A Genome-wide Association Study In 2000 Glaucoma Cases With Matched Controls Using Equimoloar DNA Pools
Funder
National Health and Medical Research Council
Funding Amount
$610,267.00
Summary
Glaucoma is a common cause of loss of vision worldwide but we are unable to predict which people are at high risk of blindness. We aim to discover the genetic risk factors for glaucoma. We will use cutting edge genetic technology to assess the whole genome in thousands of patients with glaucoma. We hope to identify important new glaucoma genes, which could lead to the development of diagnostic tests and treatments which will provide the most cost-efficient ways to prevent glaucoma blindness.
Exposure To High Dose Estrogens In Adolescence: Long Term Effects On Mammographic Breast Density
Funder
National Health and Medical Research Council
Funding Amount
$89,050.00
Summary
Breast density is a well established risk factor for breast cancer, and has been shown to be reversibly influenced by hormone exposures in adult life. As one of the important roles of sex hormones during puberty is mammary cell proliferation, it is plausible that exposures at this earlier life stage might have a sustained influence on breast tissue composition and density, and subsequent breast cancer risk. This project aims to increase our understanding of the influence of sex hormones in adole ....Breast density is a well established risk factor for breast cancer, and has been shown to be reversibly influenced by hormone exposures in adult life. As one of the important roles of sex hormones during puberty is mammary cell proliferation, it is plausible that exposures at this earlier life stage might have a sustained influence on breast tissue composition and density, and subsequent breast cancer risk. This project aims to increase our understanding of the influence of sex hormones in adolescence on breast cancer risk by testing the hypothesis that exposure to large doses of sex hormones during adolescence has long-term effects on mammographic density. This will be done by comparing the mammographic densities of women who were treated with high doses of estrogen for tall stature during adolescence with women who were similarly assessed for tall stature but not treated. No previous study in humans has examined the long-term effects on breast tissue of high dose estrogen exposure at this early life stage. This is not surprising, given the difficulty in finding a suitable exposed population. This cohort of women, assessed or treated for tall stature, provides us with a unique opportunity to examine these influences. This research will add to our understanding of the influence of sex hormones in adolescence on mammographic density and breast cancer risk. If hormonal factors in adolescence are shown to influence mammographic density, this may lead to new avenues for breast cancer prevention efforts that are targeted much earlier in life. This information may lead to new research directions examining adolescent hormonal exposures (both endogenous and exogenous) and their influence on breast tissue.Read moreRead less
Enhancing The Cardioprotective Effect Of Diadenosine Tetraphosphate: Designing Inhibitors Against Ap4A Hydrolase
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitocho ....Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitochondrial ATP-dependent potassium channel may be in common with most pathways. Pretreatment with the compound diadenosine tetraphosphate (Ap4A) mimics ischemic preconditioning with noticeable reductions in tissue necrosis (cell death). This treatment has been shown in experimental work to protect the heart during periods of stress such as in heart surgery or recovery from an ischemic event. The biological site of action by Ap4A may be the mitochondria ATP-dependent potassium channel or an associated protein. Ap4A can be degraded by enzymes located inside and on the outside of heart cells, notably by two forms of Ap4A hydrolase. We will use antibody assays to understand the specific localization and amount of Ap4A hydrolase before and after ischemia and after ischemic preconditioning in human heart muscle and blood vessels. We propose to determine the structure of the enzyme and use novel computer methods to screen databases for potential inhibitors. These inhibitors of Ap4A hydrolase activity could aid the design of a potent inhibitor that would prevent Ap4A hydrolase from degrading Ap4A and therefore enhance the cardioprotective properties of Ap4A as well as minimizing side effects from the break down of Ap4A. We will also use these inhibitors and other known non-degradable Ap4A analogues in bioassays to test the relative significance of Ap4A hydrolase present in different cellular locations.Read moreRead less
A Case-control Study Of Environment And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$808,948.00
Summary
Breast cancer is the most common cancer in Australian women and there have been a number of recent events which have raised public concern that occupational exposures are contributing to the increasing occurrence of this cancer. In this study, we will investigate occupational causes of breast cancer, particularly shift work, industrial solvent use and combustion products. We will compare occupations of 1000 women with breast cancer and 2000 women without cancer.
Markers Of Androgen Action, Genetic Variation And Prostate Cancer Risk
Funder
National Health and Medical Research Council
Funding Amount
$798,907.00
Summary
This proposal aim to follow up evidence from a number of studies that genetic and non-genetic markers of hormonal action in different periods of a man's life are associated with prostate cancer risk using a collection of three large, independent epidemiologic studies on prostate cancer named the Prostate Cancer Program. A principal objective is to collect exposure data on acne and digit ratio, and genotype cases and controls across the studies of the Prostate Cancer Program for common genetic va ....This proposal aim to follow up evidence from a number of studies that genetic and non-genetic markers of hormonal action in different periods of a man's life are associated with prostate cancer risk using a collection of three large, independent epidemiologic studies on prostate cancer named the Prostate Cancer Program. A principal objective is to collect exposure data on acne and digit ratio, and genotype cases and controls across the studies of the Prostate Cancer Program for common genetic variants in 4 candidate genes in the hormonal pathway. The established risk factors for prostate cancer are only age, race and family history. We anticipate that this project will cast light on the role of hormones in prostate cancer and that we will identify new markers of risk of prostate cancer and markers of disease aggressiveness. These outcomes will help us identifying men who are at risk for prostate cancer to target screening and surveillance, and plan prevention strategies. Furthermore, they will also form the basis for research on treatment targets.Read moreRead less
Evaluation Of An Instrument For Management Of Behavioural And Psychological Symptoms Of Dementia.
