McCann , Anjali Henders , Sonia Shah , Dominic B Rowe , Garth A Nicholson ,
2
1
Naomi Wray , Ian P Blair
1 Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, NSW, Australia
2 Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia
Background: Motor neuron disease (MND) is a late-onset fatal disorder characterised by progressive degeneration of upper and
lower motor neurons. Mutations in just two genes, C9ORF72 and SOD1, account for more than half of Australian hereditary
MND cases. Substantial variation is seen in age of onset and progression of disease, including among patients with identical gene
mutations. Comorbidity with frontotemporal dementia (FTD) is frequently observed, especially in patients with the C9ORF72
repeat expansion. The absence of a clear genotype-phenotype correlation provides strong evidence for the role of highly
penetrant modifying factors, including epigenetic changes, in disease onset and progression.
Aim: To identify phenotypic modifiers of disease using DNA methylation data from our mutation-known Australian familial MND
cohort, including families with substantial disease discordance.
Methods: We are examining both genome-wide and gene-specific DNA methylation in a large cohort of MND and/or FTD
families with C9ORF72 repeat expansions or SOD1 missense mutations. The discovery cohort comprises 315 individuals from 84
families, including patients with MND and/or FTD, pre-symptomatic individuals (i.e. carry a disease-causing mutation but
currently unaffected) and controls. gDNA samples have undergone genome-wide methylation quantitation using the Illumina
HumanMethylation450K BeadChip. Custom designed EpiTYPER amplicons determined quantitative methylation of 56 CpG units
in the SOD1 and C9ORF72 CpG islands. Strict QC protocols will be developed for normalisation and analysis of methylation data.
Results: R packages including methylumi, minfi and RnBeads combined with PLINK have being used to develop rigorous threestep QC protocols for the methylation data. QC analysis determined several important covariates including 450K chip ID, chip
position, tissue type, sex and processing laboratory. Initial analysis of normalised methylation data quantitatively characterised
the methylation status of the SOD1 and C9ORF72 CpG islands in their respective sample cohorts. We have observed a
substantially higher level of C9ORF72-CpG island methylation in the single “pure FTD” patient in this cohort. Although global
methylation analysis identified no significant differences between C9ORF72 cases compared to controls, similar genome-wide
-9
analysis identified a highly significant differentially methylated CpG site (p=5x10 ). The CpG cite falls within the promotor region
of a gene encoding an RNA-binding protein. RNA processing dysfunction is one of the two major pathogenic mechanisms
implicated in MND. Identical experiments in the replication cohort (n>150 samples from >20 families, including multiple “pure
FTD” cases) are currently underway.
Conclusion: We are implementing both genome-wide and targeted strategies to investigate epigenetic mechanisms influencing
phenotypic expression of MND. Discovery of epigenetic modifiers will not only provide insight into the phenotypic discordance
observed in MND, but highlight dysfunctional pathways in the disease. If we can identify the factors contributing to disease
duration, we can seek therapies to extend life in these terminally ill patients.
FhHDM-1, a Peptide Secreted by the Helminth Fasciola hepatica, Prevents Autoimmune Diabetes and Reduces Disease
Severity in Multiple Sclerosis in Two Murine Models
1,2
3
1,2
1,2
1,2
1,2
Maria Lund , Judith Greer , Raquel Alvarado , Padraig McCauley Winter , Joyce To , Akane Tanaka , Andrew
1
4
1
1
4
1,2
Hutchinson , Mark Robinson , Ann Simpson , Bronwyn O'Brien , John Dalton , Sheila Donnelly
2 The ithree Institute, University of Technology Sydney, Ultimo, NSW, Australia
3 UQ Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia
4 School of Biological Sciences, Queen's University, Belfast, Northern Ireland
Populations in which helminth parasite infections are endemic exhibit a lower incidence of autoimmune and inflammatory
diseases, such as Type 1 Diabetes (T1D) and Multiple Sclerosis (MS), as compared to nations in which these infections have been
largely eradicated. This observation has been largely attributed to the ability of helminth parasites to tightly regulate
mammalian immune responses, specifically by suppressing the development of a pro-inflammatory immune response (which
mediates autoimmunity), whilst initiating and maintaining an anti-inflammatory/regulatory immune response. Harnessing the
immune modulatory ability of helminth parasites (and their excretory/secretory molecules) opens an exciting avenue for the
therapy of autoimmune/inflammatory disorders. We have shown that delivery of the excretory/secretory molecules from the
helminth parasite Fasciola hepatica (termed FhES), prevented the development of autoimmune diabetes in nonobese diabetic
(NOD) mice, a clinically relevant model of human T1D.
Here, we show that a single peptide within FhES, which we have named F. hepatica helminth defence molecule (FhHDM-1) and
produced synthetically, prevents autoimmunity in two murine disease models. Intraperitoneal delivery of only 6 doses of
FhHDM-1 to NOD mice significantly reduced the incidence of autoimmune diabetes. In a murine model of human MS,
experimental autoimmune encephalomyelitis (EAE), intravenous delivery of FhHDM-1 significantly delayed the onset, and
ameliorated clinical symptoms of disease. Critically, protection from disease was neither associated with altered T-cell
responses, nor was it attributable to global immune suppression. In vivo and in vitro cellular binding studies showed that
FhHDM-1 bound preferentially to macrophages, of both murine and human origin. This binding prevented macrophages from
eliciting pro-inflammatory immune responses after challenge with lipopolysaccharide (LPS). Pro-inflammatory macrophages are
central to the development of autoimmunity in both T1D and MS, and other autoimmune diseases. These data suggest that
FhHDM-1 specifically modulates macrophage function to prevent autoimmune disease, making FhHDM-1 an attractive
candidate for clinical translation.
WEDNESDAY 25th NOVEMBER 2015
JOHN HAMBLEY, DOUGLAS PIPER, AND MACQUARIE PRIZE SESSION (Honours, MSc, 1st year PhD)
Novel Drug Treatments in Mild Traumatic Brain Injury
1
1
1
1
1
1
1,2
1
Claire Linnane , Hui Chen , Yilin Mao , Yik Lung Chan , George Herok , Tara Nguyen , Sonia Saad , Cathy Gorrie
Background: The world health organisation has predicted that by the year 2020, traumatic brain injury (TBI) will be the third
leading cause of death and disability across all age groups. Mild TBI has been linked to persistent cognitive and motor sensory
impairment and it is also believed to account for 70-90% of all hospital-treated TBI, yet currently there is no definitive treatment
for this severity of injury.
Aims: Oxidative stress and mitochondrial dysfunction and have been identified as major factors in other neurological injury, such
as stroke. This study aims to investigate the impact of neuro-protective drug Exendin-4 (Exd-4) and antioxidant L-Carnitine (LC),
in reducing lesion size and improving functional outcomes in rats with a mild TBI in the short and long term. It also aims to
determine if improved neurological outcome is attributable to reduced brain oxidative stress and/or improved mitochondrial
function.
Methods: A mild cortical contusion was induced with the New York University weight-drop impactor (10g, 5cm height, 2.5mm
diameter impact head) targeting the somatosensory region of the right cortex. Adult female Sprague-Dawley rats (n=48) were
divided into four groups; sham (n=12), TBI-only (n=12), TBI+LC (n=12), TBI+Exd-4 (n=12). The rats were harvested at 24-hours
and six-weeks post-surgery. The rats underwent behavioural testing at 24 hours and then weekly. Rats were tested for sensory
receptiveness with a sticky-tape test, motor function with the error ladder test, short-term memory with the novel-objectrecognition test, and anxiety with the elevated plus maze. Brain tissue was analysed with western blotting for the protein
expression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD), mitochondrial import receptor subunit
TOM20 homolog, and oxidative phosphorylation (OXPHOS) complexes. Brain sections were stained with haematoxylin and eosin
(H&E) and immunohistochemistry (IHC) for astrocytes, neurons, progenitor cells, and activated microglia/ macrophages.
Results: At 24 hours post-injury, sensorimotor deficits were noted in the TBI-only rats and this was improved in both treatment
groups. The error ladder test found improved motor function in both treatment groups compared to the TBI-only group. In the
elevated plus maze test, the rat of TBI+LC and TBI+Exd-4 were found to become more relaxed over the time. There were
significant differences in the gross anatomy of the brain surface at 24-hours and 6-weeks post-injury. While the 24-hour TBI-only
brains showed a contusion at the site of impact and enlarged blood vessels in the surrounding tissue, the 6-week TBI-only brains
showed large cavities at the site of impact. IHC showed signs of reactive astrogliosis, proliferation of progenitor cells, and
activated microglia/ macrophages at 6 weeks. There were significant changes in mitochondrial markers (TOM20 and OXPHOS
complex I) between the sham and TBI-only rats at both 24-hour and the 6 weeks, but not in MnSOD or the other OXPHOS
complexes.
Conclusions: Both LC and Exd-4 treatment seem to have some improvement on the functional outcome of the TBI rats in the
short term.
Investigating the Effects of Manuka Honey on Bacterial Growth Using Model Organism Pseudomonas aeruginosa
1
2
1
Daniel Bouzo , Karl A Hassan , Elizabeth J Harry
1 ithree Institute, University of Technology Sydney, Ultimo, NSW, Australia
2 Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW, Australia
Background: Antibiotic resistance has been described as an ‘apocalyptic’ threat to human health (WHO, 2014). As resistance to
antibiotics is common soon after they are introduced to clinical use, there is little investment in their development (Shaban et al,
2013). Consequently, there is increasing interest in natural products as alternative sources of antimicrobials. Honey has been
used as a topical wound treatment throughout history, primarily due to its antimicrobial activity (Zumla & Lulat, 1989; Molan &
Betts, 2004). Honeys derived from different nectar sources exhibit vastly different levels of activity, and manuka honey (from
Leptospermum scoparium trees) has broad-spectrum antimicrobial activity (Molan & Russell, 1988). Manuka honey is effective
against antibiotic resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA) and ciprofloxacin-resistant
Pseudomonas aeruginosa (Blair et al, 2009). However, manuka honey remains underutilised in the clinic largely due to a lack of
understanding surrounding its mechanism of action (Jull et al, 2015).
Aims: 1. Investigate the effects of whole manuka honey and its components on the growth of the common wound pathogen, P.
aeruginosa.
2. Develop a holistic transcriptomic approach investigating the mechanisms of action of manuka honey against this organism.
Methods: A microdilution technique was used to determine the minimum inhibitory (MIC) and bactericidal (MBC)
concentrations of manuka honey, key manuka components (including methyglyoxal (MGO)) and an artificial honey control (with
similar osmotic properties to natural honey) against P. aeruginosa. Growth curve experiments were conducted to determine the
lowest concentration of manuka (and its components) that affected bacterial growth rate. A pilot qPCR analysis of cells treated
with a sub-inhibitory concentration of honey at mid-exponential phase was carried out to attempt to identify up- or downregulation of genes there were determined to be potential targets of manuka honey.
Results: The MIC and MBC of manuka honey against P. aeruginosa were 10% and 12% (w/v), respectively, significantly lower
than the MICs for artificial honey and artificial honey with added MGO (30% and 25%, respectively). The MBCs for artificial
honey ±MGO were greater than the highest concentration tested (30%).
The lowest concentration of honey required to induce changes in the growth rate of P. aeruginosa in mid-exponential phase was
between 3 – 4 %. This concentration was used in subsequent qPCR experiments, for which 51 genes were identified as possible
targets. qPCR pilot runs are being undertaken at this time.
Conclusions: This research provided insights into the impacts of whole manuka honey and its major components on P.
aeruginosa growth. It also sheds light on the contribution of manuka constituents to the antimicrobial activity of this honey,
showing that whole manuka honey is significantly more effective than the osmotic activity or presence of MGO can account
for. Over 50 genes were identified as possible targets for manuka honey, and the development of a method to investigate the
mechanisms of action using a transcriptomic approach with RNA-Seq has commenced. This will further elucidate the mechanism
of action of manuka honey, providing clinicians with the evidence they need to confidently exploit the broad-spectrum
antimicrobial activity of manuka honey.
Role of the TXA2 Receptor in the Development and Host Response to Melanoma
1,2
2
2
1
1
2
Yunjia (Carmen) Zhang , Michelle Koekemoer , Kelly McKelvey , Narelle Woodland , Najah Nassif , Sharon McCracken , Katie
2
2
L Powell , Anthony W Ashton
Background: Australia has the highest incidence and mortality of malignant melanoma worldwide. While targeted therapies are
available, such as vemurafenib and dabrafenib, many patients develop recurrent disease. Recent evidence shows that
thromboxane A2 (TXA2) signalling is involved in the development of prostate, breast, and lung cancer. However, its role in
melanoma is unknown.
Aims: (i) To document thromboxane receptor (TP) isoform (TPa and TPb) expression in melanoma, (ii) to identify the mechanism
by which TXA2 signalling drives melanoma development, and (iii) to determine the direct (tumour) or indirect (host) roles for
TXA2 signalling in melanoma growth.
Methods: TP, expression in normal human melanocytes, melanoma cell lines and engineered murine melanoma B16-F10 cells
was assessed by PCR and immunoblotting. Effects of stable knock down of TXA 2 synthase (TXA2S (KD)) on B16-F10 proliferation
was quantified by cell counting (using the typan blue exclusion method) and cell migration by chemokinetic assays. Biochemical
analysis of pathways regulating proliferation and migration were examined by immunolotting. Subcutaneous growth of B16-F10
murine melanomas cells or TXA2S KD in WT (C57/Bl6) mouse, TP knock out (TP-(KO)), TXA2 synthase knock out (TXA2S (KO)) mice,
and chimeric mice (irradiated and reconstituted with WT or TP-KO bone marrow cells (BM)). Tumour weights, necrosis,
proliferation (pCNA) and vascularisation (CD31) were examined by histology and immunohistochemistry.
Results: TP expression was higher in melanoma cells compared to normal melanocytes. TPα was detected in melanoma cell lines
may be indicating that amplification of TPα was driver neoplastic transformation in these cells. TXA2S (KD) reduced tumour cell
migration at 48 hrs (p<0.01) compared to B16-F10 cells transfected with empty vector. Knock down of TXA2S suppressed
proliferation at 24, 48 and 72 hrs (p<0.001) and was associated with G1/S phase arrest, with decreased cyclin A and phospho-Rb
levels. In WT (C57/Bl6) weight and necrotic area of tumours formed by TXA2S (KD) B16-F10 cells were decreased by 60% (p<0.01)
and 4-fold (p<0.05), respectively compared to empty vector alone. By comparison deletion of TXA 2S in the host (TXA2 S (KO)
mice) resulted in tumours derived from B16-F10 cells showing reduced necrosis (10-fold less, p<0.05), but increased
proliferation (pCNA+, 1.5 fold; p<0.05) and neovascularisation (CD31+, 2 fold; p<0.05) compared to WT (C57/Bl6) mice were
observed. Abrogation of TXA2 (KO) mice response to tumour reduced tumour growth by 75% compared to WT mice and
associated with complete loss of vasculature. Comparison of tumour growth from B16-F10 cells in chimeric mice, determined
WT
TP KO
TP KO
host TP played a more significant role in regulating vasculogenesis (BM -Mouse
) than angiogenesis (BM
Wt
WT
TP KO
WT
WT
Mouse ). Moreover, tumours derived from BM -Mouse
had reduced proliferation (pCNA+) compared to BM -Mouse .
