IHBI Advances December 2016 Edition 28

December 2016 edition 28

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Institute of Health and Biomedical Innovation

IN THIS ISSUE

ADVANCES Effective strategies needed to reduce or prevent elder abuse Tapping into the brain a vital step in sustained weight loss Study identifies patients at risk of developing cancer metastasis Infrastructure a key to building healthy Brisbane cycling culture Protective protein at core of newly funded cancer research Executive Director’s report

Professor Christian Langton

Novel new method brings brain disorder diagnosis a step closer Ultrasound has the potential to provide a low-cost and portable method for diagnosing brain disorders such as Parkinson’s disease. IHBI Professor Christian Langton has taken a step forward in developing the method, inventing an approach aimed at enabling ultrasound waves to pass through the skull without distortion.

Professor Langton heads the Quantitative Ultrasound Imaging and Characterisation (QUIC) research group at IHBI, with its researchers focused on developing a number of novel diagnostic imaging systems.

He had previously developed a ‘flat-bed’ ultrasound scanner that was initially used to assess the skeletal status of very low birthweight premature neonates and has since been applied to predict soft and hard tissue breakdown in the diabetic foot.

Collaborations with IHBI researchers are enabling QUIC team members to investigate ultrasound uses in predicting the mechanical integrity of bones and improving cancer tumour diagnosis and treatments.

HOW DOES ULTRASOUND WORK? Ultrasound is a high-frequency sound wave transmitted by a transducer through tissues.

Partially reflected echoes from tissues in the body are detected by the same transducer and displayed as an image.

WHAT ARE THE BENEFITS OF ULTRASOUND? Ultrasound is both non-ionising and non-electromagnetic, so it doesn’t require a special screening room or operator. It offers real-time imaging, is relatively low cost and portable, making it particularly suitable to serve rural and remote communities, as well as point-ofcare specialties such as paramedics and armed services personnel.

Professor Langton has turned his attention to overcoming the challenge of transmitting ultrasound waves through bone, including the skull, without distortion. The result is a novel approach that has potential to be used on any part of the body, but has particular benefit in imaging the brain.

‘This is probably the most exciting and groundbreaking project of my 35-year research career,’ Professor Langton says.

Ultrasound waves have traditionally not been able to pass undistorted through bone, so ultrasound technology could not be used to evaluate the brain. Cranial ultrasounds could only be performed on babies before the bones of the skull grew together or on adults after the skull had been surgically opened.

To create an image, an ultrasound scanner transmits waves and determines how long it takes a return echo to be received, as well as how strong the echo is. Changes in thickness and composition of the skull create significant variability in the transit time of echoes, leading to distortion of the ultrasound wave.

Clinicians are presently using an ‘active’ solution to vary transmission delay in an effort to overcome distortion, with electronic control of each individual transmission. Professor Langton’s approach is passive, involving an ultrasound phaseinterference compensator consisting of a 3D-printed twin-layer placed on the skull aimed at providing a constant transit time.

‘My fascination is in better understanding, and solving the problem of, ultrasound propagation through bone,’ Professor Langton says. ‘Parkinson’s disease is one of several

neurological disorders, including Alzheimer’s disease, that could be diagnosed and treated using my innovation, along with brain cancers.’

Diagnosis of Parkinson’s disease is difficult, with present ultrasound brain imaging restricted to an ‘acoustic window’ in the temporal bone, an area at the sides of the skull where the bone is thin. Even then, a clinically usable image cannot be obtained in a significant number of patients due to wave distortion.

Parkinson’s disease is a progressive disease of the nervous system marked by tremor, muscular rigidity and slow, imprecise movement, chiefly affecting middle-aged and elderly people.

The underlying cause of Parkinson’s symptoms relates to a decline in the production of a brain chemical called dopamine.

Many of the cells which produce dopamine are in the basal ganglia in the middle of the brain.

One in every 350 Australians lives with Parkinson’s disease, with 30 more people diagnosed each day. The incidence has grown by 17 per cent during the past six years. Parkinson’s disease is Australia’s second most common neurological disease and is more common than prostate, bowel and many other cancers.

