In type 1 diabetes the body becomes deficient in insulin production from pancreatic b cells because the immune system mistakenly attacks and destroys b cells as if they were an invading infection. Recurrence of autoimmune destruction of b cells also occurs following transplantation of whole pancreas or islet cells and may occur in the future when other engineered insulin producing cells are transplanted. The focus of this program is to better understand how b cells are killed by the immune syste ....In type 1 diabetes the body becomes deficient in insulin production from pancreatic b cells because the immune system mistakenly attacks and destroys b cells as if they were an invading infection. Recurrence of autoimmune destruction of b cells also occurs following transplantation of whole pancreas or islet cells and may occur in the future when other engineered insulin producing cells are transplanted. The focus of this program is to better understand how b cells are killed by the immune system and to test ways of protecting beta cells from these mechanisms. Because of the inaccessibility of the pancreas to study (particularly biopsy) in humans with diabetes, much of the proposed work will be carried out in b cells derived from non-obese diabetic (NOD) mice, the best available mouse model of type 1 diabetes. It is clear from the literature that a molecule called perforin found in cytoxic T lymphocytes (CTL) is a major, if not the major, mechanism the immune system uses against b cells. For this reason we will try to better understand the interaction between b cells and perforin and ultimately design ways of them from perforin-mediated cell death. It is equally clear that there are other mechanisms besides perforin that can cause b cell death and the program will also address discovery of these mechanisms and new ways to block them. Beta cells in NOD mice will be protected from perforin or other mechanisms by the addition of protective genes or removal of harmful genes using transgenic knockout technology. Addition or removal of genes involved in cell death can be done systematically and each protocol tested using NOD mouse model. The process of cell death that b cell undergo in type 1 diabetes is called apoptosis. Apoptosis is a general mechanism by which cells of all types die. Experts in the biology of apoptosis and perforin are important members of the program, providing the opportunity to translate the latest advances in cell death research to diabetes. This research addresses several of the specific research areas of interest to JDRF. It focuses on the prevention of b cell death in individuals with type 1 diabetes receiving islet transplants. It may be applicable in the future to protection of stem or precursor cells that have been differentiated into b cells or even to devising strategies to prevent the development of diabetes.Read moreRead less
A Randomised Controlled Trial Of The Cost-effectiveness Of Supportive Care Coordination For Advanced Cancer
Funder
National Health and Medical Research Council
Funding Amount
$147,269.00
Summary
The study will test the cost-effectiveness of two models of supportive care coordination for advanced cancer against usual care: a Telephone Caseworker model and an Oncologist-GP model. Both models are aimed at improving patients' and their informal caregivers' health and psychosocial status; are patient-centred, evidence based and readily transferable across health care settings. The Telephone Caseworker model has the additional advantage of reaching people isolated through geography, physical ....The study will test the cost-effectiveness of two models of supportive care coordination for advanced cancer against usual care: a Telephone Caseworker model and an Oncologist-GP model. Both models are aimed at improving patients' and their informal caregivers' health and psychosocial status; are patient-centred, evidence based and readily transferable across health care settings. The Telephone Caseworker model has the additional advantage of reaching people isolated through geography, physical disability or age.Read moreRead less
Development Of A Palliative Care Service For Rural And Remote Communities
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
This project will develop, implement and evaluate a new model of providing palliative care to individuals in rural and remote communities that will utilise existing health and community resources to provide palliative care. As the number of patients requiring palliation in rural and remote communities is small, the service may not function at all times but come together (pop-up) as required. Evaluation of the model in three different types of rural communities will be undertaken in three states ....This project will develop, implement and evaluate a new model of providing palliative care to individuals in rural and remote communities that will utilise existing health and community resources to provide palliative care. As the number of patients requiring palliation in rural and remote communities is small, the service may not function at all times but come together (pop-up) as required. Evaluation of the model in three different types of rural communities will be undertaken in three states (New South Wales, Queensland and West Australia). Phase I will develop a framework to assist rural communities undertake a critical palliative care service review. Phase II will implement and evaluate the model, leading to recommendations for provision of best practice palliative care more generally in rural communities.Read moreRead less
Phosphoproteomics: Metabolic And Exercise Signalling Markers For Sedentary And Trained Individuals
Funder
National Health and Medical Research Council
Funding Amount
$1,222,500.00
Summary
It is widely recognized that diet and exercise have a major influence on the health and fitness. Sedentary lifestyles predispose people to obesity and the early development of age onset diseases. In the past decade we have gained considerable insight into the regulatory links between exercise and metabolism particularly involving the AMPK signalling pathway. This project is concerned with the phosphoproteome of trained and untrained skeletal muscle, fat and erythrocytes as a marker of fitness.