Conclusion: TXA2S signalling is important for melanoma cell proliferation and TP expression by mesenchymal cells and promotes
tumour growth. TXA2S signalling is also important for host suppression of tumour development and viability. Inhibition of the
TXA2S signalling pathway in conjunction with chemotherapeutics may be a viable therapeutic strategy for the treatment of
melanoma.
RET-altered Non-coding RNA in Medullary Thyroid Cancer
1,2
3
1,2,4
2,5
6
1,2,6
Jin Suk Lauren Joo , Justin S Gundara , Anthony R Glover , Anthony J Gill , Matti L Gild , Bruce G Robinson , Stanley B
1,2,4
1,2
Sidhu , Jing Ting Zhao
1 Cancer Genetics Laboratory, St Leonards, NSW, Australia
3 Upper Gastrointestinal Surgical Unit, St Leonards, NSW, Australia
4 Endocrine Surgery Unit, The University of Sydney, St Leonards, NSW, Australia
5 Department of Anatomical Pathology, St Leonards, NSW, Australia
6 Department of Endocrinology, Royal North Shore Hospital and The University of Sydney, St Leonards, NSW, Australia
Background: Medullary thyroid carcinoma (MTC) accounts for 5-10% of all thyroid cancers and arises from the parafollicular
cells (C-cells) of the thyroid gland which represent less than 0.1% of the epithelial cell mass. Surgery remains the only effective
treatment for the disease and up to 50% of patients will develop recurrence, thus exposing them to the risks of re-operative
surgery. The human REarranged during Transfection (RET) proto-oncogene is a key driver of MTC tumorigenesis. This has
previously been targeted by tyrosine kinase inhibitors (TKIs) but their efficacy has been modest. Due to these challenges it is
imperative to discover novel therapeutic interventions to control tumour progression. MicroRNAs (miRNAs) are small noncoding RNAs which regulate gene expression through RNA degradation and translational inhibition. Deregulation of miRNAs in
cancer is often associated with the initiation and progression of malignancy and cancer behavior can be modified by targeting
miRNA expression. There is currently limited knowledge of the role of miRNA regulation in RET driven cancers.
Aims: We aimed to identify miRNAs whose expression is altered by the RET proto-oncogene in MTC with the ultimate goal of
establishing systemic miRNA-based treatment as a novel therapeutic regimen.
Methods: Human MTC cells (TT and MZ-CRC cell lines) were transfected with RET siRNA or treated with a TKI, cabozantinib
(XL184) to silence the RET proto-oncogene. RET knockdown was confirmed by Western blotting. An enriched miRNA sample was
prepared using the QIAGEN miRNeasy© kit. Small RNA sequencing with a minimum of 12.5 million reads coverage was
performed by the Australian Genome Research Facility and bioinformatics analysis was employed to identify miRNAs of
potential significance. miRNA/mRNA expression validation was performed using RT-qPCR.
Results: Protein expression of RET, phosphorylated-RET (pRET) as well as phosphorylated-extracellular signal-regulated kinases
(pERK) was significantly reduced by ~70-80% after siRNA or XL184 treatment. Comparisons of miRNA profiles of MTC cells before
and after RET knockdown allowed us to identify a list of significantly differentially expressed miRNAs which will be presented.
Discussion: To date, no study has focused on miRNA expression between normal C-cell and MTC due to lack of normal C-cell
availability. This study overcomes such experimental limitations by silencing the RET proto-oncogene to identify potential
miRNAs involved in the pathogenesis of MTC and RET driven malignancy. To our knowledge, this is the first study identifying
RET-altered miRNAs in MTC. Future functional studies and elucidation of molecular mechanisms of such miRNAs may offer the
potential to identify novel biomarkers and therapeutic targets to improve clinical outcomes.
Comorbidities in Patients with Psoriatic Arthritis (PsA): Analysis from the Australian Rheumatology Association Database
(ARAD)
1,2,3
3
4,5
6
7,8
Premarani Sinnathurai , Alexandra Capon , Rachelle Buchbinder , Vibhasha Chand , Marissa Lassere , Joanna
1,2
1,2,3
Makovey , Lyn March
1 Institute of Bone and Joint Research, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St
2 The University of Sydney, Camperdown, NSW, Australia
3 Department of Rheumatology, Royal North Shore Hospital, St Leonards, NSW, Australia
4 Monash Department of Clinical Epidemiology, Cabrini Hospital, Malvern, VIC, Australia
5 Department of Epidemiology and Preventative Medicine, Monash University, Prahran, VIC, Australia
6 Centre of Cardiovascular Research and Education in Therapeutics, School of Preventative Medicine, Monash University,
Melbourne, VIC, Australia
7 University of New South Wales, Sydney, NSW, Australia
8 Department of Rheumatology, St George Hospital, Kogarah, NSW, Australia
Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis which can lead to significant
joint deformity and disability. Comorbidities may adversely impact physical and mental health in patients with PsA.
Aim: To describe prevalence of comorbidities in patients with psoriatic arthritis in ARAD, and to compare the prevalence of
comorbidities by treatment type and also with patients with rheumatoid arthritis (RA) in ARAD.
Methods: ARAD is a voluntary national registry collecting longitudinal health information from patients with inflammatory
arthritis. Every 6 months, participants complete questionnaires which include demographic information, treatments, medical
history and patient-reported outcome measures such as the Health Assessment Questionnaire (HAQ). Self-reported
malignancies are verified via record linkage with the National Cancer Statistics Clearing House (NSCCH) or via histology report or
th
clinical verification with the treating doctor. Data from baseline questionnaires were extracted from ARAD 4 February, 2015
and analysed using descriptive statistics. Between-group comparisons were carried out using parametric and non-parametric
methods (IBM SPSS Statistics 22). A p values less than or equal to 0.05 were considered statistically significant.
Results: At the time of analysis, 490 participants with PsA had completed baseline surveys in ARAD. 57.8% of participants
reported two or more comorbid conditions and 41.8% reported three or more. Hypertension and depression were the most
commonly reported comorbidities, 38.2% and 35.9% respectively. Features of the metabolic syndrome were prominent with
high cholesterol reported by 25.3% of patients and diabetes mellitus by 14.9%. When compared with patients with RA in ARAD,
patients with PsA had significantly higher rates of depression, high cholesterol and diabetes (p<0.001). In participants with PsA,
119 self-reported cases of malignancy were verifiable by histopathology, cancer registry data or by clinical confirmation. There
were 63 patients (12.9%) with a verified history of malignancy. Non-melanoma skin cancer was by far the most commonly
reported malignancy (73.1%). Infections were also common in this cohort; 263 patients (53.7%) reported at least one infection in
the six-month period preceding the baseline survey. For the reported infections, skin (138, 28.2%), ear, nose and throat (108,
22.0%) and viral (62, 12.7%) were the most common. There were 55 patients (11.2%) who reported at least one severe infection.
There were 313 participants who were taking biologic agents and 177 who were not on a biologic agent at baseline. There was
no significant difference in the number of infections in patients currently taking a biologic compared with those not on a biologic
agent (Mann-Whitney U Test; p=0.6). Furthermore, there was no significant difference between the groups for the distribution
of severe infections (Mann-Whitney U Test; p=0.3).
Conclusions: Comorbidities, history of malignancy and infections are common amongst patients with PsA. These factors need to
be considered in the long-term management of patients with PsA as they may impact treatment choices and complications,
disease progression and quality of life.
Novel Interaction between Succinate Dehydrogenase Subunit B and Assembly Factor 3 Associated with Phaeochromocytoma
and Paraganglioma Syndromes
1,2
1,2
3
4
1
1, 2
5
Edward Kim , Trisha Dwight , Un Na , Ying Zhu , Anne Louise Richardson , Bruce G Robinson , Katherine M Tucker ,
2,6,7
1,2
1,2
3
Anthony J Gill , Dianna E Benn , Roderick J Clifton-Bligh , Dennis R Winge
1 Cancer Genetics, Hormones and Cancer, Kolling Institute, NSLHD and, St Leonards, NSW, Australia
2 Sydney Medical School Northern, The University of Sydney, St Leonards , NSW, Australia
3 Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, United States of America
4 Hunter New England Health, Royal North Shore Hospital, NSLHD, Sydney, NSW, Australia
5 Hereditary Cancer Service, Prince of Wales Hospital, Sydney, NSW, Australia
6 Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia
7 Northern Cancer Translational Research Unit, Royal North Shore Hospital, NSLHD, St Leonards, NSW, Australia
Background: Succinate dehyrogenase (SDH) is a vital mitochondrial enzyme, playing an integral role in both the tricarboxylic
acid cycle and electron transport chain. Although germline mutations in each of the four genes encoding SDH, SDHA-D, are
associated with the development of phaeochromocytomas and paragangliomas (PC/PGLs), an increased risk of malignancy has
been linked with SDHB mutations. Recently, studies involving yeast showed that SDHAF3 assists in the maturation of SDHB.
Aim: Investigate the role of SDHAF3 in the development of PC/PGLs by: (i) determining whether mutations in SDHAF3 are
associated with these tumours; and (ii) assessing whether mutations in either of these genes (SDHAF3 and/or SDHB) impair the
maturation of SDHB, and ultimately function of SDH.
Method: DNA was extracted from 18 PC/PGLs (15 sporadic, 3 familial) and the blood of 37 individuals with germline SDHx
mutation. Massively parallel sequencing was used to screen for mutations in a custom gene panel, containing SDHAF3 as well as
eight known PC/PGL susceptibility genes. GFP-tagged wildtype and disease-associated mutant SDHB constructs, FLAG-tagged
wildtype and mutant SDHAF3 constructs were generated using site directed mutagenesis. Plasmids were transfected into
HEK293 cells. Western blotting of co-immunoprecipitated (Co-IP) proteins were analysed to determine whether interaction
between SDHB and SDHAF3 was hindered by mutation in SDHB ± SDHAF3. Wild type or SDHAF3 variant were introduced into
yeast strains lacking Sdh7 (a yeast ortholog) to assess impact on SDH function. SDH activity assay was also used to dissect
functions affected by SDHB and SDHAF3 mutations.
Results: Massively parallel sequencing identified a SDHAF3 variant occurring in 6.6% of PC/PGLs compared to 2.1% in a normal
population (p=0.0063). Interestingly, the SDHAF3 variant was observed in PC/PGL affected individuals with known germline
SDHB mutation. In silico prediction tools indicated this SDHAF3 variant could be damaging to protein function, hence we
assessed functional consequences in yeast and mammalian cells. Through our analysis in yeast strains lacking SDHAF3 ortholog,
we showed that introduction of the SDHAF3 variant resulted in impaired SDH function. In mammalian cells, we showed that
wildtype SDHAF3 was able to interact with wildtype SDHB using Co-IP. This interaction with wildtype SDHAF3 was impaired
when mutant SDHBs were introduced. Pulling down on product of SDHAF3 variant showed impaired interaction with wild type
SDHB and this was further impaired with SDHB mutants.
Conclusion: Our study shows that a variant in SDHAF3 is more prevalent in individuals with PC/PGLs. Further, we identified a
vital interaction between SDHB and SDHAF3, revealing novel insights into the biogenesis of SDH.
Psychophysical responses in patients receiving a mock laser within context of an acupuncture clinical trial: an
interoceptive perspective
1
1
1
1
Shohreh Razavy , Weihong Li , Christine Berle , Christopher Zaslawski
Background: A variety of sham interventions have been used as placebo controls for acupuncture clinical trials. One such control
is mock laser device that appears operational and seems to deliver a laser dosage to an acupoint. Indeed, such mock lasers have
been used as placebo controls in several acupuncture clinical controlled trials. Result from a recent study indicated that placebo
laser acupuncture might share some of the same nonspecific effects with needle acupuncture.
The psychophysical responses induced by verum acupuncture are characterised by a constellation of unique sensory responses
and in the traditional acupuncture are associated with the concept termed De Qi (Lit: obtaining the energy of Qi). Although the
underlying mechanism of De Qi is partially explained by neuroscience, elicitation of De Qi without any cutaneous sensory input
further suggested that some aspects of De Qi might be a central phenomenon of awareness and consciousness. The patient’s
expectancy of a specific effect was also regarded to be partly based on ‘self-relevant’ introspective information (e.g. thoughts,
memories), and ‘self-referential’ introspection. The anterior insula has been acknowledged as a relay station integrating the
centrally processed sensory information (visceral and autonomic).
Aims: The study aim is to quantify and qualify the psychophysical responses associated with the administration of mock laser
within the context of a randomised clinical trial.
Methods: The study was embedded in a multi-centre, randomised clinical trial, the Tennis Elbow Acupuncture - International
Study - China, Hong Kong, Australia, Italy (TEA IS CHAI). De Qi was measured utilising a validated instrument, the Massachusetts
General Hospital Acupuncture Sensation (MASS) questionnaire on 37 patients in the mock laser (control placebo) group to
assess the effectiveness of acupuncture for lateral epicondylitis. Mock laser was employed at two acupoints LI 10 and LI 11,
consisted of 2 minutes involvement at each acupoints with ten minutes rest between each intervention. Data was collected
immediately following the mock laser at the first and the ninth intervention session.
Results: While no significant difference was found when comparing MASS scores measured at the two time points (p= 0.619),
the scores were slightly higher at the second measurement time. The result suggests that patient’s expectations and conscious
perception of sensations from inside the body that is acknowledged as ‘interoceptive awareness’ may be considered as
important influential factor when measuring De Qi. Among the psychophysical responses recorded ‘Aching’ (1.40%), ‘sharp
pain’ (1.22%), and ‘soreness’ (1.08%) were rated as the three leading intensities respectively among the three study centres. This
was in contrast to the group receiving the verum acupuncture who demonstrated significantly higher MASS scores than the
mock laser (p <0.001) and a different psychophysical response profile; ‘soreness’ (4.5%), ‘fullness/ distension’ (3.7%) and ’aching’
(3.6%) among the four study centres.
Conclusion: The current study has collected and analysed psychophysical responses associated with the administration of the
mock laser intervention. Factors such as expectancy, awareness, focus of attention on the acupuncture points, or general
treatment setting may play a significant role in the elucidation of sensory responses experienced during an acupuncture clinical
trial.
Text Classifiers for Automated Encoding of Surgeries
1
Georgina Kennedy
1 Australian Institute of Health Innovation, Sydney, NSW, Australia
Background: The record of what occurred during a surgical procedure is typically represented in the electronic health record as
a combination of unstructured text blocks (the operative report) with limited associated structured data. Billing codes fail to
account for significant variance in procedures, thus although much of this information is valuable for real-time patient safety
interventions, it is infrequently available for automated analysis
Aim: A review of natural language processing applications in the clinical domain found numerous mature tools; however, none
were specifically designed to target the operative report. The following experiments examine the feasibility of using statistical
text classification to classify operative reports based on their surgical specialty, approach (open or closed) and laterality, and
compare the results to widely available clinical text-mining tools.
Methods: A set of 881 operative reports were collated from a private tertiary care hospital in Sydney. Bag-of-words, bi-gram, trigram and lemmatized term frequency distributions were created. A list of medical suffixes and affixes was collated to create a
clinically tuned stemming algorithm MedStem that is able to stem for clinically relevant matches at either the beginning or the
end of a word.