The estimated burden of disease in 2011–12 was valued at $7.6 billion, in terms of lost quality of life and premature mortality for people with Parkinson’s disease. An estimated 20 per cent of people with Parkinson’s disease are of working age. The disease cost the Australian economy about $775 million in 2011–12, including about $480 million in health system costs and $110 million in lost productivity.

Effective strategies needed to reduce or prevent elder abuse Elder abuse is a global issue that is associated with significant illness and even premature death. Interventions have been introduced in various countries, but IHBI research shows their efficacy in reducing or preventing abuse remains unclear.

Professor Philip Baker

IHBI’s Professor Philip Baker has been investigating elder abuse as part of a collaboration with researchers from the University of Malaysia.

He says about 10 per cent of older people experience some form of abuse, including physical, psychological and sexual abuse, neglect and financial exploitation. ‘The abuse can often come from someone who they know well or have a relationship with, such as a spouse, partner, family member or friend.’

The abuse is responsible for up to 2500 deaths a year in Europe and results in great economic costs to the elderly people and the healthcare system. Figures are expected to increase with ageing populations and people living longer.

Professor Baker says interventions to prevent the occurrence and reoccurrence of abuse have been initiated globally, but little systematic research has been conducted into their ELDER ABUSE

efficacy. Before authorities determine how to intervene, they need to understand the mechanisms contributing to the abuse and identify effective interventions that can potentially make a difference. They need clear knowledge produced through a systematic review, a rigorous scientific method that objectively summarises the effects of health strategies.

Investigations involving Professor Baker and his Malaysian collaborators found there was some evidence that teaching coping skills to family carers of people with dementia might make the situation better. ‘Some interventions appear to improve the knowledge and attitudes of carers, but may not reduce the abuse.’ Professor Baker says.

The findings were part of a systematic review published in the Cochrane Library, a world-wide independent network of health practitioners, researchers, patient advocates and others from more than 120 countries preparing high-quality information to support health decisions.

The review found poor-quality research into interventions had the potential to mislead, create confusion and add to uncertainty. ‘We need to avoid such research,’ Professor Baker says. ‘Frontline agencies need to be supported in undertaking critical evaluations of their services and integrating findings into practice or policy. Systematic reviews are vital.’

Mistreatment of an older person that is committed by someone with whom the older person has a relationship of trust.

POSSIBLE RISK FACTORS: Dementia, caregiver burden and disability.

EFFECTIVE INTERVENTIONS MAY INCLUDE:

Professor Baker says the Cochrane Library review aimed to address a gap in evidence, assessing the effectiveness of interventions. ‘We screened through almost 30 000 records.

We found much of the evidence to be of very low quality. It is concerning that decision makers may be relying on this evidence.’

Providing elderly people and their families with skills to communicate effectively, manage stress, resolve conflict and promote healthier relationships.

Encouraging positive attitudes towards older people by increasing meaningful interactions between elderly and younger people.

Poor-quality research is unable to determine whether the interventions used around the world have been effective, safe and the strategies appropriate.

While the incidence of abuse is thought to be between 2.7 and 27.5 per cent of the population aged more than 60 years, only a fraction of cases are reported or referred to social services agencies. Available data shows that 19.4 per cent of elderly people report mental abuse, 3.8 per cent report financial abuse and 2.7 per cent report physical maltreatment.

‘Older people with dementia, disabilities and chronic health problems that result in increased dependence on caregivers are particularly at risk of elder maltreatment,’ Professor Baker says. ‘Low social support, loneliness, social isolation and lack of social networks among the elderly perpetuate maltreatment.’

Likely risk factors for predisposing elderly people to maltreatment include mental illness among perpetrators, high levels of hostility, substance abuse and psychological distress. A perpetrator being dependent on an elderly victim for accommodation and financial support appears to add to the risk. Community factors that exacerbate elder maltreatment include high crime rates, social disorganisation, lack of social resources and networks, and poverty.

In Australia, costs due to hospital admissions for elder maltreatment are estimated to be between $9.9 million and $30.7 million.

‘There is a need for future research using high-quality comparative designs to evaluate new and existing interventions,’ Professor Baker says. ‘Our elders deserve better.’

