An X-ray Crystallographic Investigation Into The Adaptive Immune Response To Epstein Barr Virus
Funder
National Health and Medical Research Council
Funding Amount
$521,961.00
Summary
This proposal is focussed on understanding the precise shape of proteins that control the immune response to Epstein Barr Virus. EBV is an ubiquitous human pathogen that has been linked to a number of cancers. This research proposal will further our understanding of the immune response to EBV, which will lay the foundations for developing therapeutics against this disease.
Foetal Determinants Of Sleep Disordered Breathing In Infants
Funder
National Health and Medical Research Council
Funding Amount
$174,691.00
Summary
Obstructive sleep apnea (OSA) has been identified and recorded in infants, however the factors that lead to the development of OSA and its prevalence in infants is unknown. We have recorded OSA in some infants and we demonstrated that the severity of apnea was at its peak at approximately 2 months of age and then resolved by 1 year. We hypothesised that these infants possibly had a maturational delay of breathing control during sleep. This project is designed to examine the development and preva ....Obstructive sleep apnea (OSA) has been identified and recorded in infants, however the factors that lead to the development of OSA and its prevalence in infants is unknown. We have recorded OSA in some infants and we demonstrated that the severity of apnea was at its peak at approximately 2 months of age and then resolved by 1 year. We hypothesised that these infants possibly had a maturational delay of breathing control during sleep. This project is designed to examine the development and prevalence of sleep and breathing disorders in infants. The prenatal factors that possibly influence development of sleep and breathing disorders in infants, in particular, the effects of maternal smoking will be determined. Pregnant women will be recruited for the study during their third trimester. The foetal movements, foetal breathing movements, heart rate and sleep state will be monitored continuously overnight in the patients home between 32 and 36 weeks gestation using a newly developed foetal movement monitor. The infants will be subsequently studied using overnight polysomnography at 2 months of age to assess their breathing, sleep patterns, arousal behaviour, and the presence and severity of central and obstructive apnea. A group from these infants will be selected and studied longitudinally to examine the development of sleep and breathing disorders more closely. These infants will undergo overnight sleep studies during the first week of life, then at 2 and 6 months of age. A detailed medical history will also be collected regarding the pregnancy, the perinatal history of the infant, exposure to cigarette smoke during pregnancy and postnatally, and the medical history of other family members. We will examine the quality and quantity of foetal movements and its association with the development of OSA. The occurrence of sleep and breathing disorders in the infants will be correlated with the foetal behaviour and, the prenatal and postnatal factors.Read moreRead less
Osteoarthritis is the major cause of disability in elderly Australians. It is a disease of unknown aetiology that results in deterioration of the structure and function of articular cartilage. Current treatment is palliative or involves joint replacement, which is very costly. No preventive strategies are currently available. These facts have led to 2000-2010 being labelled the Bone and Joint decade. Studies have consistently indicated a higher risk of this disease in families. This study will e ....Osteoarthritis is the major cause of disability in elderly Australians. It is a disease of unknown aetiology that results in deterioration of the structure and function of articular cartilage. Current treatment is palliative or involves joint replacement, which is very costly. No preventive strategies are currently available. These facts have led to 2000-2010 being labelled the Bone and Joint decade. Studies have consistently indicated a higher risk of this disease in families. This study will examine for novel genes for this condition in a large family study involving over 500 subjects. Identification of susceptibility or severity genes in OA is of marked importance as it is likely to lead to a better understanding of the biochemical basis of these disorders, and translate to rational therapeutic strategies and preventative strategies in at-risk individuals in the longer term.Read moreRead less
Retinal Vascular Signs As Predictors Of Systemic Disease Outcomes: 10-year Evolution In A Population-based Cohort
Funder
National Health and Medical Research Council
Funding Amount
$389,575.00
Summary
Recent U.S. data from two population-based studies have highlighted retinal microvascular signs as being predictive of systemic vascular and other important health outcomes in middle-aged or older individuals, particularly stroke and heart attack and mortality, independent of traditional vascular risk factors. The present application proposes to evaluate the 10-year development and progression of retinal microvascular signs and their relations to the development of stroke and other important sys ....Recent U.S. data from two population-based studies have highlighted retinal microvascular signs as being predictive of systemic vascular and other important health outcomes in middle-aged or older individuals, particularly stroke and heart attack and mortality, independent of traditional vascular risk factors. The present application proposes to evaluate the 