Modelling The Effects Of Immunity On Influenza Transmission - Implications For Prevention And Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$275,767.00
Summary
There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our proj ....There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our project will use data from historic and contemporary outbreaks of influenza and build mathematical models to explain the rate of growth of an influenza outbreak in terms of: 1. The proportion of people exposed to influenza who do not become ill (although there can be evidence of infection if careful studies are made). This proportion is about 33%. 2. The proportion of people who are protected from influenza by immunity, whether induced by vaccination or by past exposure to natural influenza infection (this can vary from 0% in isolated populations which have not seen influenza for many years up to 80 or 90% in urbanised populations that are exposed to influenza almost every season). 3. Different rates of contact between different people and groups of people - some may be exposed so often that their immunity is boosted regularly without them becoming severely ill; others, living in more isolated circumstances, may be rarely exposed, but when they are, they are more likely to become severely ill. 4. The effects of influenza vaccine in inducing protective immunity - it is well known that there is good protection if the vaccine is well matched to the circulating virus. 5. The effects of live virus infection in inducing (short-lived) protection against a wider range of influenza viruses. Our model results will be used to guide vaccine design and pandemic planning.Read moreRead less
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
Measuring The Productive Efficiency Of Hospitals - A Comparison Of Parametric And Non-parametric Approaches
Funder
National Health and Medical Research Council
Funding Amount
$61,815.00
Summary
In the face of rising health service costs, an ageing population, and falling private health insurance rates, the efficient use of scarce health service resources has become a central theme in health system reform. Productive (or technical) efficiency is a key aspect of health system reform - that given health services are produced with the minimum feasible amount of resources. Despite the importance of technical efficiency there have been few published studies in Australia which measure technic ....In the face of rising health service costs, an ageing population, and falling private health insurance rates, the efficient use of scarce health service resources has become a central theme in health system reform. Productive (or technical) efficiency is a key aspect of health system reform - that given health services are produced with the minimum feasible amount of resources. Despite the importance of technical efficiency there have been few published studies in Australia which measure technical efficiency in the health sector. This study will develop theoretical and empirical approaches to measuring technical efficiency in the production of hospital services using data from Victoria. Measures of hospital technical efficiency will be developed using two quantitative modelling approaches: stochastic frontier modelling and data envelopment analysis. Results will be used to investigate the impact of patient and hospital characteristics on efficiency, and to identify economies of scale and scope in the provision of hospital services. The robustness of results to changes in variables, the sample of hospitals studied, and model assumptions will be tested, and two techniques will be compared to assess their appropriateness in the health services context which has not previously been done. Criteria for assessing the approaches include the degree to which: assumptions affect the robustness of results; the techniques capture the salient features of health services production; and the techniques produce similar rankings and estimates of inefficiency. The methods used will represent a significant contribution to international knowledge of hospital efficiency measurement, and the relationships between hospital characteristics, casemix, and efficiency. The study wil provide improved measures of hospital efficiency in Victoria, and will inform debate on hospital funding policy.Read moreRead less
Antigen Selection In The MHC-restricted Cellular Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$175,570.00
Summary
The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally appare ....The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally apparent when molecules called antigens are released by microorganisms and captured by the body's cells. This activates lymphocytes resulting in an immune response capable of eliminating the microorganisms. Scrutiny of the body's cells by lymphocytes occurs continuously even when there is no infection present in the body. Following infection of a cell, microbial antigens reveal the infection by their appearance on the cell surface where they are detected by the immune system's lymphocytes. This occurs through a mechanism called antigen presentation. During antigen presentation the proteins inside the cell, including those of any invading microorganism, are first degraded into shorter molecules called peptides. This event is called antigen processing. A fraction of the peptides created by antigen processing are captured by specialised receptors present on all cells. These receptors are called HLA or histocompatibility molecules. This project examines the molecular events which mediate the capture of peptide antigens by HLA molecules. The main focus is on those peptide antigens which elicit killer T cell responses by the immune system. A knowledge of how these peptides are selected for presentation and how they are captured and carried to the cell surface is fundamental to understanding immune responses to microorganisms, tumours, allergens, transplants and self tissues as in autoimmunity. Therefore the study is of great general relevance.Read moreRead less
Cytokine Signalling And Insulin Resistance In Obesity.
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
Western communities are experiencing an epidemic of obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating why being overweight and obese causes diabetes. Improved understanding about how hormones regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.
