Cardiovascular Research Capacity Program

Over 7 million Australians have musculoskeletal conditions. While drug development has produced biologic therapies that can improve symptoms, these drugs do not cure, there is no clear evidence base for predicting who needs them or will respond, they are expensive, and pose serious side effects. This A3BC is a network of scientists & doctors for improving treatments and outcomes for people living with arthritic and autoimmune conditions and ultimately finding ways to prevent and cure them. We need to study a wide range of health data and samples from a large population to allow the latest computer analyses to answer these important questions.

More information:
https://a3bc.org.au/

The Sydney Catalyst ‘Embedding Research (and Evidence) in Cancer Healthcare – EnRICH’ program is a prospective clinical cohort of 1000 patients with lung cancer, which aims to better define, treat and care for patients in Sydney Catalyst member hospitals, and to provide infrastructure for translational cancer research. The program is capturing diagnostic tumour specimens and serial blood samples for molecular and biomarker studies, with matched demographic, clinical and outcome data (including patient reported outcomes) to answer defined program core research questions, and support further translational research in lung cancer in NSW through linked sub-studies.

More information:
https://www.sydneycatalyst.org.au/

The 45 and Up Study cohort, comprising over 267,000 Australians, offers a unique opportunity to leverage detailed health records spanning 15 years via data linkage, combined with cutting edge genomics data and blood biomarker analysis. We will perform a series of studies to examine the health outcomes and trajectories of individuals from the 45 and Up Study with bipolar disorder, and who have increased rates of many other common medical conditions, to aid both diagnosis and treatment. This research has the potential for development of stratified interventions, tailored treatment and improved prognosis for people living with this severe psychiatric illness.

More information:
https://www.neura.edu.au/

Cystic Fibrosis (CF) is the most common, fatal genetic mutation in the Australian population. It results in defective function of a crucial protein that leads to thick sticky mucus. This builds up in the lungs and other organs, causing recurring infections and eventually premature death. New medications that improve the working of this protein are about to become available. This proposal will collect blood, sputum and tissue from all the CF clinics in NSW, during the introduction of these drugs. Clinical data is already captured on a national data registry the Australian CF data registry. This will then be a powerful tool to better understand disease progression in CF and assess the impact of novel treatments and determine in whom they work best.

More information:
https://www.newcastle.edu.au/research-and-innovation/centre/card/about-us

Stroke is a leading cause of death and disability in Australia. The provision of this grant will establish an Australia-first NSW-wide brain clot bank that would allow improved diagnostic pathways and opportunities for research in stroke patients. Brain clots retrieved after mechanical procedures will be collected as part of the clot bank. The emergence of endovascular thrombectomy (EVT) has significantly improved standards of care and outcomes in ischemic stroke patients and opened doors to critically examine brain clots retrieved after the procedure.

The purpose of the Sydney Sleep Biobank (SSB) is to create a research platform that can support a diverse range of research initiatives to better understand sleep health and its link to chronic diseases, leading to advances in Precision Sleep Medicine. As sleep interacts with a range of other diseases (cardiovascular, metabolic, cancer, neurocognitive), whole blood collection is vital to understanding these interactions and has the potential to make advances across a number of priority health areas. Competitive advantages of the SSB include access to high clinical activity across busy NSW Hospitals with world class clinical sleep programs, unique high-throughput phenotypic tools, establishment of processes for data linkage, and access to state of the art data science capabilities.

We have established a large, well characterized study of patients with biobanked blood +/- tissue and imaging data (BioHEART), to address the question being asked by the increasing number of heart attack patients who are asking “why me”? This grant will support the extension of this from the ~1500 subjects currently recruited under the protocol, to ~7000, and will facilitate the discovery of new mechanisms and markers of both coronary disease susceptibility, as well as resilience using state-of-the artmetabolomics/proteomics/genomics. The resource and the anonymized data will be valuable for a broad range of researchers in NSW and beyond.

A strategic goal of the Australia and New Zealand Gynaecological Oncology clinical trials group, ANZGOG, is to build capacity for translational research by supporting the collection of biospecimens associated with allANZGOG trials. This grant will support collection of biospecimens from NSW Health Pathology (NSWHP) centres, biospecimen processing, storage and dissemination to maximize the use of biospecimens through research. The ability to further interrogate biospecimens associated from clinical trials will add enormous value to the contributions that patients have made by identifying biomarkers associated with good treatment response and those associated with resistance, thereby contributing to implementation of new treatments and design of future trials.

A strategic goal of the Australia and New Zealand Gynaecological Oncology clinical trials group, ANZGOG, is to build capacity for translational research by supporting the collection of biospecimens associated with allANZGOG trials. This grant will support collection of biospecimens from NSW Health Pathology (NSWHP) centres, biospecimen processing, storage and dissemination to maximize the use of biospecimens through research. The ability to further interrogate biospecimens associated from clinical trials will add enormous value to the contributions that patients have made by identifying biomarkers associated with good treatment response and those associated with resistance, thereby contributing to implementation of new treatments and design of future trials.

What happens when we age? The LinkUp study, the collection of biospecimens is an extension of the 45 and Up study, the largest ongoing study of healthy ageing in the Southern Hemisphere aims to gathered information which will give governments the tools to make better decisions about healthcare for people as they age. The Study is also a rich source of information for researchers, with more than 600 of them currently using it in research projects ranging from sleep and physical activity to investigating the causes of early retirement.

More information:
https://www.saxinstitute.org.au/our-work/45-up-study/

The purpose of this project is to develop new therapies to reduce costs associated with deaths and illnesses from large myocardial infarctions (heart attacks) and resulting heart failure. Cardiovascular disease is the largest killer of Australians and heart attacks are a large cause of this. Heart attacks affect an estimated 258.45 people per 100,000 US population (Global Data 2017), and potential for treatment costs are estimated to reach US$1,726.3 million by 2023 (Zion Market Research).

Treatment of heart attack includes immediate measures to salvage the parts of the heart muscle at risk of permanent damage (scarring). Most patients who receive sufficient treatment survive. However, as a result of their heart injury, these patients frequently progress to heart failure. The potential for treatment costs for chronic heart failure in the US is estimated to reach US$12,137 million by 2026.

Our research explores two broad themes to achieve these treatment goals: 1) use of heart muscle grafts derived from stem cells; and 2) changing how the scarring of the heart occurs after a heart attack. My previous training and my group's unique techniques will push these research themes forward. These techniques include: developing a stem cell culturing technique on a clinical scale (billions of cells), and developing the stem cells into heart muscle cells; small animal models (mouse and rat) and large animal models (sheep and pig) of heart attack and heart failure; and new, cutting-edge molecular and imaging analysis.

I am translating our most promising therapeutic methods towards clinical trials so that this research may one day lead to new therapies for patients who have had a heart attack, are in heart failure and who have heart rhythm abnormalities. A patent has already been filed and the University of Sydney is commercialising our methods.

Professor Figtree is a clinician researcher whose integrated program of research extends from fundamental discovery through to clinical trials, interventional cardiology and implementation. She coordinates a team of multi-disciplinary researchers, driven by the increasing number of heart attack patients who are asking “why me”? While it is imperative that we treat established risk factors, this approach “misses” a substantial group of patients who are not identified as “at risk”. Indeed, the proportion of patients presenting with life-threatening heart attacks to Professor Figtree’s hospital with 0 standard modifiable risk factors [SMuRFs] has increased from 13% 10 years ago to ~30% in 2014. Her driving hypothesis is that major residual mechanisms for atherosclerosis can be unravelled by comprehensive molecular characterisation of such “athero-vulnerable” and “athero-resilient” patients.

Professor Figtree has established and continues to expand a suite of biobanks that combine state-of-the-art imaging of the heart with a panel of high-technology “omics” measures and clinical data. Through novel computational bioinformatics approaches she plans to unravel new mechanisms and biomarkers of both coronary artery disease susceptibility and resilience.

Given coronary artery disease kills approximately 3x more Australians than the leading individual cancer, the expanding group with “SMuRFless” coronary artery disease has enormous public health significance. Furthermore, new mechanistic pathways will likely have broad relevance, bringing improved risk stratification and targeted preventative management to all patients at risk of atherosclerosis. She has established a collaboration with Professor Alex Brown to ensure novel markers can be tested for efficacy in the Indigenous population.

Discoveries made during the proposed program of work will guide the design of dedicated trials testing the ability of new markers to guide clinician decision making above and beyond traditional risk factor profiling, with beneficial outcomes on health. Existing intellectual property (USA14/069913), a formal research agreement with NSW Health Pathology and CDA with Abbott Diagnostics highlights Professor Figtree’s commitment to commercialisation and translation. Her position in national and international clinical leadership groups and extensive network of collaborators leading cardiovascular advances and practices will ensure rapid translation and benefit to international patient populations.

In addition to the risk identification and prognostic value of Professor Figtree’s study, her team is well positioned to discover completely novel pathophysiological pathways relevant to atherosclerosis. These will pave the way for testing new therapeutic targets. Her team are well placed to capitalise on such discoveries, with an established pipeline for drug development that progresses from preclinical disease models to humans.

Spontaneous coronary artery dissection (SCAD) is a tear in an artery that supplies blood to the heart. It is a potentially fatal problem that presents as a heart attack or sudden death, affecting relatively young (45-52 years old) women (95% of cases) with few heart disease risk factors, and is, therefore, often overlooked. The underlying defect causing SCAD is entirely unknown, however, our work and that of others suggests that it is most likely due to a gene change that enhances susceptibility to vessel rupture.

Our purpose is to better understand, treat and prevent SCAD by identifying factors that predispose the coronary artery to spontaneous tearing. Our objectives are to investigate the genetics and cell biology, as well as blood pressure and heart function responses, of our familial SCAD survivors versus controls. The proposed research brings together multi-disciplinary, internationally-competitive researchers to dissect the molecular mechanisms underlying SCAD, with the objective of identifying targets for the development of effective preventative and treatment strategies, irrespective of ethnicity. This research will thus be equally effective, impactful and applicable to the health needs of priority populations, such as the Aboriginal and Torres Strait Islander people, individuals from CALD backgrounds and socio-economically disadvantaged groups.

Scientifically, the work will change how the field views SCAD, and will pave the way for others, thus rapidly increasing progress. Technologically, the work is underpinned by powerful, contemporary methodological approaches that will allow deep interrogation of genomics and cardiac biology, as well as the elucidation of innovative approaches to SCAD risk identification and management. The latter has translational and therapeutic significance and has the potential to lead to simple, evidence-based implementable therapies, irrespective of ethnicity. The findings of the study will be disseminated in leading international journals, at major national and international meetings, and through our patient groups, media and social media to increase exposure, awareness and public engagement.

Heart failure is a modern epidemic and carries a similar five-year mortality to many common cancers. We aim to thoroughly understand mechanisms underlying a type of “stiff” heart failure common in diabetics, where the heart doesn’t relax properly. It now accounts for over half of all cases and there is no specific therapy.

However, for the first time, there is promise on the horizon. Recently, three independent clinical trials showed that a new class of type 2 diabetes medication called “SGLT2 inhibitor” improved outcomes for this type of heart failure. We will analyse blood plasma from one of these international clinical trials, the CANVAS study.

These medications raise levels of particular nutrients in the blood that are used by the diabetic heart to provide energy.

Our initial work using human hearts revealed several classes of nutrients that are deprived in heart failure. We will now determine those that are specific to diabetic cardiomyopathy using our diabetic cardiomyopathy clinic, CANVAS trial samples, and mouse and cell models of disease.

Aboriginal Australians are affected disproportionately by this disease. We are collaborating with indigenous researchers in Redfern NSW, and with a leading Australian Aboriginal researcher, Prof Alex Brown, who now has a joint appointment at our Institute, and who will provide plasma samples and relevant imaging and clinical measures.

To determine mechanisms underlying cardiac nutrient changes in this disease, we will use a mouse model established in our lab where the mice develop stiff hearts and the same cardiac nutrient changes as humans. Furthermore, we will use a technique to trace the fate of labelled nutrients in mouse hearts with this disease. Finally, we will deliver candidate nutrients that are depleted in diabetic cardiomyopathy to the mice, and compare effects on heart function with those of SGLT2 inhibitors.

A key aspect of our clinic is patient education. We find that our patients are extremely enthusiastic to join our study, learn more about their disease, and contribute to finding a solution for all. We are launching an awareness campaign to make the public more aware of this condition, which will also help recruit patients. As our project includes pre-clinical work, alongside two clinical cohorts, and has engaged hospital and Local Health District senior administration, we are in a strong position to take forward any potential new therapies into human clinical trials, and to contribute to local policy-making regarding diagnosis and treatment of this condition.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality globally. Our health system is largely still a medicalised and facility (hospital or clinic) based model of care. This model of care is rapidly out-stripping our ability to resource it especially as it is faced by an aging population and the increasing prevalence of complex chronic health care conditions. A greater focus on a prevention is needed. We should develop innovative approaches to maintain health and prevent deterioration of health in patients with existing or chronic health conditions. This should also include systems to enable earlier identification of those at risk and implementation of interventions to prevent catastrophic health events e.g. heart attack, stroke or premature mortality.

My research to date in CVD prevention has involved novel approaches such as using mobile and digital health interventions to support patients after a heart attack modify their health behaviours and support them to take their healthcare treatments. My program of work in the next five years will focus on innovative opportunities to strengthen CVD prevention through enhanced clinical approaches and enhanced health service delivery. This will involve integrating the digital health interventions and other new interventions we have developed into clinical pathways and the health system as well as creating new care models. The goal of my research is to cultivate a program of work that utilises innovative, practical and scalable approaches to improve CVD preventative care for patients and populations.

Heart attacks and strokes are among the major causes of death in Australia. While some of these events can be explained by risk factors such as high blood pressure, cholesterol diabetes, age and smoking, many are unexplained. Aboriginal Australians, patients with schizophrenia and women with preeclampsia (a disease of high blood pressure during pregnancy) are at increased risk of heart disease and stroke at a young age, for reasons we do not understand. In this study we will investigate if these people have reduced capacity to clear cholesterol from their body using new methods never before applied to these Australians. It will involve taking a small volume of their blood and specialised testing for the ability of that blood to remove cholesterol from cells and to deliver it to the liver for clearance. As part of this project we will also develop a new rapid version of one of these tests that will make these tests available to large numbers of people in the community.

Our hypothesis is that inability to clear cholesterol from the body is one of the causes of premature heart disease and stroke. Our study will investigate if this is true in three Australian populations. If this is confirmed, we will use this information to predict who is at risk of having future heart attacks and stroke, and identify future therapies by overcoming those areas where the clearance of cholesterol is slowed. Our studies are therefore directly relevant to Australian populations. We will work closely with experts in the fields of Aboriginal health, schizophrenia, and women’s health to publish our work, present it at scientific and educational meetings, and apply it to the wider Australian population.

Heart attacks and strokes are caused by the build-up of cholesterol (called a plaque) in the arteries of the heart or brain, a process named atherosclerosis, which leads to death of heart or brain tissue. Animal studies have shown that vaccination against the Pneumococcus bacterium reduces the size and number of plaques. The mechanism appears to be that the cell wall of the bacterium contains a fat that looks like the bad cholesterol that builds up in the plaque. Vaccination triggers the production of antibodies towards this cell wall fat and these antibodies cross react with the bad cholesterol, attacking and basically “clearing away” the plaque.

The obvious question has been whether pneumococcal vaccination can do the same thing in humans. Observational human studies are promising, indicating that people who receive the pneumococcal vaccine have a lower risk of heart attack and stroke than those who do not. Unfortunately, these studies are not randomised and it is possible that these results are confounded.

The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE) is the first and only registered study worldwide to test this hypothesis in a randomised controlled clinical trial. Funded by NHMRC ($1.8 million) in 2013, it has recruited 4725 people across six centres nationally, with half receiving the pneumococcal vaccine and half receiving placebo. It is one year into the six year follow-up needed to have sufficient power to detect a 17% reduction in heart attacks and strokes. While waiting for endpoints to develop over the next five years, we will investigate the potential mechanisms of a protective effect; this was not covered by the original grant. One thousand participants have given blood samples at baseline and one month after vaccination, and agreed to undergo measures of atherosclerosis at baseline and two and four years after vaccination. We anticipate that those who get and respond to the vaccine will show a reduction in plaque during follow-up.

If a vaccine can protect against heart attacks and strokes, it will be a major public health advance. The vaccine has a well-established safety profile but is underused. If this study is positive, coverage could be increased (currently less than a third of those eligible get the vaccine) and the target age could be reduced from 65 to 55 to cover more of the population at risk. This fits squarely with the NSW Health priority of “Keeping People Healthy”.

This project will use novel and innovative approaches to answer key research questions related to the clinical and genetic basis of inherited heart diseases, such as muscle or electrical problems of the heart, and sudden cardiac death, particularly in the young. While there has been significant progress in defining the genetic causes of many of these inherited heart diseases, no cause is identified in over 50% of these inherited heart diseases. Furthermore, in those where a genetic diagnosis has been made, how these genetic faults lead to heart disease, and what factors influence how the disease develops, remain unclear. Finally, how to translate these key genetic discoveries to improved diagnostic, therapeutic and prevention approaches in families with inherited heart diseases remains unclear.