A Support Vector Machine classifier was chosen as it was expected to be effective in the high-dimensional space of surgical
specialty. A 10-fold cross-validation methodology was followed.
Results: Overall, for well-defined tasks, classifiers outperform existing tools. Whether a surgery is open or closed can be
detected with high precision (0.945) and an f-score of 0.931, compared to the best performing available method, which had an fscore of 0.78.
It is intuitive that the MedStem routine is the most effective for determining whether a procedure is open or closed (f-score
0.931) due to the way that clinical terms are built – laparoscopy, cystoscopy and arthroscopy being grouped together based on
their suffix creates a much more strongly indicative feature than any of these terms individually. Similarly, high performance of
bigram and trigram features for surgical specialty classification makes sense when re- viewing the most informative bigram and
trigram features – many of these contain both an action and a location, which aligns with expected surgical specialty strongly
differentiating features. The task of identifying the laterality of a surgical procedure seems at a surface level to be the most
trivial, however, this is seen to perform the most erratically in practice. This is likely to be due to the low number of meaningful
features which are then overwhelmed with erroneous features in this small sample size. This task is better suited to a heuristic
search method and performs very well without the assistance of a classifier (f-score 0.996).
Conclusion: There is no one-size-fits-all approach to NLP for operative reports. These experiments have demonstrated that for
each encoding sub-task, an individually tuned approach is required, which may be either heuristic or statistical. This is a high
effort and high cost solution, however given the restricted input domain, can be expected to pay off with high accuracy
classification.
51
Defining Naivety: Human Peripheral Blood Naïve T cells as Defined by 13-Parameter Multi-colour Flow Cytometry, Molecular
Analysis and Illumina Sequencing
1
2
1
Nicoleen Gasparillo , Seray Adams , Lisa Sedger
1 Department of Clinical Medicine, Faculty of Medicine & Health Science, Macquarie University, North Ryde, NSW, Australia
2 Department of Biomedical Science, Faculty of Medicine & Health Science, Macquarie University, North Ryde, NSW, Australia
Healthy human peripheral blood contains diverse T cell subsets, each being present at varying frequencies. These include easily
relatively abundant numbers of CD4+CD25++FOXP3+ T regulatory cells, and CD4+RORgt+ IL-17- and IFNg- producing Th17 cells.
Less frequent are CD4+Tbet+ IFNg- producing Th1 cells and CD4+GATA3+ IL-4-producing Th2 cells, unless one is examining blood
from actively recovering individuals e.g. from acute virus infection or with active allergies etc. Also present, however, are newly
produced or recirculating naïve T cells. These cells can be defined by a combination of markers including CD45RA/RO, CD62L,
CCR7, and CD27. Naïve T cells are further categorized by examination of CD31, where CD31+ defines recent thymic emigrants
cells, and CD31- cells are peripherally expanded naïve T cells. Thus, here, we report, a 13-parameter multi-parameter flow
cytometry analysis of human peripheral blood that identifies Th1, Th2, Th17, Treg, as well as T naïve cell subsets. Next, since
naïve T cells are, by definition, recent thymic emigrants, we can confirm our flow cytometry analysis by PCRs detection of TCR
excision circles (TREC) DNA; TREC-lo cells being older naïve peripheral T cells sustained by homeostatic expansion, whereas
TREC-hi cells are the “youngest” of the recent thymic emigrants. Finally, these definitions are confirmed by molecular analysis
(TCR spectratyping) and Illumina sequencing. In summary, since humans are antigen-experienced individuals (unlike antigennaïve SPF mice), these definitions of T naïve cell subsets are of value to many diverse human immunology studies, including
vaccination, transplantation, and/or clinical trials and monitoring in diverse human diseases.
CONCURRENT ABSTRACT SESSION 3.1: NOVEL THERAPEUTICS AND DELIVERY SYSTEMS
Pancreatic Transdifferentiation in the Livers of a Humanised Mouse Engineered to Express Insulin
1
1
2
1
1
1
1
Binhai Ren , Bronwyn A O'Brien , Ian E Alexander , Najah T Nassif , Yi Tan , Rosetta Martiniello-Wilks , Ann M Simpson , Que
1
T La
1 School of Life Science, University of Technology Sydney, Ultimo, NSW, Australia
2 The Children's Hospital at Westmead, Children's Medical Research Institute and The University of Sydney, Westmead, NSW,
Australia
Background: Type I diabetes (TID) results from the T-cell mediated autoimmune destruction of the insulin producing pancreatic
beta (β) cells. Gene therapy is one treatment that is being examined to cure the disease. In earlier studies using an improved
surgical technique that isolates the liver from the circulation, we introduced furin-cleavable human insulin (INS-FUR) to the livers
in several animal models of diabetes. Reversal of diabetes with normal glucose tolerance and pancreatic transdifferentiation of
the liver tissue was seen in streptozotocin (STZ)-diabetic Wistar rats, non-obese spontaneous diabetic mice and
pancreatecomised diabetic pigs using the HMD lentiviral vector to deliver the INS-FUR.
Aims: The aims of the present study were (1) to determine if STZ-diabetes could be reversed in the FRG mouse model in which
chimeric mouse-human livers can be readily established, and (2) to determine if pancreatic transdiffereniation was evident in
both the engrafted human hepatocytes and the mouse hepatocytes.
Methods: Successful engraftment of human hepatocytes was verified by measurement of human albumin levels and diabetes
8
was subsequently induced by injection of streptozotocin to the mice. Following delivery of the INS-FUR vector (3.5x10
transduction units) to overtly diabetic FRG mice (blood glucose >13mM), mice were monitored for changes in body weight and
blood glucose levels.
Results: Reversal of diabetes was seen for a period of 2 months, which was the experimental endpoint. Intraperitoneal glucose
tolerance tests (IPGTTs) of the INS-FUR-transduced animals were not significantly different from nondiabetic, control animals.
Double fluorescent staining for human albumin and insulin was seen in transduced liver samples. RT-PCR showed expression of
human and mouse insulin, glucagon and somatostatin and a number of human and mouse β-cell transcription factors, including
Pdx1, Neurod1, Nkx6.1 and Nkx2.2, indicating pancreatic transdifferentiation of both mouse and human hepatocytes in vivo.
Quantitative RT-PCR of the same samples showed expression to varying degrees of the different mouse and human pancreatic
hormones and β-cell transcription factors, with no definitive trend to indicate which transdiffereniated cell type contributed the
most to diabetes reversal. However, when non-fasting human c-peptide levels (5.61 ± 0.9 pmol/L, n=4) in INS-FUR-treated FRG
mice, were compared to non-fasting mouse c-peptide levels (1.8 ± 0.22), it seems likely that trandiffereniated human cells made
a greater contribution to diabetes reversal. Neither human or mouse c-peptide was detectable in untreated diabetic animals.
Conclusions: We have shown, for the first time that using our technology, human hepatocytes can be induced to undergo
pancreatic transdiffereniation in vivo. These human hepatocytes have likely contributed to the reversal of diabetes seen in the
animals. Our data suggest that this regimen may ultimately be employed clinically to cure TID.
Protein Cargo of Plasma Microparticles Released during Experimental Cerebral Malaria: Source of Biomarkers and Role in
Disease Pathogenesis?
1,2
2
2
2
2
1
Natalia Tiberti , Sharissa Latham , Amy Cohen , Annette Juillard , Georges E Grau , Valéry Combes
1 School of Life Sciences, Faculty of Sciences, University of Technology Sydney, Ultimo, NSW, Australia
2 Vascular Immunology Unit, Department of Pathology, The University of Sydney, Camperdown, NSW, Australia
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This syndrome, affecting mainly children in
sub-Saharan Africa, is responsible for a high number of deaths and long term disabilities. The pathogenesis of CM remains
incompletely understood but a number of mechanisms have been proposed, including the sequestration of parasitized red
blood cells in brain microvessels and an excessive immune response to the presence of the parasite with the subsequent cell
activation and cytokine release. An additional important feature of CM is represented by plasma microparticles (MP), submicron
vesicles released by all cell types that carry proteins and nucleic acids derived from the mother cell. In CM, MP number is
increased in patients’ circulation and, in the mouse model, they can be localised within inflamed vessels, suggesting their
involvement in the vascular damage.
In the present work we define, for the first time, the protein cargo of MP during experimental cerebral malaria (ECM) with the
overarching hypothesis that characterising MP content could help in better understand CM pathogenesis.
MP from infected (ECM) and non-infected (NI) mice were investigated using qualitative and quantitative high-throughput
proteomics. Overall, we identified more than 390 proteins and 47 were significantly differentially expressed after quantitative
comparison using the TMT® isobaric labelling. All proteins over-expressed in ECM (n=41) and those only identified in ECM (n=28)
were analysed using IPA® Ingenuity to evaluate their potential implication in disease pathogenesis. Two important networks
were significantly represented among these proteins: the first was associated with erythrocyte numbers, morphology and
functionality and the second with myeloid cell migration and activation, platelet adhesion and endothelial cell inflammatory
response; all mechanisms already proposed to be involved, to different extents, in CM. To confirm our results, two ECMassociated proteins involved in these networks, carbonic anhydrase I (CA I) and S100A8, were selected for further verification
based on their expression level and their potential interest in CM pathology. CA I (ECM/NI ratio = 2.7) is a protein mainly
expressed in red blood cells were it participates to the maintenance of the acid-basis homeostasis, a process often altered in
severe malaria. S100A8, uniquely identified in ECM samples, is an inflammatory marker expressed by myeloid cells that, in the
extracellular environment, seems to have a cytokine-like pro-inflammatory effects. When assessed by western blot on newly
collected samples (n=16), both proteins were confirmed to be significantly over-expressed in ECM MP (p≤0.001).
Altogether, these results indicate that MP proteins reflect the pathological status of the sample and might be actively involved in
disease pathogenesis. The determination of their cellular source and their downstream effects on the host response might
contribute in revealing new pathophysiological features. Additionally, this approach is currently being translated to paediatric
clinical samples to investigate the cargo of plasma MP as a source of prognostic markers in CM patients.
The Effect of Metformin on Inflammatory and Fibrotic Responses in Renal Tubular Cells
1
1
1
1
Hao Yi , Chunling Huang , Xin-Ming Chen , Carol Pollock
1 Renal Medicine, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, Sydney, NSW,
Australia
Background: Metformin is currently the first-line drug treatment for type 2 diabetes (T2D). In addition to its glucose-lowering
effect, a protective action of metformin against several cardiovascular diseases associated with T2D has been documented. To
date, the role of metformin in renal fibrosis has not been reported. It is well accepted that TGFβ1 plays a central role in various
types of renal fibrosis. The present study aimed to determine whether metformin inhibits TGFβ1-induced inflammatory and
fibrotic responses in renal proximal tubular cells.
Aim: To investigate the potential role of Metformin in renal tubular fibrosis.
Methods: HK-2 cells (human renal proximal tubular cell line) were incubated with TGFβ1 (2ng/ml) in presence or absence of
metformin (0, 1, 2, 4, 8 and 10uM) for 48hrs respectively. The supernatants were collected, total RNAs extracted with RNeasy
kits and cell lysates prepared with RIPA buffer. The renal fibrotic markers collagen IV, fibronectin and PAI-1; inflammatory
marker MCP-1; and TGFβ1 signalling molecules ERK and p38 were examined by real-time PCR and Western blots, respectively.
Results: The data have shown that TGFβ1 significantly upregulated mRNA and protein expressions of fibronectin and collagen Ⅳ
compared to control, which was normalised by metformin (2uM) in HK-2 cells (n=4; P<0.01). The real-time PCR also showed that
TGFβ1-induced mRNA expressions of MCP-1 and PAI-1 compared to control was significantly suppressed by metformin (2uM)
(n=4; P<0.01). Moreover, TGFβ1-increased the phosphorylation of p42/44 and p38 compared to control was reversed by
metformin (2uM) (n=4; P<0.01).
Conclusions: The data demonstrated that metformin attenuates TGFβ1-induced fibrotic and inflammatory responses in HK-2
cells and animal studies to validate the effect of metformin in renal fibrosis are warranted.
Plasma Levels of Endothelial and B cell-derived Microparticles Restored by Fingolimod Treatment in Multiple Sclerosis
1
1
2
1, 3
1
Anna Zinger , Sharissa Latham , Velery Combes , Simon Hawke , Georges Grau
1 Pathology Department, The University of Sydney, Camperdown, NSW, Australia
3 Sydney Neurology, Brain and Mind Research Institute, Camperdown, NSW, Australia
Background: Multiple sclerosis is considered an autoimmune disorder where auto-aggressive T cells target the CNS, causing
inflammation. Whilst a greater number of highly effective treatments are becoming available the long-term efficacy of
treatment remains unknown. There are no molecular markers currently used for monitoring disease activity of Multiple
Sclerosis. Microparticles are subcellular fragments that released to vasculature by cells not only from circulating blood cells, by
also from endothelium, and importantly from brain endothelium. Plasma microparticles characterization can potentially give us
a snap shot of the blood brain barrier activity.
Aims: In the present study we analyzed the profile of plasma microparticles from multiple sclerosis patients and the impact of
fingolimod treatment on it.
Methods: The study population consisted of 15 non-treated, 19 fingolimod-treated patients and 19 healthy donors.
Microparticles were isolated from plasma by high-speed centrifugation and stained with monoclonal antibodies against cell
type-specific markers, then quantified by flow cytometry. The effect of fingolimod on endothelial cells vesiculation was accessed
in vitro by flow cytometry and confocal microscopy.
Results: The total number of microparticles is increased in non-treated patients with multiple sclerosis compared with healthy
controls and patients treated with fingolimod. Specifically, significant increase was found for microparticles derived from
5
endothelial cells in non-treated patients (mean±SE, 5.2±0.87×10 microparticles/ml plasma), compared with healthy donors
5
5
(1.7±0.19×10 microparticles/ml plasma, p<0.01) and fingolimod treated patients (1.4±0.19×10 microparticles/ml plasma,
5
p<0.001) . However, levels of B-cell derived microparticles were significantly decreased in non-treated patients (0.7±0.16×10
5
microparticles/ml plasma) compared with healthy donors and fingolimod treated patients (2.2±0.3×10 microparticles/ml
5
plasma, p<0. 01 and 1.96±0.2×10 microparticles/ml plasma, p<0. 001, respectively). Furthermore, fingolimod treatment
significantly inhibited microparticles production by stimulated endothelial cells in vitro (50ng TNF) by 76% (p<0.05).
Conclusions: Fingolimod restores dysregulated endothelial and B-cell plasma microparticles levels. Considering fingolimod ability
to inhibit vesiculation of endothelial cells in vitro and amend microparticles profile in vivo, microparticles plasma levels could
serve as biomarker of disease activity in future.
LOXL2 Inhibition Reduces Glomerulosclerosis and Albuminuria in a Mouse Model of Diabetic Nephropathy
1
1
1
1
2
1
1
Stefanie Stangenberg , Sonia Saad , May Y Wong , Amgad Zaky , Anthony Gill , Carol A Pollock , Muh Geot Wong
1 Renal Research, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St Leonards, NSW,
Australia
2 Cancer Research & Pathology, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St
Background: The lysyl oxidase family consists of lysyl oxidase (LOX) and four lysyl oxidase-like proteins (LOXL1-LOXL4). They play
a key role in extracellular matrix (ECM) stabilization and are elevated in many fibrotic diseases. LOXL2 in particular has been
implicated in kidney fibrosis, which is an inevitable common pathway of chronic renal failure irrespective of the initial cause.