Predictors And Correlates Of Developmental Language Problems: A Longitudinal Study From Infancy To Pre-school Age
Funder
National Health and Medical Research Council
Funding Amount
$537,750.00
Summary
Language impairment is a disabling condition, thought to affect between 7% and 15% of 4 year old children. It has serious and lasting implications for social and emotional development, cognition, behaviour and literacy. A link has been demonstrated between language impairment and later psychiatric disorders in adolescence and adulthood. Given the potential of enhancing the language development of young children, it is critical that effective prevention and early intervention programs are availab ....Language impairment is a disabling condition, thought to affect between 7% and 15% of 4 year old children. It has serious and lasting implications for social and emotional development, cognition, behaviour and literacy. A link has been demonstrated between language impairment and later psychiatric disorders in adolescence and adulthood. Given the potential of enhancing the language development of young children, it is critical that effective prevention and early intervention programs are available. However, current knowledge is liminted in that there are no entirely satisfactory methods for detecting children who at much younger ages, 8 months, 12 months, 2 years and 3 years, are at risk of later impairment. In this study we aim to: examine the risk factors (many are thought to exist) that contribute to language impairment learn more about the natural history of this disabling disorder in children between 8 months and 4 years of age Ultimately, we aim to identify early signs that might warn health professionals and parents of language impairment so that such problems can be detected much earlier. Early identification will mean that help is available at an earlier age to children who currently go on to have persisting and extremely disabling language impairment.Read moreRead less
Dissecting The Pseudoexfoliation Syndrome With Complementary Genetic, Proteomic And Biophysical Strategies
Funder
National Health and Medical Research Council
Funding Amount
$490,352.00
Summary
Pseudoexfoliation syndrome (PEX) is an eye condition in which flaky material deposits in the eye, greatly increasing the risk of cataract and glaucoma which can lead to blindness. PEX is also associated with heart disease, strokes and aneurysms. Cataract surgery in PEX patients has a higher rate of complications. In this project we will determine the nature of PEX material and why it forms. This knowlege will facilitate better diagnosis and treatment of PEX preventing associated blindness.
Ventilation Heterogeneity And Airway Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$522,586.00
Summary
Asthma is a common and important as a cause of significant symptoms and even death. Associated with asthma is narrowing and stiffening of the arways which causes uneven ventilation of the lungs and reduced lung function. We have developed a new technique of imaging the lungs, as well as new lung function tests which measure uneven ventilation and stiffening of airways. This will help us design better medications, and help predict those who are at risk or severe asthma and death.
Randomised Double-blind Placebo-controlled Trial Of Aspirin In Primary Prevention Of CVD Events Or Dementia In The Aged.
Funder
National Health and Medical Research Council
Funding Amount
$3,532,500.00
Summary
The single most important risk factor for cardiovascular disease is age. All men aged 75 years have a 10-15% risk of having a stroke or heart attack in the next 5 years. Low dose aspirin has been shown to prevent further strokes and heart attacks in people who have already had one. It has been also shown to protect people who have not had a heart attack or stroke but who are at increased risk. Given that the elderly are at increased risk why do we need to do a trial in this particular group? The ....The single most important risk factor for cardiovascular disease is age. All men aged 75 years have a 10-15% risk of having a stroke or heart attack in the next 5 years. Low dose aspirin has been shown to prevent further strokes and heart attacks in people who have already had one. It has been also shown to protect people who have not had a heart attack or stroke but who are at increased risk. Given that the elderly are at increased risk why do we need to do a trial in this particular group? The reason is that relatively few elderly patients were included in the previous prevention trials. Also while the elderly may have the most to gain from treatment, they also have the most to lose because they are more likely to suffer from side-effects. Aspirin prevents heart attacks by stopping clots forming in blood vessels. This also means that people taking it have an increased tendency to bleed. Thus though it may prevent strokes due to clots it may also increase the risk of strokes caused by bleeding. Bleeding from the gut is another major problem as aspirin tends to erode the lining of the stomach. Minor bleeding from the gut can also lower blood oxygen carrying capacity which may exacerbate other diseases associated with ageing, e.g. heart failure. Dementia may be caused by repeated clots in small or large vessels. Dementia is a particular problem in the elderly affecting 10% of 85 year olds. It is a major cause of loss of quality of life and a significant cost to the community. Aspirin may reduce the progression of such a disease leading to a maintained quality of life (QOL) for individuals and their families. As our age increases our years of life remaining decreases. This is self-evident. Thus the potential to add years to life reduces and the potential of diseases to adversely affect quality of life becomes more important. Thus it may be more important to prevent a nonfatal stroke that leads to institutionalisation than a fatal stroke. Hence QOL will be assessed.Read moreRead less