The three-year research study will focus on the identification of new disease genes in families with inherited heart disease and sudden cardiac death using state-of-the-art genetic approaches which allows us to study thousands of genes at one time, so-called whole exome and genome sequencing. This cutting-edge technology will allow us to understand how these genetic discoveries lead to human inherited heart disease, and how to apply this new knowledge in the clinical setting to assess patients and their families. The overarching purpose of this study is to be able to gain new genetic knowledge about inherited heart diseases and then translate these findings to improved diagnostic and therapeutic approaches, with the ultimate goal to improve the care of families with inherited heart diseases, including the prevention of sudden cardiac death in the young.

A key aspect of this study is to translate these findings immediately into practice, with the improved diagnosis and management of patients and their families with inherited heart diseases. The findings will lead to the development, for the first time, of evidence-based best practice guidelines for the investigation of inherited heart disease families and sudden cardiac death in the young. The findings will be disseminated to patient, clinicians and to the wider public not only within NSW, but across Australia, and internationally, such that the care of these families is improved globally.

The ultimate goal of our research is to be able to take a sample of your blood, predict how likely you are to suffer a heart attack or stroke, decide if you need a new medication to reduce your risk, then retest your blood to see if you responded to the treatment.

Our research focuses on understanding blood platelets, tiny cells that form clots to stop us bleeding. Platelets need to be able to activate, otherwise we would bleed to death, but when they are too active, or their activity occurs in the wrong place, you can suffer a heart attack or stroke. Aspirin, one of the main drugs that reduces death from heart attack, works by inhibiting platelet function. However, despite current best anti-platelet drugs, thousands of people continue to have heart attacks and strokes every day.

Our research has shown that not all platelets are the same, that different populations within our platelets have different roles. There is one particular sub-population that stimulates the circulating blood clotting proteins to make blood clots bigger and more stable. Our research has found that these “procoagulant platelets” are made in excess in patients during heart attack or stroke, but they are less important in stopping bleeding. Until now, there was no easy way to measure these “procoagulant platelets”. We developed a blood test that can measure how many procoagulant platelets you make when your blood is exposed to the stimuli that it would experience during heart attack or stroke. We further refined this into a test that measures the balance of an individual’s platelet sub-populations with the intention to give more information about your risk of heart attack and to determine whether you need extra treatment to reduce the risk. We hope this will eventually become a diagnostic test available to people with coronary disease within in a routine diagnostic laboratory and have partnered with a company with experience making platelet function tests into test kits.

Procoagulant platelets are not affected by aspirin, so new drugs are needed. Our research also has a drug discovery arm using our novel assay and state-of-the-art drug discovery methods. We have found a potential drug that affects the interaction between the stimulant and the platelets, bringing the hyperactivity in coronary disease patients back to normal without affecting bleeding. Test-tube based experiments have been promising, and we are moving into the next phase of testing.

Heart Disease in Women has been universally described as “under recognised, under treated and under researched.” Australian and international evidence demonstrates poorer outcomes for women with heart disease as well as an extreme paucity of data on female-predominant heart conditions.

Dr Zaman will build a nationally leading and internationally recognised program of research that improves outcomes for women with heart disease. This program of work will be most successful by gaining the mentorship from experienced clinical researchers within the Westmead Applied Research Centre (WARC) of The University of Sydney and, by locating it within a population of need in the Western Sydney Local Health District; a socioeconomically disadvantaged area with a culturally and linguistically diverse population.

Dr Zaman’s two research flagships are (i) atherosclerotic heart disease in women and (ii) improving care of Female-Predominant Cardiac Conditions. The potential impact will be discovering new interventions for women’s heart disease including the development of innovative models of care. Ultimately, these findings will be translated to clinical guidelines and address the large burden of cardiac disease in women.

In Australia, 6% of adults have diabetes mellitus (DM), which is associated with a doubled risk of heart attack, precipitated by atherosclerotic cardiovascular disease. In the past 25 years, the prevalence of DM in Australia has more than tripled and projected to rise.

An estimated one-third of young adults will develop DM during their lifetime, translating to increased risk of cardiovascular (CV) events.

Despite the high CVD burden associated with DM, the pathways responsible for elevated risk are incompletely understood. CV risk factors often seen in conjunction with DM include
hyperglycaemia, atherogenic dyslipidemia, insulin resistance and low-grade systemic inflammation - all of which may contribute to platelet and myeloid hyperactivity. Platelet hyperactivity is independently associated with long-term mortality and CV events. Notably platelets from DM subjects are more hyperreactive and less responsive to current antiplatelet, antithrombotic-based therapies.

Dr Barrett has recently found that platelets primarily associate with macrophages in atherogenesis, the inflammatory hallmark of lesions, and directly mediate myeloid inflammatory responses accelerating atherogenesis [12, 13]. Moreover, Dr Barrett has found myeloid cells and platelets to be hyper-inflammatory in DM indicating these interactions are exacerbated in DM.

Dr Barrett’s research proposes that an unbiased approach to assess DM platelet hyperactivity will provide insight into the mechanisms by which they contribute to
unresolved inflammation, an increasingly appreciated risk factor for CVD. Additionally, this approach is likely to facilitate the development of a new class of therapeutics to suppress platelet inflammatory potential (i.e. distinct from therapies that curtail their thrombotic actions, aspirin & P2Y12 inhibitors) translating to reduced platelet-mediated inflammation in CVD, especially in those with DM.

The sympathetic nervous system (SNS) is a key regulator of cardiovascular (CV) and metabolic function. Targeting the SNS to inhibit its activation therefore has great potential to improve both CV and metabolic health. A pioneer in exploring potential therapeutic targets to inhibit SNS activation, Professor Schlaich currently leads a first-in-human study to assess the BP lowering effect of transluminal ablation of the carotid body (CB) and is involved in a first-in-human study of catheter-based hepatic denervation to improve glucose metabolism in patients with T2DM. Mechanistically, he has demonstrated a link between SNS activation and other drivers of CV and metabolic disease such as the immune system14,15. This work provides the foundation for the proposed highly innovative research program. Prof Schlaich will utilize the University of Sydney’s resources to perform further studies and translate these novel therapeutic approaches and technologies into clinical practice. The program’s 5 projects are highly likely to result in significant knowledge gain and changes in clinical practice within 5 years.

Professor Jason Kovacic is among the world’s leading authorities on PHACTR1, with his studies demonstrating the key role of this gene in multiple vascular diseases including fibromuscular dysplasia (FMD), spontaneous coronary artery dissection (SCAD) and coronary artery disease (CAD). Due to its profound complexity, prior research efforts spanning almost a decade have struggled to understand this critical gene. In response, Prof. Kovacic has set about to systematically understand PHACTR1 and wishes to establish a cutting-edge program of research in NSW to finally understand its causative mechanisms.

To do so, he has created unique mouse models where the entire PHACTR1 gene is deleted. Partnering with an Australian mouse engineering company (Ozgene), this important resource is now validated ready for immediate transfer to NSW and the VCCRI to facilitate these studies. The vital importance of these studies is underscored by the multiple vascular diseases where a role for PHACTR1 has been shown, including FMD, SCAD, CAD, migraine, cervical artery dissection and hypertension. Thus, the patient populations that stand to benefit from his proposed studies are substantial. PHACTR1 is a causative gene in multiple vascular diseases that afflict a broad spectrum of our population. Due to higher rates of obesity and smoking, CAD, a focus area of this proposal, disproportionately affects socioeconomically disadvantaged groups. Furthermore, PHACTR1 is also involved in the pathobiology of FMD and SCAD – both being diseases that affect women at about a 10:1 ratio over males. Thus, the proposed studies are of major relevance for priority population groups in NSW.

The overarching aim of this study is to understand the cellular, molecular and genetic causes of hypoplastic left heart (HLH), a condition that is among the most severe of heart defects occurring in babies at birth. HLH babies are born with a small cardiac left ventricle, the main pumping chamber of the heart. While HLH fetuses are viable after birth without treatment, HLH is inevitably lethal. Therapy involves three surgeries, during which the heart is radically reconstructed. Even though HLH is relatively infrequent (4-8% of all heart defects) and advances in surgery have brought survival to 76% at 25 years, there are many possible complications, sometimes necessitating heart transplantation. There is also a massive cost to the health care system, and a life-long economic and emotional burden on families.

Researchers can now create a type of super stem cell (induced pluripotent stem cells) from any tissue such as skin, from any individual. Stem cells of this sort can be grown in a dish and directed with chemicals to form virtually any mature cell type in the body, including heart muscle cells. This has brought the exciting possibility of studying human disease using (previously inaccessible) patient-specific human tissue. Developments in stem cell culture now allow the formation of cardiac mini-organs (called 3D organoids) containing muscle, vessels and other heart cells, enabling analysis of disease at a whole organ level.

Our team of researchers and clinicians are studying the causation of HLH using super stem cells. We have made stem cells from 10 HLH patients and their parents, who serve as genetically well-matched healthy controls. Researchers previously thought that HLH arose from altered blood flow and pressure secondary to the valve and vessel defects seen in HLH hearts. However, our preliminary studies show that HLH cardiac muscle has underlying growth and functional defects, and reduced expression of genes associated with both heart and brain development, potentially connecting heart structural defects with the poor learning outcomes seen in HLH babies after birth. Our aims here are to delve more deeply into the molecular causes of HLH using 3D beating cardiac stem cell organoids, and to identify and test individual causative genes for this disease. We will also use the organoid model to screen for drugs that overcome muscle growth and functional defects seen in HLH, which could be further developed into therapies that support the post-surgical HLH heart throughout life.

Cardiovascular disease (CVD) affects 22% (4.2 million) of Australians. It is expected that in 2019, some 80,000 Australians will be admitted to hospital with acute coronary syndrome (ACS), with more than 55,500 suffering a heart attack. The major cause of heart attacks is atherosclerosis, a progressive disease of large arteries that culminates in the rupture of unstable (or ‘soft’) atherosclerotic plaque, which can lead to a blood clot, the abrupt blocking of the artery and acute, life-threatening heart attack (or stroke).

While death from CVD in Australia has declined over the last decades, the rate of heart attacks has paradoxically increased, and in NSW, the population-adjusted number of heart attacks has remained above the nation’s average. The annual cost of ACS to the Australian Government is around two billion dollars, of which ~75% is due to hospitalisation. To reduce these costs and save lives, it is important to prevent avoidable hospital admission and improve patient outcomes by targeting those most at risk and by improving the diagnosis and treatment of high-risk people.

Currently, the assessment of coronary plaque relies on information obtained from the physical contour of the arterial lumen (coronary angiography) and plaque burden (computed tomography coronary angiography). While these methods have significantly improved the treatment and management of heart disease, they cannot detect ‘soft’ plaques, the rupture of which is thought to cause up to half of all fatal heart attacks. Therefore, identifying and treating ‘soft’ plaque and subjects at high risk of developing an acute event remain major unresolved problems in clinical cardiology and could save the lives of 30-50% of those experiencing a heart attack.

This proposal addresses these important contemporary issues in clinical cardiology, by using novel non-invasive imaging methods to selectively detect ‘soft’ plaque, based on measuring inflammatory activity in arteries; and specific drug-induced inhibition of this arterial activity to prevent plaque rupture and associated thrombosis.

To facilitate translation of the research findings from bench-to-bedside, the investigating team includes clinicians and scientists to provide relevant expertise and practical advice in pre-clinical models (development of novel methods and tools); clinical cardiology (current clinical needs, alignment and improvement of methods to be developed with current practice in ACS diagnosis and patient treatment stratification); cardiovascular imaging (development of probes and specialised imaging sequences for coronary arteries, e.g., for motion correction); thrombosis (assessment of clinically relevant parameters); and industry (economical and intellectual property considerations).

Congenital heart disease (CHD) is the most common human congenital defect, occurring in just under 1% of live-births. CHD is the biggest single cause of child mortality and hospitalisation, excluding communicable diseases. Despite this, only a minority of CHD cases are genetically diagnosed, partly because about 90% of families are not offered the opportunity of having a genetic diagnostic test through the Australian healthcare system. Thus, families are denied the real and the potential benefits enabled by such a genetic diagnosis. Moreover, they are unaware of the impact that CHD will have on their child, and on their lives, as the broad impact has not been studied.

A genetic diagnosis brings immediate benefits to families as they receive information concerning the chance of CHD occurring in subsequent pregnancies. In Australia, with the growing adult CHD population (64,000 living with CHD, half now adults) such family-specific information to manage reproduction is becoming increasingly relevant. Moreover, a genetic diagnosis can in some cases inform a child’s clinical care or predict complications and risk factors for surgery or treatment.

The purpose of this research is to improve the lives of patients and families with congenital heart disease. We will tackle this by: 1) providing families with a genetic diagnosis, 2) improving the rate of genetic diagnosis, and 3) studying the health and education outcomes of CHD patients.


The project makes use of cutting-edge technologies. For example, whole-genome sequencing will determine the sequence of each of 6 billion base pairs of DNA in each patient and their parents so that we can find the genetic mutation that caused their CHD. Likewise, CRISPR technology will improve the rate of genetic diagnosis by helping us rapidly test gene function (in a mouse model) not previously known to cause CHD.

Once we find mutations that cause CHD in each family, this genetic diagnosis will be given to the families’ clinician so that they can be counselled concerning the ramifications of the diagnosis. We will also study aspects of the journey and outcomes associated with the life of a child with CHD in the hope of identifying key points where various activities might improve their lives long-term. In these ways, this research aims to benefit the health of NSW society by improving the quality of life of people with CHD and their families.

The heart is a companion we must rely on 24/7 all our life. It cannot rest and keeps our blood flow going. This incredible organ stoically transforms electrical into chemical and finally, mechanical signals, ultimately cycling between filling and pumping sequences, like a piston pump. It has to react to changes in load and blood demand, e.g. in exercise and heavy work. Thus, the workload must also be sensed in terms of sensing the mechanical strain on the heart walls and each heart cell reacts with signal modulations. Some of these cellular mechanical biosensors comprise mechanosensitive ion channels (MSC) on the surface membrane of cardiomyocytes (CMs) that are supposed to open in response to wall strain to allow Ca2+ influx into CMs, to not only modulate electrical activity and chemical signalling, but also to support growth and cell anchorage during our life. Under disease conditions, in particular with the very common condition of cardiac hypertrophy and heart failure in Australia, the heart is exposed to reduced pumping force, resulting in increased residual filling pressure and thus, aberrant activation of MSC and downstream signalling. Thus, to control the MSC activity in disease would represent a new tool to control heart failure. Development of the MultiStretcher platform in this project presents a significant step in this direction.

In our project, we will study responses of cardiac model cells to define strains pulling individual cells in multiple directions applying a novel biomechatronics ‘stretch rack’ systems technology that will be re-engineered for high throughput/content application to NSW cardiac research. This international Australian-German partnership will contribute to NSW’s capacity building for better understanding the underlying causes of CVD and their prevention/treatment in the future that, in particular, will benefit adult males and females living in the lowest socioeconomic areas. We will determine the crucial involvement of a specific type of MSC, called Piezo1, in driving aberrant heart signals in response to overstretch of heart cells and will employ pharmacological agents to control this mechanical biosensor.

We expect our fundamental research, which combines cardiac research, biophysics and biotechnology, will be applied to clinical settings using human cells as a validation after completion of our project, resulting in translation of pharmacology insights into drug development pipelines. We will disseminate our research findings though publications in high-impact international scientific journals and presentations at national and international meetings.

The spectacular developments in sequencing the human genome have led many to speculate that we will soon enter an era of personalised genome guided precision medicine. However, the speed with which we can now “read” the human genome far exceeds our capacity to interpret how gene mutations affect protein function and clinical outcomes. We urgently need to dramatically improve our skills at characterising how mutations affect gene outputs, i.e. functional genomics.

Mutations in the KCNH2 gene are a well-established cause of sudden cardiac death, caused by disturbed electrical signalling, in otherwise healthy young people. Yet, we now appreciate that the majority of variants identified in the KCNH2 gene do not change its function. The planned global efforts to sequence millions of genomes in the next few years will result in thousands of variants being identified in the KCNH2 gene; some of these will identify patients at increased risk of sudden death but most of these variants will be benign.

To cope with this deluge of variants of unknown significance we will develop a high throughput functional assay to assess how every possible mutation in KCNH2 affects the electrical function of heart cells. To achieve this, we will utilise state-of-the art robotic platforms to first help generate thousands of mutations in KCNH2 and then to assess the electrical consequences of these mutated genes. This data will be made available to geneticists, treating physicians and their patients through publicly accessible databases, such as ClinVar, so that all patients (both in NSW and throughout the world) who have their genome sequenced can access this data. Successful completion of this project would pave the way for using a similar approach to tackle other genes associated with sudden cardiac death and ultimately any cardiac disorder where it is possible to develop a high throughput assay to quantify altered function. It will also help to establish the Victor Chang Cardiac Research Institute and NSW as a world centre for functional genomics for inherited heart diseases.

Ischaemic stroke is caused by blockage of an artery supplying a portion of the brain. In most cases, this blockage is caused by a blood clot. Successful treatment of stroke depends on removal of this blood clot, which can be accomplished mechanically with a catheter inserted into the brain artery, or using a drug commonly known as a ‘clot buster’, which can be injected into a vein in the arm. Although catheter-based therapy has been shown to be effective up to 24 hours after onset in carefully selected patients, clot busters are approved for use only within 4.5 hours of onset. Unfortunately, many patients present with blood clots that are in small arteries that cannot be reached with a catheter. If these patients present more than 4.5 hours after their stroke began, they cannot be treated at all. We plan to use the same selection techniques that were used to prove catheter- based treatment can be effective for up to 24 hours after onset to select patients for clot buster therapy.