Aim: To study the renoprotective effect of a selective LOXL2 inhibitor in a mouse model of diabetic nephropathy.
Methods: Diabetes was induced in endothelial nitric oxide synthase (eNOS) knockout mice using streptozotocin. Diabetic mice
were treated with a selective LOXL2 inhibitor (provided by Pharmaxis Ltd) or Telmisartan as comparative limb of current best
practice and outcomes compared to untreated diabetic mice. Urine and kidneys were collected after 24 weeks of treatment and
examined for albuminuria and renal histology. The cortical expression of Fibronectin and Collagen I as well as the inflammatory
markers MCP-1 and F4/80 were examined by real-time PCR and immunohistochemistry.
Results: Diabetic mice had increased urinary albumin/creatinine ratios that were significantly attenuated by the LOXL2 inhibitor
as well as Telmisartan. Glomerulosclerosis was reduced in the LOXL2 inhibitor treated mice to the same extent as in the
Telmisartan treated group with further reduction when both treatments were combined. There was a reduction of Collagen I
and Fibronectin by immunohistochemistry in diabetic mice that had received either LOXL2 inhibitor or Telmisartan. LOXL2
inhibition had no effect on the upregulation of inflammatory markers observed in the diabetic animals.
Conclusion: LOXL2 inhibition had a beneficial effect in preserving glomerular structure and reduced albuminuria in a mouse
model of diabetic nephropathy. Thus, it might be a potential therapeutic target in diabetic nephropathy.
Exploring Phenotypic Changes in Differentiating Adult Stem Cells for use in Regenerative Medicine
1,2
1,2
3
1
2
2
2
Jerran Santos , Krishneel Singh , Innocent Macha , Marcelo Moreno , Shell Whetu , Naomi Koh Belic , Daniel Egan ,
4
4
1
2
Emmanuelle Kergourlay , David Grossin , Matt Padula , Bruce Milthorpe
1 Proteomics Core Facility, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia
2 Advanced Tissue Engineering and Drug Delivery Group, School of Life Sciences, Faculty of Science, University of Technology
Sydney, Ultimo, NSW, Australia
3 Department of Chemistry and Biomaterials Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia
4 CIRIMAT, University of Toulouse (INPT), Toulouse, France
Introduction: Regenerative medicine and stem cell therapies has rapidly come into vogue and remained in the public and
research spotlight for the last decade due to the bountiful applications it promises. A large number of clinical applications now
exist for a wide variety of injuries or disease states, ranging from skin damage in burn victims to degenerative joints in aged
patients and, in a limited capacity, the repair of neuronal tissue. Notwithstanding these advances, there is an insufficiency in the
knowledge base regarding a stem cell’s fate and characterisation of the extent of differentiation. This accumulation of research
presents a broad proteomic investigation of differentiated stem cells derived human adipose tissue.
Materials and Methods: The breadth of this body of work investigated the cellular and secreted proteome changes of
homogenous Adipose Derived Stem Cells (ADSC) cultures directed toward various phenotypic lineages by means of induction
media and/or biomaterials. These differentiated lineages included osteocytes, chondrocytes, myocytes, adipocytes and neuronal
phenotypes. For a marked comparison, primary derived cells from the relevant mature tissue were used as a benchmark
measure for the extent of differentiation in the majority of the differentiation experiments. These comparisons aimed to expand
our current knowledge about the depth of change occurring during each ADSC differentiation with respect to the mature
primary derived cells.
Results: This study focuses on the extent of differentiation in cells in the presence of various inducers, comparing the difference
between chemical and growth factor stimulated differentiations. The proteomic profiles presented a vast array of similarities
and differences dependent on the produced cell type and the final intended cell type. The cell’s proteome indicated that certain
inducers had an overall cellular distress whilst others proved superior; producing a higher population of cells that exhibited
cellular morphological properties as well as a wide variety of functionally and structurally related proteins.
Conclusions: The novel application and findings based differentiation methods lay down the ground work for the development
into a clinical and pharmaceutical application to disease models.
Systemic Delivery of a Connexin43 Mimetic Peptide in Rats Improves Hindlimb Locomotor Function following Spinal Cord
Injury
1
2
1
3
3
3
2
1
Yilin Mao , Ryan Tonkin , Tara Nguyen , Simon O’Carroll , Louise Nicholson , Colin Green , Gila Moalem-Taylor , Cathy Gorrie
1 University of Technology, Sydney, Ultimo, NSW, Australia
2 University of New South Wales, Sydney, NSW, Australia
3 University of Auckland, Auckland, New Zealand
Background: A major challenge in the management of spinal cord injury is the development of an effective treatment that can
be delivered to patients in a timely manner following a traumatic accident. In a rat model of spinal cord injury a mimetic
peptide, Peptide5 (P5), against the gap junction protein connexin43, has been shown previously to reduce tissue damage and
improve functional outcomes when delivered directly to the lesion site.
Aims: In this study we asked whether acute systemic delivery of peptide5 is protective at doses known to block connexin43
hemichannels.
Methods: Intraperitoneal injections of P5 or control scrambled peptide (SP) were given immediately after a mild contusion
injury in rats using the NYU impactor model, with injections repeated at 2 and 4 hours post-injury. Rats were then assessed for
locomotor recovery and euthanised at different post-injury time points.
Results: The preliminary data of open field and error ladder tests showed an improvement in hindlimb locomotor function in P5
treated rats between 3 and 6 weeks following injury (p<0.05). Immunohistochemistry was performed on longitudinal tissue
samples and results showed that P5 treatment reduced Cx43 protein and increased the proportion of phosphorylated Cx43
protein 8 hours after injury compared to SP treatment (p<0.05). At 6 weeks a reduction in lesion size, astrocytes (GFAP) and
activated macrophages/microglia (ED1/Iba1) were seen (p<0.05). In addition, neuronal (NeuN) numbers were higher in the P5
treated animals compared to the SP rats at 6 weeks (p<0.05).
Conclusion: These results suggest that Peptide5, administered systemically to block the pathological opening of connexin43
hemichannels, has a positive effect in ameliorating the damage resulting from spinal cord injury.
Efficacy of Species-Specific Protein Antibiotics In a model of acute Pseudomonas aeruginosa lung infection
1
2
2
2
2
Laura C McCaughey , Neil D Ritchie , Thomas J Evans , Gillian Douce , Daniel Walker
1 ithree Institute, University of Technology Sydney, Ultimo, NSW, Australia
2 Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
Increasing rates of antibiotic resistance, coupled with a lack of new antibiotics for ‘difficult to treat’ pathogens, has resulted in
an urgent need for alternative approaches to antibiotic development. This is particularly true for Gram-negative pathogens, such
as P. aeruginosa and Enterobacteriaceae, which, due to intrinsic, acquired and adaptive resistance mechanisms, are now the
leading cause of hospital-acquired infections. This is exemplified in cystic fibrosis patients where, despite aggressive antibiotic
therapy, chronic lung infection with P. aeruginosa, coupled with the concomitant intense inflammatory response and
progressive loss of lung function, is the major cause of morbidity and mortality in this patient group.
An alternative strategy for antibiotic development is to utilise S-type pyocins. These are highly specific and extremely potent
protein antibiotics (bacteriocins) used by P. aeruginosa for intraspecies competition.
This work demonstrates the potential for the therapeutic application of pyocins. The exceptional potency of pyocins, previously
demonstrated in vitro, translated well to a murine model of acute P. aeruginosa lung infection (as measured by a reduction in
colony forming units) for a range of clinical and environmental isolates. Additionally, the concentration of pyocin required to
afford protection from a lethal P. aeruginosa infection was several orders of magnitude lower than tobramycin, the most widely
used antibiotic against this pathogen. Importantly for a protein therapeutic there was no evidence of inflammation or damage to
lung tissue after a single administration of pyocin and the repeated administration of pyocin, 5-log units in excess of its effective
therapeutic dose, produced only very low levels of pyocin-specific IgG. Additionally, pyocins were able to afford protection
against a lethal P. aeruginosa infection in the presence of these pyocin-specific antibodies.
This is the first study investigating the use of bacteriocins from Gram-negative bacteria as therapeutics in a murine model.
Bacteriocin encoding genes are frequently found in microbial genomes and could offer a ready supply of potent antibiotics
specifically targeted against problematic Gram-negative bacterial pathogens.
The Impact of L-Carnitine on Brain Mitophagy in Male Offspring of Smoking Dams
1
2
3
1
Yik Lung Chan , Sonia Saad , Nicole Jones , Hui Chen
2 Renal Group, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St Leonards, NSW 2065,
Australia
3 Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
Objective: In order to maintain the integrity of mitochondria, mitochondrial specific autophagy, also known as mitophagy,
recycles damaged mitochondria through processes of fusion and fission. Maternal cigarette smoke exposure (SE) during
gestation can lead to lifelong adverse impact on offspring’s brain. Our previous study confirmed that brain mitochondrial
function in adult offspring is compromised by maternal SE due to increased oxidative stress. However, the impact of maternal SE
on brain mitophagy in the offspring is unknown. It is also unclear whether maternal treatment using an antioxidant L-Carnitine
can ameliorate the adverse impact of maternal SE.
Method: Female Balb/c mice were exposed to cigarette (SE) for 6 weeks prior to mating, during pregnancy and lactation with
control mice exposed to air (SHAM). In a sub-cohort of the SE breeders, L-Carnitine (1.5mM) was supplied in the drinking water
during gestation and lactation (SELC). Male pups were sacrificed at postnatal day (P) 1, P20 and 13 weeks. Western blots were
performed to analyse proteins of interest.
Results: At P1, there was a significant increase in light chain (LC) 3A/B-II to LC3A/B-I ratio in the SE offspring, which was reversed
by L-Carnitine. There was an increase in fission proteins (Dynamin-1-like protein (Drp)-1, Fission-1 (Fis)-1, phophatase and tensin
homolog-induced putative kinase (PINK)-1, Parkin-8) and decrease in fusion protein (Optic atrophy 1 (OPA)-1), however without
statistical significance. L-Carnitine significantly increased Drp-1 and reduced Opa-1 and LC3A/B-II to LC3A/B-I ratio. At P20, there
was no difference in the markers among the 3 groups. At 13 weeks, there was a significant decrease in Drp-1, Fis-1 and Opa-1
proteins in the SE offspring. Maternal L-Carnitine supplementation significantly increased brain protein levels of Drp-1, Pink-1
and Opa-1 in the SELC offspring. In contrast, Parkin-8 level was reduced in SELC offspring.
Discussion: Unchanged markers of mitophagy at P20 is consistent with unchanged mitochondrial function reported in our
previous study, which might reflect protective actions of breast milk. However, at 13 weeks, the protection from dams was lost.
Maternal SE decreased mitochondrial fission and fusion in the offspring, whereas L-Carnitine increased these proteins back to
similar levels as SHAMs, possibly a mechanism to recycle damaged mitochondria in the SE offspring. Thus, L-Carnitine might
provide an option for the female smokers during the pregnancy to protect the health of their offspring.
YOUNG INVESTIGATOR PRIZE SESSION (Senior PhD Student)
A Qualitative In-vitro Test for the Detection of Six High-risk Oral Cancer Markers in Human Serum
1
1,2
Samantha Khoury , Nham Tran
1 University of Technolog, Sydney, Ultimo, NSW, Australia
2 The Sydney Head and Neck Cancer Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Introduction: Oral cancer (OC) rates are increasing worldwide. Several studies in the last twenty years have shown that twothirds of patients are diagnosed at stages III and IV and as late stage discovery is directly correlated with increased mortality
rate, this poses a grave public health concern. With a 70% survival rate in patients diagnosed early, compared to a 37% survival
for late diagnosis, immediate early disease detection is critical for the overall survival of OC patients. Currently, there are no
consistently reliable FDA-approved blood-based diagnostic methods for early detection on the market. Recently, small noncoding RNAs such as microRNAs (miRNAs) were shown to be highly stable and could be found in bodily fluids such as serum.
Given this, circulating miRNAs found in the blood of early stage OC patients could act as potential clinical biomarkers for early
detection. At the non-coding RNA group in the Centre for Health Technologies, UTS this urgent need has been addressed with
the development of a qualitative multiplex assay that provides a serum miRNA signature for the early detection of oral cancer.
Aim: To discover novel serum biomarkers for the early detection of oral cancer.
Methods: Using Agilent miRNA microarrays we screened for the expression of circulating miRNAs in patient sera (n=52) and in
sera isolated from normal individuals (n=11). These OC biomarkers were then validated for clinical relevance using a new cohort
of patients (n=259) and healthy (n=84). Prior to this step, all serum samples were screened for haemolysis using the Drabkin
assay. Samples with >5mg/ml Hb were excluded from the final analysis. After this quality control check, an absolute RT-QPCR
was utilized to assess if the expression of these serum miRNAs biomarkers were clinically relevant.
Results: The validation indicated that early stage OC patients presented with a four-fold higher concentration when compared
to age and gender matched healthy controls. It is important to note that in order for the patient to have received a positive
diagnosis; all six biomarkers must be overexpressed in this assay. Furthermore, these serum biomarkers are robust, exhibiting
expression levels independent of hemolysis. Lastly, the data also demonstrated that these biomarkers had a sensitivity and
specificity of approximately 90%.
Discussion: We have delivered a panel of serum miRNAs for the early detection of oral cancer. As these miRNA biomarkers are
serum based, less invasive sample collection techniques can be utilized. This alternate method of diagnosis reduces both the
suffering of, and cost to the patient and caregivers as well as the healthcare system that supports them. Additionally, this 48hour pipeline has been purposefully designed to utilise current technological platforms, allowing sample preparation and
detection to take place in all pathology labs throughout the world. With increasing rates of oral cancers notably in the United
Kingdom, United States of America, India and certain locales in Europe these results would have an international impact on
cancer care and control. The use of miRNA biomarkers would revolutionize OC detection, and improve survival for those with
Oral Cancer.
Post-traumatic Osteoarthritis: The Role of Joint Trauma Versus Instability
1,2
2
2
1
Carina Blaker , Christopher B Little , Sue Smith , Elizabeth Clarke
1 Murray Maxwell Biomechanics Laboratory, Institute of Bone & Joint Research, Kolling Institute, NSLHD and Sydney Medical
School Northern, The University of Sydney, St Leonards, NSW, Australia
2 Raymond Purves Bone & Joint Research Laboratories, Institute of Bone & Joint Research, Kolling Institute, NSLHD and Sydney
Medical School Northern, The University of Sydney, St Leonards, NSW, Australia
Background: Anterior cruciate ligament (ACL) injury/tear significantly increases the risk of developing post-traumaticosteoarthritis (ptOA) of the knee within 10-20 years by ~5-fold compared to non-injured joints. ACL injuries commonly occur in
adolescence, potentially resulting in ptOA by 30-40 years of age and an extended life-time burden of disease. The prevailing
paradigm is that joint instability following ACL injury is the primary driver of ptOA development, and thus reconstructive surgery
is usually recommended. However, up to 50% of younger individuals with ACL injury do not develop OA, and the number
affected is not altered by surgery. Furthermore, while a history of knee injury is associated with incident OA in an older cohort,
loss of ACL integrity is not. This suggests that joint trauma as a whole may play a greater role in ptOA risk than simply the loss of
ACL integrity and altered biomechanics.