Tapping into the brain a vital step in sustained weight loss Up to 63 per cent of Australians are overweight. Yet there is overwhelming evidence that even if people lose weight, they quickly regain it. IHBI neuroscientist Professor Selena Bartlett believes that is because people ignore their brains.

Professor Selena Bartlett

Professor Bartlett says a person’s brain silently drives behaviour in the same way it did in ancient humans living in prehistoric conditions. She is unlocking avenues for taming the ancient brain and living a healthy life in the modern world.

‘The brain is an amazing organ that has developed in complexity as humans have evolved,’ Professor Bartlett says.

‘As a consequence, we have three distinct sections within the brain: survival, emotional and rational.’

THE FIVE SIMPLE PRINCIPLES TO MANAGE STRESS AND TRIM THE BODY:

2. B ecome aware of the moments when the amygdala urges you to seek pleasure. Identify your particular stress reactions.

3. L earn to respond, not react, to these moments. Recognise when you are feeling stress.

Retrain your brain for healthier habits.

4. M anage your stress through better eating. Reduce sugar, fat and alcohol intake.

Manage stress with healthy rewards.

5. M anage stress through movement. Improve cardio fitness, trimming your body and improving brain plasticity.

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Professor Bartlett’s research has shown that sugar releases a neurotransmitter that binds to the dopamine receptors in the brain in the same way as alcohol and nicotine. Regular consumption changes the brain, leading to the need to consume more and more to feel the same level of pleasure. A sudden decrease will lead to withdrawal symptoms and cravings.

‘In today’s stressful world of work, finances, relationships and parenting, the body responds by releasing stress hormones such as cortisol,’ Professor Bartlett says. ‘They have a profound impact on the brain.’

She is confident people can override the ancient brain with practical tools and practice, putting the rational brain in charge and achieving sustainable weight loss.

Stress hormones reduce the number of synapses in the brain, which are the small finger-like cells that communicate within the brain. It impacts on the rational brain and can reduce impulse control.

1. G et to know your brain. Awareness of how the amygdala drives your behaviour is critical to overriding unhealthy impulses.

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The survival section controls the heartbeat and breathing. The emotional section, in particular the amygdala, protects against perceived danger. In a millisecond it can take over the body and instigate a ‘fight or flight’ response. The rational section drives executive functions, including impulse control, planning and decision making.

To counteract the damage from stress hormones, the ancient, emotional part of the brain drives people to find pleasure. When experiencing pleasure, the body is flooded with hormones such as dopamine, serotonin and endorphins. They bind to receptors in the brain and reduce the damaging effect of stress hormones.

The brain constantly seeks a balance. The more stress experienced, the more the brain seeks pleasure to counter it.

‘When our ancient brain demands a pleasurable experience, it is common to reach for alcohol, sweet treats and comfort food.

They are high in calories, leading to weight gain, and they are addictive.’

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Drawing on 20 years of neuroscience and addiction research and her personal experience, Professor Bartlett has written a book describing how the brain processes stress and reward— that is, when the amygdala urges people to seek pleasure.

‘The exciting news is your brain doesn’t care where the pleasure hormones come from, so choosing movement instead of comfort food is a matter of awareness and forming new habits,’ Professor Bartlett says. ‘Any number of other methods can help: exercise, meditation and deep breathing can override the impulses stemming from the emotional brain.’

Professor Bartlett is sharing the tools in her newly published book Miggi Matters: how to train your brain to manage stress and trim your body.

Visit www.miggimatters.com

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Study identifies patients at risk of developing cancer metastasis

Arutha Kulasinghe

Working with patients and their samples ensures research has relevance outside the lab and has potential to improve the lives of sick and injured people. PhD candidate Arutha Kulasinghe is the first to screen patients with head and neck cancers using a recently developed culturing process.

Mr Kulasinghe is finalising his PhD under the supervision of Associate Professor Chamindie Punyadeera and Professor Colleen Nelson, investigating metastasis in head and neck cancers. He is using cancer cells present in blood, circulating tumour cells (CTCs), that are seeds for metastasis.

The research involves collaboration with IHBI Professor Rik Thompson, Princess Alexandra Hospital (PAH) ear, nose and throat specialists Associate Professor Chris Perry and Professor William Coman, medical oncologist Professor Ken O’Byrne, PAH urologist Dr Ian Vela and Royal Brisbane and Women’s Hospital (RBWH) senior radiation oncologist Dr Liz Kenny.