Clot busters can be used in many more hospitals than catheter-based methods, which require specialised equipment and personnel to perform the operation. This means we can treat many more patients living in rural and small urban centres far from specialised hospitals found in only two cities in NSW.

We will use an advanced form of brain imaging, known as ‘CT Perfusion’. This allows us to measure the blood flow to different parts of the brain. Brain blood flow measurements can be used to predict who will respond to therapy, even when they present late (more than 4.5 hours after onset) and who will not. We will use CT Perfusion to select patients for treatment. They will be randomly (like the flip of a coin) assigned to receive a clot buster known as tenecteplase (‘TNK’) or the standard treatment, which is a baby aspirin. We will then re-image the patients at 24 hours and measure their clinical symptoms for the next three months.

We believe that patients treated with TNK will have better outcomes than those given aspirin. Our research will be the first to show that clot busters can be used safely and effectively in patients presenting to hospital more than 4.5 hours after onset. This will allow treatment of a group of stroke patients who currently have no options available to them, including many who live in rural areas. This study has the potential to change guidelines and treatment approaches almost immediately.

Age is the greatest risk factor for disease, particularly heart disease, diabetes and dementia. One in three deaths in Australia are from cardiovascular disease. With the ageing population, and the obesity epidemic, it is imperative that new strategies are developed that can be used to limit the morbidity of age.

These cardiovascular diseases show early changes in the blood vessels and in particular in the structure and function of a highly specialised cell type called endothelial cells. Endothelial cells line the blood vessels and act as a selective barrier between the blood and the tissues. Changes in the endothelial cells result in the loss of the protective barrier function resulting in leaky blood vessels and in a chronic inflammatory state. Such changes have been shown to contribute to the initiation and progression of age-associated disease.

Our ultimate goal is to develop new therapeutics directed towards the age-damaged endothelium, in order to alleviate the scourge of age-associated diseases. To this end, we are defining the molecular changes in endothelial cells as they undergo cellular ageing. Using sophisticated biological analysis and state-of-the-art computer-generated learning technologies in collaboration with national and international experts, we will determine new targets in the ‘aged endothelial cells’ that may be amenable to manipulation. This will be the initial step in development of new drugs that specifically target, for removal, the ‘aged’ endothelium.

Our research findings will be presented in international peer reviewed journals to give maximum exposure to the international scientific field. The scientists involved in the program will also attend relevant national and international meetings where poster or oral presentations of the work will be expected. The Centenary Institute has an active publicity group and any major discoveries will be advertised to the public through this forum. In addition, through symposia organised by Gamble, the work will be disseminated to focussed NSW and Australian researchers.

Inherited heart diseases are a collection of heart muscle diseases and abnormal heart rhythm disorders. They can affect people of any age and may lead to heart failure or even sudden death. The inherited heart diseases are caused by variants (faults) in DNA sequence. If a person is diagnosed with an inherited heart disease they can undergo genetic testing to look for the disease-causing DNA variant. Finding the genetic cause of disease enables screening of immediate family members who may also have inherited the variant and are at risk of developing the disease. Family members who have inherited the variant and can be clinically monitored more closely whereas those family members who have not inherited the variant are released from life-long clinical surveillance.

Genetic testing for the inherited heart diseases can be improved. Commercial genetic testing currently focuses on screening the protein coding regions of genes, which represents only 1% of our DNA. The purpose of this research project is to develop new and improved approaches to find disease-causing variants in non-coding DNA. This project will develop new methods to find disease causing variants in non-coding regions of our genome, and new assays to confirm that the variants are responsible for disease development.

The project will translate to new genetic testing approaches for the inherited heart diseases with higher diagnostic yield. This will result in earlier identification of at-risk family members, thereby allowing earlier initiation of clinical management with the potential to prevent sudden cardiac death. The new genetic testing approaches will be integrated into clinical practice by our multidisciplinary team, who are recognised internationally in the field of inherited heart disease and sudden cardiac death.

During the course of this research project we will provide free state-of-the-art genetic testing to a large NSW-based patient population, including people who would otherwise not be able to afford to pay for genetic testing. The ultimate beneficiaries of this research project will be NSW-based families with potentially lethal inherited heart disease.

Before new drugs come to market, we need to ensure that they not only work, but they are safe. It is well known that drugs that unintentionally block the hERG ion channel in the heart can cause fatal cardiac rhythm disorders. This is a major problem for development of new therapeutics since it is estimated up to 70% of all compounds can bind to hERG channels. Consequently, testing for block of hERG as well as prolongation of action potential duration is a mandatory part of preclinical development. This approach has been effective in that no new dangerous drugs have come to market since they have been in place. However, there is widespread agreement that this measure is not specific, resulting in false positive results that have led to premature termination of potentially valuable therapeutics that could prolong or enhance the quality of patient’s lives. The economic implications are also huge, with around $5 billion per annum spent on these screens.

The shortcomings of current methods are that they rely on measures that are poor surrogates for risk that are not mechanistically linked to arrhythmias. We propose that rather than analysis of the duration of repolarisation, that the shape of the cardiac action potential is a much richer source of information about underlying electrophysiology, and that subtle changes in this shape precede the emergence of the irregular activity that triggers arrhythmias. In this study we will test the hypothesis that parameters extracted from quantitative analysis of the shape of action potentials recorded from stem cell derived cardiomyocytes can more accurately predict drug-induced arrhythmia than changes in repolarisation duration. We will build and validate a screening workflow and accompanying software that can be incorporated into preclinical safety screening pipelines that will permit more accurate allocation of cardiovascular safety liabilities and increase the output of new drugs to benefit patients.

The project will leverage the technology infrastructure in the Victor Chang Innovation Centre, which was recently established with a $25 million investment from NSW Health. As part of the iPSC phenotyping core facility we have installed robotic, automated platforms for culture and differentiation of iPSC and functional characterisation of iPSC derived cardiomyocytes. We are the only facility in Australia with access to these combined enabling technologies that will be built on to develop drug screening infrastructure and establish NSW as an internationally recognised centre for safety pharmacology.

Heart failure is a very common and costly disease that is defined as the inability to pump adequate amounts of blood to meet the body’s needs. A particularly large group of heart failure patients that are difficult to both diagnose and treat, is heart failure due to high blood pressure, diabetes, and/or obesity. This large category of heart failure is particularly associated with three problems, (I) inefficient filling of the heart, (II) thick walls of the heart, and (III) a reduction in blood flow to the smallest vessels of the heart. These three problems are more common with increasing age, are more common in women and indigenous populations, and have been shown to be associated with hospital admission and death.

The purpose of this research is to develop and use state-of-the-art magnetic resonance imaging (MRI) to better understand, diagnose, and evaluate a new treatment heart failure. Specifically, the research focuses on the challenges related to identifying and treating inefficient filling, thick walls, and small vessel disease.

With regards to evaluating inefficient filling, this requires accurate measurement of the speed of movement of the heart during filling, and blood pressure in different chambers of the heart. We have developed pioneering new MRI methods to measure these movements and pressures, and will be evaluating these new non-invasive MRI measures compared to reference measurements in patients. Furthermore, we have found that surgical reduction in the size of the left atrium of the heart may improve the efficiency of filling. Thus, we will evaluate the ability of this new surgical treatment to improve filling efficiency in patients undergoing open-heart surgery.

With regards to evaluating thick walls of the heart, we have developed new methods to better diagnose thick walls by both MRI and the electrical activity of the heart using electrocardiography (ECG). The accuracy and utility of these new methods will be evaluated in patients. Also, the accuracy of a new ECG method to diagnose small vessel disease, as shown by MRI, will be evaluated.

The development and evaluation of these new diagnostic methods and treatment will establish their utility for use in every day care in patients with heart failure who otherwise currently may be incorrectly diagnosed and lack treatment options.

Gene therapy, or the use of genes as medicine, has immense therapeutic potential in the treatment of many genetic diseases and cancers that are currently difficult or impossible to treat. While progress in the development of the underpinning gene transfer technology (vectors) has been hard won, we are finally witnessing astounding successes in human clinical trials in both children and adults.

This in turn has led to a global upsurge in clinical trial activity for a vast number of troubling diseases, and unprecedented demand for gene transfer vectors prepared to the exacting GMP manufacturing standards required for human clinical use. This demand has dramatically out-stripped supply and has created a clinical trial log-jam that threatens to slow the realisation of therapeutic benefit to the many potential beneficiaries of gene therapy.

This project will develop CAR T cells to target a broad range of paediatric tumours, and CAR T cells to protect kidney transplants from chronic allograft nephropathy, as well as gene viral vectors to target blinding eye disease and to treat childhood kidney disease. This will allow us to quickly initiate desperately needed paediatric trials for cancer, eye and kidney disease.

Bone marrow transplants (also known as blood stem cell or stem cell transplants) are the only way to cure the worst types of leukaemia and lymphoma in adults and children.

Patients undergoing bone marrow transplant often die of infection rather than the disease for which the transplant was performed because for a year or more after the transplant, the patient’s new immune system is immature and does not function properly.

Cell therapy involves growing infection and malignancy fighting cells called T-cells in the laboratory, training them to recognize infection and disease, and then giving them to patients soon after the transplant. The idea is to make the patient’s immune system functional and strong soon after transplant and to avoid the period when the patient is most vulnerable to dying.

The proposed clinical trial will test the theory that adding cell therapy to standard antibiotic treatment for infection in patients after bone marrow transplant will improve the immune system leading to better control of serious infections, less serious illness and fewer deaths.

In Australia chronic pain is estimated to cost over $30 billion per year to the overall economy, and current therapies do not adequately address pain for most patients.

The primary aim of this proposal is to generate GMP-grade clinic ready transplant material and then test the safety and efficacy of this material in rodents and large mammals. By moving these new technologies to the pain clinic, we can start to provide some relief to the millions of people currently living with untreatable and devastating chronic pain.

We have developed a long-lasting stem cell therapy that can reverse neuropathic pain, and here we will develop this technology for human use.

The adeno-associated virus (AAV) is gaining widespread use in gene therapy due to its ability to safely and efficiently deliver a genetic payload into a broad range of tissues.

In the clinic, AAV has successfully been used to treat patients with the bleeding disorder haemophilia by delivering a good copy of the Factor IX gene to replace a faulty copy in patient livers. Limitations of previous studies have included a failure to achieve a sustained therapeutic dose and recognition of the AAV particle by the host immune system.

While these problems have been addressed by designing custom AAVs, a tremendous opportunity still remains to further boost therapeutic efficacy by identifying the specific cell entry mechanism or receptor used by AAV’s. We will identify the specific receptors that allow entry of two liver-specific AAVs, one which is already in clinical use, using biochemical and genetic approaches.

We will identify genetic variants that may affect receptor expression and enable us to screen patients for those who will be better responders. We will then screen a ‘library’ of clinically-approved drugs to boost receptor expression and AAV uptake in liver cells in mice. This study will identify new avenues to enhance therapeutic efficacy in patients undergoing gene therapy.

Sudden death or cardiac arrest occurs when the heart goes into a fatal heart rhythm called ventricular tachycardia (VT). These fatal rhythms almost invariable occur due to underlying scar tissue in the heart from a variety of heart diseases. Cardiac arrest survivors receive a specialised form of pacemaker, called an implanted cardiac defibrillator (ICD) placed under the skin that automatically delivers an internal shock if VT recurs, thereby aborting otherwise inevitable sudden death. However, ICDs do not prevent VT from occurring in the first place, they only treat VT when it occurs. Cardiac arrest survivors will experience recurrent VT at an annual rate of 30-50 per cent/year. Recurrent shocks are painful, cause tremendous psychological trauma and lead to increased risk of death. They also lead to frequent hospital visits, and exponential health care utilisation.

Recurrent VT can be treated with strong doses of anti-arrhythmic (AAD) medications but these tend to be minimally effective, and with potent side effects. An alternative is to perform a cardiac ablation (CA) procedure that entails electrical wires navigated up through the veins to the heart, to identify, cauterise and thus destroy the electrical short circuits causing VT. Some studies have shown that CA is highly effective in curing VT, reducing VT burden and improving quality of life in patients with scar tissue due to coronary heart disease (blocked arteries). It is unknown if CA is just as effective for a large population of patients who have scar related to genetic (familial) disease, or infection or inflammation of the heart (termed non-ischemic cardiomyopathy). This group is important as the incidence of non-ischemic cardiomyopathy is rising; such patients tend to be young (30-60 years), and are very likely to experience toxic side effects from AAD and thus stand to gain the most benefit from CA. This research proposal is for a randomised trial that will examine if CA is superior to AAD in the treatment of VT in patients with non-ischemic cardiomyopathy.

Results of this study will be disseminated through clinicians at scientific meetings/publication in journals (and via their social media channels), and by engagement of Sydney Health Partners, NSW Agency for Clinical Innovation and major national/international cardiac societies. Findings will lead to major practice and policy change nationally and globally. Engagement with patients and the general public will be via novel e-health social media channels such as Facebook and Twitter, as well as involvement of charitable foundations.

Atherosclerosis and related complications are a major cause of death and disability in NSW. This project will use see-through zebrafish to literally shed new light on what happens in atherosclerotic plaques using microscopy of the disease inside living zebrafish. We will be able to ask fundamental questions about how plaques form, mature, and harm us by observing the course of disease in zebrafish embryos.

To find new cures of atherosclerosis and it’s complications, the project will take two arms. The first arm will investigate a treatment that may prevent the blood vessel damage necessary for atherosclerosis to get a foothold in our blood vessels while a second arm of the project will set up a zebrafish system to discover new drugs to prevent or reverse the build up of bad fats in atherosclerotic plaques.

Death and disability from stroke is a massive burden on the healthcare system and society. In Australia, it is estimated that one million people will be living with the effects of stroke by 2050 - more than double the number of strokes in 2017. Ischaemic stroke is caused by a blocked artery, leading to a lack of blood flow and oxygen supply to a specific region of the brain supplied by that artery, resulting in brain cell death (infarction). Up to 38 per cent of ischaemic stroke patients present to hospital with mild or rapidly improving symptoms, yet final outcomes are poor, >50 per cent require assistance with self-care at three months post stroke. This delayed progression of stroke due to early neurological deterioration (END) within the first 24hrs post-stroke remains a clinically significant, yet unresolved problem - the number of patients totalling more than the annual number of new cases of multiple sclerosis, Huntington’s disease and motor neuron disease combined. However, its cause and the underlying mechanisms are poorly understood. Currently there are no guidelines or diagnostic tests that can predict the outcome of these patients. Understanding the true pathophysiology and recognising those at risk are key first steps.

Dr Patabendige and her team will use advanced medical imaging analysis and a novel non-invasive method to measure the pressure within the skull, intracranial pressure (ICP) to provide definitive evidence to confirm that ICP elevation causes infarct expansion, and that it is associated with neurological deterioration. In addition, their previous studies confirm that oedema (swelling of the brain) was not the primary cause for this ICP rise. Therefore, Dr Patabendige will investigate whether cerebrospinal fluid (CSF, the fluid that bathes the brain and spinal cord) volume increase is responsible, and if confirmed, show that short-duration hypothermia reverses this.

These findings will provide evidence to confirm the cause for END, and provide for the first time a clear pathological explanation for why these patients, who seem to be improving when initially presenting to the hospital progress to neurological deterioration.

Expected key outcomes:
1. Provide significant fundamental knowledge about a highly clinically relevant, yet unresolved problem of END
2. Help future diagnosis, prevention and management of stroke patients that are at risk of developing END, thereby making a significant reduction in stroke morbidity in the longer term
3. Prove the effectiveness of a potential treatment that is safe, easy to apply and generalizable .

Chest pain is one of the most common presentations to adult emergency departments. Its management requires specialist assessment and tests, which places a significant burden on hospital resources and patients. To address this, Royal North Shore Hospital has implemented a rapid access Chest Pain Clinic (CPC) – a new model of care, for which I am director. As part of this, there is the need for cardiac investigations that are feasible, diagnostic, and cost-effective. Two advanced cardiac diagnostic techniques have untapped potential in this setting in Australia – cardiovascular magnetic resonance (CMR) and advanced electrocardiography (A-ECG). This fellowship seeks to develop new insights into health service of acute chest pain by the application and development of these state-of-the-art investigations to create a paradigm shift in chest pain management and improve healthcare costs.

CMR is the future of non-invasive cardiology, and is utilised widely in clinical practice and research worldwide but less so in Australia because of slow adoption and restrictions with Medicare rebate. In European and UK healthcare models, CMR with stress testing (‘stress CMR’) has been shown to be cost-effective in the management of suspected coronary disease with high diagnostic and prognostic performance. There is a lack of evidence of stress CMR in the Australian healthcare setting. Part 1 of this study will assess the cost-effectiveness of stress CMR in the CPC, in order to optimise its use in Australia.

The traditional ECG is a fundamental cardiac test. Standard analysis depends on visual assessment. Novel methods for computerised ECG measurement permit the application of advanced digital analysis techniques collectively known as A-ECG, which have dramatically higher diagnostic accuracy for detecting disease. Currently, A-ECG is only available in a handful of international centres outside Australia. Part 2 of this study will assess A-ECG in the CPC to show its diagnostic performance, ability to influence downstream tests, and power to predict cardiovascular outcomes. A-ECG could be the much needed paradigm shift in chest pain management – to allow patients to be managed safely as outpatients, thus avoiding hospital admission and unnecessary tests, and improving healthcare costs.