Aim: To determine the role of excess loading, joint trauma and instability in the development of ptOA pathology using two
preclinical models of ACL injury.
Methods: ACL injury was induced in C57Bl6 mice through surgical transection (ACLT) or controlled loading of the knee
(mechanically-controlled rupture; MCR). Acute anterior-posterior joint laxity was measured ex vivo (n=6/model), and the
distribution and severity of joint histopathology (cartilage erosion, subchondral bone sclerosis and enthesophyte development)
scored at 2 and 4 weeks post-injury (n=7/model/time). Naïve joints were used as controls.
Results: ACLT and MCR both induced ACL rupture with no acute structural damage to other joint tissues. Both significantly
increased anterior-posterior laxity of the joint (1.95-2.20-fold; p<0.001) but with no difference between models. Despite
equivalent initial injuries and instability, the location, severity and progression of OA pathology differed markedly. Specifically:
cartilage erosion after MCR was always worse in medial versus lateral femoro-tibial compartments (p<0.05) while ACLT was only
compartmentally different in the tibia at 4 weeks (medial>lateral; p<0.05). In MCR medial femoral cartilage erosion was
significantly greater than both ACLT and controls at both time points (p<0.01) whereas ACLT was only greater than controls in
the lateral femur at 4 weeks (p<0.05). Both ACLT and MCR resulted in enthesophyte development, at 4 weeks significantly larger
in MCR than ACLT (p<0.05). Tibial subchondral bone sclerosis was similarly greater in MCR than ACLT (p<0.05 at 2 weeks).
Conclusion: Loss of ACL integrity results in an immediate and similar increase in joint laxity irrespective of the injury mechanism.
However, the rate and severity of OA pathology was vastly different between injury models, being significantly worse when ACL
rupture was caused by and associated with excessive knee loading. This study provides the first in vivo experimental evidence
demonstrating that ptOA development is influenced by more than the acute joint instability. The injury mechanism and
associated trauma to other tissues has a major impact on ptOA susceptibility. Using these models to define specific risk factors
and improve prognostic capability will not only provide new therapeutic strategies but enable better patient stratification and
appropriate treatment selection following joint injury.
Prediction of Osteoporotic Fracture by Genetic Profiling
1
2
2,3
1
1,2
Thao P Ho-Le , Jacqueline R Center , Joln A Eisman , Hung T Nguyen , Tuan V Nguyen
1 Centre for Health Technologies, University of Technology Sydney, Ultimo, NSW, Australia
2 Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
3 School of Medicine, Notre Dame University, Sydney, NSW, Australia
Background and Aim: Osteoporotic fracture, a major health problem among the elderly population, is determined by an
interplay between genetic and environmental factors, including bone mineral density (BMD). Many common genetic variants
have been identified to be associated with BMD, but it is not clear whether these variants have predictive value of fracture risk.
The present study sought to develop a genetic profile for predicting fracture risk in elderly men and women.
Methods: The study was part of the Dubbo Osteoporosis Epidemiology Study, in which bone health of participants over 60 years
old has been monitored continuously since 1990. Fragility fracture was ascertained from X-ray reports. BMD at the femoral neck
was measured by dual-energy X-ray absorptiometry (GE-LUNAR CORP, WI). Seventy one single nucleotide polymorphisms
(SNPs), which were previously shown by GWAS associated with BMD, were genotyped. A polygenic risk score (GRS) was created
by summing the weighted number of minor alleles for each SNP, with the weight being log odds ratio. Three logistic regression
based predictive models were constructed: (1) clinical factors only, (2) clinical factors with GRS, or (3) clinical factors and 71
variants as individual factors. We used the area under the receiver operating characteristic curve (AUC) to assess the degree of
discrimination between fracture and non-fracture, and model performance improvement.
Results: The study involved 80 fracture cases and 532 non-fracture controls. Individuals with a fracture had greater GRS than
those without a fracture (P<0.001). Each score increase in GRS was associated with an odds ratio of 2.07 (95% CI, 1.56 to 2.75) of
fracture. When this score was adjusted with clinical risk factors, the odds ratio did not significantly change, with estimate being
2.01 (95% CI, 1.49 and 2.72). The AUC for the model with age, sex, BMD, prior fracture, and fall was 0.74 (95% CI, 0.68 to 0.81).
When GRS was added to the model, the AUC value was increased to 0.78 (95% CI, 0.72 to 0.83), and the integrated
reclassification index was improved by 6%. When all 71 SNPs were considered together with the clinical risk factors, the AUC
value was 0.84 (0.80 - 0.89), the integrated reclassification index was improved by 25%.
Conclusion: These data indicate that a polygenic risk score constructed from BMD associated genetic variants could improve the
prediction of fracture risk over and above that of clinical risk factors alone. Given the high prevalence of fracture in the general
population, the clinical utility of cumulative genetic risk score can help stratify individuals by fracture status.
9
The Long Noncoding RNA - PRINS as a Novel Recurrence Biomarker and Tumour Suppressor for Adrenocortical Carcinoma.
1,2,3,4
1,2,4
1,2
2,4
1,2
1,2,3,4
Anthony Glover
, Jing Ting Zhao , Lauren Jin Suk Joo , Anthony Gill , Bruce Robinson , Stan Sidhu
1 Cancer Genetics Laboratory, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia
2 Sydney Medical School Northern, Royal North Shore Hospital, The University of Sydney, St Leonards, NSW, Australia
3 University of Sydney Endocrine Surgery Unit, Royal North Shore Hospital, St Leonards, NSW, Australia
4 Sydney Vital Translational Research Unit, Northern Sydney Local Health District, St Leonards, NSW, Australia
Background & Aims: Adrenocortical carcinoma (ACC) has recurrence rates of ~50% and new methods of predicting recurrence
are required to complement existing biomarkers (Ki-67 staining) to tailor adjuvant therapy. We have shown expression of
PRINS, a long noncoding RNA (lncRNA) can predict ACC recurrence, which is the first clinical association of this lncRNA with
outcome in cancer. In keratinocytes where PRINS was discovered, PRINS interacts with the protein nucleophosphmin (NPM)
allowing its translocation from the cytoplasm to the nucleus. In the nucleus NPM binds to TP53 to increase its transcriptional
activity. TP53 mutations are a key driver of ACC. The aim of this study was to establish a biological basis for PRINS as a biomarker
by investigating a tumour suppressor RNA action in ACC.
Method: PRINS expression was quantified in clinical samples using RT-qPCR and Ki-67 staining using immunohistochemistry
(IHC). PRINS expression in ACC cells (NCI-H295R) was restored using the mammalian expression vector containing full length of
PRINS cDNA transcript (pcDNA3.1[PRINS]). Cell phenotypes were compared to cells transfected with an empty vector
(pcDNA3.1[Blank]). Transcriptome analysis was performed on clinical samples of ACC (n=10) and normal adrenal cortex (n=6)
using the ArrayStar Human LncRNA V3.0 microarray.
Results: Using RT-PCR NCI-H295R cells were found to have low expression of PRINS compared to clinical samples of normal
adrenal cortex (Fold change 0.37, P<0.05) and ACC (Fold change 0.51, P<0.05). Transfection with pcDNA3.1[PRINS] lead to
restoration of PRINS expression above that of normal adrenal cortex (P<0.05). In the pcDNA3.1[PRINS] NCI-H295R cells, rates of
apoptosis were increased by 49.8% as assessed by Annexin V assays (P<0.05) and cPARP protein expression compared to
pcDNA3.1[Blank] transfected cells. Reduced cell proliferation of 30-40% was also found using MTS assays (P<0.05) in PRINS
transfected cells. Using RNA FISH, PRINS was localised to the cell cytoplasm. Correlation of ~26,000 mRNA transcripts found
PRINS expression to be correlated with 48 mRNAs (Pearson Correlation Coefficients > 80%, corrected P<0.05), including p53
related genes – TNFRSF11B, MKI-67 and TTK. MKI67 codes for the protein Ki-67 and in clinical samples, PRINS relative
2
expression had a moderate negative linear relationship to Ki-67 IHC scoring (n=14, R =0.38, P=0.02). Following PRINS restoration
in NCI-H295R cells, MKI-67 was unchanged, however TP53 was increased (Fold change 1.5, P<0.001) and TNFRSF11B reduced
(Fold change 0.56,P<0.05) supporting a mechanism of increased apoptosis.
Conclusions: This first report of PRINS acting as a tumour suppressor in cancer supports the association with ACC outcomes. As
PRINS is also under-expressed in many other cancers (including breast, prostate, melanoma and colorectal cancer), these results
support investigation of PRINS as a potential biomarker of recurrence in cancers other than ACC and opportunities for research
into a novel mechanism of TP53 action in cancer.
Gross Motor Performance in Primary School Aged Children Living in High-risk Drinking Communities in Remote Australia – the
Lililwan Project
1,2,3,4,5
4
6
7
1,4
8
Barbara R Lucas
, Jane Latimer , Robyn Doney , Rochelle E Watkins , Tracey W Tsang , Genevieve Hawkes , James P
1, 4, 7
9, 10
11
1,4,12
Fitzpatrick
, June Oscar
, Maureen Carter , Elizabeth J Elliott
1 Discipline of Paediatrics and Child Health, Clinical School, The University of Sydney, The Children's Hospital at Westmead,
Sydney, NSW, Australia
2 Poche Centre for Indigenous Health, Sydney School of Public Health, The University of Sydney, Poche Centre for Indigenous
Health, NSW, Australia
3 Physiotherapy Department, Royal North Shore Hospital, Sydney, NSW, Australia
4 The George Institute for Global Health, Sydney Medical School, The University of Sydney, Poche Centre for Indigenous Health,
NSW, Australia
5 Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, Sydney, NSW, Australia
6 School of Public Health, Curtin University, Perth, WA, Australia
7 Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
8 Derby Allied Health Service, Western Australian Country Health Services, Derby, WA, Australia
9 Marninwarntikura Women’s, Resource Centre, Fitzroy Crossing, WA, Australia
10 University of Notre Dame, Broome Campus, Broome, WA, Australia
11 Nindilingarri, Cultural Health Services, Fitzroy Crossing, WA, Australia
12 The Sydney Children’s Hospital Networks, (Westmead), Sydney, NSW, Australia
Background: A particular strength of Australian Aboriginal communities is the high level of physical activity and sport that occurs
during childhood (Gwynn et al., 2010). The important contribution of sport to physical and emotional wellbeing in Aboriginal
communities is well documented (Safin et al., 2013), however, the gross motor outcomes of children living in remote Australian
Aboriginal communities have not previously been reported. In some Aboriginal communities, child development, including gross
motor performance is compromised by high rates of prenatal alcohol exposure (PAE) (Fitzpatrick et al., 2015). Aboriginal leaders
have been concerned that high risk maternal drinking during pregnancy may have impacted developmental outcomes, physical
skills and future potential. PAE is associated with neurological impairment in multiple domains of function including gross motor
impairment (Lucas et al., 2014; Kyllerman et al., 1985; Roebuck et al., 1998) and therefore the concerns of Aboriginal leaders
may be justified. Our project arose following an invitation from Aboriginal leaders in the Fitzroy Valley to evaluate the impact of
PAE on the community’s children. We aimed to characterise gross motor performance in predominantly Australian Aboriginal
children living in very remote communities where rates of prenatal alcohol exposure (PAE) and fetal alcohol spectrum disorders
(FASD) are high. Gross motor performance was assessed and the relationship between gross motor skills, Fetal Alcohol
Spectrum Disorder and PAE was explored.
TM
Methods: Gross motor performance was assessed using the Q-Global GM Composite of the Bruininks-Oseretsky Test of Motor
Proficiency, Second Edition (BOT-2) Complete Form, in a population of children born in 2002-2003 and living in the Fitzroy
nd
th
Valley, Western Australia. Gross Motor Composite scores ≥2SD (2 percentile) and ≥1SD (16 centile) below the mean were
used respectively to indicate impairment to contribute to a FASD diagnosis and referral for treatment. PAE was categorized using
the Alcohol Use Disorders Identification Test-Consumption test. FASD diagnoses were assigned using modified Canadian
Guidelines and were a subcategory of children with PAE.
Results: A total of 108 children (Aboriginal: 98.1%; male: 52.7%; mean age 8.7 years) were assessed. The mean (SD) Gross Motor
Composite score (47.0 ±8.4) approached the BOT-2 normative mean (50.0±10) but was lower in children with FASD than without
(p=0.006). The mean Gross Motor Composite score was comparable between children with and without PAE (p=0.27).
Prevalence of gross motor impairment at ≥2SD below the mean was 2.8% among all participants, 3.3% in children with PAE,
9.5% in children with FASD, and 0% in children without PAE or FASD.
Conclusions: The prevalence of gross motor impairment in children with FASD was four times higher than children without.
Assessment of gross motor performance should be included in children with FASD to optimise child development through
targeted therapy.
Identification of Novel Gene Mutations causing Amyotrophic Lateral Sclerosis in Australian Families
1
1
1
1
1,2,
1
1
Jennifer A Fifita , Kelly L Williams , Shu Yang , Katharine Y Zhang , Garth A Nicholson , Dominic B Rowe , Ian P Blair
1 Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, NSW, Australia
2 Molecular Medicine Laboratory, Concord Hospital, Sydney, NSW, Australia
Background and Aims: Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease, MND) is a fatal
neurodegenerative disease characterised by the progressive death of motor neurons. Ten percent of cases are familial, with the
remaining 90% considered sporadic. To date, the only known causes of ALS are gene mutations, however known mutations only
account for 60% of familial ALS. We aim to identify the remaining gene mutations that cause ALS. The identification of novel ALS
genes will increase our knowledge of disease biology and provide tools for diagnosis and long-term therapeutic discovery.
Methods and Results: We apply both unbiased and hypothesis driven gene discovery strategies to analyse exome sequence data
from Australian familial ALS cases. We have completed whole exome capture and sequencing of probands from 74 ALS families,
as well as ten individuals from three multigenerational ALS families. Custom bioinformatics analysis of these families has
produced small lists (5, 10, and 18) of novel candidate gene mutations. All variants were prioritised for functional studies based
on factors such as protein predictions, conservation across species and gene function. The top-ranking candidate from Family
One (with five candidate gene mutations) has undergone functional studies to examine its potential pathogenicity, the results of
which have strongly supported a pathogenic role of this mutant protein in vitro.
Our ALS gene discovery strategies also include the identification and analysis of functional candidate genes, as well as mutation
analysis of recently published ALS genes. Our standardised exome sequence data from probands allows rapid interrogation of
candidate genes. This is illustrated by our analysis of MATR3 and TBK1, two recently reported ALS genes, that demonstrate that
mutations in these genes are a rare cause of Australian familial ALS.
The penetrance of mutation-linked disease in familial ALS varies substantially, ranging from classic Mendelian inheritance to
apparently sporadic disease. As such, familial ALS genes were also examined in apparently sporadic ALS cases. Rapid sequencing
of 624 sporadic ALS cases using Fluidigm Access Array and Illumina MySeq sequencing has been completed to identify variation
in known ALS genes, including one novel gene identified by our laboratory.