Mr Kulasinghe is detecting and culturing CTCs, enabling the increase of cell numbers to a point of critical mass for testing HEAD AND NECK CANCER The seventh most common cancer globally. About 50 per cent of patients die within five years.

CIRCULATING TUMOUR CELLS Cells shed from a tumour, carried around the body and seeding additional tumours in distant organs, triggering metastasis.

METASTASIS The spread of cancer from one organ to another without being directly connected with it.

Metastasis is responsible for more than 90 per cent of cancer-related deaths.

IMMUNOTHERAPY A treatment designed to boost the body’s natural defences to fight the cancer.

medicines. Testing can be completed quickly in a laboratory and can potentially save a patient from receiving ineffective medicines.

The work is being conducted in collaboration with the University of Queensland, the University of New South Wales, the University Medical Center Hamburg-Eppendorf and the National University of Singapore. It involves screening the cultured CTCs of 120 patients from PAH and RBWH using multiple platforms.

‘We were able to successfully develop a culture methodology to increase head and neck tumour cell numbers outside the patient’s body,’ Mr Kulasinghe says. ‘That is a first for head and neck cancer and provides models for understanding the biology of metastatic disease.’

Moreover, Mr Kulasinghe says it provides avenues for drug sensitivity testing as a means of developing a precision medicine approach. The approach involves tailoring medical treatment for each patient, in recognition of the differences between cancer cell types and their behaviours.

In a proof of principle study, Mr Kulasinghe has demonstrated that tumour cells in circulation express PD-L1, a protein that is believed to be responsible for suppressing the immune system. The study shows that PD-L1 is a promising target for immunotherapy, a type of treatment designed to boost the body’s natural defences to fight cancer.

Importantly, PD-L1 could be used as a biomarker for predicting a patient’s likely response to immunotherapy, helping determine probable outcome of the costly treatment.

Mr Kulasinghe’s research aims to develop minimally invasive techniques to identify head and neck cancer patients who are at an increased risk of metastasis—or who are not responding to therapy. CTCs have been used to determine the prognosis of patients with breast, prostate and colorectal cancers.

However, low numbers of CTCs has been a limiting factor in head and neck cancers. As a result, very sensitive methods are needed to isolate and identify CTCs. ‘We believe we have conducted the first pilot study to culture head and neck CTCs ex-vivo—that is, in the laboratory,’ Mr Kulasinghe says.

Findings also lead Mr Kulasinghe to believe that the human papillomavirus (HPV) may play an important role in the culturing success. CTCs from head and neck cancer patients testing positive to HPV have been found to promote better culture success.

Identifying a patient’s HPV status is important, given the prognosis and treatment differ between head and neck cancer patients testing positive and negative.

Diagnostic methods for head and neck cancers presently include clinical assessment, imaging and tissue biopsy. When metastasis is evident, the only available treatment is palliative in nature. There are no methods to predict which patients will develop metastases. The ability to do so would potentially enable oncologists to escalate treatment following early diagnosis.

Infrastructure a key to building healthy Brisbane cycling culture New bikeways encourage people to cycle rather than take a car, bus or train for the daily commute to Brisbane’s central business district. But IHBI studies suggest more needs to be done to encourage women and children to cycle.

Dr Kristi Heesch

IHBI’s Dr Kristi Heesch is passionate about encouraging more people to cycle for transport, while gaining health benefits and reducing the city’s carbon emissions. Her research aims to predict cycling behaviour and how infrastructure such as new bikeways will increase the number of people cycling, the number of trips they make and the distances travelled by bike.

‘I want to encourage more people to cycle for transport and influence government policy toward cycling and cyclists,’ Dr Heesch says. ‘There is growing evidence that supports the health, social and environmental benefits of transport cycling—that is, cycling to get to and from places—and active transport more generally.’

CYCLING IN THE NETHERLANDS Nearly a third of all trips are made by bike.

The Netherlands is a densely populated and flat country, making trips short, even between towns.

