From Maps To Efficient Multi-parasite Control In The Philippines
Funder
National Health and Medical Research Council
Funding Amount
$358,121.00
Summary
Schistosomiasis and soil-transmitted helminths are major parasitic infections in Asia, causing anaemia, poor growth and poor school performance and death in some chronic schistosomiasis cases. We will use maps to demonstrate the geographic distribution of these parasites in the Philippines. We will estimate the impact and costs and benefits of parasite control programmes. This research will help plan more efficient parasite control and reduce the impact of these infections in the Philippines.
Fitness Versus Fatness: Disentangling Their Effects On Disease Outcomes And Estimating The Population Burden Of Disease
Funder
National Health and Medical Research Council
Funding Amount
$188,537.00
Summary
Overweight and physical inactivity are two of the major risk factors for cardiovascular disease and diabetes. With increasing population levels of overweight, governments are increasingly advocating public health measures aimed at increasing physical activity levels or otherwise decreasing weight. There has been much research concerning which of these factors is the key prognostic factor for adverse health outcomes, but an ongoing lack of clarity of research findings has led to uncertainty as to ....Overweight and physical inactivity are two of the major risk factors for cardiovascular disease and diabetes. With increasing population levels of overweight, governments are increasingly advocating public health measures aimed at increasing physical activity levels or otherwise decreasing weight. There has been much research concerning which of these factors is the key prognostic factor for adverse health outcomes, but an ongoing lack of clarity of research findings has led to uncertainty as to the direction of recommendations for preventive health strategies and population lifestyle changes. In addition, the risks of overweight, in particular, have been accused of being exaggerated in both the scientific and lay literature. This is often due to the difficulty of dealing appropriately with time varying confounders which are also intermediate factors (such as hypertension). To date, no studies have performed careful longitudinal modelling of the joint effects of physical inactivity and overweight on cardiovascular events and diabetes while taking into account the effects of factors, such as hypertension or atherosclerosis, that influence both physical activity and overweight as well as disease, and simultaneously are consequences of these risk factors. Standard statistical methods are known to produce biased estimates in these situations but we will apply more recently developed statistical techniques to provide much improved estimation of these effects. After the statistical modelling stage, we will model the burden of diabetes, cardiovascular disease and mortality associated with given levels of overweight and physical inactivity. These will be combined with population levels of overweight and inactivity to identify the fraction of the current and future burden of disease attributable to these risk factors.Read moreRead less
Statistical Methods For The Analysis Of Trends In Coronary Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$112,747.00
Summary
Coronary heart disease is a leading cause of mortality, morbidity and medical costs in Australia. During the 1950's and 1960's, rates of coronary disease increased rapidly, then in the late 1960's they started to decline. This decrease has continued steadily for 30 years. While some other westernised countries have had this same experience, in Eastern Europe and in many developing countries coronary disease is increasing. There is a huge amount of evidence from experimental studies in animal and ....Coronary heart disease is a leading cause of mortality, morbidity and medical costs in Australia. During the 1950's and 1960's, rates of coronary disease increased rapidly, then in the late 1960's they started to decline. This decrease has continued steadily for 30 years. While some other westernised countries have had this same experience, in Eastern Europe and in many developing countries coronary disease is increasing. There is a huge amount of evidence from experimental studies in animal and human subjects and population studies in many countries that the major determinants of coronary disease are high blood pressure, cigarette smoking and high cholesterol (and other lipids) as well as dietary factors, obesity and physical inactivity. Recently several large multicentre studies have found unexpectedly weaker associations between heart risk factors and disease rates. It is hypothesised that this is due to inappropriate analyses in which data from populations at different stages of the coronary epidemic have been combined. The aim of this study is to develop improved statistical methodology to help understand recent findings from large scale studies, such as the World Health Organization's MONICA Project, the US ARIC study and the Seven Countries study. It will provide new theoretical results and statistical software for their implementation. From a public health perspective the most important outcome will be clarification of recent apparently anomalous findings about the importance of established risk factors and effective treatments in reducing coronary disease at the population level.Read moreRead less
Conditional Gene Targeting Of An X-linked Activator Of Cytochrome C: Modelling Of An Infantile Cardiomyopathy.