Discussion: The pathogenic basis of ALS remains poorly understood, and this is reflected in the lack of treatments or a cure for
ALS. The identification of novel ALS genes increases our knowledge of disease biology, and provides tools for the development of
cell and animal models and long-term therapeutic discovery. Furthermore, these discoveries can add to diagnostic regimes in
the clinic. For example, the identification of a gene mutation within MND families allows for pre-implantation genetic diagnosis
and IVF before pregnancy preventing the inheritance of mutations that cause this devastating disease.
CONCURRENT ABSTRACT SESSION 3.2: BRIDGING THE LIFESPAN
Placental Exosomes: A New Mechanism to Improve Intrauterine Growth Restriction
1
1
1
1
1
Gaayathri Ariyakumar , Anthony Ashton , Kelly McKelvey , Jonathan Morris , Sharon McCracken
1 Division of Perinatal Medicine, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St
Introduction: Intrauterine growth Restriction (IUGR) is a leading cause of perinatal death with no proven preventative or
therapeutic strategies. Mechanisms underlying the pathology of IUGR are unknown; however recent evidence implicates a
predominance of pro-inflammatory Th1/Th17 immunity. Our previous research revealed that in normal pregnancy, NF-kB (p65)
is degraded in T-cells and this regulates T-cell responses. We have shown that maternal plasma can induce this suppression and
induce apoptosis in Jurkat T-cells. Despite apoptosis being partially reversed by inhibiting both TRAIL and Fas activation, only Fas
activation suppressed p65 expression, suggesting that Fas signalling underlies the regulation of T-cell responses in pregnancy.
Aims: (i) To determine the particulate source of p65 suppression from maternal plasma. (ii) To identify which subset of T cells
express Fas and whether the expression levels are altered in pregnancy. (iii) To determine whether Fas signalling is perturbed in
pregnancies complicated with IUGR.
Methods: Exosomes derived from non-pregnant or pregnant plasma, were isolated by differential ultracentrifugation and
sucrose gradient. Jurkat T-cells were stimulated with 0.625ug/mL Fas activating antibody (CH11) or FasL+ exosomes overnight
and lysates were subjected to western blotting. Peripheral blood mononuclear cells from non-pregnant and pregnant women
were isolated by Ficoll gradient. NFkB (p65) and Fas expression in T-cell subsets was quantitated using flow cytometry as follows:
Th1 (CD4+/Tbet+), Th2 (CD4+/GATA3+), Th17 (CD4+/RORgt+), Treg (CD4+/FOXP3+), CTL1 (CD8+/Tbet+), CTL2 (CD8+/GATA3+).
Placentae from normal and IUGR were assessed by immunohistochemistry and western blotting for FasL expression.
Results: Specific Fas activation of Jurkat T-cells suppressed both p65 and CD3-zeta expression. FasL+ exosomes isolated from the
particulate fraction of maternal plasma induced p65 suppression which was reversed by inhibiting Fas activation. In normal
pregnancies, the proportion of Fas+ Th1 and Th17 cells was increased relative to non-pregnant controls. FasL+ exosomes in
maternal plasma are derived from both the mother and the placenta. FasL was shown to be expressed in normal placentae and
levels of expression were reduced in placentae from IUGR pregnancies.
Discussion: Our data shows that Fas activation mediates p65 suppression and apoptosis as well as T-cell function by suppressing
CD3-zeta. An increased expression of Fas in Th1/Th17 cells makes these inflammatory cell types more susceptible to FasL
interactions thus controlling their response in pregnancy. Since exosomes in maternal plasma express FasL, Fas/FasL signalling
between maternal T-cells and placentally derived exosomes may induce T-cell apoptosis and regulate maternal T-cell immunity.
Therefore, reduced expression of FasL in the placenta of IUGR may explain the rise in inflammatory responses associated with
IUGR.
Maternal Obesity Suppressed SIRT1 Signalling and Related Autophagy in Offspring’s Kidney at Weaning
1
2
2
1
1
Long T Nguyen , Hui Chen , Yi Lin , Carol Pollock , Sonia Saad
1 Renal Medicine, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St Leonards, NSW,
Australia
Background: Obesity is a global health concern, an independent risk factor of various comorbidities including chronic kidney
diseases (CKD). Strikingly, it has been suggested that the risk is transmissible due to foetal programming. The underlying
mechanisms however are yet to be elucidated. Autophagy is a protective catabolic mechanism targeting damaged or
dysfunctional cellular components, whose dysregulation has been suggested to mediate kidney injuries in diet-induced obesity.
Therefore, we hypothesized that autophagy mediates the link between maternal obesity and kidney disorders in the offspring.
Aims: This study aims to determine how renal autophagy is regulated in the offspring of the obese mothers.
Methods: Female Sprague-Dawley rats (8 weeks old) were fed high fat diet (HFD) or chow for 6 weeks before mating,
throughout gestation and lactation. At weaning (20 days), pups were measured for body and organ mass, blood glucose and
glucose intolerance. The kidneys were collected for quantitative real-time PCR and Western Blot analyses.
Results: Offspring from the HFD-fed mothers (MHF) showed significant increases in body weight (P<0.05), kidney weight
(P<0.05), adiposity (P<0.001), and glucose intolerance (P<0.05). Renal protein expression of the autophagy markers, Beclin-1,
Atg7, Atg12-Atg5, LC3-I and LC3-II were significantly changed by maternal obesity (P<0.05, P<0.05, P<0.001, P<0.001 and P<0.01
respectively). These changes were associated with reduction in SIRT1 (P<0.05), FOXO3a (P<0.01) and PGC-1α (P<0.01),
components of the SIRT1 signalling pathways that have been shown to regulate autophagy and other metabolic stress responses
such as oxidative stress. In this regard, MnSOD as a target antioxidant of the SIRT1-FOXO3a-PGC-1α network was also
significantly downregulated (P<0.01), indicating impaired kidney antioxidant defence in the offspring born to obese mothers.
Conclusion: These results suggest the effects of maternal obesity to impair the autophagy machinery, likely contributing to renal
oxidative stress in the offspring. As this is associated with downregulated SIRT1 signalling, SIRT1 activation therapy could be
effective against the transgenerational risk of maternal obesity-related kidney diseases.
When Young People have a Parent Living with Dementia: A Social Model Perspective
1
1
Karen Hutchinson , Chris Roberts
1 The University of Sydney, Hornsby, NSW, Australia
Background: The social model of disability was originally developed to help our understanding of the cultural, economic and
environmental barriers people face mainly living with a physical impairment (Barned et al, 2011). There has been a growing
amount of research using this model in the mental health sector (Tew et al, 2012; Beresford et al, 2010) but very little utility in
the dementia sector to date from an individual or family member perspective (Gilliard et al, 2005; Hutchinson et al, 2014).
Aim: To explore the benefits of the social model of disability as a theoretical framework to help understand the societal impact
on young people’s lives having a parent with YOD.
Methods: We conducted a thematic analysis on 12 semi structured interviews and 1 focus group with impacted young people
using the social model of disability as a theoretical framework to understand how society adds to their emotional distress and
marginalisation.
Results: Taking a social model of disability perspective highlights young people in these families do face socially constructed
disablement feeling invisible, disengaged and excluded. This disablement itself leads them to being social disadvantaged and
face social barriers to living a life equal to their peers. Many young people experience hurdles to full participation in society
similar to their parent with YOD which is socially unacceptable and this contributes to their emotional distress and feelings of
hopelessness.
Conclusion: We concluded that socially constructed disablement affects all family members impacted by YOD, not just specific
to the individual with an impairment. This disablement is transferred to significant others in families by a society who fails to
adequately support and understand all family member’s needs to maintain full citizenship. This research demonstrates how this
model can be useful for generating ideas on social change and eliminating social barriers supporting a better future.
Hospital Pharmacists’ Perspectives in Optimising Statin Therapy in Older Inpatients
1,2
2,3
2,3
1,2
Angela Wu , Emily Reeve , Sarah Hilmer , Danijela Gnjidic
1 Faculty of Pharmacy, The University of Sydney, Camperdown, NSW, Australia
2 Clinical Pharmacology and Aged Care, Royal North Shore Hospital, NSLHD & Kolling Institute, NSLHD and Sydney Medical
School Northern, The University of Sydney, St Leonards, NSW, Australia
3 Cognitive Decline Partnership Centre, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St
Introduction: Indications for starting statin therapy are guided by established national and international guidelines. However,
there is concern about their appropriate use with significant rates of over- and under-treatment with statins in older patients.
Optimising statin therapy in this patient group may require multi-disciplinary effort, and in an acute care setting, pharmacists
are well-positioned to be involved.
Aims: This study aimed to explore hospital pharmacists’ perspectives in optimising statin therapy in older inpatients.
Methods: An anonymous questionnaire using a five-point Likert scale and open-ended questions was developed and piloted to
capture pharmacists’ attitudes towards their role in optimising statin therapy, compliance of therapy with guidelines, knowledge
of statin-related side effects, and making clinical recommendations. An online questionnaire was advertised and distributed
through the Society of Hospital Pharmacists’ Australia e-newsletter.
Results: In the first two weeks of distribution, 54 practising hospital pharmacists have completed the questionnaire. Ninety-six
percent (95% CI 90.7% - 100.0%) of pharmacists agreed that they have an important role in providing advice to physicians
regarding the initiation, continuation or cessation of statin therapy. However, 38.9% (25.9% - 51.9%) were unsure that older
patients were prescribed statins in accordance with clinical guidelines. In addition, 98.1% (94.4% - 100.0%) agreed that cessation
or deprescribing of statins may be appropriate in some patients, but only 51.9% (37.0% - 64.8%) regularly make
recommendations about deprescribing in older people, and this was not dependent on years of practice (P=0.123). Interestingly,
over 90% (84.6% - 98.1%) identified a need for guidelines for deprescribing statins in older adults.
Discussion: Whilst pharmacists recognise that they have an important role in optimising statin therapy, there is a need for
specific guidelines, particularly in regards to when it is appropriate to continue and deprescribe statins in older people.
Ageing and Drug Induced Liver Injury: Insights from Animal Studies
1,2,3
2,3
1,2,3
4
5
6
3,7
John Mach , Aniko Huizer-Pajkos , Alice Kane , Catriona McKenzie , Sarah Mitchell , Leo Phillips , Brett Jones , Raphael
5
3,8
3,8
1,2,3
de Cabo , Victoria Cogger , David Le Couteur , Sarah Hilmer
1 Laboratory of Ageing and Pharmacology, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of
2 Department of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, NSW, Australia
3 Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia
4 Pathology Department, Royal Prince Alfred, Sydney, NSW, Australia
5 Translational Gerontology Branch, National Institute of Aging, Baltimore, Maryland, United States
6 Mass Spectrometry Imaging and Proteomics Laboratory, Kolling Institute, NSLHD and Sydney Medical School Northern, The
University of Sydney, St Leonards, NSW, Australia
7 Laboratory of Gastroenterology, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St
8 Centre for Education and Research on Ageing and Anzac Research Institute, Concord Hospital, Sydney, NSW, Australia
Background: Historically, older people (≥65 years) were thought to be at increased risk of drug induced liver injury (DILI). This
has not been well established empirically and has serious implications with determining therapeutic dosage. Paracetamol and
isoniazid are taken by older people and cause DILI.
Aim: To investigate the effect of ageing on DILI in male Fischer 344 rats.
Methods: Young and old rats were treated via intraperitoneal injection with toxic regimens of either paracetamol (single dose of
800mg/kg) or isoniazid (4 doses/day: 100, 75, 75, 75mg/kg every 3 hours over 2 days) or vehicle controls. After rats were
euthanised, sera and liver were collected to measure drug and metabolite levels and assessed for toxicity.
Results: Paracetamol treatment resulted in higher serum drug levels in old than in young animals, and elevated serum liver
toxicity markers in young animals (Alanine transaminase (ALT): saline 55±3U/L, paracetamol 109±14U/L and aspartate
transaminase (AST): saline: 112±11U/L, paracetamol: 350±34U/L, p<0.05) but not old. In contrast, hepatic DNA fragmentation
was increased in old animals treated with paracetamol when compared to all other groups (young saline: 100±8%, young
paracetamol: 335±40%, old saline: 158±30%, old paracetamol: 1397±276%, p<0.05). Only minor necrosis was observed with
paracetamol treatment in both age groups. Isoniazid treatment resulted in higher metabolite levels in old than in young animals,
and elevated AST in young animals (vehicle 131±14U/L, isoniazid 200±19U/L, p<0.05), but not in old. Histological assessment
showed a trend towards increased necrosis in young isoniazid treated rats, and an increase in hepatic microvesicular steatosis in
old isoniazid treated rats, compared to corresponding age control groups (p<0.05).
Conclusion: Our animal studies indicate that old age affects the pattern and risk of DILI from paracetamol or isoniazid
differently. Future research is required to translate this in humans to guide dosing and diagnosis of DILI in patients of all ages.
CONCURRENT ABSTRACT SESSION 3.2: IMPROVING HEALTHCARE
Bridging Pragmatic Gaps: Strategies to Inform Feedback on Communicative Practice for Medical Educators and Internationally
Trained Doctors
1
2
3
2
Maria R Dahm , Kathryn Ogden , Lynda Yates , Kim Rooney
1 Centre for Health Systems and Safety Research, Australian Institute of Health Innovation,
3 School of Medicine, University of Tasmania, Launceston, TAS, Australia
4 Department of Linguistics, Macquarie University, North Ryde, NSW, Australia
Background: Australia’s medical workforce relies heavily on internationally trained doctors to meet ever growing demands. In
rural and remote areas up to 50% of doctors were trained outside Australia, with the majority coming from non-English speaking
backgrounds (NESB). Due to cultural and linguistic difference these doctor might struggle to adapt to Australian models of care
and experience communication difficulties in consultations with patients. Available language support is often limited, and
medical educators and supervisors have to address medical and communication issues. This approach risks leaving international
doctors with predominantly generic comments that are clinically focused rather than specifically directed toward improving
their communication skills.
Aims: This interdisciplinary study aims to explore the potential of linguistic, particularly pragmatic, analysis to improve the
communication feedback provided by medical educators to international NESB doctors, and, in turn, to improve the
communicative practices of these doctors.
Methods: We collected five video-recorded encounters between chronic patients and five international NESB doctors, and the
quantitative and qualitative feedback on these performances by medical educators using the Rating Instrument for Clinical
Consulting Skills. The doctor-patient data were transcribed and analysed for the pragmatic strategies, e.g. variability and
appropriateness, focusing how strategies that facilitated timely yet patient-centred elicitation of information, patient
examination and management discussions. Medical educator feedback related communication difficulties was further analysed
and compared with the pragmatic analysis of the doctor-patient interactions.
Results: Clinical educators were able to identify communication difficulties based on their tacit knowledge as native English.
However, they often did not address underlying pragmatic issues nor provided specific guidance on how to improve on these
issues.
