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Scheme : NHMRC Project Grants
Australian State/Territory : NSW
Research Topic : Biological Control
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  • Funded Activity

    Sympathetic Control Of Cutaneous Blood Flow And Blood Pressure In Human Spinal Cord Injury

    Funder
    National Health and Medical Research Council
    Funding Amount
    $242,002.00
    Summary
    While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracol .... While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracolumbar segments. Complete decentralization can result in autonomic dysreflexia (autonomic hyperreflexia), in which sensory stimuli originating below the lesion evoke a reflex increase in sympathetic drive to the blood vessels, causing them to constrict. Because of this, blood pressure may rise suddenly and remain at such high levels that stroke and (occassionally) cardiac arrest may occur. This phenomenon, autonomic dysreflexia, is considered a medical emergency. The typical subjective signs of autonomic dysreflexia include a throbbing headache, tingling in the head or nasal congestion; sweating and flushing above the lesion are clinical signs that prompt medical staff to measure blood pressure and to locate the source of sensory irritation (usually a distended bladder or impacted colon, sometimes a pressure sore or ingrown toenail). Commonly, however, subclinical episodes go undetected, and this phenomenon of silent dysreflexia is of increasing concern. This project will develop means of assessing the integrity and state of the sympathetic nervous system below a lesion in patients with spinal cord injury and characterize the firing properties of reflexly activated sympathetic neurones.
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    Funded Activity

    The Australian Parkinson's Project - Uncovering Genetic Risk Factors For Sporadic PD

    Funder
    National Health and Medical Research Council
    Funding Amount
    $768,546.00
    Summary
    Parkinson s disease (PD) is a progressively disabling movement disorder afflicting many elderly Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemicals and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration, but it is believed that complex interactions between inherited (genetic) and environmental factors contribute significantly to the phenomenon. This .... Parkinson s disease (PD) is a progressively disabling movement disorder afflicting many elderly Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemicals and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration, but it is believed that complex interactions between inherited (genetic) and environmental factors contribute significantly to the phenomenon. This project aims to learn more about these complex interactions and their association with PD. People with PD and unaffected individuals will be recruited from throughout Australia and we will look for specific combinations of genetic, environmental and lifestyle factors that either increase or decrease an individual's risk for PD. This research will identify the most common dominant genetic and environmental influences for PD in Australia, enabling scientists to focus on the most relevant biological pathways to target therapeutically.
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    Funded Activity

    A Parent Education And Skills Training Early Intervention For Children With Autism

    Funder
    National Health and Medical Research Council
    Funding Amount
    $305,674.00
    Summary
    Autism is a severely handicapping disorder adversely affecting social interaction, communication, and behaviour, interests and activities. Over the past 9 years our team has conducted a follow-up study of a large group of 111 Australian children and adolescents with autism. The young people have continued to have very high levels of emotional and behavioural disturbance and generally do not improve. Parents of children with autism are under significant amounts of stress; reporting high levels of .... Autism is a severely handicapping disorder adversely affecting social interaction, communication, and behaviour, interests and activities. Over the past 9 years our team has conducted a follow-up study of a large group of 111 Australian children and adolescents with autism. The young people have continued to have very high levels of emotional and behavioural disturbance and generally do not improve. Parents of children with autism are under significant amounts of stress; reporting high levels of disturbed family functioning and mental health problems. Although there is no cure, children benefit most when early help is provided (under 5 years). There are several promising interventions based on intensive behaviour and educational management, for example requiring 40 hours per week of therapist contact over 2 years. Such programs are costly and impractical as widely available treatment options. Training parents to understand and manage their child also shows promise. This study will evaluate the effectiveness of a parent skills training and education treatment program compared to supportive therapy, and to generally available community services. The therapists will follow a treatment manual that will ensure a consistent and replicable approach. The progress of the children with autism and their families will be reassessed immediately after treatment, and at 1 and 2 years post-treatment in order to ascertain immediate and long-term effects of the treatment. If treatment proves to be of use, we will have established a defined, cost efficient, practical and effective model of early treatment that can be easily taught to professionals and widely disseminated throughout early childhood services.
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    The Australian Maternity Outcomes Surveillance System: Improving Safety And Quality Of Maternity Care In Australia