Funder
National Health and Medical Research Council
Funding Amount
$183,266.00
Summary
Irregularities in heart rhythms are a significant cause of sudden and unexpected death in infants. The past few years has seen a dramatic increase in the identification of genetic abnormalities underlying such irregularities. In particular, a significant proportion of these abnormalities (known as mitochondriopathies) have been shown to be due to deficiencies or defects in the mitochondrial DNA, which encodes some of the components necessary for the generation of cellular energy stores. In contr ....Irregularities in heart rhythms are a significant cause of sudden and unexpected death in infants. The past few years has seen a dramatic increase in the identification of genetic abnormalities underlying such irregularities. In particular, a significant proportion of these abnormalities (known as mitochondriopathies) have been shown to be due to deficiencies or defects in the mitochondrial DNA, which encodes some of the components necessary for the generation of cellular energy stores. In contrast, surprisingly few examples exist where this type of disorder has been shown to be due to a defect in the DNA from the nucleus, despite the numerous components it encodes. We have strong genetic and biochemical evidence to suggest that a new gene (encoded by the nuclear DNA) underlies the sex-linked disorder, oncocytic cardiomyopathy, the major clinical features of which are sudden and irregular heart rhythms usually causing death in female infants before the age of two years. We will utilise a new and powerful genetic technique to reproduce the disorder in laboratory mice to enable a thorough investigation into how the disease manifests itself. It is hoped that this disease model will provide valuable clues towards our understanding of other disorders with sudden heart rhythm abnormalities. It may also give additional support to the likelihood that similar nuclear-encoded defects contribute to the prevalence of, and-or susceptibility to, sudden infant mortality. The novel approach taken will also, for the first time, directly investigate the mechanisms that govern the severity of presentation of the disease in females. These studies will also complement other biochemical studies that are ongoing in our laboratory and will likely have implications for the clinical presentation of numerous other X-linked genetic disorders.Read moreRead less
Altered Hepatic Pharmacokinetics As A Consequence Of Drug- And Disease-induced Changes In Hepatic Vascularity.
Funder
National Health and Medical Research Council
Funding Amount
$498,088.00
Summary
Many drugs are broken down by the liver or are removed from the liver out into the intestine by the bile, as well as being removed by the kidney and other organs. The effectiveness of the breakdown and removal by the liver depends both on whether the drug can get into the liver cells and on how well the enzymes in the liver are working. Cardiovascular and liver diseases and certain drugs can affect both of these processes. This work is concentrating on those processes which mainly affect the upt ....Many drugs are broken down by the liver or are removed from the liver out into the intestine by the bile, as well as being removed by the kidney and other organs. The effectiveness of the breakdown and removal by the liver depends both on whether the drug can get into the liver cells and on how well the enzymes in the liver are working. Cardiovascular and liver diseases and certain drugs can affect both of these processes. This work is concentrating on those processes which mainly affect the uptake process. The diseases of most interest are liver cirrhosis, fatty liver disease, atherosclerosis and chronic heart failure, all of which together are leading causes of death in Western countries. They are also associated with liver dysfunction due to effects on liver vessels. We have a poor understanding of how the effects of these diseases and a number of drugs on liver vessels affect the functioning of the liver, especially in terms of how they affect drug breakdown or removal of drugs. This project seeks to understand these effects and proposes a number of animal studies as well as human studies to provide insight. The drugs to be studied are those most commonly used in patients with cardiovascular and liver diseases, as one of our main goals is to provide better therapeutic management in these patients.Read moreRead less
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
Effect Of Liver Pathophysiology On Hepatic Pharmacokinetics
Funder
National Health and Medical Research Council
Funding Amount
$457,500.00
Summary
The liver is the main organ in the body for the metabolism and biliary excretion of natural and foreign solutes. Various liver diseases such as cirrhosis, alcoholic liver disease, diet and drug induced fatty livers can affect the uptake and metabolism of drugs and their suitability- dosing needs. Some liver diseases such as fatty livers are very common but how rapidly drugs are metabolised in these patients is not well described. The work is important as it may help us better design new drugs an ....The liver is the main organ in the body for the metabolism and biliary excretion of natural and foreign solutes. Various liver diseases such as cirrhosis, alcoholic liver disease, diet and drug induced fatty livers can affect the uptake and metabolism of drugs and their suitability- dosing needs. Some liver diseases such as fatty livers are very common but how rapidly drugs are metabolised in these patients is not well described. The work is important as it may help us better design new drugs and better choose which drugs to give and, if so, in what doses. In addition, many liver diseases require a biopsy for a definite diagnosis of the likely function of the liver. Estimation of liver function is particularly important in estimating whether there will be sufficient reserve on resection of a cancer or deciding if a liver transplant is needed. The liver is also a very complex organ which can trap or breakdown solutes by a range of different systems. Also of importance is how those diseases affect drug disposition in the liver given that an altered hepatic drug disposition may affect systemic response to the drugs and their metabolites. This work seeks to answer these questions.Read moreRead less
Understanding Influenza Mortality And The Effects Of Vaccination In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$446,877.00
Summary
We will analyse mortality from influenza and other causes to estimate the numbers of deaths from other causes that are triggered by influenza in elderly persons, and to test the value of vaccination in preventing those deaths. Our results will help to decide whether an expensive clinical trial is really needed to show the benefit of influenza vaccination on all-cause mortality in the elderly.