A National Resource For Mouse Models Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$483,643.00
Summary
Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resour ....Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resource to maintain and distribute these cell lines. In addition, we describe a new transgenic mouse model in which mesotheliomas are rapidly induced in the peritoneal cavity after exposure to asbestos, recreating the natural tumour development much more accurately. These mice have been engineered to express the cancer causing protein of a monkey virus (SV40 large T antigen) in their mesothelial cells because it has been suggested that the virus has a role in the development of mesothelioma. This application also seeks funding to use the MexTAg mice to test the usefulness of different therapies for the prevention or treatment of mesothelioma. These animals give us the ability to investigate the disease in a more realistic environment than previous models. In parallel collaborative studies with other groups investigating different aspects of the biology of this cancer, we plan to analyze the earliest changes in the development of the disease and search for early markers using proteomics and gene expression studies. We anticipate that this model will generate information more directly relevant to understanding the human disease and will provide essential experimental data for clinical trials.Read moreRead less
Confirming The Burden Of Disease Associated With Dementia Using New Empirically Driven Australian Based Disability Rati
Funder
National Health and Medical Research Council
Funding Amount
$138,084.00
Summary
The amount of burden the population experiences as a result of individual diseases influences health policy. The Australian Burden of Disease project quantifies the relative burden associated with each disease. New estimates are to be released this year will outline the magnitude of burden associated with dementia now and estimate that for the year 2023. Although the projections use the best data available, three improvements to the methodology would improve the accuracy of the dementia burden e ....The amount of burden the population experiences as a result of individual diseases influences health policy. The Australian Burden of Disease project quantifies the relative burden associated with each disease. New estimates are to be released this year will outline the magnitude of burden associated with dementia now and estimate that for the year 2023. Although the projections use the best data available, three improvements to the methodology would improve the accuracy of the dementia burden estimates. First, the dementia calculations currently use a “disability weight” metric derived from a Dutch study. This is problematic in that the weights do not reflect an Australian experience of dementia, nor do they reflect the preferences of people closely affected by the disease (e.g. carers). Second, the dementia estimates do not include cases of mild cognitive impairment (considered a precursor state of dementia). Hence the dementia estimates may not estimate the full impact of dementia in Australia. Finally, there is no evidence that the method used by the Burden of Disease study to account for the impact of disease comorbidity adequately deals with the comorbidity associated with dementia. Consequently, there is need to develop a new and comprehensive set of disability weights for dementia that are Australian-based, include all stages of dementia severity and account for comorbidity. The proposed project aims to develop a new set of empirically derived Australian-based disability weights for dementia. The project will entail three studies. The first study will generate empirically based case vignettes that describe a range of dementia case scenarios. These descriptions will then be used in rating exercises (Study 2) to develop new disability weights. The second study involves Australian health practitioners, carers and lay persons reading case vignettes and completing health valuation rating exercises to generate new disability weights for dementia. The third study uses the new disability weights to re-calculate the burden of disease estimates for dementia. The new estimates will be compared to those reported by the 2007 Australian Burden of Disease project. In knowing the accuracy of the estimates, policy makers can use the burden data for dementia with confidence when engaging in service planning for the future.Read moreRead less
Identifying EHealth Literacy And Readability Issues For Palliative Care Consumers
Funder
National Health and Medical Research Council
Funding Amount
$29,375.00
Summary
Access and use of health information can affect a patient’s health experience and potentially their health outcomes. Increasingly health information is being provided and sought through the internet and online resources. Palliative care patients and their carers have specific information needs relating to the nature and progress of their disease, their symptoms and their current and pending quality of life. However, their ability to find and use information relies on many factors such as individ ....Access and use of health information can affect a patient’s health experience and potentially their health outcomes. Increasingly health information is being provided and sought through the internet and online resources. Palliative care patients and their carers have specific information needs relating to the nature and progress of their disease, their symptoms and their current and pending quality of life. However, their ability to find and use information relies on many factors such as individual skills and experiences and how information is presented and made available. eHealth literacy is a measure of the mix of skills required by consumers to successfully access and understand palliative care information. Readability is one aspect of eHealth literacy and readability scales can be used to identify how effective websites are in providing appropriate written information for palliative care consumers. This research will help assess eHealth literacy levels and hence potential intervention needs of palliative care patients and carers as well as determining whether the readability requirement of palliative care websites and information is too high.Read moreRead less
Novel Probiotics And Naturally-sourced Extracts As Treatment Strategies For Chemotherapy-induced
Funder
National Health and Medical Research Council
Funding Amount
$322,183.00
Summary
Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have be ....Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have been anecdotal claims of medicinal application for so-called ‘bioactive’ extracts and formulations derived from a range of mammalian, marine and plant sources. Specifically, Lyprinol (an extract derived from the New Zealand Green-Lipped Mussel), Emu Oil (derived from Emu meat) and the herbal extract Iberogast, have been reported to possess antiinflammatory properties. Indeed, these agents are used widely for the adjunctive relief of symptoms associated with arthritis and joint pain. However, these agents have yet to be tested for their potential to treat or prevent intestinal mucositis. For the first time, utilizing proven, controlled animal model systems, the current submission will explore the therapeutic potential of these agents, alone and in combination with indicated probiotics, for their capacity to treat or prevent mucositis. Should efficacy be demonstrated, a potential mechanism of action will be sought by investigating effects on intestinal stem cells.Read moreRead less
An Investigation Of Care Planning Decisions In Advanced Pulmonary And Cardiac Illness In The Bayside Health Care Region
Funder
National Health and Medical Research Council
Funding Amount
$47,726.00
Summary
There has been little Australian research to develop interventions that facilitate end of life decision making. This project will provide a framework for understanding the issues in the planning of end of life care for people with chronic and life limiting illness and the relationship of this planning to organizational policy. The care decisions in hospital records of people with advanced lung and heart disease will be reviewed and people with those diseases interviewed about the issues they exp ....There has been little Australian research to develop interventions that facilitate end of life decision making. This project will provide a framework for understanding the issues in the planning of end of life care for people with chronic and life limiting illness and the relationship of this planning to organizational policy. The care decisions in hospital records of people with advanced lung and heart disease will be reviewed and people with those diseases interviewed about the issues they experience in planning their future care. Professionals from a range of health organisations will be interviewed about their experiences of care planning for people with life limiting lung and heart disease. As a pilot, this project will be used to contribute to the development of a model for a coordinated multidisciplinary process that brings together the health care services in a region and contributes to the systematic, ongoing development of infrastructure to improve end of life care.Read moreRead less