    Funder
    National Health and Medical Research Council
    Funding Amount
    $820,438.00
    Summary
    There is currently no Australian system of monitoring severe complications of pregnancy. Many of these complications are rare, making them difficult to study and limiting knowledge as to their true frequency, cause and best treatment. We intend to introduce a national reporting system- Australian Maternity Outcomes Surveillance System which would provide the research structure to study these rare conditions, thus aiming to improve the safety and quality of maternity care provided in Australia.
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    Funded Activity

    Randomised Controlled Trial Of Virtual Reality Therapy After Stroke

    Funder
    National Health and Medical Research Council
    Funding Amount
    $452,264.00
    Summary
    Stroke is the second largest cause of disability in Australia. There is no cure, so patients must rely on therapy to restore movement. We want to make rehabilitation more effective. This study compares virtual reality game therapy (using the Nintendo Wii) to current best practice (constraint therapy). We anticipate patients will improve more with Wii therapy. Because it is fun, patients will enjoy therapy and spend longer training resulting in a greater recovery and better movement ability.
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    Funded Activity

    A Survey Of The Sexual Behaviour And Sexual Health Of Australian Prisoners

    Funder
    National Health and Medical Research Council
    Funding Amount
    $591,000.00
    Summary
    The Australian Study of Health and Relationships telephone survey recently reported on the sexual attitudes, knowledge, health and behaviour of over 19,000 Australians. One of the groups that was omitted from that survey was prisoners. Yet prisoners are a high-risk group for sexual ill health. Prisoners are mostly drawn from the most disadvantaged groups in society: they are more likely to be unemployed, they have less education and lower incomes than other Australians, and many suffer from mino .... The Australian Study of Health and Relationships telephone survey recently reported on the sexual attitudes, knowledge, health and behaviour of over 19,000 Australians. One of the groups that was omitted from that survey was prisoners. Yet prisoners are a high-risk group for sexual ill health. Prisoners are mostly drawn from the most disadvantaged groups in society: they are more likely to be unemployed, they have less education and lower incomes than other Australians, and many suffer from minor intellectual disabilities and-or mental illness. This proposed survey of inmates in Australian prisons will fill in this missing data. Prisoners are the forgotten population in many countries. Only a few surveys of prisoners' health have been performed. There are some surveys of sexual behaviour in particular prisons overseas, though most of them concentrate on HIV risks and do not explore the sexual lives of prisoners in the same way as the major national sex surveys in the US, the UK and France did for people living outside prison. Prison is itself a dangerous place for people's sexual health. In prison, much of the sex that occurs is not voluntary. Sexual assault in prisons can lead to serious physical injury as well as risk of sexually transmitted diseases including HIV-AIDS. Although some of these injuries can be sufficiently serious to require surgery, only a small proportion are reported to the authorities. Younger prisoners (aged 18-25) and those who are small, slightly built or gay, are at higher risk of being assaulted. This study will explore the factors surrounding sexual assault in prison and make recommendations for preventing it.
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    Funded Activity

    A Randomised Phase III Study Of Radiation Doses And Fractionation Schedules In Non-low Risk DCIS Of The Breast

