Direct And Indirect Assessment Of 5 Ability Structures Underlying 7 Categories Of Childhood Psychopathology
Funder
National Health and Medical Research Council
Funding Amount
$263,311.00
Summary
This research has four main aims. First, we aim to obtain detailed knowledge of how normal children develop a range of different abilities, including motor coordination, language skills, the ability to understand other people, self-control, and general cognitive ability. Second, with this knowledge of normal development we will be able to identify cases in which normal development does not occur and to identify the exact ability area(s) in which development is abnormal. Patterns of abnormal deve ....This research has four main aims. First, we aim to obtain detailed knowledge of how normal children develop a range of different abilities, including motor coordination, language skills, the ability to understand other people, self-control, and general cognitive ability. Second, with this knowledge of normal development we will be able to identify cases in which normal development does not occur and to identify the exact ability area(s) in which development is abnormal. Patterns of abnormal development will be studied in children with one of seven disorders, including Autistic Disorder, Intellectual Disability, and Developmental Coordination Disorder. Third, we will assess whether deficits in some ability correspond to impairments in just one basic psychological structure (e.g., language deficits are related to impairment in the ability to recognise sounds) or whether they can be due to impairments in several structures (e.g., the ability to recognise faces or the ability to maintain attention). Finally, we will investigate whether and how impairments in one or more basic psychological structures can result in deficits in one or more of the ability areas that are the basis for the diagnosis of one or more developmental disorders. This research is expected to lead to an enhanced ability to assess the exact nature of any given developmental disorder which, in turn, should enhance clinical care of the child.Read moreRead less
Genetic, Family And Social Determinants Of The Burden And Outcome In Rett Syndrome: A Population-based Investigation
Funder
National Health and Medical Research Council
Funding Amount
$332,550.00
Summary
Rett syndrome is a severe disorder of the nervous system mainly affecting females. At birth children with Rett syndrome often seem normal but in their second year lose skills. With time it becomes clear that they are severely intellectually and physically handicapped. In 1999 the link between Rett syndrome and a mutation in the gene, known as MECP2, was found. In Australia since 1993, we have had a register of basic information on all girls and young women diagnosed with Rett syndrome. Over thre ....Rett syndrome is a severe disorder of the nervous system mainly affecting females. At birth children with Rett syndrome often seem normal but in their second year lose skills. With time it becomes clear that they are severely intellectually and physically handicapped. In 1999 the link between Rett syndrome and a mutation in the gene, known as MECP2, was found. In Australia since 1993, we have had a register of basic information on all girls and young women diagnosed with Rett syndrome. Over three quarters of the register s 248 cases have now been genetically tested. In 2000 and again in 2002, extra information on ability to do everyday tasks, behaviour, hand function, medical conditions, and use of health and education services was collected. In 2002 questions on family well being were also included. From 2004 to 2007, further information will be gathered on function, health and well being of the affected child and their family. This will be by telephone interview, questionnaire, video recording, existing medical records, clinical assessments and tests. This will include in 2004 completion of calendars which will provide information needed to estimate health and medical care costs for these children. Similar information by questionnaire and calendar will also be collected from the parents of children with Down syndrome in 2004. The information will be used to compare the social and financial burden of Rett syndrome with Down syndrome, a commoner cause of intellectual disability. The research will also show if it is possible to predict from early genetic test results how severely a child with Rett syndrome will later be affected. It will also determine whether some ways of management improve the long-term outlook for the girl and her family. Finally this study will investigate why some families cope better with this devastating disorder than others. This research is only possible in Australia because of the ongoing register we have set up here.Read moreRead less
Characterization Of Neutralizing Antibody Responses In HCV Infected Individuals.
Funder
National Health and Medical Research Council
Funding Amount
$478,076.00
Summary
Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attri ....Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attributed to the development of a strong cellular immune response and antibody is belived to play a monir role in achieving viral clearance. However, measurememnt of antibody responses in HCV infected pateints is routinely performed using conventional diagnostic tests that do not measure antibody that can help neutralize and clear virus. We have developed an assay that accurately measures the level of NAb in patient sera. We have found that chronically infected patients have broadly reactive neutralizing antibodies but that patients who clear virus, naturally or through treatment do not have broadly reactive neutralizing antibodies. Possibly explaining this phenomenon is that early during infection, antibody is frequently specific only to the infecting virus therefore to detect neutralizing antibodies, homologous viral sequences must be examined. In addition, we have found evidence that HCV can evade neutralzing antibodies through masking of sites to which antibodies bind. We propose to explore whether acutely infected patients develop NAb to autologous viral sequences, and how do these viral sequences and the antibody titre change throughout the course of infection and treatment. We also plan to determine the mechanism of neutralization resistance through the use of mutagenesis of resistant HCV glycoproteins. These studies are aimed at gaining a thorough understanding of the true role of antibody in HCV infection and its influence on viral evolution.Read moreRead less
The human hepatitis B virus (HBV) is a member of the hepadnavirus family that includes a number of other very similar host-specific viruses. Acute HBV infection can produce extreme variation in disease, ranging from asymptomatic infection, to acute transient hepatitis with jaundice, or fulminant hepatitis leading to liver failure (Hollinger, 1996). The identification of viral genes that affect the severity of disease is a major current goal in medical virology. For example, there is considerable ....The human hepatitis B virus (HBV) is a member of the hepadnavirus family that includes a number of other very similar host-specific viruses. Acute HBV infection can produce extreme variation in disease, ranging from asymptomatic infection, to acute transient hepatitis with jaundice, or fulminant hepatitis leading to liver failure (Hollinger, 1996). The identification of viral genes that affect the severity of disease is a major current goal in medical virology. For example, there is considerable interest in identifying the genes of the influenza genome responsible for high mortality outbreaks; with the human immunodeficiency virus, the virus that causes AIDS, variants deleted in the nef gene region cause a less rapidly progressing infection and have attracted attention as a possible prototype for an attenuated vaccine. We propose to investigate how the different genes of hepadnaviruses affect the course of infection and type of disease produced. Studies will be performed in ducks infected with the duck hepatitis B virus (DHBV) as these animals provide the only model system available in Australia. We will study both experimentally and naturally derived DHBV variants to explore the effects of genetic changes on the outcome of infection. This will enhance our understanding of this virus family and will provide models for comparison with HBV infection. This knowledge may then contribute to our ability to manage and control HBV disease in humans.Read moreRead less