Discussion: Interdisciplinary Research is well equipped to bridge linguistic and pragmatic gaps in Educator feedback. Insights
from linguistic experts can provide clinical educators and supervisors with a toolkit to make their tacit language knowledge
explicit. This will allow them to target their communication related feedback because they can draw in tools to identify, explain
and offer remedies for pragmatic communication difficulties experienced by International NESB doctors.
A Systematic Review of Interventions to Deprescribe Benzodiazepines and other Hypnotics among Older People
1,2
2, 3
1,2
4
1,2
Magdalene Ong , Emily Reeve , Angela Wu , Jesse Jansen , Danijela Gnjidic
1 Faculty of Pharmacy, The University of Sydney, Camperdown, NSW, Australia
2 Department of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, NSLHD & Kolling Institute, NSLHD and Sydney
Medical School Northern, The University of Sydney, St Leonards, NSW, Australia
3 Cognitive Decline Partnership Centre, Kolling Institute, NSLHD and Sydney Medical School Northern, The University of Sydney, St
4 School of Public Health, The University of Sydney, Camperdown, NSW, Australia
Introduction: Long-term use of benzodiazepines in older adults is associated with harms including falls, physical and cognitive
impairment. However, there is limited evidence on which interventions are safe and beneficial in withdrawal of benzodiazepines
in older patients.
Aims: To critically evaluate the effectiveness and outcomes of interventions used to reduce benzodiazepine and other hypnotic
use among older people.
Methods. A search was conducted in PubMed, Embase, Informit, International Pharmaceutical Abstracts, Scopus, PsychINFO,
Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL for studies conducted in older adults (≥65 years)
published between January 1995 to July 2015 using relevant key words. Two authors independently reviewed all articles for
eligibility and extracted the data.
Results: Seven studies of benzodiazepine withdrawal were identified. No studies were found which investigated withdrawal of
other hypnotics. The benzodiazepine discontinuation rates ranged from 27% to 35% in studies which trialled patient education
and tapering (n=2), whereas the combination of psychological support and tapering yielded an 80% discontinuation rate at six
months in one study. Three studies trialled pharmacological substitution and one study trialled academic detailing, with
successful discontinuation rates reported between 62-80%. Out of the seven studies, five measured clinical outcomes following
benzodiazepine discontinuation. Most studies observed no difference in withdrawal symptoms or sleep quality, while one study
reported an improvement in sleep quality in those who discontinued benzodiazepine versus those who continued.
Discussion: Current evidence shows that benzodiazepine withdrawal is feasible in the older population, but may vary according
to type of intervention employed. However, as the benefits and sustainability of these interventions are unclear, further studies
should be conducted to explore this.
Breathlessness in Individuals with Chronic Heart Failure and Associated Outcomes
1
1
1
1
1
1
1
Gursharan K Singh , Caleb Ferguson , Sara Lal , Serra E Ivynian , Cleo CJ Crossley , Sally C Inglis , Phillip J Newton
Introduction: Breathlessness is a hallmark symptom in individuals with chronic heart failure (CHF). Research into this symptom is
gaining momentum due to its complex nature and link to hospitalisations in this population. This study aimed to identify the
prevalence and intensity of breathlessness in people with CHF, the predictors of breathlessness and the outcomes at 30 days.
Methods: One hundred and thirty-six inpatient and outpatient individuals with CHF from St Vincent’s Hospital, Sydney
participated in this longitudinal cohort study which began in 2012. Breathlessness was measured using the Edmonton Symptom
Assessment Scale. Multiple logistic regression was undertaken to assess independent predictors of breathlessness. At 30 days,
the participant was contacted by phone to collect information on rehospitalisation and mortality.
Results: The participants were young (59±16 years) and were mostly male (77%). Just over half (52%) were inpatients and the
median length of stay in hospital was ten days. The most common comorbidities in these individuals were hypertension (44%),
myocardial infarction (34%) and lung disease (27%). Eighty-one participants (60%) were classified as breathless at a clinically
significant level (≥4/10). Breathlessness had the highest intensity (4.6±3.1), indicating that participants viewed breathlessness as
the most severe symptom they experienced. Age, depression, anxiety, use of beta-blockers and sleep apnoea were independent
predictors of breathlessness. Results for outcomes at 30 days are yet to follow.
Conclusion: The symptom of breathlessness is common and carries the highest intensity rating among symptoms in individuals
with CHF. Addressing the causes of breathlessness such as anxiety, depression and sleep apnoea can reduce the prevalence of
breathlessness in these individuals. The 30 day follow-up data will inform the deleterious relationship this symptom has with
outcomes, further informing the need for a focus on this symptom in CHF research.
Venous Thromboprophylaxis following Caesarean Section: Current Clinical Practice in Four Tertiary Hospitals in New South
Wales
1
1
2
3
4
4
1,5
Kata Kraljevic , Natasha Nassar , Gemma Blain , Stephanie Lou , Sue Downing , Peta Armstrong , Tanya Nippita , Christine
1
2
3
4
1,5
1,5
Roberts , Jon Hyett , Brian Trudinger , Michael Peek , Jonathan Morris , Sean Seeho
1 Clinical and Population Perinatal Health Research, Kolling Institute, NSLHD and Sydney Medical School Northern, The University
of Sydney, St Leonards, NSW, Australia
2 Central Clinical School, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
3 Western Clinical School, Westmead Hospital, Westmead, NSW, Australia
4 Nepean Clinical School, Nepean Hospital, Kingswood, NSW, Australia
5 Northern Clinical School, Royal North Shore Hospital, St Leonards, NSW, Australia
Background: Venous thromboembolism (VTE) is a significant cause of maternal morbidity and mortality. National and
international guidelines advocate the use of thromboprophylaxis following caesarean section (CS); however, current practice
and the number of women who qualify for guideline-recommended thromboprophylaxis is unknown.
Objectives: To examine current thromboprophylaxis practice after CS in four tertiary hospitals in NSW, and determine the
proportion of women who would qualify for thromboprophylaxis if Royal College of Obstetrics and Gynaecology (RCOG), Society
of Obstetric Medicine of Australia and New Zealand (SOMANZ), or American College of Chest Physician (ACCP) guideline
recommendations were followed.
Methods: A prospective audit was conducted over a three-month period, Oct, 2014-Jan, 2015 at Royal North Shore, Royal Prince
Alfred, Westmead and Nepean hospitals.Data was prospectively collected from medical records using a standard data
abstraction form across all sites and information on maternal demographics, antenatal, medical history and pregnancy
conditions as well as VTE risk factors were collected.
Results: Overall, 1,402 women delivered by CS, of which 1003 (72%) were included in the study. There was wide betweenhospital variation in the proportion of women administered low molecular weight heparin (LMWH) after CS, ranging from 24.2%
to 95.6%. Of all women (574/1003) administered LMWH, 96.9% were prescribed enoxaparin 40 mg daily. LMWH was commonly
recommended for two days (29.5%); three days (30.1%); and four days (20.9%). The proportion of women who had a CS and met
guideline criteria was calculated- eight out of 10 women would receive post-CS LMWH if there were adherence to RCOG
recommendations; six out of 10 women would receive LMWH if SOMANZ recommendations were followed; and only one in four
women would qualify for LMWH if ACCP recommendations were followed.
Conclusions: There is wide variation in clinical practice regarding post-CS thromboprophylaxis between hospitals. A considerable
and larger proportion of women undergoing CS would qualify for LMWH if RCOG and SOMANZ recommendations were adhered
to compared with ACCP guideline recommendations.
Developing a Logic Model to Evaluate Accreditation in Australian Acute Care Hospitals
1
1
Virginia Mumford , David Greenfield
1 Australian Institute of Health Innovation, Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, NSW,
Australia
Background: Health services accreditation programs are designed to strengthen quality and safety improvement efforts through
assessment of compliance with clinical and organisational standards. Australian hospitals have been undergoing accreditation
since 1974, but there has been little evidence that the benefits of accreditation have been clearly articulated, and even less
evidence that the benefits had been assessed relative to the costs of accreditation.
Aims: To use logic model methodology to inform an evaluation of accreditation in acute care. The aim of the model was to set
out a clear visual pathway to make explicit the rationale and expected inputs, activities, outputs, outcomes and impacts of acute
care accreditation.
Methods: We convened a stakeholder meeting comprising health services researchers and key stakeholders from policy,
quality and accreditation bodies from the acute, primary and aged care health domains. We conducted interviews with key
quality, governance and management personnel in six hospitals across four Australian States and Territories.
Results: The input section of the model included items that affect accreditation through external constraints such as state and
federal rules and regulations. The accreditation standards and results from previous accreditation surveys and self-assessments
were included. This is especially pertinent if a survey results in a “recommendation for action”, as subsequent surveyors will be
particularly focused on this area to ensure the recommendations have been implemented and maintained. The activities section
relates to the actions required to meet the standards being surveyed, such as ensuring policies and procedures are updated, and
training and information sessions are held for staff. The outputs of the model are the direct results of accreditation in the form
of scores received for each mandatory criterion surveyed and whether the hospital was granted full accreditation status. The
outcomes of accreditation included process related issues. These are allied with the government indicators of appropriateness
of care such as adherence to clinical pathways and guidelines, in so far that these measure processes of care rather than clinical
outcomes. Examples included adherence to clinical pathways in terms of correct drugs given, measures of patient experience,
and hand hygiene compliance rates. Impacts comprise indicators of effectiveness of care, and include hospital-based indicators
such as mortality rates and hospital acquired infection rates. However, these indicators are often not suitable for direct
comparison across the hospital sector unless risk adjusted to allow for the patient mix and complexity of care across different
hospitals.
Conclusion: A logic model aids in evaluating complex interventions through making explicit the assumptions and aims from the
perspective of the implementation agency and also from a societal perspective that includes the effects on the health system,
patients, and their families. Assessing and understanding the barriers and enablers during the implementation phase creates a
critical feedback loop for continuous improvement. The activities section of the model forms a basis for activity based costing
analysis in an economic evaluation, and the outcomes and impacts of accreditation can be used to identify and quantify the
benefits of accreditation.
POSTER ABSTRACTS
Posters are listed alphabetically by the last name of the presenting author:
EXHIBITOR POSTER
In situ Imaging and Quantitation of CD4+, CD8+ and FOXP3+ T Cells in Squamous Cell Carcinoma FFPE Sections
Kerhan Woo, PerkinElmer
Cancer immunotherapy is rapidly changing the landscape of cancer treatment, and monitoring the immune status of a patient is
a critical aspect of research in this field. One particular area of interest in immuno-oncology is the role of regulatory T cells.
Beginning with the discovery of CD4+/CD25+/FOXP3+ positive cells in 1995, the list of T cell subsets and their function in
tumours and other tissues has grown considerably. While quantifying specific subsets of immune cells is routine using flow
cytometry, monitoring the numbers and distribution of this same subset of immune cells in FFPE biopsies of solid tumours
remains difficult with standard methods.
To address this we present a methodology for staining, imaging and analysing the CD4+/CD25+/FOXP3+ phenotype of regulatory
T cells in head and neck squamous cell carcinoma FFPE specimens.
A sequential multiplex staining technique using tyramide signal amplification conjugated fluorophores with DAPI nuclear
counterstain was utilised. Imaging was performed using a multispectral imaging system, which enabled the quantitative
separation of the fluorophores and elimination of autofluorescence. Image analysis was executed using an automated image
analysis program. Each 20x image underwent a morphologic segmentation into tumour or stromal. The CD4+/CD25+/FOXP3+
phenotype cells were identified and enumerated in the tumour and in the stroma of the sample, therefore providing not just
their cell counts, but also the context of their locations. Results from this study showed that counts of Cytotoxic T cells or Helper
T cells could be automated and measured what percentages were in the tumour as well as their densities.
This study shows the utility of automating the assessment of the various phenotypes of T regulatory cells in FFPE tissue sections.
This methodology can be expanded to 7 or 8 markers across various cell and tissue types, to provide a context-rich images.