Funder
National Health and Medical Research Council
Funding Amount
$598,468.00
Summary
Behavioural and Psychological Symptoms of Dementia (BPSD) distress the patient and others. The behaviours, and not the underlying causes, are often treated with antipsychotics, despite side effects and low efficacy. An assessment instrument for care staff to determine and address causes of BPSD will be implemented. We predict training will reduce inappropriate prescribing and other reasons for distress. Where medication is required, detailed information will assist more targeted prescribing.
A Randomised Controlled Trial Examining Stability Of New Types Of Highly Porous Surfaced Acetabular Components In Total Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$216,490.00
Summary
Numbers of total hip replacements are steadily increasing. The most common complication of hip replacement is late implant loosening, which can be predicted by early migration. We will examine early migration of a trabecular metal acetabular cup without screws, compared to a titanium fibre metal acetabular cup fixed with screws. Ideally, an acetabular cup would achieve a level of initial stability by press-fit alone without screws, as screws increase the risk of bone loss around the prosthesis.
Antagonist Of Corticotrophin Releasing Hormone As Therapeutic Agents For The Prevention Of Premature Birth In Humans
Funder
National Health and Medical Research Council
Funding Amount
$376,650.00
Summary
In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow ....In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow the extension of pregnancy term The development of protocols that will in turn reduce neonatal mortality. Additionally we believe that these new agents will be useful in preventing the onset of labour after fetal surgery. Currently there are no effective treatments capable of substantially changing delivery dates. Available therapeutics delay the onset of labour, at best, 24 hours. However, recent exciting results from our laboratories show that rising concentrations of the placental peptide Corticotrophin Releasing Hormone (CRH) are associated with the onset of labour. Further, we have also delayed the onset of labour in pregnant sheep by infusing a relatively insoluble CRH antagonist into the sheep fetus. Labour commenced ONLY AFTER the drug was withdrawn from the mother. This project builds upon an interdisciplinary team: medicinal chemists, molecular modellers, pharmacologists and endocrinologists, to further develop an exciting Australian discovery. Successful completeion of this research will, for the first time, allow the control of pregnancy duration MAXIMISING the benefits to mother and child, reducing mortality and later life morbidities typically associated with premature birth.Read moreRead less
New High-risk Variants For Colorectal Cancer: The Post-GWAS Era
Funder
National Health and Medical Research Council
Funding Amount
$710,105.00
Summary
Our aim is to discover new genes that greatly increase bowel cancer risk. If we can identify these carriers we may be able to prevent them getting cancer. By studying DNA related to bowel cancer, using a novel family design, we will identify families most likely to carry the new genes. We will focus genetic testing, using new techniques, to look for mutations in these prioritised families. Identified mutations will be tested in a 3,500 bowel cancer cases to see how important they are.
A Behavioural Intervention For The Adoption & Maintenance Of Physical Activity In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$334,955.00
Summary
For people with type 2 diabetes (T2DM) it is essential that blood glucose levels are managed well to reduce the risk of developing complications. Physical activity is essential for maintaining glucose levels because it helps make the muscles use glucose more effectively. In particular, being active through strength training not only improves blood glucose levels, but can be very effective for maintaining good physical functioning, which is known to be reduced by having T2DM. This study builds on ....For people with type 2 diabetes (T2DM) it is essential that blood glucose levels are managed well to reduce the risk of developing complications. Physical activity is essential for maintaining glucose levels because it helps make the muscles use glucose more effectively. In particular, being active through strength training not only improves blood glucose levels, but can be very effective for maintaining good physical functioning, which is known to be reduced by having T2DM. This study builds on our earlier research which demonstrated significantly improved blood glucose levels from a strength training program for older adults with T2DM. The strength training program is to be administered nationally in a research to practice trial (Lift for Life); however, the original research found that those who did not complete the program as it was intended (ie, poor adherence) did not show significant improvements in blood glucose levels. Furthermore, maintenance of strength training exercises after completion of the program was poor and resulted in return of blood glucose levels back to pre-starting levels. In people without diabetes, we have collected pilot data that shows that the use of behavioural strategies based on behavioural theories whereby each person's motivations and barriers are taken into consideration is more effective than the traditional one-treatment-fits-all approach. This study will evaluate the effectiveness of using behavioural strategies for improving adherence and maintenance to the Lift for Life strength training program (Enhanced L4L) for older adults with T2DM compared with the Standard L4L program. It will also follow-up participants 6 months later to determine the extent to which the changes in behaviour can be maintained. The study will provide information that will assist in the design, delivery and uptake of programs to improve treatment strategies in older adults with T2DM through the maintenance of healthier behaviours and lifestyles.Read moreRead less