The overarching goals are aligned with Sydney Health Partners’ Cardiovascular Stream and the Northern Sydney Local Health District. Collaboration with international centres of excellence will support the science and the technology. Translation of findings and implementation into clinical practice will be led by the research team, which includes engagement with key stakeholders and hospital administration.

Chest pain is one of the most common presentations to adult emergency departments. Its management requires specialist assessment and tests, which places a significant burden on hospital resources and patients. To address this, Royal North Shore Hospital has implemented a rapid access Chest Pain Clinic (CPC) – a new model of care, for which I am director. As part of this, there is the need for cardiac investigations that are feasible, diagnostic, and cost-effective. Two advanced cardiac diagnostic techniques have untapped potential in this setting in Australia – cardiovascular magnetic resonance (CMR) and advanced electrocardiography (A-ECG). This fellowship seeks to develop new insights into health service of acute chest pain by the application and development of these state-of-the-art investigations to create a paradigm shift in chest pain management and improve healthcare costs.

CMR is the future of non-invasive cardiology, and is utilised widely in clinical practice and research worldwide but less so in Australia because of slow adoption and restrictions with Medicare rebate. In European and UK healthcare models, CMR with stress testing (‘stress CMR’) has been shown to be cost-effective in the management of suspected coronary disease with high diagnostic and prognostic performance. There is a lack of evidence of stress CMR in the Australian healthcare setting. Part 1 of this study will assess the cost-effectiveness of stress CMR in the CPC, in order to optimise its use in Australia.

The traditional ECG is a fundamental cardiac test. Standard analysis depends on visual assessment. Novel methods for computerised ECG measurement permit the application of advanced digital analysis techniques collectively known as A-ECG, which have dramatically higher diagnostic accuracy for detecting disease. Currently, A-ECG is only available in a handful of international centres outside Australia. Part 2 of this study will assess A-ECG in the CPC to show its diagnostic performance, ability to influence downstream tests, and power to predict cardiovascular outcomes. A-ECG could be the much needed paradigm shift in chest pain management – to allow patients to be managed safely as outpatients, thus avoiding hospital admission and unnecessary tests, and improving healthcare costs.

The overarching goals are aligned with Sydney Health Partners’ Cardiovascular Stream and the Northern Sydney Local Health District. Collaboration with international centres of excellence will support the science and the technology. Translation of findings and implementation into clinical practice will be led by the research team, which includes engagement with key stakeholders and hospital administration.

Cardiovascular diseases, including heart attack and stroke, are a leading cause of disease and death. In patients who have experienced a cardiovascular event such as a heart attack, smoking increases the risk of future events and death. Programs supporting cardiac patients to quit smoking improve survival and quality of life, and reduce the burden on the hospital system. However, smoking remains undertreated in cardiac patients. Prescribed medicines, including Zyban, Champix and Nicotine Replacement Therapy, are the most effective strategies available to help smokers quit, but there have been highly publicised concerns regarding their safety among cardiac patients, contributing to reluctance to prescribe and use these treatments.

This project will examine whether these safety concerns are supported by Australian data. It will also determine which of the three medicines is most likely to have the greatest long term benefit for cardiac patients, and the extent to which each of these medicines are currently used by cardiac patients after discharge from NSW hospitals. It will achieve this by linking records of filled prescriptions with other data from health services in NSW. This will be the largest study of the safety and effectiveness of prescribed medicines for smoking cessation conducted to date, and the first conducted in Australia. It will use sophisticated statistical techniques that allow data to be analysed in a way that closely replicates the characteristics of a clinical trial.

This project will provide clinically useful information about the risks and benefits of prescribed quit aids when used by cardiac patients. This will allow cardiac patients and health care providers to make informed decisions about whether a smoking cessation medicine and which one(s), should be used. This evidence, together with statistics on how many patients receive these quit aids after they leave hospital, will indicate whether efforts to promote or discourage use of any of these treatments among cardiac patients are needed. The research team will communicate the findings to staff of NSW Health services, cardiology units in particular, so that protocols and guidelines for the discharge of cardiac patients can be updated. Likewise, the findings will be shared with general practitioners to guide the in-community prescribing of smoking cessation aids to patients with cardiovascular disease. By informing changes to the care of cardiac patients who smoke, this project has the potential to improve the survival of patients with cardiovascular disease and reduce healthcare costs.

Atrial fibrillation (AF), the most common abnormal heart rhythm (arrhythmia), is a major risk factor for both stroke and heart failure. With an ageing population tackling the problem of arrhythmias, in particular AF, will be a major challenge for healthcare in the coming decades. At present, we lack good drugs to treat AF. As a result there is a pressing need for new strategies to study and better understand the molecular basis of these arrhythmias. This is the best way to identify and develop novel therapeutic avenues.

While clinically we accept that altered mechanical load in the chambers of the heart leads to structural and electrical changes, the molecular mechanisms of how these mechanical forces underpin arrhythmias are not understood. This project aims to identify novel mechanical pathways that underlie arrhythmias in conditions like AF.

This project will identify these new cellular pathways underlying arrhythmia generation by evaluating how mechanical stress affects the cells that line the chambers of the heart. We have access to a unique cell type mimicking the single cell layer that lines the inner wall of the heart chambers. Using state-of-the-art technology to simulate blood flow this project will assess how these cells may provide mechanically-regulated signals to the underlying heart muscle cells and assess how this may contribute to arrhythmias. This crucially acknowledges the inseparable function of the specialized cells that line the heart chambers and the muscle cells in the overall performance of the heart. Understanding these molecular pathways and their effect on the underlying heart muscle will likely identify novel therapeutic targets for prevention but also for management of arrhythmias.

Aside from unearthing targets for therapy, these pathways are also likely to contain candidate genes for genetic studies in patients with inherited heart arrhythmias and atrial fibrillation. Thus data generated in this study will be used to look for disease causing gene variants in studies already ongoing such as a NSW Health funded project aimed at sequencing the genomes of a large cohort of patients with cardiomyopathies, many of whom will develop AF and associated arrhythmias. As a result this project is likely to provide tangible outcomes for patient and family management and counselling.

Cancer and heart disease are the two most common disease conditions and the leading causes of death. Chemotherapy is more effective than ever at treating cancer, but has a price. There are over 400,000 cancer survivors in Australia and this figure is expected to increase due to a continuous decline in cancer death rates: there is a 70 per cent chance of survival from cancer in Australia. However, up to 25 per cent of these cancer survivors die from chemotherapy-induced cardiotoxicity (CIC) within 7 years, making it the leading cause of death in cancer survivors.

Cardio-oncology, an under-recognised area in Australia, is the intersection of heart conditions in cancer patients, an emerging field with immense potential to improve quality of life and cardiovascular burden in a growing number of cancer survivors.

The main reason for long-term cardiovascular and healthcare burden is delay in early detection of CIC due to imperfect diagnostic techniques. This is a major limitation, as early detection and treatment of CIC can lead to prevention of heart failure, and recovery of heart function. In addition, lack of an integrated, patient centred approach in Australia results in the fact that most cancer patients are still largely unaware of this adverse drug reaction and tend to neglect care for risk factors that may precipitate cardiotoxicity.

Thus, our program aims to address poor outcomes for the many cancer survivors who go on to develop CIC by discovering simple blood test(s) that could detect early onset of CIC as well as providing better education and facilitating self-care and empowerment for cancer patients/survivors.

Specifically, I will utilise state-of-the-art high through-put techniques that can gather a large amount of data to identify:
1) proteins in blood that change with early onset of CIC
2) genetic markers
3) chemotherapy-induced changes in genetic dispositions (epigenetics).

This data will be combined with latest imaging modalities to develop an individualised risk prediction tool for our patients. As risk assessment and early detection are cornerstones of early treatment and improved outcomes, this could in future lead to change in clinical practice/guidelines and translate in earlier discontinuation/change in chemotherapeutic regimen and initiation of cardioprotective therapy. I will also establish and facilitate a dedicated cardio-oncology nurse-led program of patient education and empowerment. This would achieve both improved interdisciplinary communication related to the diagnosis, monitoring and therapy of cancer treatment related cardiovascular complications and improved patients’ journey and outcomes through improved and dedicated cardiovascular care.

Blood clots blocking the blood supply to the heart and the brain, known as arterial thrombosis, cause heart attack and stroke – the leading cause of death and disability in the Australia. Platelets are the cells that form these blood clot, thus drugs targeting platelets such as aspirin are the mainstay of heart attack and stroke prevention. Yet current treatment has limited effectiveness with optimal therapy – up to 30 per cent of patients will have a recurrent event within three years, and more effective therapies often lead to bleeding side effects.

Our work has identified a particular sub-set of platelets within people with cardiovascular disease that increase blood clots, but are not turned-off by aspirin. These are called procoagulant platelets. Measurement of procoagulant platelets in patients has initially been very difficult due to the lack of sensitive and specific tests. We have recently developed a way to measure procoagulant platelets in people at risk of heart attack and stroke, and have shown that more procoagulant platelets are indeed formed during stroke and heart attacks. It is therefore this sub-set of platelets in people with cardiovascular disease that we would like to target more specifically when designing new drugs, in order to increase the beneficial effect and at the same time reduce the bleeding side effect when treating patients.

Interestingly, a simple non-invasive process called remote ischaemic preconditioning (RIPC), which is performed by inflating and deflating a blood pressure cuff three times, was able to reduce procoagulant platelets in people with heart disease when aspirin and other anti-platelet drugs could not. Others have previously shown that RIPC can protect the heart muscle and brain from damage during heart attack and stroke, but the mechanism by which it does this is unknown.

My studies indicate that RIPC affects procoagulant platelets by affecting the platelet mitochondria. Mitochondria are organelles inside the platelet that converts glucose to energy. My project investigates the link between procoagulant platelets, platelet mitochondrial function and cardiovascular disease. In addition to providing the rationale for RIPC, these studies aim to identify platelet mitochondrial pathways as a novel target for cardiovascular disease that will work in addition to existing cardiovascular drugs without causing bleeding. Ultimately, our work would be able to provide more tailored therapies for patients, reduce our patients’ waiting time, pain and risk of receiving treatments, improve their disease outcome, and reduce medical cost for the NSW health system.

Heart failure rates are increasing exponentially in Australia and worldwide. One in two people diagnosed with severe heart failure will die within one year of diagnosis. This burden of heart failure is underpinned by the heart’s limited capacity for self-repair after injury. This limitation could be overcome by stimulating newly discovered stem cell populations residing within the adult heart itself. We recently discovered a cardiac colony-forming stem cell population and have found that the molecule Platelet Derived Growth Factor (PDGF) can improve the heart function of mice and pigs after induced heart attack. PDGF does this by activating and rejuvenating resident heart stem and stromal cells. Before this promising therapy can be considered for clinical trials in humans, further testing to validate its safety is required.

This project will build on over a decade of preliminary work in mice and pigs, validating our results in a preclinical large animal model. In the second phase of this work, new materials such as nanoparticles will be used to more selectively deliver PDGF therapy to the heart. Outcomes of this project include expedited progression of this promising therapy, from the laboratory into the clinic, where thousands of heart failure patients could one day benefit.

Note: This project received project funding only. This project did not received full Fellowship funding.

Heart defects are the most common form of birth defects, occurring in ~1 per cent of live born babies. In 80 per cent of families it is not known why they occur. We use the latest technologies to study the genetic code of families with children that are born with heart defects. We aim to identify mutations, i.e. changes in the genetic code that are the cause of these defects.

The genetic code of each individual is stored in large datasets. Our goal is limited by the current methodologies to analyse such large datasets to identify causal mutations. Currently, a large percentage (~70 per cent) of families we study cannot receive a personalised genetic diagnosis. We propose to develop new quantitative and analytical approaches to improve our ability to identify mutations that are the cause of heart defects in every family.

Our research has specific and immediate clinical benefit for the families affected with heart defects that have been recruited. Increasing the genetic diagnosis of heart defects will help more families receive an accurate genetic diagnosis, personalised advice concerning the disease in their family and a better estimate of the risk of having a subsequent child with a heart defect.

Identifying the genetic causes of heart defects not only has benefits for the patient and the family but also for the community. Currently, efforts to identify causes of disease require large costs, and it can include multiple medical screens and procedures. We expect that systematic adoption of genetic testing in clinical practise will improve the financial sustainability of the health system.

Note: This project received project funding only. This project did not received full Fellowship funding.

Hypertrophic cardiomyopathy (HCM) is a clinically variable disease, ranging from asymptomatic diagnoses, to heart failure and sudden cardiac death. It occurs in 1 in 200-500 of the general population, and given it is an inherited disease close family members are recommended to undergo lifetime clinical surveillance. Due to the wide variability in disease presentation and features, there is little ability to predict who will develop the worst outcomes, despite decades of research.

Recent advances in genetic technologies have allowed an opportunity to better understand the underlying genetic causes of HCM, but have also challenged the prevailing view that HCM is primarily an inherited disease. My recent paper in Circulation: Cardiovascular Genetics proposed for the first time that a non-familial sub-group of HCM exists and that it occurs in approximately 40 per cent of cases. Non-familial HCM patients have a less severe disease and while current clinical guidelines recommend lifetime clinical screening of their first-degree relatives, our finding suggests this is not necessary.

No study to date has focused exclusively on the familial HCM sub-group. Reassessment of risk algorithms in a more homogeneous patient population will allow development of accurate risk prediction scores. Until now, risk scores have been developed in populations including both nonfamilial and sarcomere positive HCM and not surprisingly show poor predictive ability. To date, no scores have incorporated genetic variables, and based on my recent work there is a strong likelihood that genotype can impact outcomes.

For the first time, genetic testing could offer a clearer way to understand the disease, allowing us to make more precise recommendations for family screening and better predict those more likely to have poor outcomes. This will reduce uncertainty, but also minimise unnecessary health care resources from clinical screening family members who are not at increased risk of disease.

Note: This project received project funding only. This project did not received full Fellowship funding.

The purpose of this research project is to develop and validate a blood test that can be widely used, e.g. hospital outpatients, and general practitioner offices, to detect a new molecule in blood that we discovered. It will indicate whether a patient has liver fat and whether they are at risk of developing diabetes, which frequently leads to heart disease and stroke.

We are facing a global epidemic of obesity and related diseases. Almost three-quarters of Australians are now overweight or obese, and childhood obesity is at an all-time high. Overweight and obese people have a high risk of developing fatty liver disease and/or type 2 diabetes. Fatty liver disease is often the first stage leading to type 2 diabetes, and puts patients at increased risk of fat deposits in their blood vessels that may cause heart attacks and strokes, which are the most common causes of death in these patients.

We are failing to prevent the catastrophic obesity epidemic. It is a global challenge. The numbers are far greater in developing countries. In China, for example, 114 million people have type 2 diabetes and half a BILLION have prediabetes. These staggering numbers underscore the enormity of this healthcare challenge globally.Although obese people with diabetes most commonly die from heart attacks and strokes, the rate at which this occurs is highly variable, and until now, we cannot predict who is most at risk and who will have an event.

Our results indicate that the new blood molecule discovered by us can predict, more than a decade in advance, who will develop diabetes. This is tremendously important, as it will allow us to target those most at risk with interventions to prevent them from developing diabetes, thereby reducing complications such as heart attacks and strokes. It has been repeatedly shown that the best way to prevent diabetes and its complications is early intervention – by the time of diagnosis a lot of damage has been done, most of it irrevocably.

The way we currently measure this molecule is not widely accessible, limiting its availability to populations that need it most. In this project, we aim to develop a test that can be used everywhere -- even at the bedside, outpatients, general practitioner offices -- and will be fast, precise, and reliable. We will ensure that the public, patients, and clinicians are fully aware of all aspects of this assay.

Note: This project received project funding only. This project did not received full Fellowship funding.

Increasing life expectancy has resulted in a higher proportion of older individuals (≥65 years) in the population compared to a decade ago. As the population ages, demand will increase for hospital and aged care services, including permanent residential aged care (RAC), respite RAC, and transitional care (TC). The number of injury-related hospitalisations for older individuals are growing, accounting for 27 per cent of hospitalised injury.

Following an injury, older individuals may require assistance to perform activities of daily living (ADL), either transitionally as they return to their prior ability, or on a more permanent basis. Prior research has identified that age, functional ability, cognitive impairment, depression, multimorbidity and falls are commonly associated with aged care placements. However, individual and psychosocial characteristics associated with admission/return to RAC have not been examined following a hospitalised injury at a population-level, nor have factors associated with entry into supplementary care programs, such as TC or respite RAC, been identified. For older individuals, there is limited information available regarding their care transitions between the home, hospital, RAC, respite RAC and TC following a hospitalised injury in NSW. Suboptimal care transitions may result in diminished ADL and increased costs, including through re-hospitalisation.

This research will examine factors that influence older individuals transitioning between services and will advance the understanding of the influence of individual and psychosocial characteristics on post-acute care placement of individuals who are hospitalised following an injury. Ultimately, this information will be invaluable in influencing policy, driving change, and informing planning of the post-acute phase healthcare for older individuals in NSW and to identify future priority areas for research.

The promise of e-health interventions as a solution to overcome current healthcare challenges such as accessibility and cost have been hampered by poor translation into the community. Despite major advances in the availability of evidence-based mental health programs there is a serious shortfall in the delivery of such programs in practice, with an estimated 17-year delay between the identification of an effective program and its integration into practice and policy domains (IOM, 2001; Westfall, 2007). A significant contributor to this problem is the lack of available skills and knowledge to conduct rigorous interdisciplinary implementation science research.