Morphometric Analysis Of Normal Airway Structure In Childhood And The Influence Of A History Of Asthma On This Structure
Funder
National Health and Medical Research Council
Funding Amount
$186,113.00
Summary
The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For ex ....The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For example, the walls of the airways are much thicker in patients with lung disease. This thickening means that the airways are much narrower and therefore not able to carry as much air as in people with healthy lungs. In addition, the muscle within the airway wall, which is normally very sparse, is much denser in people with asthma and bronchitis. Thus, the airways can be squeezed closed more easily. It is not known if these changes are present in children who have lung disease. X-rays and sophisticated breathing tests suggest that these children may also have thicker walls and more muscle in their airways. The major difficulties in assessing whether such changes are present in children, is the lack of information on the normal structure in infants; how this changes as they grow to adulthood; or if there are any gender differences. This project aims to obtain this information from the airways of male and female children from 0-18 years. This information can then be used as a basis for comparison with the structure found in children with lung disease, in particular asthma, and therefore assist in making assessments as to the cause of their breathing difficulties. With more knowledge about these causes, we will be in a better position to design new and better treatments and produce ways of preventing them ever occurring.Read moreRead less
A Structural And Functional Basis For The Regulation Of Gene Expression By Nuclear Retention Of RNA
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
The nuclear retention mechanism is a novel way used by cells to control which genes are made into proteins - a fundamental process for all diseases, particularly cancers. This project will employ cutting edge structural and proteomic techniques to determine the molecular details underpinning nuclear retention. These insights will be important for the development of new tissue-restricted gene therapy applications and drugs targeting the cancers that rely on this mechanism.
LONG TERM FUNCTIONAL ABILITY AND COSTS OF STROKE SUBTYPES.
Funder
National Health and Medical Research Council
Funding Amount
$270,604.00
Summary
Stroke is the third most common cause of death in Australia, and is more common in the older age groups. Because the population most at risk of developing stroke is growing faster than the rest of the population, it is likely that there will be a large increase in the number of strokes occurring in coming years. At 1 year after stroke about one-third of patients have died, a third remain severely disabled and a third recover with minimal disability. In Australia, there is little information on o ....Stroke is the third most common cause of death in Australia, and is more common in the older age groups. Because the population most at risk of developing stroke is growing faster than the rest of the population, it is likely that there will be a large increase in the number of strokes occurring in coming years. At 1 year after stroke about one-third of patients have died, a third remain severely disabled and a third recover with minimal disability. In Australia, there is little information on outcome beyond 1 year. It is thought that at 5 years after stroke about 55% of patients will die, and a further 10% will have another nonfatal stroke. Stroke is estimated to cost the community in excess of $1 billion a year. Little is known about the long-term costs of stroke to survivors and their relatives. These costs are likely to be substantial, and are likely to include costs related to hospitalisations, outpatient visits, general practitioner visits, medications, aids and community services. It is also likely that substantial informal care is provided by relatives and friends (e.g. assistance with shopping and personal care). The aim of this study is to assess the long-term outcome of patients with stroke. These will include measures of survival, stroke recurrence, and ability to perform usual daily activities. In addition, we aim to determine the long-term use of health care and community resources and the costs incurred by patients, their carers, and the community. Information on survival patterns, stroke recurrence and disability will provide information of great value for health service planning. Such information will also be useful to patients, their families, and medical staff who treat these patients. Information on the costs of stroke will provide the only information about the patterns of long-term health care and community resource use among stroke patients in Australia. This information will be useful for health service planning.Read moreRead less
Airway Wall Thickness And Heterogeneity Are Key Determinants Of Asthmatic Airway Function.
Funder
National Health and Medical Research Council
Funding Amount
$207,509.00
Summary
Asthma is a common disease which is typified by excessive narrowing of the airways in response to stimuli that are trivial to non-asthmatic individuals. However, little is known about what causes asthmatic airways to be able to narrow so excessively. In this study, we will be looking at the importance of thickening of the airway walls in relation to excessive airway narrowing in asthmatics. We will also look to see how patchy the airway narrowing is in asthmatics and how this relates to excessiv ....Asthma is a common disease which is typified by excessive narrowing of the airways in response to stimuli that are trivial to non-asthmatic individuals. However, little is known about what causes asthmatic airways to be able to narrow so excessively. In this study, we will be looking at the importance of thickening of the airway walls in relation to excessive airway narrowing in asthmatics. We will also look to see how patchy the airway narrowing is in asthmatics and how this relates to excessive airway narrowing that occurs in severe asthmatic attacks. We will therefore be studying asthmatics of varying degrees of disease severity as well as those admitted to hospital because of acute severe attacks of asthma, and comparing them with a group of non-asthmatic subjects.Read moreRead less
The activation of T lymphocytes is essential part of our immune system to fend off harmful intruders. Our research aims to understand the process of T cell activation, in particular, the contribution of fats. We found that fats create a highly ordered patch at the T cell activation site. We want to understand how lipids and proteins work together to activate T cells, how this ordered regions function in T cell activation and whether dietary lipids alter these patches and thus T cell activation.