DELEGATE POSTERS
Activation of Telomerase Expression by Thyroid Cancer-Associated ETS Factors
Helena M Aberg, Kolling Institute
Maternal L-Carnitine Supplementation Reversed Kidney Underdevelopment and Adulthood Renal Dysfunction in Male Mice
Offspring of Cigarette Smoke Exposed Dams
Ibrahim Al-Odat, UTS and Kolling Institute
The Cathelicidin-like Peptide FhHDM-1, Secreted by Fasciola hepatica, Prevents the Production of IL-1 via Inhibition of
NLRP3 Activation in Macrophages
Raquel Alvarado, ithree Institute, UTS
Cell-wall Defective -lactam-induced Pseudomonas aeruginosa Spheroplasts use Alternative Proliferation Mechanisms
Ibrahi Awadh, ithree Institute, UTS
A Combined Strategy for the Eradication of Pseudomonas aeruginosa Biofilms
Giulia Ballerin, ithree Institute, UTS
The Australian Leishmania Story: Possible Implications for Australian Health
Joel Barratt, ithree Institute, UTS
Integrative Analysis of LincRNA Expression and Clinical Annotation Reveals a Signature of Genes with Prognostic Significance
in Acute Myeloid Leukemia
Dominik Beck, UTS and Prince of Wales Clinical School and Lowry Cancer Centre, UNSW
The Function of the cedA Gene of Uropathogenic Escherichia coli and its Importance to Urinary Tract Infections
Tamkia Blair, UTS
Modulation of the Cerebellum using Theta-Burst Stimulation in People with Cervical Dystonia
Lynley Bradnam, UTS
Rehabilitation of Severe Upper Limb Impairment after Stroke using Bimanual Training to Induce Neuroplasticity:
Neurophysiological Underpinnings for the Design of a Medical Device
Lynley Bradnam, UTS
Transcranial Magnetic Stimulation Reveals Differences in Cortical Neurophysiology between Controls and Chronic Shoulder
Pain Patients and the Effect of a Suprascapular Nerve Block on Brain Function In Patients
Lynley Bradnam, UTS
The Microbiome of Skin and Chronic Wounds in Type II Diabetes
Catherine M Burke, UTS
Development of a Variant Analysis Pipeline for the Identification of Vaccine Candidates for Eukaryotic Pathogenic Organisms
Larissa Calarco, UTS
The Effect of Biomass Smoke Exposure on Rhinovirus Infections in the Progression of COPD
Sarah Capistrano, UTS
HIF1 is Stabilized in the Placenta of Patients with Severe Preeclampsia +/- Intrauterine Growth Restriction through
Abnormal Interactions with von Hippel-Lindau Factor
Tamara Carrodus, UTS and Kolling Institute
The Impact of L-Carnitine on Brain Mitophagy in Male Offspring of Smoking Dams
Yik Lung Chan, UTS
LOX and LOXL2 Inhibitors as a Treatment for Ovarian Cancer
Angela Cho, Kolling Institute and UTS
Colliding Paradigms: Modern Chinese Acupuncture Versus its Classical Roots
Victoria Choi, UTS
Dynamin-Like Proteins in the Gastric Pathogen Helicobacter pylori
Emma M Dawson, ithree Institute, UTS
Equivocation in Surgical Meta-evidence
John Delaney, Sydney Medical School - Northern, The University of Sydney
Characterising the Functional Domains of an E3 Ubiquitin Ligase, MND Candidate Protein
Kimberley A Duncan, Macquarie University
Hematochezia is a Growing and Resource Intensive Clinical Management Problem
Kar Yin Fok, NSLHD (RNSH) and The University of Sydney
Interventional Radiology and Hematochezia: It is all about Pills
Kar Yin Fok, NSLHD (RNSH) and The University of Sydney
Enhancing Surgical Recovery
David Gillat, Macquarie University
Prostate Cancer Research Networks: The Research Trifecta
David Gillat, Macquarie University
Using Animal Models to Study Diabetes and Renal Complications
Sarah Glastras, Kolling Institute and NSLHD (RNSH)
Identification of a Potential Virulence Factor Gene in Dientamoeba fragilis
Rory C Gough, UTS
Determining the Frequency and Involvement of PTEN Pseudogene (PTENP1) Expression in Cancer Cells
Nahal Haddadi, UTS
Elongation Factor Thermo Unstable (Ef-Tu) is Proteolytically Processed and Surface Exposed in Staphylococcus aureus
Kate L Harvey, ithree Institute, UTS
P14ARF-p53-p21: Reprogramming Metabolic Regulation and Function in Breast Cancer
Diana Hatoum, UTS
Sphingosine Kinase 1 (SK1-43kDa) Isoform Expression may Contribute to Cancer Aggressiveness
Diana Hatoum, UTS
Application of Tethered Membranes for the Detection and Screening of Spontaneous Membrane Inserting Proteins Carried by
Exosome Particles
Leonie Herson, UTS
Generation of Novel Zebrafish Models of Motor Neuron Disease using Traditional and Emerging Transgenic Techniques
Alison L Hogan, Macquarie University
Elucidating the Mechanism for Sterol Regulation of Chloride Intracellular Ion Channel Protein Interactions with Lipid
Membranes
Khondker R Hossain, UTS
Blockade of KCa3.1 Attenuated Diabetic Tubulointerstitial Fibrosis through Induction of Autophagy
Chunling Huang, Kolling Institute
Explosive Cell Lysis in Pseudomonas aeruginosa Biofilms
Amelia L Hynen, ithree Institute, UTS
Investigation into the Role of a Novel Genomic Island in Vibrio cholerae
Nathasha D Jayatillelleke, ithree Institute, UTS
Autocrine Ligands Activate the Expression of Immediate Early Response Genes and Late Response Genes at the Time of
Embryonic Genomic Activation in the Mouse 2-cell Embryo
Xingliang Jin, The University of Sydney
YB-1: A Potential Target in Malignant Pleural Mesothelioma
Thomas Johnson, Asbestos Disease Research Institute and UTS
Investigating Blood Glucose Levels and Fatigue in the NSW Police Force: Implications for Metabolic Disorders
David N Kalatzis, UTS
Investigating Cognitive Function in Clinical and Healthy Samples using Electroencephalography and Psychometric Assessment:
A Comparative Study
George Kalatzis, UTS
Paracetamol Hepatotoxicity in Mice: Effect of Age, Frailty, N-acetyl Cysteine and Exposure Type
Alice Kane, Kolling Institute
Leishmania spp. are Endemic to Australia: Isolation and Molecular Characterisation of a Second Australian Leishmania
Parasite
Alexa Kaufer, UTS
The Application of Synthetic Biology for the Detection of Mercury in the Environment
William King, UTS
Neuronal Differentiation and Analysis of Multiple Sclerosis Patient Adipose Derived Stem Cells
Naomi Koh Belic, UTS
Neonatal Intensive Care: A Current Global Perspective of the Role of the Pharmacist
Natalia Krzyzaniak, UTS
Implementing Modern Genome Editing Technologies for Cancer Research
Sergey Kurdyukov, Kolling Institute
Measurement Properties of Tools to Assess Stump Volume in Amputees: A Systematic Review
Li Khim Kwah, UTS
Heart Rate Variability in NSW Teachers: An Exploratory Study Investigating Implications for Cardiac Risks
Sara Lal, UTS
Green Tea Polyphenols Stimulate Osteogenic Processes in Adipose Tissue-Derived Stem Cell Differentiation
Wiliam Lao, UTS
Effect of DNA Methyltransferases on the Reprogramming of Methylation during Early Mouse Embryo Development
Yan Li, The University of Sydney
Tumourigenesis Cascades of wnt Signalling and MAPKinase Interact with TERT in Craniopharyngioma Mutagenesis
Grace Lim, NSLHD (RNSH)
Defining the Relationship between Joint Pathology and Pain in Osteoarthritis using Genetically Modified Mice
Christopher B Little, Kolling Institute
An Optimised Approach for the Isolation of Exosomes using Small Volume of Serum
Jin Lu, UTS
Interventions to Improve Gross Motor Performance in Children with Neurodevelopmental Disorders: A Meta-analysis
Barabara Lucas, NSLHD (RNSH)
Characterisation of Lipoprotein MPN_284, a Potential Adhesin of Mycoplasma pneumonia
Kayla Madonis, UTS
Cognitive Function Associations to Mental States In Nurses
Shamona Maharaj, UTS
Effects of Heel Heights on Muscle-physiological Parameters
Hong Man, UTS
Coordinating Bacterial Cell Division with Nutrient Availability: A Role for Glycolysis
Riti Mann, ithree Institute, UTS
Assessing Mutant p53 in Primary High-grade Serous Ovarian Cancer using Immunohistochemistry and Massively Parallel
Sequencing
Deborah J Marsh, Kolling Institute
Uropathogenic Escherichia coli Genes Promoting Reversible Bacterial Filamentation
Daniel G Mediati, UTS
Paediatric Antimicrobial Stewardship Programs: Driving Standardisation and Improved Clinical Evaluation
Mona Mostaghim, UTS
P14ARF-p53 Plays a Major Role in Mitochondrial Dynamics in Breast Cancer Cells
David Moulder, UTS
Somatic Fumarate Hydratase (fh) Mutation in a Paraganglioma
Cornelia Nellgård, Kolling Institute
The Contribution of Hypothalamic Cellular Stress Response to Appetite and Metabolic Regulation in Offspring of the Obese
Mother
Long T Nguyen, Kolling Institute
The Karora Pathovarience System
Matthew O’Rourke, UTS
Self-medication Among People Living with Hypertension: A Review
Riana Rahmawati, UTS
Evaluation of Commercial Enzyme-Linked Immunosorbent Assays for the Detection of Coxiella Burnetii Specific Phase 2 IgG
Antibodies in Human Serum
Benjamin Sealy, UTS
Adipose Tissue Accumulation is Accompanied with Inflammation and Altered Tryptophan Metabolism in Advanced Cancerrelated Lymphedema
Lisa M Sedger, Macquarie University
Patellofemoral Joint Osteoarthritis (PFJ OA): Incidence, Progression and Pathophysiology in Association with Tibiofemoral OA
in a Mouse Model
David Shbla, UTS
Assessment of Facial Expressions of Emotion Using Optical Flow Analysis
Lina Sidavong, UTS
The Proteomic comparison of Seeded Adult Adipose Derived Stem Cells on Hydroxyapatitie Scaffolds to Investigate
Osteogenic Lineage
Krishneel Singh, UTS
Intensity of Emotional Expression in Asians and Caucasians: An Investigation of Facial Expression as an Indicator of Emotion
for Predicting Anti-Social Behaviour
Elisha Siwan, UTS
Dynamin-like Proteins in the Gastric Pathogen Helicobacter pylori
Nina I Sulkowski, UTS
Loss of BAP1 IHC Expression Occurs Rarely to Never in Pancreatic Ductal Adenocarcinoma
Michael Tayao, UTS
Role of the -Isoform of the Thromboxane A2 Receptor in Breast Cancer
Sandra Tieger, Kolling Institute
Long Non-coding RNAs Harboring miRNA Seed Regions are Enriched in Prostate Cancer Exosomes
Nham Tran, UTS
Relationship between Human Papillomavirus 16 and miRNA Expression in Oropharyngeal Cancer
Nham Tran, UTS
The Unique Co-regulation of the Tumor Suppressor PDCD4 by miR-21 and miR-499
Nham Tran, UTS
Detection of Deception Using Electro-dermal Response Compared with Facial Image Analysis
Andrew Walton, UTS
Multiple Roles for Elongation Factor Tu in Mycoplasma Pneumonia
Michael Widjaja, ithree Institute, UTS
Detecting Delivery of MicroRNA-based Drug
Patrick PW Winata, UTS
Cold-induced Morphological Change of Platelet Concentrates may be Mediated by Alterations in Cytoskeletal Proteins
Ben Wood, Australian Red Cross Blood
UPS Dysfunction as a Common Biomarker in Motor Neuron Disease (MND) Patient Fibroblasts
Shu Yang, Macquarie University
Functional Pipeline for Determining Pathogenicity of Candidate Gene Mutations Causing Motor Neuron Disease
Katharine Y Zhang, Macquarie University
Wound Healing Promoting Effects of a Novel Engineered Activated Protein C
Ruilong Zhao, Kolling Institute
The Effect of Twelve Weeks of Tai Chi Practice on Anxiety in Healthy but Stressed People Compared to Exercise and Wait List
Comparison Groups: A Randomised Controlled Trial
Shuai Zheng, UTS
GENERAL INFORMATION
CONFERENCE LOCATION
Dr Chau Chak Wing Building (Building 8), Ultimo NSW 2007.
Central Station
Broadway
Shopping
Centre
Railway Square
CAR PARKING
Limited car parking is available at UTS for mobility-impaired visitors. Local car parking buildings include:
Wilson Parking Market City
2 Quay Street, Haymarket NSW 2000
24hrs/7days
Phone: 1800 727 5464
Website: www.wilsonparking.com
Broadway Shopping Centre Car Park
Bay Street, Broadway NSW 2007
24hrs/7days
Phone: 02 9911 5635
www.broadway.com/centre-info
BUS
A number of bus routes pass UTS. Major stops are Railway Square or Central Station. See PDF for bus
routes: http://www.sydneybuses.info/uploads/file/pdfs/university-maps/uts-busservices.pdf
TRAIN
T1, T2, T3, and T4 trains stop at Central station. For directions from Central Station to UTS see:
http://www.uts.edu.au/sites/default/files/uts-tag.pdf . From the South Concourse or Railway Square
follow the Goods Line or TAFE signage for direct access to the Dr Chau Chak Wing Building.
SMOKING
Smoking is banned on UTS campus, except for within designated smoking areas. Smoking is specifically
prohibited within 4 metres of a pedestrian access points to a building.
DR CHAU CHAK WING BUILDING FLOOR PLANS
LEVEL 2 (STREET LEVEL)
Entry
Entry
Auditorium
08.02.005
LEVEL 3
Oval Room
08.03.002
Entry
Collaborative
Theatre
08.03.005
08.02.005
 Goods Line pedestrian walkway from Central Station and Railway Square
SPONSOR & EXHIBITOR INFORMATION
GOLD SPONSOR
SPRUSON & FERGUSON
Contact:
Martin O’Brien
Address:
Level 35, 31 Market Street,
Sydney NSW 2000
Tel:
02 9393 0100
Email:
MObrien@spruson.com
Website:
www.spruson.com
EXHIBITORS & OTHER SPONSORS (in alphabetical order)
ACCUGEN SYSTEMS PTY LIMITED
Contact:
Nicola Boulter
Address:
Level 3, 11 Julius Avenue,
North Ryde NSW 2113
Tel:
n/a
Email:
nicolab@accugen.com.au
Website:
www.accugensystems.com.au
BIO-RAD LABORATORIES
Contact:
Raj Najir
Address:
5/446 Victoria Road,
Gladesville NSW 2111
Tel:
02 9914 2800
Email:
raj_nair@bio-rad.com
Website:
www.bio-rad.com
BECKMAN COULTER
Contact:
Sancia Gracias
Address:
23-27 Chaplin Drive,
Lane Cove NSW 2066
Tel:
1800 060 880
Email:
SGRACIAS@beckman.com
Website:
www.beckmancoulter.com
BIOLINE AUST PTY LIMITED
Contact:
Amanda Wernicke
Address:
PO Box 122,
Alexandria NSW 1435
Tel:
1800 454 433
Email:
amanda.wernicke@bioline.com
Website:
www.bioline.com
BIOSCIENTIFIC PTY LIMITED
Contact:
Christine Crossingham
Address:
21 Monroe Street,
Kirrawee NSW 2232
Tel:
02 9521 2177
Email:
christine@biosci.com.au
Website:
www.biosci.com.au
MEDIKANE
Contact:
Address:
Tel:
Email:
Website:
Michael Stovin-Bradford
Unit 2, Level 2,
706 Mowbray Road
Lane Cove NSW 2066
02 9925 4304
mfs@medikane.com.au
www.medikane.com.au
MERCK-MILLIPORE
Contact:
Heather Glazebrook
Address:
Ground Floor, Building 1,
885 Mountain Highway
Bayswater VIC 3153
Tel:
1800 335 571
Email: heather.glazebrook@merckgroup.com
Website:
www.merckmillipore.com
PERKINELMER
Contact:
Kerhan Woo
Address:
3 Massey Street,
Gladesville NSW 2111
Tel:
1800 033 391
Email:
kerhan.woo@perkinelmer.com
Website:
www.perkinelmer.com
PHARMAXIS
Contact:
Dr Wolfgang Jarolimek
Address:
20 Rodborough Road,
Frenchs Forest NSW 2086
Tel:
02 9454 7200
Email: wolfgang.Jarolimek@pharmaxis.com.au
Website:
www.pharmaxis.com.au
POCD SCIENTIFIC
Contact:
John Lee
Address:
14/76 Reserve Road,
Artarmon NSW 2064
Tel:
1800 640 075
Email:
jlee@pocdscientific.com.au
Website:
www.pocdscientific.com.au
ROWE SCIENTIFIC
Contact:
Carl Casella
Address:
11 Challenge Boulevard,
Wangara WA 6065
Tel:
08 9302 1911
Email:
carl.casella@rowe.com.au
Website:
www.rowe.com.au
SAPPHIRE BIOSCIENCE PTY LIMITED
Contact:
Katie Chan
Address:
Unit G1/44-70 Rosehill Street,
Redfern NSW 2016
Tel:
02 9698 2022
Email:
katiec@sapphirebioscience.com
Website:
www.sapphirebioscience.com
SIGMA-ALDRICH AUS & NZ
Contact:
Oliver Distler
Address:
PO Box 970,
Castle Hill NSW 1765
Tel:
1800 800 097
Email:
oliver.distler@sial.com
Website:
www.sigma-aldrich.com
THERMO FISHER SCIENTIFIC
Contact:
Stephanie Georgalas
Address:
5 Carribean Drive,
Scoresby VIC 3168
Tel:
03 9262 3772
Email: stephanie.georgalas@thermofisher.com
Website:
www.thermofisher.com.au
TRENDBIO PTY LIMITED
Contact:
Amarette Petersen
Address:
Unit 9, 72/74 Chifley Drive,
Preston VIC 3072
Tel:
1300 720 574
Email:
amarettep@trendbio.com.au
Website:
www.trendbio.com.au
VWR INTERNATIONAL PTY LIMITED
Contact:
Megan Townsend
Address:
Level 1, Unit 1a,
60 Enterprise Place,
Tingalpa QLD 4173
Tel:
1300 135 123
Email:
megan.townsend@au.vwr.com
Website:
www.au.vwr.com
NOTES
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New Horizons 2015 - NSLHD Home

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