The goal of this project is to inform the implementation of an evidence-based e-health intervention to prevent the onset of depression in youth. The intervention, SPARX, is a six-session online ‘serious game’, based on the principles of Cognitive Behaviour Therapy, which we have adapted into a prevention program (SPARX-R) for adolescents. In an randomised-controlled trial conducted across 10 Sydney high schools we showed that SPARX-R prevents the onset of depression, with gains maintained at 6-month follow up (Perry et al., 2005; the trial is ongoing and 18-month outcomes are expected in August 2016). SPARX-R does not require extensive training to support its delivery, making ideal for the school context.

A better approach to bridging the gap between ‘what we know’ and ‘what we do’ in health could make a substantial contribution to improving health outcomes and efficiencies. Increasingly it has been recognised that research to bridge this gap (implementation research) requires the expertise of researchers, policy makers and practitioners to be combined; implementation projects require both a deep understanding of the real world and how it operates, along with the often sophisticated research skills necessary for complex research designs. This is commonly referred to as partnership or co-production research.

Co-production, where researchers and research users work together throughout the research process from question formation through to interpretation and dissemination of findings, appears likely to be the most effective model for partnership. Such partnerships are a relatively recent phenomenon, however, and there is much to be learnt about how best to bring the diffuse skills, needs and priorities of these groups together to drive more effective implementation research and reduce research wastage. In Australia, the promise of co-produced research has led to the creation of funding schemes designed to foster collaboration (e.g. NHMRC partnership grant, NSW Health Translational Grant Scheme) but it is unknown how effective these partnerships are or how they operate in practice.

The specific aims are to:
1. Understand how research/end user partnerships are currently enacted in New South Wales, what works and what does not: and
2. Evaluate, for the first time internationally, a suite of tools to strengthen coproduction in implementation research:
a. A training course for early career researchers to build their capacity to develop and sustain effective research partnerships with policy agencies;
b. A tool for research users to help them navigate the process of working with researchers, from the initial agreement to partner through to dissemination.

This project is a joint collaboration between the Northern Sydney Primary Health Network (PHN), Healthdirect Australia, Hornsby General Practice (GP) Unit (a NSW Health entity), Macquarie University Health Services, and the Australian Institute of Health Innovation. It is designed specifically to realise the vision of “a digitally enabled and integrated health system delivering patient-centred health experiences and quality health outcomes”, set by NSW Health in its recently released eHealth Strategy (2016-2026).

General Practitioners (GPs) tend to refer patients to the Emergency Department (ED) in order to ensure their patients receive affordable specialist care without extensive delays. They may not be aware of outpatient services available at their local hospital. This contributes to unnecessary ED access block and increased waiting times. Patients are frustrated by months of waiting for outpatient appointments, and they lack skills in self-management in the interim.

To address this, health pathways (a collaborative initiative between primary and secondary health providers to improve the referral and management of patients) have aimed to build capacity in general practice to help patients navigate the health system. Supported by the NSW Agency of Clinical Innovation (ACI), health pathways are implemented and evaluated across NSW.

This research will make use of the unique opportunity at the NHMRC Centre of Research Excellence in eHealth which is co-located within the Northern Sydney PHN. The PHN will develop its first 20 local health pathways over the next six months. We will work closely with the PHN to select two high-priority health pathways and conduct studies to 1) understand the pain points experienced by consumers in their journey through the current service landscape (e.g. inability to get timely access to specialist care; lack of self-management skills due to limited health literacy); 2) co-design a consumer portal to address these challenges with input from consumers, GPs, clinicians and health service practitioners; and 3) evaluate the acceptance of the portal from consumer, GP and health service practitioner perspectives.

Burn injury can be a traumatic event for both the child and their carer, requiring extensive, specialised care and protracted hospitalisations. For paediatric burn injuries, optimal outcomes are associated with good multidisciplinary care, consistent follow-up with high quality burns units, functioning family units, and early return to pre-burns activities. In Australia, Aboriginal and Torres Strait Islander children are over-represented in burn-related hospitalisations yet, no research until now has examined the outcomes of these children nor their access to care either immediately after the burn injury or following discharge from hospital.

In addition to being more likely to be hospitalised following a burn injury, unpublished data suggest Aboriginal and Torres Strait Islander children are less likely to be treated in a specialist tertiary burn service.(Moller, unpublished). The NSW ACI Statewide Burn Injury Service, NSW Burn Transfer Guidelines provides clear guidelines for paediatric burn referral to tertiary burn services. However, there is evidence to suggest these guidelines are inconsistently applied. The proportion of Aboriginal and Torres Strait Islander children treated at specialist tertiary burn services in NSW is lower than population expectations. Further, numbers treated in regional centres appear to be higher, suggesting children are not referred as per the guidelines.

PIDs result from monogenic mutations in genes crucial to the functioning of an intact immune system. Currently, mutations in ~290 genes have been identified that cause PID. However, there are many more cases where the genetic lesion is unknown. This project will perform WGS on these PIDs to reveal the underlying gene mutation.

This “from bedside to bench and back” approach incorporating genomics and bioinformatics will identify novel gene mutations in PID patients and provide an explanation for disease pathogenesis. While PIDs are rare, they have played an instrumental role in pinpointing the essential and non-redundant roles of genes in the development and function of immune cells. Furthermore, some of the complications affecting PID patients are prevalent in the healthy population; for example, the incidence of thrush due to chronic fungal infections. In addition to having direct affects on clinical policy/practice ie treatment regimens for affected patients, results will be disseminated via the publication of manuscripts, presentations at national/international conferences and via media outlets through the work of the Garvan Research Foundation.

The top causes of disease burden among Australians (15–44yrs) are dominated by mental health and substance use disorders. Of particular concern is the common co-occurrence (i.e. comorbidity) of disorders, with up to 50 per cent of people presenting to services with more than one disorder. Despite increased awareness and public concern leading to a major government initiative (National Comorbidity Initiative), comorbid mental health and substance use remains a major cause of disability, poor quality of life, early mortality and poses a significant challenge for the Australian health system.

Evidence suggests that integration of substance use and mental health treatment is ideal for optimal patient outcomes and to avoid patients falling through the gaps. Individuals with comorbidity however, continue to receive disparate care targeting either the mental health or substance use disorder. NSW Health is well placed to be the leader in responding to this crisis by translating high quality comorbidity research evidence to practice. The improved clinical management of comorbidity is a priority for NSW Health and is consistent with the NSW State Health Plan: Towards 2021 which aims to deliver truly integrated care by providing right care in the right place at the right time.

The purpose of this project is to directly address this priority by implementing effective models of translation to increase the capacity for NSW treatment services to respond to comorbidity. The specific objectives are to:
1. Employ standardised US toolkits for assessing comorbidity competency (DDCAT and DDCMHT) and adapt them for adolescent and adult treatment services in NSW and Australia
2. Implement these adapted toolkits and evidence-based recommendations in NSW treatment services to examine utility in assessing comorbidity competency and enhancing capacity to respond to comorbidity.

A transient Ischemic Attack (TIA) is a major warning sign for stroke. There is a 15 per cent risk of stroke ≤ 90 days following initial event and the risk of cardiovascular events remains high 10-15 years post-TIA. It is best practice for TIA patients to receive secondary medical care to determine TIA cause and to commence preventative pharmacological therapy early post-event.

Behaviour change programs which include education and group exercise (ie. advice and support to address modifiable cardiovascular disease risk factors including hypertension, inactivity, poor diet etc.) significantly reduce the odds of further cardiovascular events. These programs significantly increase the time TIA patients spend in moderately vigorous physical activity (ie. brisk walking) (5). The latter extremely important as increasing physical activity independently contributes to significant reductions in cardiovascular risk, with an inverse relationship between time spent in moderately vigorous physical activity and risk of cardiovascular events and all-cause mortality.

This project aims to :
1. Develop and implement a new service- a behaviour change program for people who have had a recent TIA (Study 1: Implementation Study)
2. Increase the minutes/week people who have had a recent TIA spend in moderately vigorous physical activity (Study 2: Outcomes Study).

Antibodies are the effector molecules of the immune system and are responsible for neutralising pathogens with remarkable specificity and memory. However, 5 per cent of Australians suffer from autoimmune diseases, such that their antibodies recognise their own cells, tissues and organs (autoantibodies). Autoantibody-mediated disorders account for a large burden of chronic disease and can be difficult to diagnose and treat due to heterogeneous symptoms ranging from arthritis, dry eyes/mouth to kidney failure and giving birth to a child with cardiac abnormalities. The unpredictability of disease outcomes reduces patient quality-of-life, while posing significant costs to healthcare systems for ongoing monitoring and treating symptoms as they occur. Treatment options are limited to non-specific steroids and expensive biologics that are only effective in a subset of patients.

The objective of this research is to use cutting-edge genomic technology to characterise human autoantibodies to improve diagnosis and monitoring of disease. This approach traces the cellular source of autoantibodies revealing novel and specific therapeutic targets.

There are two ways to characterise an antibody: i) antigen specificity - what the antibody interacts with; ii) the genes that form the antigen binding site on the antibody (variable (V), diversity (D) and joining (J) genes). For the last 40 years, the former method has been employed by clinical diagnostics to detect autoantibodies but has limited value for predicting disease outcome. For example, maternal autoantibodies binding the Ro self-antigens are associated with foetal cardiac abnormalities such that weekly echocardiograms from 12-22 weeks gestation are recommended for all Ro autoantibody-positive pregnancies. However only 2 per cent of these pregnancies result in this disease. A more specific biomarker would identify patients at highest risk, allowing for early intervention and improved disease management.

Advances in genomic technologies for sequencing antibody genes now make it possible to evaluate VDJ-genes for diagnostic purposes. Specific VDJ-genes have become useful diagnostic and prognostic indicators of lymphoma. Extending this approach to autoimmunity creates the exciting possibility of stratifying autoantibodies according to VDJ-gene usage and clinical symptoms. Previous research by others and myself has revealed distinct subsets of Ro autoantibodies that cause disease pathology. These “pathogenic” Ro autoantibodies cannot be distinguished from “quiescent” Ro autoantibodies by routine diagnostic assays. Genetic analysis of Ro autoantibodies is limited but has revealed biases in VDJ-gene usage across multiple patients. This research will extend these promising preliminary studies to evaluate the diagnostic utility of sequencing VDJ-genes and reveal where autoantibodies come from.

Mental and substance use disorders account for more years of life lost due to disability than any other disorders and are second only to cardiovascular disease and cancer as leading causes of disease burden. Comorbidity of mental and substance use disorders pose a significant challenge for the Australian health system. The silo structure of the healthcare system has historically treated clients in parallel by different treatment providers. Typically, treatment is incomplete and outcomes are poor.

The NHMRC Centre of Research Excellence in Mental Health and Substance Use (CREMS) leads the way in new research examining innovative treatments for comorbidity. NSW health services provide a unique context into which new approaches to comorbidity treatment can be embedded. Our research has demonstrated that an integrated, stepped care (ISC) approach is ideal for optimal client outcomes and to avoid clients falling through the gaps.

Integrated care involves both substance use and the mental health condition being addressed by the same provider. This can be facilitated by a stepped approach where additional care is provided for a mental health diagnosis after stabilisation from substance use, enabling the distinction between substance-related mental health symptoms versus symptoms remaining or emerging once use has resolved.

This project aims to:
i) Evaluate the impact of a Multi-modal Translation Intervention Package (MTP) to (a) increase ISC proficiency and uptake; (b) enhance clinician knowledge and attitudes; (c) improve substance use and mental health outcomes.
ii) Examine barriers and facilitators of ISC implementation using the MTP.
iii) Deliver MTP resources and sustainability recommendations to NSW Health for future rollout.
Promote identification, assessment and clinical management of comorbidity within the drug and alcohol services of NSW local health districts.

Genomic technologies, including targeted sequencing, and more recently, whole genome sequencing (WGS) have generated unprecedented insights into the molecular basis of disease. The application of WGS to patients with rare Monogenic Disorders is now identifying a molecular diagnosis in approximately 50 per cent of patients. The ability for WGS to characterise structural variants (SV) has redefined the genomic landscape of many cancers, providing treatment insights that were not possible from targeted sequencing approaches alone. One of the greatest challenges for precision medicine is the translation of bioinformatic methods developed in the research setting, often to study cohorts, into the clinic. Methods must be accurate, fast, comprehensive, interpretable by a multidisciplinary team, and must apply to the n-of-1 patient-centred situation.

The purpose of this proposal is to improve the clinical management of patients with inherited genetic disease, through increasing the diagnostic yield in rare disease, or improved tumour characterisation. The objectives of the proposal are to continue to develop a suite of bioinformatic approaches to uncover different aspects of genome biology and assess how these influence disease, and ultimately to translate these methodologies into clinically accredited tests. Many of these aspects of genome biology can only be uncovered by WGS. As we have already developed Australia’s first clinically accredited^ WGS-based diagnostic test for investigating single nucleotide variants (SNVs) and small insertions and deletions, we are uniquely positioned to achieve these objectives.

This proposal will develop critical bioinformatic and translational capability to improve patient care in NSW, and beyond.

This screening and secondary prevention project could help reduce the burden of stroke worldwide by introducing a novel, scalable, cost-effective technology to screen for post-operative atrial fibrillation (POAF) following cardiac surgery discharge. This project could influence policy and AF management guidelines to include routine monitoring for POAF recurrence.

POAF occurs in 25-40 per cent of cardiac surgery patients, and is associated with increased mortality and stroke risk. POAF is thought to be transient and self-correcting, thus patients discharged in stable sinus rhythm are rarely followed up. POAF recurrence is often missed as it is largely asymptomatic or has non-specific symptoms. Additionally, patient knowledge of the extent of AF symptoms is poor despite inpatient education. In my systematic review (n=6 studies) active monitoring post-discharge identified POAF recurrence in 33 per cent of patients with transient in-hospital POAF, and late-onset POAF in ~4 per cent with no prior POAF. I have shown self-monitoring for POAF recurrence is feasible using a smartphone handheld ECG (iECG).

The outcomes from this study will assist development of a risk score to better identify patients at highest risk of devastating complications, such as stroke, allowing clinicians to better target effective preventative therapy. The project aims to:
1. Determine the incidence and predictors, and explore the prognostic significance of recurrent POAF and late-onset POAF
2. Determine if education using a 'graphic app' improves patient knowledge, particularly awareness of POAF symptoms
3. Determine scalability of self-monitoring using an iECG.

Cardiovascular disease is the leading cause of premature death among Aboriginal Australians and there is increasing disparity in rates of cardiovascular-related deaths between Aboriginal and non-Aboriginal Australians. From 2008-2012, non-communicable diseases, such as cardiovascular disease and diabetes, accounted for 81 per cent of the gap in mortality rates. Obesity (16 per cent) and physical inactivity (12 per cent) are leading risk factors in the development of chronic disease and the overall health gap in Aboriginal Australians.

Obesity is responsible for 1-3yrs of the 10-yr gap in life expectancy. Higher levels of these modifiable risk factors that contribute to this health disparity among Aboriginal adults are already present in Aboriginal children. Compared with their non-Aboriginal peers, Aboriginal children are 1.4 times more likely to be overweight or obese, 1.8 times more likely to exceed screen time guidelines and 1.6 times more likely to have unhealthy eating habits. The risk of type 2 diabetes in Aboriginal children is 8 times higher than in their non-Aboriginal counterparts.

As cardiovascular disease is one of the leading contributors to the life expectancy gap, there is a need to better understand the key modifiable behaviours of cardiovascular disease, such as physical activity (PA) and sedentary behaviour (SB), and better understand culturally acceptable ways to promote healthy levels of these behaviours among Aboriginal children. This evidence is currently lacking for Aboriginal children and is critical to improving cardiovascular health behaviours in Aboriginal Australians.

Conducting research with Aboriginal communities is a long-term commitment, requiring respectful negotiations within the research partnership, which can only occur through continuous and consistent relationship building. This fellowship will build on a 2-year partnership with three Aboriginal communities in NSW. A priority identified by these communities is to raise healthy children and provide their children with opportunities to connect with Country and culture. This fellowship will use a behavioural epidemiology framework to understand PA and SB behaviours among Aboriginal children and how these health behaviours relate to cultural connectedness.

Specifically, this project aims to:
1. Determine the prevalence and patterns of PA and SB and their associations with cardiovascular health.
2. Identify the cultural determinants of PA and SB;
3. Design, implement and evaluate an afterschool Aboriginal cultural program to promote healthy lifestyle behaviours; and
4. Translate the evidence into dissemination strategies of Australia’s Physical Activity Guidelines to 5-12 year-old Aboriginal children.

This project will address an internationally-important healthcare problem in hospital emergency departments: with a surging demand for services, how can we ensure a safe environment for patients while still maintaining throughput?

In the first quarter of 2016 there were 672,483 presentations to NSW emergency departments (EDs) – a 9 per cent increase in triage Category 1 patients, and a 4 per cent increase in presentations overall compared with 2015. Despite introduction of National Emergency Access Targets across Australia in 2010, 25 per cent of patients were not ‘seen on time’ in accordance with Australasian Triage Scale standards, and 26 per cent of visits were not concluded within 4 hours. Increasing numbers of patient presentations, coupled with limited in-patient bed capacity, can result in long waiting times and prolonged lengths of stay in the ED. Overcrowding is becoming more prevalent, and has been associated with an increase in medical errors and poor patient outcomes, including death.

