Using Epidemiology To Inform Psychiatric Classification (DSM-V And ICD-11)
Funder
National Health and Medical Research Council
Funding Amount
$631,502.00
Summary
Classification systems are vital for scientific progress. The classifications of mental disorders of the World Health Organization and the American Psychiatric Association are both being revised and this Australian team is a principal contributor to both processes. We have access to three national epidemiological surveys (n-30,000) that will inform fundamental issues by developing models of mental disorder typology and identifying practical improvements in the classification systems.
Molecular Classification Of Carcinoma Of Unknown Primary
Funder
National Health and Medical Research Council
Funding Amount
$418,250.00
Summary
Carcinoma of unknown primary (CUP) is the fourth largest cause of cancer death. The condition has a particularly poor outlook, with a median survival of less than one year. Current methods for diagnosis of CUP include histopathology and sophisticated imaging. These are successful in approximately 40% of cases. Frequently the reason for the poor outcome in this disease is that the 60% of patients with CUP for whom no diagnosis is made do not benefit from chemotherapy specifically designed for a p ....Carcinoma of unknown primary (CUP) is the fourth largest cause of cancer death. The condition has a particularly poor outlook, with a median survival of less than one year. Current methods for diagnosis of CUP include histopathology and sophisticated imaging. These are successful in approximately 40% of cases. Frequently the reason for the poor outcome in this disease is that the 60% of patients with CUP for whom no diagnosis is made do not benefit from chemotherapy specifically designed for a particular tumour origin. These patients receive a less effective, generic, chemotherapy. The aim of this project is to use microarrays to identify the gene expression profile in many known tumours to create a molecular fingerprint of the various tumour types. By comparing the fingerprint from a CUP with the database we should be able to identify the true tumour type in CUP, and allow patients to benefit from more specific chemotherapy.Read moreRead less
Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently require ....Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently required. The sequencing of the human genome and advanced screening technology (microarrays) allow the detailed analysis of expression patterns in large numbers of specimens. We propose to study the genetic features of this disease by investigating 28 childhood ALL patients from whom we have stored specimens received at two time points, one at diagnosis and one at relapse. The hypothesis of this study is that relapsed leukaemias display genetic features which are correlated to their resistance to therapy. The specific questions we will be asking are: (1) Which genes are expressed at high levels in leukaemia specimens at the time of relapse while not expressed (or expressed at lower levels) at the time of diagnosis and vice versa? (2) What is the function of differentially expressed genes? (3) Is the pattern of gene expression correlated with resistance to the particular drug therapy used? (4) Is the leukaemia clone at relapse related or unrelated to the clone present at diagnosis, as determined by receptor rearrangement? The expression levels of identified discriminator genes will be confirmed by real-time quantitative polymerase chain reaction (PCR). The quality of this set of specimens makes them particularly suited to achieve the stated goals, providing a unique opportunity to investigate drug resistance in childhood ALL. The data generated will provide the basis for the examination of genes suitable as new therapeutic targets.Read moreRead less
VicCPchild- Prospective Cohort Study Of Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$613,587.00
Summary
Cerebral palsy is the most common cause of physical disability in children affecting 1 in 500 young Australians. While the brain lesion is static, the musculoskeletal problems are progressive and require lifelong management (cost of US$946,000 over life per person). Only large prospective population-based studies give a true indication of the incidence of physical problems, determine the pathway(s) to outcome and determine the best pathways to successful treatment and efficient resource allocati ....Cerebral palsy is the most common cause of physical disability in children affecting 1 in 500 young Australians. While the brain lesion is static, the musculoskeletal problems are progressive and require lifelong management (cost of US$946,000 over life per person). Only large prospective population-based studies give a true indication of the incidence of physical problems, determine the pathway(s) to outcome and determine the best pathways to successful treatment and efficient resource allocation. The broad aim of this project is: This population based cohort study (n - 240) aims to determine the pathway to motor outcome from diagnosis at 18 months to 5 years based on the nature of the brain injury at 24 months (structural MRI of the nature, location and timing of the brain lesion). Secondary Aims: Determine the rate of musculoskeletal deformity (hip displacement, spasticity, muscle contracture). Potential impact of medical co-morbidities (nutrition, epilepsy, respiratory problems) Patterns of participation and HRQOL. Patterns of medical resource use: treatment costs and outcomes. This study will: Allow clinicians to better the likely functional outcomes of children with CP from an earlier age based on the rate and limit of gross motor development and nature and severity of the brain lesion, determine the nature and timing of physical deformities to aid prevention and treatment; provide information on resource use for future planning and organisation of medical and therapy services. This in turn will give more accurate prognostic counseling as well as target areas for early therapy. Our multidisciplinary research group is uniquely placed to conduct this world-first study with access to two entire birth years of children linked to our Victorian Cerebral Palsy Register. Recruitment is conducted at both the Royal Children's Hospital and the Monash Medical centre in order to ensure state wide referral and easy access for families.Read moreRead less
Evaluation Of Unclassified Variants Of BRCA1 And BRCA2 Using A Multifactorial Approach
Funder
National Health and Medical Research Council
Funding Amount
$456,495.00
Summary
The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that may slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of th ....The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that may slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the sequence change. Consequently, it is not possible to offer informative genetic counselling to these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these unclassified sequence variants will be directly useful with regard to the clinical management of these women and their families, and will develop our current understanding of how different domains of these genes contribute to their role as cancer susceptibility genes. In addition, some of our experiments to classify variants may be useful as a screening tool to identify carriers of mutations, and so prioritize them for mutation screening.Read moreRead less
This project aims to establish agreement on appropriate methods to analyse evidence in support of medical treatments directed at laboratory tests (such as blood cholesterol) and to classify the evidence according to how convincing it is. The goal of those developing new drugs targeting one of these laboratory tests is to have their evidence sufficiently convincing that the drug will be approved for sale and used because doctors and patients believe its use will translate into a patient benefit.