Many town centres are only accessible to cyclists and pedestrians, so drivers have lengthy detours via a ring road while cyclists have direct routes.

The needs of cyclists are taken into account in all stages of urban planning.

Nature strips generally separate bike paths from parallel roadways for safety.

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Active transport and a resulting increase in physical activity are directly linked to benefits in a person’s cardiovascular health and a reduced risk of other chronic diseases.

‘Evidence suggests that the health benefits gained from increasing levels of physical activity through increasing the number of people using active modes of transport far outweigh the health risks from increases in traffic accidents,’ Dr Heesch says.

Survey data showed 10 per cent of cyclists on Veloway 1 during the morning peak had switched from other modes of transport. However, Veloway 1 had not shifted cyclists away from using a nearby major arterial, Logan Road.

Dr Heesch says ‘strong and fearless’ cyclists who prefer the most direct, high-speed roads do not use the veloway, even though Logan Road comes with a greater risk of accidents and hospitalisation.

A recent study involved Dr Heesch evaluating the Brisbane Veloway 1’s third completed stage, stretching south 2.3 kilometres along the Pacific Highway, from Ekibin Park near the Greenslopes Busway Station. The study aimed to understand the impact of cycling infrastructure on behaviour, given the Queensland Government’s increasing investment.

Nor did the veloway attract many women or children. ‘Cyclists surveyed on the veloway were almost exclusively adults and most were men. It means that the infrastructure is important, but does not overcome barriers to increasing cycling’s appeal, especially for groups under-represented among cyclists in our city, such as women and children.’

A government cycling infrastructure policy requires that new transport infrastructure include off-road bike paths and on-road bike lanes, resulting in a greater per-capita spend than all of the remaining states and territories except the Australian Capital Territory.

Infrastructure likely to attract women to cycling includes bikeways that encourage short trips to destinations such as shops and schools, Dr Heesch says.

Dr Heesch says the study included face-to-face surveys of cyclists en route, bike counts and GPS tracking. It examined the impact of a new segment of bikeway on cycling behaviour, the type of cyclists using it and if cyclists were attracted away from other, less safe routes for cycling.

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Some of the best cycling infrastructure in the world is found in the Netherlands, she says, with 31.2 per cent of people listing the bike as their main mode of transport for daily activities and cycling accounting for 27 per cent of all trips made.

‘I would like Brisbane to learn from the Netherlands,’ Dr Heesch says. ‘Their infrastructure is set up to support cycling. No matter why you’re on the road and where you are headed, cycling is safe and easy, including for women and children.’

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Protective protein at core of newly funded cancer research A Noosa businessman and artist are funding an IHBI researcher who has found a link between volcanic pools and cancer research. IHBI has appointed Associate Professor Derek Richard to the position of Chenhall Research Scientist.

Associate Professor Derek Richard

The trustees of the estate, Paul Bone and Anna Richardson from Cartwright Lawyers in Noosa, have worked closely with IHBI team members to create the position of Chenhall Research Scientist.

Associate Professor Richard says he is honoured to take up the new position and conduct important cancer research on behalf of the Chenhalls. It builds on his studies and research positions at the University of St Andrew’s in Scotland, where he established the connection between volcanic pools and cancer research.

ASSOCIATE PROFESSOR DEREK RICHARD Obtained his PhD in microbial biochemistry from the University of Dundee in Scotland.

Worked as a Postdoctoral Fellow studying archaeal DNA repair systems in the laboratory of Professor Malcolm White.

Moved to Queensland in 2004 to join Professor Kum Kum Khanna at QIMR Berghofer.

Moved his research team to IHBI in 2011.

EXECUTIVE DIRECTOR’S REPORT

IHBI conducts research in a dynamic environment— one that creates challenges and provides opportunities for our goal of bringing about better health in our lifetime.

Our researchers partner with clinicians and industry and use the latest technology to progress their research from the lab to hospitals, clinics, aged care facilities and people’s homes, to make a difference.

Their ultimate aim is to impact on the lives of Australians, be it through developing new diagnostic tools and therapeutics, improving hospital treatments, preventing injury and illness or encouraging and supporting wellness before, during and after treatment.