    Funder
    National Health and Medical Research Council
    Funding Amount
    $1,751,209.00
    Summary
    Treatment of ductal carcinoma in-situ (DCIS), a preinvasive form of breast cancer, is aimed at preventing invasive cancer recurrence. Women with higher-risk DCIS have an increased risk of recurrence. This study aims to individualise treatment for women with DCIS to achieve long-term tumour control with minimal treatment toxicity. After local excision of DCIS, radiotherapy (RT) to the whole breast reduces the recurrence rate. However, it is unclear if escalating radiation dose to the tumour bed i .... Treatment of ductal carcinoma in-situ (DCIS), a preinvasive form of breast cancer, is aimed at preventing invasive cancer recurrence. Women with higher-risk DCIS have an increased risk of recurrence. This study aims to individualise treatment for women with DCIS to achieve long-term tumour control with minimal treatment toxicity. After local excision of DCIS, radiotherapy (RT) to the whole breast reduces the recurrence rate. However, it is unclear if escalating radiation dose to the tumour bed in higher-risk women increases tumour control. It is also uncertain if giving fewer but larger radiation doses over 3-4 weeks would achieve the same tumour control as the standard 5-7 week course of RT to improve patient convenience and access to RT. Thus, this multicentre study of 610 women with higher-risk DCIS will investigate if adding a tumour bed radiation boost after whole breast RT improves tumour control, and the shorter RT course achieves the same tumour control as the standard longer course. Currently, the ability to predict the malignant potential of DCIS and RT toxicity is limited. This study will investigate if there are biological and genetic markers predictive of invasive recurrence and normal tissue toxicity in women with DCIS using state of the art technology. Women need to weigh up the likelihood of cancer control against adverse treatment effects to make an informed treatment decision. However, very little is known about the quality of life (QoL) consequences of the diagnosis and treatment of DCIS. In this study, the QoL, psychological distress, perceived risk of invasive cancer recurrence and perceived cosmetic outcomes of women with DCIS, will be assessed using a questionnaire of validated measures. This study will refine treatment for women with DCIS according to their risks of recurrence. It will significantly advance the understanding of the biology of DCIS and its psychological and QoL outcomes after treatment.
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    Funded Activity

    Molecular Regulation Of Metabolism And Body Composition By Ski Via Crosstalk With Nuclear Hormone Receptor Signalling.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $558,441.00
    Summary
    Obesity is a common and burdensome health problem in the community which leads to diabetes and heart disease. A number of factors, including hormones play important roles in determing risk of obesity. This study proposes to investigate whether the Ski gene which is a regulatory factor for many hormones affects metabolism in transgenic mouse models of altered Ski function. The proposed studies may identify Ski as a target for therapy for obesity and improvement in sketal muscle metabolism.
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    Funded Activity

    Structure-function Studies Of Ion Permeation And Selectivity In Recombinant Glycine Receptor Channels

    Funder
    National Health and Medical Research Council
    Funding Amount
    $331,300.00
    Summary
    Ligand-gated ion channels (LGICs) are members of a superfamily of receptor channels, with very significant structural and functional similarities, which play a major role in fast synaptic neurotransmission within the brain and spinal cord, and underlying the complex behaviour of the nervous system, but when dysfunctional can result in major neurological problems. Glycine is one of the two most important inhibitory neurotransmitters in the central nervous system. Impaired glycine-mediated neurotr .... Ligand-gated ion channels (LGICs) are members of a superfamily of receptor channels, with very significant structural and functional similarities, which play a major role in fast synaptic neurotransmission within the brain and spinal cord, and underlying the complex behaviour of the nervous system, but when dysfunctional can result in major neurological problems. Glycine is one of the two most important inhibitory neurotransmitters in the central nervous system. Impaired glycine-mediated neurotransmission underlies a range of inherited neurological diseases and already, it has been shown that the human disorder, familial Startle disease (hyperekplexia) occurs because of point mutations that have impaired the permeation and activation of the glycine receptor (GlyR). Similarly, certain epilepsies are now known to be caused by mutations in, or close to, the channel region in the excitatory acetylcholine receptors (AChRs), which affect channel activation and ion permeation. However, because of their very significant structural and functional similarities, information obtained in one member of the LGIC family of receptors has strong potential application to the other members and the GlyR with its simpler structure has certain advantages for investigation. The first aim of this project is to investigate how the molecular biological structure of these ion channels controls permeation, how it affects how different ions are selectively allowed to move through it and how it affects channel activation. A second related aim is to learn more about the process of desensitization of GlyR receptors, whereby a sustained presence of a high concentration of agonist can cause a reduction in receptor response. A third aim is to specifically investigate the mechanisms underlying the mode of molecular disruption resulting from two new Startle disease mutations, which, in addition to their own inherent clinical value, can also give general information about receptor function.
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