When EDs get overloaded, things are more likely to go wrong (e.g diagnostic errors, medication errors, delayed treatment). The processes we put in place to prevent errors from occurring often add to workload in the ED, paradoxically making it even more likely that things will go wrong. A new way to solve this dilemma is to shift our focus from preventing things going wrong, to increasing the number of things that go right. We call this ‘productive safety’. The purpose of this project is to design and implement ED processes to improve productive safety in NSW public hospitals. This project will seek to identify key quantitative and qualitative measures that are predictive of productive safety in response to unexpected events and periods of peak patient demand in the ED. Based on these measures, processes will be developed for assessing and improving productive safety. By doing so, we will assist ED leaders and clinicians to evaluate their organisation, and implement action to improve the number of things that go right when faced with challenging or unanticipated conditions. Such a proactive effort is likely to strengthen ED responses to threats and crises, and thereby save money and lives.

The project aims are to:
1. establish baseline measurement of productive safety in EDs in NSW public hospitals
2. refine productive safety processes, following an in-depth study of two NSW ED cases
3. develop a suite of context-dependent and generic tools to support re-design of processes to improve productive safety in EDs in NSW public hospitals.

Mitochondrial diseases are the commonest group of inherited metabolic disorders. Children often present with severe disease that is fatal in two thirds of patients before the age of 16. Adults tend to endure chronic and progressive disease that is often be severely debilitating and precludes them from employment. Mitochondrial diseases are notoriously difficult to diagnose due to the diversity of genetic causes (>300 mutations in mitochondrial DNA and >150 known nuclear disease genes), the extreme variability in clinical presentation (the same mutation in a family can manifest very differently) and a lack of comprehensive and definitive diagnostic tools.

The current diagnostic pathway involves invasive, expensive and inaccurate testing that often results in patients going undiagnosed or being misdiagnosed and spending years trying to access appropriate healthcare. This project will evaluate two new diagnostic tools, metabolomic biomarker profiling and genomic sequencing, in order to define a rapid, cost-effective, comprehensive and accurate diagnostic pathway that will improve the diagnosis of mitochondrial diseases.

Accurate diagnosis enables specialist clinicians to encourage disease modifying lifestyle changes, to administer appropriate treatments, identify and avoid contraindicated pharmacological agents (e.g. the common antiepileptic sodium valproate can cause death in mitochondrial disease patients presenting with seizures) and to provide informed family planning. The accurate diagnosis of mitochondrial diseases would also have a significant impact on the cost to NSW Health associated with undiagnosed or misdiagnosed patients, would enable treatment development through better understanding of disease pathophysiology in defined disease-specific cohorts, would define patient cohorts for genotype-specific clinical trials and enable appropriate treatment administration to those who will benefit most.

As genomic sequencing and bioinformatic analysis costs are still considerable, the first objective of this project is to develop metabolite signatures (combinations of small molecules that can be used to define a disease discriminatory test) of the mitochondrial disease group and individual mitochondrial diseases. This frontline indication of disease will inform clinical decision-making on whether to progress to other diagnostic testing, including comprehensive genomic sequencing.

As a result of recent technological advances, it is now possible to simultaneously and comprehensively sequence both mitochondrial and nuclear genomes. However, the very recent introduction of this technique means that objective research evidence for its applicability to genomic healthcare and how best to integrate it into clinical practice is lacking. Therefore, the second objective of this project is to develop a robust bioinformatic approach for the identification of causative mitochondrial disease mutations.

Inflammation is central to the pathogenesis of atherosclerotic plaque progression and athero-thrombotic vascular events with systemic inflammatory markers correlating strongly with prognosis in acute coronary syndrome (ACS) patients. Indeed, these patients are particularly vulnerable to recurrent ischaemic events in the early post-ACS period, likely driven by pan-coronary inflammation, resulting in a higher prevalence of vulnerable non-culprit plaque.

Moreover, percutaneous coronary intervention (PCI) to treat culprit coronary stenoses in the setting of ACS, is strongly associated with a relatively high rate of peri-procedural myocardial infarction and adverse cardiovascular outcomes, due in part, to distal embolisation of inflamed plaque fragments with microvascular obstruction. Therefore, suppression of atherosclerosis-associated inflammation is of critical importance to stabilise vulnerable plaque (AIM 1); to decrease inflammatory mediator release after PCI of vulnerable lesions (AIM 2); and to reduce plaque progression/instability, which itself is strongly linked with adverse cardiovascular outcomes (AIM 3).

The principle aim of this project is to investigate a new, innovative, and cost-effective approach to reduce the deleterious effects of atherosclerosis-associated inflammation, based on our discovery that oral colchicine, a safe and well established drug, widely used in non-vascular inflammatory disorders, has marked anti-inflammatory properties in ACS patients. Notably, SP’s recent published studies have elucidated that colchicine, within hours of ingestion, markedly reduces (1) secretion of the pro-inflammatory cytokine IL-1β by circulating monocytes and (2) local coronary levels of the inflammatory cytokines IL-1β and IL-18, together with downstream IL-6, a cytokine strongly linked with future coronary events.

Based on these findings, colchicine’s acute effects on plaque stability will be studied, as well as its more long term effects on plaque volume/inflammatory content. Such studies have enormous clinical relevance as they have the potential to directly improve outcomes in patients presenting with unstable coronary syndromes, particular in the context of PCI, as well as ‘stable” patients with established atherosclerosis. Moreover, as colchicine is safe, readily available and cost-effective, it can be rapidly included as part of the standard therapy for both ACS and stable coronary disease patients.

Delirium, a transient confusional state, is an increasing problem for Australia’s ageing inpatient demographic. Incidence rates from international studies range between 3-29 per cent for patients over 65 years, equivalent to 116,731 – 1,128,400 inpatients using Australian 2013-14 admissions data.

Higher rates of 47-63 per cent have been observed in surgical patients over 65 years, and critically ill patients with delirium have substantially higher prevalence rates (up to 70 per cent) and longer hospital stays (by 6.5 days). Delirium has a significant health impact as inpatients developing delirium are 2.6 times more likely to die during admission, and have a higher risk of developing dementia (adjusted relative risk of 5.7, CI 1.3-24.0). The presence of pre-existing dementia increases the risk of developing delirium two to five times.

A key factor for this research is that delirium is largely preventable, using evidence based guidelines for implementing pharmaceutical, physical, and care delivery changes to inpatient care. The Australian Commission for Safety and Quality in Health Care is releasing a new Delirium Clinical Care Standard (Standard) in 2016 which incorporates this multi-component approach. This is therefore a critical time to investigate and evaluate the impact and effect size of implementing the new Standard, whether the Standard is being implemented as planned, and whether the Standard is effectively addressing the need to identify, prevent and treat delirium.

This study will provide critical data for assessing the benefits to patients and cost-savings gained through preventing and treating delirium in a rapidly ageing population, using a novel combination of applied health economic and implementation science principles. Delirium incidence rates in study hospitals will be measured before, and after, the implementation of the multi-component intervention that forms the basis of the Standard. In addition to standardised clinical outcomes, the study will assess barriers and enablers to the implementation and provide vital feedback to policy makers to understand and improve translation of the evidence based guidelines into practice. Despite existing research on the design of the multi-component interventions, the financial impact of delirium to the health system, and effectiveness of interventions for clinical outcomes, the unique contribution of this study is in determining the cost-effectiveness of these multi-component interventions in Australian acute care and the factors that ensure success.

Medial tibial stress syndrome, commonly known as ‘shin splints’ is an overuse injury that affects up to one third of athletes every single year. Despite this vast number of sufferers, the injury is poorly understood and treatment options are limited to extensive rest and physiotherapy. While physiotherapy works, it is expensive, extremely time-consuming and the high rate of recurrence of the injury is incredibly frustrating to both the physiotherapist and the athlete.

The Solushin is the world’s first medical device clinically validated to treat shin splints. By combining two effective principles of treatment: softtissue therapy and bone-remodelling, this patented product has effectively demonstrated in a clinical setting (double-blinded randomized controlled) its ability to get athletes back to pain free training within 5-weeks.

In a market saturated with products distrusted by physiotherapists (calf compression sleeves), the Solushin is the first medical device with supporting clinical evidence. With the long-term goal of saving 134,000 hours of treatment time per year in NSW alone, the results from the trial are firstly being presented at the 2019 ASICS Sports Medicine Australia Conference in October. Our goal is to have our first batch registered and manufactured for sale by this date.

Current prosthetic sockets are still made by the very time consuming and inaccurate process of forming a plaster cast to create a mould for the socket manufacturing. In addition to being very time consuming and labour intense, it can also result in a poor fitting socket. This poor fit can cause skin irritation, uncomfortable or painful sensations and impact the balance or ability to walk correctly. The X-Limb approach undertakes a 3D-scan of the residual limb to create a digital image, allowing for a digital workflow. The prosthetist can then make quick electronic adjustments to the digital image to suit the patient specific needs and send the file for a prompt and accurate creation using 3D-printing technologies.

During the next 12 months we will undertake software development and refinement to ensure it is built around prosthetist needs and to enable the best outcome for their patients. We will undertake comparative testing against traditional manufacturing techniques to demonstrate the improved workflow and increased accuracy, whilst ensuring a strong and comfortable prosthetic socket.

Heart failure with preserved ejection fraction (HFpEF) accounts for as many as half of all hospital admissions with a diagnosis of heart failure. Aortic stiffness is a major risk factor for HFpEF. Studies have examined various classes of antihypertensive medications to treat HFpEF, yet there are still no well validated treatment strategies which have shown a significant mortality benefit.

Vascular Pivot is developing a medical device to restore function of the largest artery in the human body, the aorta, to improve the quality of life for patients with HFpEF. Our device is improving the elasticity of an old and stiff blood vessel. This allows an aged and failing heart to maintain its effectiveness as a pumping unit. Our self-powered device is a chronic implant and treatment of hypertension.

A second market for Vascular Pivot’s technology is to improve aortic prosthetic graft compliance.

Benchmarking our device’s underlying principal with computer simulations and in-vitro benchtop testing, we can demonstrate significantly increased compliance. Over the next 12 months we will conduct an animal trial with a stiffened aorta to test the safety and efficacy of our device, preparing us for first-in-human trials.

We aim to reduce the health cost burden by targeting earlier therapeutic intervention in the heart failure cycle. A key to Vascular Pivot’s technology is long term prevention of hospitalisation which represents 60% of heart failure costs.

The occurrence of dental cavities and associated oral conditions is increasing worldwide. According to the World Health Organization (WHO), in 2012, 60-90% of children and nearly 100% of adults worldwide had dental cavities. Currently, the prevention to the most common dental diseases, such as dental cavities related to biofilm build up by oral bacteria (commonly referred to as plaque), highly relies on the individuals. A daily routine of oral hygiene, i.e. brushing and flossing of teeth, combined with a healthy diet and regular checkup is recommended, which is always compromised.

Our technology provides a fully covered protective coating on the tooth surface, which is robust enough to function in the complex oral environment and withstand the wear and tear experienced by teeth. The safe, cost-effective and long-lasting coating for the tooth surface will effectively prevent the colonisation of bacteria and the formation of biofilm, leading to a significant reduction in dental problems and diseases.

In the next 12 months, the long-term efficacy of our teeth coating will be tested in a simulated oral condition. Meanwhile, we will engage with the key partners to further explore our business model canvas.

Microbial diagnostics that use PCR or culturing techniques, struggle to quantify infectious microbes when identifying them from a mixed sample.

Being able to accurately determine the amount of a microbe in a mixed sample is important when the quantity of that microbe dictates whether it is a benign condition or a serious infection.

An example of this is lung infections by the fungus aspergillus. Fleeting colonisation of the lungs by aspergillus is common and benign, but invasive aspergillosis is a lifethreatening fungal infection.

We are working on a nanopore based DNA sequencing test that can not only identify the microbe present in a sample but can also estimate the amount of the microbe present, relative to background benign microbes or patient cells.

Our test will hopefully allow for clinicians to accurately and quickly diagnose fungal lung infections like invasive aspergillosis. The benefit of which is that clinicians can stop resorting to prophylactic and empiric uses of antifungals, since antifungals are costly and toxic and their overuse results in increased antifungal resistance.

Medical conditions with a genetic cause account for nearly half of Australia’s paediatric hospital admissions. Splicing variants are commonly suspected causes of these genetic conditions, though a definitive clinical diagnosis is rare. GENEie is a laboratory clinical
decision support tool that can establish whether suspicious splicing variants are the actual cause of a genetic disease in more than 99% of cases.

Current technologies offer little meaningful assistance to laboratories in resolving this diagnostic conundrum. GENEie is a paradigm shift in variant analytics that is conspicuously differentiated by its clinical actionability, scientific validation and diagnostic accuracy
with the hardest-to-resolve cases.

GENEie is a Software-as-a-Service commercial opportunity, with global genomic testing service providers our primary market. By the end of 2019, we will achieve clinical validation and customer evaluation milestones, in partnership with leading Australian genomic testing reference centres. Our goal is to achieve our first commercial sales in Australia in 2020.

One in ten people around the world have problems going to the toilet. The biggest barrier to recovery is patients not complying with their treatment plan. Patients are frustrated with not being able to see their progress at home and the need to revisit clinics for training.

The In & Out Trainer is an insertable device that guides users through muscle exercises in their back passage while providing real-time feedback on their smart phones. Users follow clinically proven exercises that are designed to be fun and engaging while treatment progress is tracked through a free mobile app. The value to our users is the ability to train every day at home instead of once a month at a clinic, this translates to measurable improvements within days.

We are excited to be part of the industry wide shift toward patient driven healthcare. In & Out enables patients to be an active participant in the management of their healthcare and the ability to partner with health providers in the decision making process for their treatment.

The cornea is the clear window at the front of the eye, and corneal disease is the third most common cause of blindness worldwide. Corneal ulceration is extremely painful and accounts for 55,000 presentations to hospital each year across Australia. Current medical treatments do not adequately address issues of pain relief, infection, or the development of scar tissue. Infection and scarring may necessitate lengthy hospital stays and further treatment.

The iFix system developed by iFix Medical is a handheld 3D printer that can deliver a 3D-printed structure directly onto the eye to treat defects. It comprises two components: iFixInk™ and its delivery device, the iFixPen®.

The system involves the printing of a transparent structure that seals the wound and prevents pathogen infiltration. It relieves pain, accelerates healing and is biodegradable. The ink formulation can be tailored to clinical need and can contain antibiotics and or other active regenerative agents.

The iFix Medical team has conducted small animal studies demonstrating the system worked for two conditions: corneal ulceration and perforation. In the next 12 months, the team will conduct and complete a large animal study and prepare for a first in human pilot study.

Spasticity is an overactivity of the spinal reflexes which leads to tight muscles and painful spasms. Our focus is on alleviating the disability associated with spasticity that results from cerebral palsy, the leading cause of childhood disability in the world. Our aim is to restore freedom of movement enabling children to live an active life without muscle tightness and pain.

It is our belief that implantable electronics, similar to cochlear implants or cardiac pacemakers, have the capability to control this nwanted electrical activity. Our technology is a closed loop spinal cord stimulator that delivers patientspecific electrical impulses exactly when and where they are needed. Other spinal cord stimulators on the market have shown a limited benefit in spasticity, but only in tightly controlled research scenarios. No other commercial device has closed loop control which we believe will be critical to solving spasticity. Our goal is to commence a 30 patient clinical trial within the next 12 months.

Being fixated on a problem and a patient group where there is an extremely high demand for new disruptive treatments, and being flexible regarding the exact technology that solves this problem, can enable a rapid progression from concept to market.

SleepCardio is a cloud-based software using off shelf sensors for home-based sleep tests. Sleep apnoea is a serious health issue which involves a reduction or complete halt of airflow during sleep. The hospital sleep test for diagnosis of sleep apnoea requires attachment of 22 wires and sensors to patients during sleep and an overnight stay in the hospital. It is also expensive with long waiting time. Thus, 90% of the sufferers remain undiagnosed and if it remains undiagnosed it can lead to cardiovascular diseases and stroke. Current home-based sleep tests either interfere with sleep or are not accurate enough to eliminate the need of follow up hospital test. SleepCardio only use two sets of sensors a wrist band for measuring blood oxygen level and a chest band for measuring heart rate and respiration. Using modern machine learning techniques and signal processing methods, more information is extracted from fewer numbers of signals and by combining the information provide an accurate diagnosis of sleep apnoea. Also this device can predict serious cardiac disorders and stroke.

Thus, the doctors can begin the treatment before noticing any cardiovascular clinical symptoms. It will reduce costs and saves many lives.

Organ transplantation is a lifesaving procedure; however the major challenges are shortage of suitable organs and complex logistical coordination to minimise organ injury during the transportation, since organs are no longer receiving oxygen.

OxyLone is a protein capable of retaining oxygen to a much greater extent than current organ preservation solutions, providing a better environment for organ maintenance during transfer. Betterpreserved organs result in better transplantation outcomes as well as expanding the pool of usable organs.

OxyLone transforms the way transplantations are performed by enabling better timing of the transplant operations to avoid night time procedures, increasing flexibility in transportation and preventing problems or delays in graft function. This protein is derived from an Australian aquatic organism and is capable of releasing oxygen similar to haemoglobin, but can bind 40 times more oxygen molecules than haemoglobin.