10-year development and progression of retinal microvascular signs and their relations to the development of stroke and other important systemic health outcomes in the population-based cohort of residents attending the Blue Mountains Eye Study (BMES. Two types of retinal signs will be evaluated: firstly, the presence of specific clinical signs, such as focal narrowing of small retinal vessels (arterioles), nicking of retinal veins as arterioles cross them or presence of retinopathy (haemorrhages and other signs) secondly, measures of generalized retinal vessel calibre (narrowing) using a computer-assisted method developed for the U.S. studies. We will also develop new grading methods for two other signs. Late and will compare computer-assisted grading from 35mm slides to automated grading of vessels using a scanning device (being developed) to screen the eyes of older persons. This project builds upon our current 3-year NHMRC grant (ID153948; 2001-2003) Retinal vascular signs as risk markers for incident stroke or cerebrovascular death: A population-based assessment . In the last 2 years, this has explored different aspects of measurement and grading of these signs, has documented their relation to blood pressure and has begun to assess whether these features predict vascular events and other systemic outcomes in older Australians. The new project will assess the evolution of retinal microvascular signs over a 10-year period, using data and retinal photographs from the 10-year examinations of the BMES cohort, currently being collected, in a further current NHMRC grant (ID211069; 2002-2004).Read moreRead less
Retinal Vascular Signs As Risk Markers For Incident Stroke Or Cerebrovascular Death: A Population-based Assessment
Funder
National Health and Medical Research Council
Funding Amount
$410,199.00
Summary
Stroke remains a major cause of disability and death in Australia. Preliminary data from the Blue Mountains Eye Study suggest that blood vessel changes observed in the retina at the back of the eye may provide signs of an increased risk of stroke or death from stroke. Importantly, although stroke is strongly associated with elevated blood pressure, the risk associated with these blood vessel signs seems to be independent of blood pressure. The proposed study will conduct a detailed re-grading of ....Stroke remains a major cause of disability and death in Australia. Preliminary data from the Blue Mountains Eye Study suggest that blood vessel changes observed in the retina at the back of the eye may provide signs of an increased risk of stroke or death from stroke. Importantly, although stroke is strongly associated with elevated blood pressure, the risk associated with these blood vessel signs seems to be independent of blood pressure. The proposed study will conduct a detailed re-grading of retinal photographs taken on people who attended the Eye Study during 1992-4 and 5-year follow-up exams during 1997-9. We will grade these photographs manually (using a stereo-viewer), and with computer assistance to measure changes in the diameter of small arteries in the retina and other signs. By closely matching our grading technique to that used in a large American Study, we hope to develop reliable grading for these signs and will be able to compare our findings internationally. Our aim is to assess the frequency of abnormal retinal vessel changes in people of different age groups as well as the development and progression of these signs over time. Their relationship to well known vascular risk factors like smoking, blood pressure, obesity, diabetes and cholesterol will also be investigated. We hope to be able to discriminate those changes associated with an increased stroke risk from those due to normal ageing. We expect that the increased stroke risk associated with abnormal retinal vessel changes may be greater than shown in our early data. If confirmed, then these findings may provide a more sensitive and objective measure of stroke risk than relying on traditional risk factors, which are difficult to quantify and change with time. We may be able to develop simple rules so that doctors using an ophthalmoscope or examining a retinal photograph could identify high risk patients. These people could benefit from interventions to reduce their risk.Read moreRead less
Practical Tools For Robust Analysis Of Large Epidemiological Studies With Incomplete Data
Funder
National Health and Medical Research Council
Funding Amount
$358,492.00
Summary
Studies of the causes and consequences of health outcomes follow large cohorts of individuals for long time periods. A major challenge in analysing data from these studies is that information is often incomplete. Participants rarely complete all waves of data collection, or provide all requested information. Statistical research has led to increased use of a statistical method (multiple imputation) that recovers information from incomplete cases. This project will develop and improve this method
Hepatitis C Vaccine Preparedness Study: Investing In Infectious Disease Prevention
Funder
National Health and Medical Research Council
Funding Amount
$820,767.00
Summary
Injecting drug users (IDU) are a key target group for new vaccines designed to prevent hepatitis C virus (HCV) infection. This study will establish the feasibility of conducting HCV vaccine trials in IDUs by answering key scientific questions, generating data to inform trial design and evaluation, establishing a partnership between leading international researchers and the peak Australian body for people who inject drugs, and providing the foundation for a global HCV prevention trial network.