Research requires on-going funding. We are pleased to have secured recent funding from the Australian Research Council (ARC) and the National Health and Medical Research Council (NHMRC). The funding will progress research in developing therapeutics, medical imaging technology, eye health, child safety, substance abuse, allergies and health innovation.

The funding recognises research excellence, strategic importance and the multidisciplinary focus of our teams. Many

‘My original research saw me study an ancient organism called archaea which manages to survive in the boiling sulphuric acid pools in Iceland, one of the most extreme environments on the planet,’ Associate Professor Richard says. ‘The organism manages to survive in these damaging conditions because it contains what I call a ‘super-hero’ protein called hSSB1.’

Associate Professor Richard likens the protein to a super-hero because it protects the organism’s DNA against the fiercest attacks from the enemy, its own natural environment.

‘The exciting connection is that hSSB1 has also been found in humans and is central to protecting us from cancer-causing DNA damage.’ Associate Professor Richard says human cells are subjected to up to 30 000 ‘attacks’ every day from sources such as free radicals, ultra violet light and carcinogens that include cigarette smoke. Cancer is caused when genes are damaged and not properly repaired.

‘Without hSSB1 to protect us, our cells are much more vulnerable,’ Associate Professor Richard says.

Associate Professor Richard says he has since worked on many different research projects and is excited to see where he can take his cancer research with funding from the Chenhall Research Trust.

understand the mechanisms that cause cancer cells to develop therapeutic resistance.

Another area of research builds on this experience and involves developing therapeutics for castrate-resistant prostate cancer, targeting androgen synthesis in the prostate and understanding the role of insulin.

Androgen is a compound, usually a steroid hormone, that controls development and maintenance of male characteristics.

It binds to androgen receptors that regulate gene expression, a process critical to an organism’s development.

The ultimate goal of the research is to develop better, more effective drugs to target all cancers and to develop tools enabling oncologists to guide chemotherapeutics to the correct patients.

‘The Chenhalls are super-heroes themselves by protecting research and future generations of cancer patients,’ Associate Professor Richard says. ‘I am very grateful for their support.’

Research projects include initiatives to identify biomarkers that point to the presence of cancer and discriminate between indolent and aggressive prostate cancer, as well as to

of the IHBI researchers who secured funding will be featured in upcoming editions of IHBI Advances.

In a competitive government funding environment, IHBI researchers are excited about the opportunities that flow from building connections and receiving support from the community, specifically philanthropy.

A major step has been the appointment of Associate Professor Derek Richard as our Chenhall Research Scientist with a generous bequest from Noosa’s Bill and Hilde Chenhall, enabling him to conduct full-time cancer research during the next few years.

IHBI is entering a period of growth and change. What will not change is the research excellence that underpins our activities in translating work from the lab and making a difference in people’s lives.

Examples are Professor Christian Langton’s aim of using ultrasound technology to diagnose brain disorders such as Parkinson’s disease, and Professor Selena Bartlett’s work in linking brain mechanisms to addiction so that people can learn to override cravings for unhealthy foods. Dr Kristi Heesch is using her research to encourage more people to cycle for

transport, while Professor Philip Baker is working to better understand and ensure efficacy of interventions used to reduce or prevent elder abuse.

IHBI also prepares PhD candidates to be agents of change, meeting the innovation needs of the economy. Arutha Kulasinghe is an example of a PhD candidate who is well equipped to drive change. He is part of a pilot study enabling insights into metastasis in head and neck cancers, providing avenues for drug sensitivity testing, tailoring medical treatment and developing minimally invasive diagnostic techniques.

I would like to take this opportunity to thank the IHBI Advances readers who support important research through donations, enabling work that promises to enhance healthcare in the coming years and make steps to radically improve treatment in the future.

This is the final edition of IHBI Advances for 2016. I would like to wish you a safe and healthy holiday period, a Merry Christmas and a Happy New Year.

Professor Lyn Griffiths Executive Director, IHBI

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Associate Professor Richard’s new position has been made possible with a generous bequest from Noosa’s Bill and Hilde Chenhall. The couple passed away from cancer a year apart in 2005 and 2006. They bequeathed the bulk of their multi-million dollar estate to establish The Chenhall Research Trust to help fund research into the disease that ultimately took both their lives.