Over the next 12 months we will work with transplant surgeons Hospital to perform proof of concept experiments on small animal models to prove the efficacy of this strategy.

Medication errors cause serious harm and have been estimated to cost $1.2 billion annually in Australia. Many medication errors are dosing errors involving measurement of liquids. Liquid medication doses are commonly used for children and the elderly in an oral form, and for all patient types in injectable forms.

SetDoseTM is a smart syringe system designed to eliminate liquid medication dose errors. SetDoseTM utilises a combination of software and hardware to control medication dosing and record dose administration events. Our team of nine healthcare professionals and engineers have just filed a provisional patent for SetDoseTM and will be working on prototype refinement and software development over the next 12 months.

Lack of blinking in facial palsy leads to corneal dryness and scaring and eventual blindness in the eye. Restoring blink remains the greatest challenge in facial reanimation surgery today. Patients are managed conservatively with indefinite use of lubricants and implanting weight into their top eyelid for assisted-closure.

When this fails, the eyelids are stitched together permanently. We propose the use of an implantable device to actively restore blink. The technology aims to recreate physiological blink using a wirelesslypowered, biocompatible actuator.

BLINC will be a paradigm shift in the field of facial reanimation for effective restoration of blink. The next milestone in the development of BLINC is live animal testing over the next year.

Intellectual disability (ID) affects 3% of children, and moderate ID is usually due to one of a large number of individually rare single gene disorders. Advanced genomic sequencing now allows testing of all the known 1500 ID genes. However, the interpretation of DNA data is extremely time consuming, and despite testing all known ID genes, 60-70% of children remain undiagnosed, with an estimated 2000 ID genes still to be discovered.

As 50% of people with intellectual disability have distinct facial features which provide a clue to diagnosis, we have worked with Imagus Technology to develop FaceMatch, a computer vision algorithm which outperforms senior clinical geneticists at syndrome diagnosis within our published pilot data.

FaceMatch will have clinical utility to 1) screen children who are late meeting their milestones; 2) streamline interpretation of genomic data and 3) match the faces of undiagnosed patients. Historically, new genes have been discovered by matching the genome data of individuals who look similar.

The market advantage over our main competitor is sensitivity across a range of ages and severities. Over the next 12 months, we will continue research and development to ensure that FaceMatch reaches international quality and regulatory requirements for software as a medical device.

3D Fractional Moving Blood Volume is a non-invasive measurement of perfusion using ultrasound. This technology combines medical image analysis and power Doppler ultrasound, to enable a sonographer or doctor to evaluate the amount of blood flow (perfusion) in a particular organ, tissue or tumour. This technique provides a marker of organ function and can detect change over time. The technology uses machine learning and image analysis to automatically and in real-time generate a value of blood flow in a given area that compensates for differences in machine settings, depth and attenuation.

Having understood the challenges of commercialisation of this device, I intend to continue its development to provide strong clinical evidence of its efficacy. In parallel with this, I intend to work with partners at public clinics and eHealth NSW to understand potential cross-over in image collection and analysis at a State level.

Congenital heart disease is associated with high levels of morbidity. At least a third of patients born with congenital heart disease will require one major open-heart operation. Often, this heart surgery involves construction of a valved conduit connecting the right ventricle and pulmonary artery to repair complex defects. Current modalities for tissue repair are homografts (from cadaver) and xenografts (from animal). Both have shortfalls in biocompatibility and durability, and most importantly, growth potential. As such, paediatric patients require up to four operations to replace the conduit throughout childhood and adolescence.

At TrueHeart, we aim to overcome the key complication of reoperation through the research and translation of novel medical implants. We have conceptualised a tissue engineering solution that utilises bespoke implant fabrication and 3D printing. This technology will allow us to improve the health are outcomes and quality of life for young patients affected by congenital heart diseases.

During the Medical Device Commercialisation Training Program, we have developed a straightforward business model canvas for this technology. In the next 12 months, we will focus on two aspects of this technology. From a technical point of view, we need to conduct large animal studies to prove the functions of the designed biomaterial. On the business side, we need to continue interviewing potential customers and key partners to finalise the business model canvas boxes.

Device-related infection represents a significant public health issue and financial burden on governments around the world. Antimicrobial coatings based on antimicrobial peptides and quorum sensing inhibitors were developed by our group at University of New South Wales to prevent such infections.

Quorum sensing is a cell-to-cell communication mechanism between individual bacterial cells, which coordinates gene expression and behaviours for bacteria cells in close proximity.

Our antimicrobial coatings have broad spectrum activity against bacteria, including drug-resistant strains, as well as fungi and protozoa. The coating could be applied to a variety of materials such as polymers and metals, making it suitable for a range of applications such as contact lens and implants.

The antimicrobial coatings are composed of two classes of bioactive agents, antimicrobial peptides and quorum sensing inhibitors with unique advantages over current antibiotics. Antimicrobial peptides are nature’s defence against bacteria found in humans as well as a variety of animals and plants. These peptides act primarily through the disruption of bacteria membrane, which bacteria is unlikely to develop resistance for, leading to cell death.

I would like to apply all the things I’ve learnt in the Medical Device Commercialisation Training Program to make the technology into a viable business. In the next 12 months, we will look to conduct further experiments and product development to gather data to satisfy the substantial regulatory approval process required for the future.

StandingTall is an engaging home-based exercise program using mobile technology for preventing falls in older people. StandingTall runs on any tablet device and can be used at home. It is tailored to the user’s ability and utilises advanced algorithms to progress difficulty over time. Because of this and the large variety of exercises, it is motivating and effective.

Now that I have completed the Program, I plan to revisit some of the topics. I will perform additional customer interviews to validate my current business model. These steps will allow me to advance the business case for StandingTall and put us in a good position to seek funding.

With a current world population of 900 million people aged 65 and over, a number that is expected to double by 2050, injurious falls and their prevention are a major, and growing societal issue. Implementation of cost-efficient and scalable fall prevention, such as StandingTall, is timely and urgent.

The Allegra Orthopaedics fully synthetic spinal cage, works to regenerate bone under spinal load conditions and be completely resorbed by the body, leaving it and the intervertebral space free of foreign materials. This is a one-of-a-kind innovation.

The device is 3D-printed from a synthetic bone bioceramic (Sr-HT-Gahnite) invented at the University of Sydney and licenced globally by Allegra Orthopaedics. The synthetic bone possesses the mechanical strength required for load-bearing conditions, bioactivity needed for outstanding bone regeneration, and resorbability that reduces the risk of rejection and infection all in a customisable structure. No bone graft is required as the device material induces bone graft.

Over the next 12 months I will continue with my customer interviews and discussions with surgeons who are supportive of the technology. My key goal is to design and implement much of the pre-clinical studies.

SIXTH SENSE – Your Balance Right tests peripheral vestibular (balance) function. If you have ever had motion sickness or alcohol poisoning, then you may have experienced a balance sensor dysfunction. For vestibular patients these acute symptoms last weeks and chronic symptoms can be permanent and notoriously difficult to diagnose. Patients are incapacitated and terrified they have a brain tumour, a stroke, are dying or ‘going crazy’. Patients go from general practitioner to neurologist to rehabilitation for years, with no diagnosis or the wrong diagnosis (migraine, depression, mental illness) in some instances.

Around four per cent of adults report a chronic problem with balance and 35 per cent of adults 40 years and over have experienced vestibular dysfunction. For older people (aged 65 years and older), 80 per cent have experienced dizziness.

Sensory disorders are a large health burden. The dominant test for the last 100 years, caloric irrigation, evaluates only two of 10 sensors. In 2009, we published one of our dozen vestibular testing tools (vHIT) that evaluates six sensors. Our new device, Micro Vestibular Evoked Myogenic Potentials (uVEMP), tests the remaining four sensors. Together vHIT and uVEMP can test all 10 sensors.

Coeliac disease is a condition in which the body’s immune system is unable to properly process gluten – a protein found in consumed wheat, barley and rye. It causes inflammation and damages the small intestine, and if undiagnosed can lead to small bowel cancer.

Coeliac disease effects on average one in 70 Australians. Around 80 per cent of coeliac sufferers are undiagnosed as many symptoms are similar to other disorders.

Our team has developed a noninvasive test to screen for coeliac disease by simply using saliva and obtaining a result within minutes. Our saliva-based test offers a cheap, accurate, simple and safe point-of-care test that could potentially be available to the general public and clinicians.

This Program has helped us to shape our idea and create a solid evidence for the need of our technology. We will put into practice all the skills the Medical Device Commercialisation Training Program has equipped us with and start our commercialisation journey.

We leave Cicada with a better understanding of our market and the network of people who can help us navigate the next 12 months.

InKardia is a dream that started over 10 years ago in the United States and is based on the development of the biological ink (or “bio-ink”) that acts as a mini-human heart tissue in a test tube. This technology starts from understanding how the heart develops in nature and uses patient-derived stem cells. The bio-ink is used to build human heart tissues using a “bioprinter” that 3D prints, layer-by-layer, within a cardiac-tailored bio-paper (“hydrogel”). Patient-specific bioinks are used as diagnostics for cardiovascular disease patients or to prevent side effects. Bioprinted heart tissues are also used to treat heart failure in patients that cannot receive a heart transplant.

In Australia, only 95 out of over 13,000 heart failure patients received a heart transplant in 2015. Given the calibre of the potential market for this technology and the lack of heart transplants available for patients, in the next year my main goal is to establish a company based on this novel technology, and seek funding to support clinical studies. I will also look to partner with experts with different skills in the commercialisation of medical devices to take with me in this long journey.

Respia is an asthma management system that tracks and records the wearer’s respiratory health. It’s a wearable patch for children with asthma that detects early signs of asthma before they become noticeable symptoms or worse, asthma attacks. It’s a communication link between parents and children with asthma. Our goal is to reduce the number of preventable hospitalisation events for kids with asthma. In doing so, we will save children from trauma, parents from stress, and the public health system money.

In the next 12 months Respia will open a seed round of funding. We will use this funding to build a higher fidelity prototype for upcoming clinical studies and trials. Respia is also looking to strengthen its management team with business and regulatory expertise.

The long-term vision of Respia is to provide preventative health solutions to markets where reactivity is the established norm. Respia wants to help parents understand their child’s asthma and make informed decisions on how to best manage the condition.

Rheumedica is a precision medicine company that is transforming the way we diagnose patients with autoimmune arthritis. The company has made a ground-breaking discovery that explains the pathological mechanisms involved in autoimmune arthritis. The device is a companion diagnostic to the current test and the first specific test for these patients. This technology has greater accuracy compared to the current test which has on average a 30 per cent false-negative result. This is the only specific test which is accurate and specific to autoimmune arthritis.

Over the next 12 months we will work in collaboration with rheumatologists and dermatologists to complete a clinical trial using our technology. We will publish the results in a reputable journal and apply for compliance/registration of the technology in the main continents. We will work with our early market adopters to achieve market share and partner with an established company to distribute our technology.

We are establishing a new service to test for human papillomavirus (HPV) and vaginal microflora for women to take their own vaginal swab samples in the privacy of their own home. Self-sampling is a simple procedure which involves collecting a vaginal sample by the woman. After collection, the sample is sent to a registered pathology lab for testing with the results sent to the woman via a general practitioner. This provides an alternative to presenting at a doctor’s office in managing a woman’s vaginal health and can increase the detection of HPV by encouraging more participation in screening.

My goal after completing the Medical Device Commercialisation Training Program is to gain more knowledge about business. As most ambitious people, I came into the course thinking that I could be an entrepreneur and start my own business. The course has made me recognise that in order to be a successful entrepreneur I need to obtain specific business knowledge and develop my skills, which is now my goal for the coming year.

The invention is a bioresorbable subdural drain to be used for the treatment of chronic subdural haematomas. The drain design includes a z-bend in the cranial end for ease of insertion through a burr hole, bioresorbable tubing to be tunnelled through subcutaneous tissue to land within a pouch formed for drainage and interstitial absorption. This drain will reduce recurrence rates of chronic subdural haematomas, the need for surgical revision, allow patients to move soon after the procedure, and reduce the overall hospital length of stay.

Over the next few months my goal is to continue working on a viable prototype which will eventually be implanted and trialled. If the drain proves viable and becomes the standard for treatment of chronic subdural haematomas, I would like to see its possible applications expanded beyond neurosurgery into other surgical specialties.

A diagnosis of a brain disorder is often made worse by the lack of effective treatments and the substantial side effects of current treatment. Despite over 200 million people facing this problem, many companies have stopped developing new brain disorder treatments. Current methods for predicting the effectiveness of brain disorder drugs have shown to be of little help, with failures costing the industry many hundreds of millions of dollars in the past decade.

VitroQuest is addressing this problem by providing a drug validation service built on the actual human disease biology to test ineffective treatments early in development. By using our validation platform, drug developers will reduce the risk of future efficacy failures and increase their confidence in the remaining treatment candidates. This will improve the financial viability of developing brain disorder treatments.

The Program content together with the learnings from the customer discovery interviews has given me the confidence to bring this technology to the market. I am confronted daily by the desperate need for better treatments of brain disorders. I believe I can help improve this dire situation by putting all my energy into making this technology available to drug developers.

Proton-X is a revolutionary patient positioning system for use in proton therapy systems. This patient positioning device integrates into current Proton therapy systems. It introduces two major changes to proton therapy:
- positioning the patient in an upright position from the horizontal plane delivers better clinical results and allows proton vendors to fix their radiation beams, and
- rotating the patient rather than the machine reduces infrastructure size and cost.

Having completed the Medical Device Commercialisation Training Program, I have strengthened my commercial skills along with my overall understanding of how product development fits within the wider business context. Over the next 12 months I would like to take the business model canvas developed during this course and expand on it, working with a proton therapy vendor to strengthen the business case for upright proton therapy.

The end goal will be to see an upright proton therapy patient positioning device delivered to the market through an Original Equipment Manufacturer relationship between Leo Cancer Care and a leading proton therapy vendor.

Watery, blurry, red, itchy or dry eye, are all symptoms of dry eye disease. This disease is caused by the tears of the eyes not forming an effective protective film over the eyes after blinking. In severe cases, this diminishes the quality of life to the same level as having a badly broken hip. Confirmation that these symptoms represent dry eye
disease is difficult because it is a complex disease with multiple causes and current diagnostic tests for dry eye disease are not effective. Even though dry eye disease
affects 15 per cent of the population, 82 per cent of clinicians believe it is under-diagnosed. As diagnosis is a problem, treatment is generally a best guess for a particular tear substitute and the treatment cannot be monitored objectively. TearView breaks this cycle because it enables visualisation of the tear film in real time which can be used to determine the nature of the dry eye disease. Consequently, the treatment can be targeted and the effects of treatment can be objectively observed and evaluated. The ability of TearView to see the tear film means that it can also be used for diagnosis of other eye problems that affect the tear film.

Focal therapy is a well-established technique of targeting and treating benign and cancerous lesions throughout the body. It has been used for years for brain, lung, liver,
bladder, pancreas and kidney cancers. In recent years more powerful MRI (magnetic resonance imaging) machines have become available and enabled clinicians to
visualise prostate cancer for the first time. The visibility of these cancers with MRI has enabled the development of ProFocal-Rx targeted laser therapy. ProFocal-Rx allows
for at least 30 per cent prostate cancer patients to have minimal invasive therapy instead of surgery or radiotherapy. It also allows curative treatment and peace of mind for patients who would have chosen active surveillance for their prostate cancer.

The ProFocal-Rx laser delivery unit is introduced in the proven abnormal cancerous area. ProFocal-Rx allows for real-time interactive treatment ensuring that the cancer is
eradicated and ablated. The treatment is performed as a short outpatient procedure with the patient going home the same day. The side effects of the treatment are less
than the diagnostic biopsies that are currently performed.

Blount’s disease is a form of bowleg, which means that as a child grows their tibia grows at a different angle to the rest of their leg. It is a progressive disease, meaning surgical intervention is required to prevent the deformity getting worse. Currently, if the child is older than around four years, the treatment of Blount’s disease involves an osteotomy, or cut in the bone, with a gradual correction using an external fixation frame. These frames are bulky, uncomfortable and require a significant and costly four to six month commitment on behalf of the patient, family and healthcare team.

The Blount’s plate is an orthopaedic plate that can be used for the internal correction of Blount’s disease. This approach transforms the surgical management of Blount’s disease into a fully internal one, meaning that there is no need for an external fixation frame. The Blount’s plate would give the patient the freedom to play as a child without the restrictions of an external frame. This plate has the potential to save the healthcare system from 4 to 6 months of intensive outpatient follow up care, including appointments with the surgeon, radiology, physiotherapy and a specialist care nurse. This plate has the potential to improve the experience and effectiveness of patients being treated for Blount’s disease without sacrificing quality of care.

Two out of every three Australian women are overweight or obese, equating to 6.5 million women nationally. Research shows that women who are overweight or obese have 2-3 times the breast volume of women of a normal body mass. With a limited range and availability of bras designed to cater for these larger sizes, this can lead to problems finding a bra to both fit and sufficiently support their breasts during exercise. As a consequence of ill-fitting or unsupportive sports bras many women with large breasts are not gaining sufficient support from their sports bra. This can lead to pain and embarrassment during physical activity and can be a barrier to participating in physical activity. Removing the bra-barrier to physical activity for overweight and obese women with large and hypertrophic breasts is important from a public health perspective in order to enable these women to enjoy the benefits of physical activity, which in turn leads to improved health outcomes.

BraVo Sports Bras provide a better solution by using accurate and detailed three-dimensional body scan data of the breasts and torsos of women in conjunction with a deep biomechanical understanding of how the breasts move during motion. That is, sports bras specifically designed to comfortably fit and support the breasts of overweight and obese women with large and hypertrophic breasts.

Current methods of obstetric monitoring are cumbersome, restrictive and rely on subjective interpretation which is known to increase intervention. This poses a problem for mother and baby, clinicians, hospitals and health systems. When a mother is monitored with current methods it can be a distressing experience, compromising her comfort and mobility while impacting outcomes for herself and her child. Subjective interpretation of data often results in inappropriate and late intervention, requiring substantial resources, placing significant burden on the health systems.

Oli is a non-invasive patch which monitors pregnancy and labour progression. The technology allows for more objective measures to identify complications, assess intervention performance and improve outcomes. Oli provides real time feedback on uterine activity, maternal and fetal well-being, exertion, movement and how these all correlate to progression. Oli allows for remote monitoring without impacting maternal activity.

One in six couples worldwide experience infertility and approximately 3-4 per cent of all babies born in most western countries are the result of advanced assisted reproductive technologies, such as in vitro fertilisation (IVF). Despite its widespread use, IVF remains inefficient with only a 17.9 per cent success rate (live birth/IVF cycle initiated) , and it is expensive. Egg (oocyte) quality is one of the key ratelimiting factors in IVF success.

Joi is the world’s first non-invasive in vitro diagnostic test that directly measures key biomarkers produced by the oocyte from multiple biological samples. By better selection and implanting a healthy egg, it is anticipated that the success rate in patients undergoing IVF treatment will be improved. Compelling evidence has been generated using a variety of clinical samples from healthy volunteers and patients with ovarian diseases. In addition, to assessing the quality of oocyte, this test may also be used to estimate the quantity of eggs available and to diagnose certain ovarian diseases such as endometriosis.

Exoskeletons promise to significantly improve the daily lives of the sufferers of paralysis, if they can be made easier to control. Spinal cord injuries are relatively rare in Australia, but they often occur to young people leading to lifelong disability. The direct costs to the healthcare system are consequently very high, estimated at more than $10 billion for cases that occurred in this year alone (Access Economics “The economic cost of spinal cord injury and traumatic brain injury in Australia”). The indirect costs to families and caregivers are even higher. XoCo is developing a closed loop neuroprosthetic controller for a lower body exoskeleton, to assist with balance and gait coordination during operation by spinal cord injured users.

With an ageing population and a growing number of people living with chronic or complex health conditions, people’s health needs are changing and demands on the health system are increasing. health.ly, a digital integrated healthcare platform, creates better connected models of healthcare that improves outcomes for health consumers by making it possible to access high quality care - anytime anywhere. health.ly improves health outcomes by providing patients with a more convenient and personalised service through informing, educating, and supporting treatment adherence. It helps with sharing of clinical information between hospitals, specialists and general practitioners, and reduces unnecessary duplication of pathology and radiology tests.

The technology also allows patients access to high quality cost efficient healthcare at home by using digital communication such as e-visits, e-prescriptions and two-way remote monitoring. As a result more patients can be cared for in the community with a reduction in avoidable hospitalisations and emergency department attendances. The patient experience is improved by enabling the right care to the right patient at the right time – each time and every time.

Incontinence affects over 5 million Australians with one in three women and one in four men over the age of 50 suffering from loss of urinary and/or faecal control. Within the ageing population, incontinence is highly prevalent affecting up to 70 per cent of all geriatric patients in residential age care and in-home community care. The problem of incontinence is not limited to the symptoms of urgency, frequency and night time waking to relieve urinary and faecal urges. It is often the loss of dignity patients feel when they are forced into managing their incontinence with adult diapers. Pharmaceutical options are often unsuitable due to polypharmacy interaction and side effects. Surgical treatment is invasive and comes with significant risk.

InConfidence is a discreet, non-invasive, wearable medical device worn around the ankle for twenty minutes a day. It works through transcutaneous electrical stimulation of the posterior tibial nerve found on the ankle. The posterior tibial nerve is a peripheral nerve of the sacral plexus which innervates both the bladder and bowel. Stimulation of this nerve normalises the neural communication between bladder/bowel and the brain. Just like a phone call on a clear line, the brain is able to ‘hear’ exactly what the bladder and bowel are trying to communicate and restore normal continent function in the patient.

Modern radiotherapy techniques allow highly conformal radiation dose delivery to cancer. Accurate positioning of patient/tumour during the delivery of treatment is paramount to ensure the correct dose is delivered to kill the cancer cells and avoid damage to nearby normal tissues. However, the tumour position during radiation delivery can be affected by patients’ involuntary movement and the motion of internal organs. Real time tumour position monitoring ensures the accurate positioning of the tumour during radiotherapy delivery. General purpose linear accelerators (radiotherapy machines) do not have this functionality.

RO-TrackerSuite is a software system that enables the real time tumour position monitoring functionality in a general purpose linear accelerator that comes with standard x-ray imaging capability. With RO-TrackerSuite, real time tumour position monitoring can be performed for the majority of treatment sites such as prostate, liver, pancreas, lung, brain and spine. RO-TrackerSuite has the functionality to perform real time position monitoring based on the radiopaque markers implanted in or in the vicinity of tumour. In the treatment sites where implants are difficult or not possible, RO-TrackerSuite has the functionality to perform real time position monitoring based on the internal anatomical surrogates that are closer to tumour.

More than 10 per cent of men experience prostate cancer in their lifetime. The prostate-specific antigen (PSA) test is the current golden standard method of prostate cancer detection. However, more than of half of PSA tests produce false-positive results which cause stress and anxiety in patients as well unnecessary biopsy examinations.

PC Diagnostics aims to revolutionise the way that prostate cancer detection and therapy are managed by introducing a urine test for the detection of the disease. This technology will avoid many unnecessary biopsy examinations by presenting more accurate results. This is important to reduce the psychological pressure on men who are screened for prostate cancer as well as avoiding unnecessary costs of biopsy tests. Development of this technology will also promote more regular check ups by men and may lead to earlier detection of cancer promoting more active surveillance. Solutions for more advanced prostate cancer are such asradiotherapy and surgery cause such as urinary incontinence and sexual dysfunction. The application of the PC Diagnostics technology will utilise simple urine tests for prostate cancer detection and will promote regular and more accurate prostate cancer screening.

According to the World Health Organisation’s Vision 2020 report, there are approximately 300 million visually impaired people in the world. In Australia alone, there are more than 2 million visually impaired people with nonrefractive eye conditions. These conditions obstruct the view, create blind spots or loss-in-detail at different locations of the eye. Due to the complex anatomy of the eye, the nervous system and how they interact together, an effective medical treatment has not yet been developed. However, technological advancement can offer an alternative pathway for people suffering from visual impairment.

SOOMA is an electronic vision enhancement device developed specifically for legally blind people who suffer from visual impairment. SOOMA is designed as a modular electronic eyewear capable of producing individually customisable images. Live videos are captured by cameras mounted in the eyewear which, through a novel near real-time image processing procedure, is then displayed in front of the eyes. This is a practical solution for addressing non-refractive eye conditions to meet the needs of individuals from childhood to adulthood.

Patients who are granted access to the clinical notes prepared by their doctor during a consultation report a greater sense of control over their healthcare and a better understanding of their health. Kyyron offers people the ability to regain a sense of control of their healthcare by helping them to manage their health and medical data.

Initially, the product is targeted at informed health consumers who either have chronic or complex health needs, or care for a person who does. The app will provide these individuals with the ability to keep track of, and prepare for, their multiple healthcare appointments, with multiple doctors and providers. It will also provide a place to make notes and collect the results associated with these appointments. This information will then be readily available to the individual, or a healthcare provider they share the information with, whenever and wherever it is needed.

Over time, the app will expand to become a personal, historical record of individual health, bringing together a personal copy of official medical records alongside the individual’s own notes and insights, to create a single, centralised repository of an individual’s health and medical data.

One in four young people in Australia suffer from mental health disorders such as depression. Further, around half of all adult mental illnesses emerge by the age of 15. Failing to address these issues in adolescence is associated with more severe clinical presentation throughout life, as well as poor academic performance, social dysfunction, substance abuse and suicidal thinking. As the human, social and economic consequence of this can be devastating, mental health is one of the greatest challenges of the 21st century. While there is considerable evidence to demonstrate that early intervention can dramatically change the course of an individual’s mental health trajectory, up to 60 per cent of young people will not seek help. The stigma associated with mental illness prevents many from reaching out, along with accessibility and cost of existing best practice treatment - face-to-face psychological therapy.

Delivering early intervention strategies to young people using technology will remove these barriers. Smartphone use is ubiquitous with more than 80 per cent of young people owning their own phone. As such, the Black Dog Institute developed an app that delivers best practice psychological therapy. The app focuses on sleep problems, a common precursor to the development of depression, which is less stigmatising and more appealing to young people. By utilising gaming technology to engage young people in treatment, the app overcomes existing barriers to help-seeking and ensures support is available 24/7. With young people preferring the privacy, anonymity and interactivity that this technology allows, this app will be key in preventing the emergence of mental health symptoms during the critical adolescent period.

Heart disease kills one Australian every 27 minutes. Heart attack as an endpoint of heart disease is unpredictable. During a heart attack, heart muscle is damaged as it is deprived of its normal blood supply. The extent of damage depends on severity of heart attack as well as the time between the attack and treatment.

Condicion is a non-invasive medical device that exercises the heart and stimulates the release of endogenous substances into the bloodstream that reach the heart to exert heart-protective effects. This may prevent damage to the heart muscle, or limit the extent of the damage during a heart attack.

The device can be used at home while sitting or lying down to prevent heart attacks. It can also be used in ambulance during patient transport to hospital to reduce the extent of heart damage following a heart attack. Another application of Condicion is in pre- and postoperative care of patients undergoing a heart procedure.

Currently CT scans are used to design and deliver radiotherapy treatments for cancer. However, MRI scanners provide more superior tumour and normal tissue imaging. Being able to use MR images in radiotherapy treatment and planning will allow the delivery of more targeted radiotherapy to cancers while reducing the impact on normal tissue. The technology required to combine a linear accelerator radiotherapy machine and an MRI scanner is complex and challenging.

MRI-Linac technology is working on a prototype combining a linear accelerator radiotherapy machine and an MRI scanner in order to deliver more targeted radiotherapy to cancers while sparing normal structures nearby. With $27 million of grant funding and world class research MRI-Linac technology is well placed to contribute to the future of radiotherapy treatment and transform the lives of cancer patients.

Over half of NSW adults are overweight or obese and this is now the second leading risk factor of disease in NSW, ahead of smoking. Malnutrition is also a major concern in requiring regular monitoring as it increases healing times, costs and readmissions.

This device provides an accurate measurement of percentage body fat in an instrument which is much smaller, safer and easier to use than comparably accurate devices that are much less practical.

Using IP developed at the University of Sydney and support from the Bill and Melinda Gates Foundation, the device has been validated against gold standards in over 650 participants. This device and service will aid dieticians, fitness instructors, nurses, and medical practitioners to address the clinical conditions of obesity, overweight and underweight.

The motivational way in which information is presented will increase adherence by participants and allow caregivers to track and provide quantified information on nutrition and exercise management. This will allow improved management of obesity and other clinical nutritional issues where optimised nutrition is desired including cancer care, paediatrics, aged care, intensive care, pregnancy, and eating disorders. Through better management quality of life will be improved and health costs reduced by reducing hospital readmissions and chronic disease.

One in three people in Australia die of cardiovascular disease. The underlying process causing the majority of these deaths is atherosclerosis. Atherosclerosis is a disease where fatty material is deposited in sections of the wall of the artery. Deaths occur when local atherosclerotic lesions rupture, stimulating clot formation, leading to occlusion of the artery. These lesions are termed ‘vulnerable plaques’. Both heart attacks and strokes can be caused by vulnerable plaques rupturing. Recent research has shown that vulnerable plaques can be identified prior to their rupture. The Stabilyzer device provides treatment that will prevent future heart attacks and strokes with the development of a locally applied treatment to stabilise these plaques.

The rise in rapid prototyping technologies has presented a unique opportunity for the creation of custom made implants. However, the logistical shift from generic high volume production systems to individually customised implants prevents its widespread usage. The Rapid Templating System aims to form patient specific implants quickly and effectively. The system involves the production of a 3D-printed guided mould, based on patient scans, to shape terminally sterilised generic materials into patient-customised implants. The generation of custom implants within packaged materials allow implants to be immediately ready for use, avoiding treatment delays due to sterilisation post production. This approach has the capacity to significantly reduce inventory costs for medical device companies, as abundant implant-size ranges are no longer required to accommodate all patient cases. Further developments in regenerative medicine may allow further customisation material properties, allowing the implant to be patient specific anatomically as well as a biomechanically.

Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic procedure that allows access into the biliary system and has revolutionised the management of bile duct pathology. However, it is a notoriously difficult procedure to learn and even in experienced hands, this procedure is associated with complications including pancreatitis, bleeding, perforation and in rare cases, death. Cannulation of the bile duct remains the most challenging step of the procedure even with current sphincterotome technology. The Pivot Sphincterotome has been developed to facilitate easier, faster and ultimately safer biliary access. The ERCP sphincterotome US market alone is worth approximately $USD150 million and with an increasingly elderly population requiring less invasive procedures, it is expected to increase. Developed by an ERCP practitioner, the Pivot Sphincterotome aims to accommodate the shortcomings of current technology making the ERCP experience more user-friendly, efficient and safe.

To develop and commercialise a novel universal screening test for the detection of breast cancer that is highly accurate, safe, cost effective, and available to all women regardless of age, race and geographic location.

Breast cancer is the most common cancer among women, therefore, the effectiveness of the screening and diagnosis technology used is a high priority. The current model relies on a woman being physically present at a clinic for breast imaging which is not always convenient. While the present technologies are currently state of the art, there is a high cost involved. There are also well known performance limitations that result in only a small subset of women who are actually eligible for screening.

BCAL Diagnostics aims to shift the paradigm in breast cancer screening and diagnosis by introducing a blood test for detection of the disease. The implication of such a technology could revolutionise the way breast cancer is managed by allowing a blood sample to be taken remote from the site of analysis. This technology will allow access to more women, anywhere in the world, who could provide a blood sample, at a time and place convenient to them. Such a test would fit into a woman’s routine health regime and be incorporated into their personal lifestyle. In addition, with such high levels of accuracy, this technology would provide greater peace of mind between annual checks. The BCAL Diagnostics technology could utilise a single blood test on multiple levels for disease prevention, diagnostic mass screening and postintervention.

Mitral regurgitation is a condition caused by a leaking heart valve and affects more than four million individuals in the USA. The standard method of fixing valves is with open heart surgery, a complex operation performed on cardiopulmonary bypass. The operation is expensive, and recovery time from the operation is measured in weeks or months. The SeCure Beating mitral heart repair device enables heart valve repair while the heart is still beating, with no need for bypass or long anaesthesia time or surgical scars. Patients can recover in hours or days and the cost of surgery can be dramatically reduced. The heart repair can be repeated if necessary and conventional surgery can also be performed at a later date. With the new technology many patients who have been deemed unfit for surgery could be given life saving treatment.

Backed by experts at the University of Wollongong and Swinburne University of Technology, Geldom is helping make condoms more wearable by replacing latex with better feeling materials called tough hydrogels. These tough hydrogels are superior to latex and can improve the experience by offering more tissue like sensation. They also have other revolutionary benefits – no bad odours or tastes, no latex allergies, inherent self lubrication, and can even be embedded with anti-sexually transmissible infections agents or stimulants.

These new options have the potential to dramatically increase condom use. The impact – not only redefining what safe sex should feel like – but the added social benefits of improved family planning and disease prevention.

This work is geared towards disrupting the $6 billion condom industry desperate for innovation. This patent pending work has been supported by the Bill & Melinda Gates Foundation and has featured on ABC’s Catalyst.

CardioFlex is the next generation of cardiac pacemaker leads. Conventional pacemaker leads are comprised of a long, coiled metal wire running from the neurostimulator to the electrode implanted in the heart. These conventional leads are prone to infection, dislodgement and mechanical failure. They are also incompatible with MRI because they act as antenna and generate unsafe amounts of heat in the body under MRI. CardioFlex leads do not use metal wires but are instead fabricated from conductive elastomers, a novel material being developed at UNSW. Conductive elastomers allow the CardioFlex lead to be soft, flexible and totally MRI compatible. This means recipients are less likely to require a surgical lead extraction and they do not need to worry about their pacemaker interfering with ongoing or future medical treatments. Other applications of conductive elastomers being investigated include flexible electrode arrays and nerve cuffs for neural interfacing.

This product allows for simple medical testing remotely from home. The home diagnostics kit consists of a small device attachable to a smartphone and together with an app, it allows for the analysis of the same urine dipsticks that are commonly used in the GP’s office. The medical results can then be shared with the GP online instead of going to the doctor, when unwell or busy. This will assist in a comprehensive assessment of the patient’s health problem currently not possible via online consultations. This smartphone diagnostics device also features recording of the test results over time opening up numerous additional applications, ranging from personalised healthcare to new testing methods for diseases.

As the healthcare sector is moving towards a digital platform, these internet connected devices will be essential in the generation of digital medical records as well as the successful implementation of online medical services.