Functional Evaluation Of BRCA1 & BRCA2 Unclassified Sequence Variants And Identification Of Critical Pathogenic Domains.
Funder
National Health and Medical Research Council
Funding Amount
$331,312.00
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 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 se ....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 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.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
A Trial Of Prehospital Rapid Sequence Intubation In Patients With Severe Head Injury
Funder
National Health and Medical Research Council
Funding Amount
$311,000.00
Summary
In Australia, major trauma is a leading cause of death in people between the ages of one and 44 years. In addition to mortality, there is a high morbidity rate and quality adjusted life-years lost from injury is vast. In broad terms, major trauma is defined as those injuries with the highest severity, requiring time critical medical care. Over 10% of major trauma patients have a severe head injury and approximately 40% of these patients die and another 40% have significant long-term morbidity. F ....In Australia, major trauma is a leading cause of death in people between the ages of one and 44 years. In addition to mortality, there is a high morbidity rate and quality adjusted life-years lost from injury is vast. In broad terms, major trauma is defined as those injuries with the highest severity, requiring time critical medical care. Over 10% of major trauma patients have a severe head injury and approximately 40% of these patients die and another 40% have significant long-term morbidity. Following severe head injury, it is common for patients to have decreased oxygen levels and this is associated with a significant increase in brain damage. To prevent or treat this, patients with severe head injury require endotracheal intubation (a tube is placed in the airway to provide oxygen to the patient) as soon as possible following injury. However, in most patients with severe head injury, endotracheal intubation requires the use of drugs to facilitate placement of the endotracheal tube. The usual technique involves the administration of both a sedative drug and an appropriate muscle-relaxant. This technique is known as rapid sequence intubation (RSI). However, it is unknown whether RSI should be undertaken by paramedics early after injury or be delayed until arrival at the hospital. Since better evidence of improved outcome is required to justify the possible risk and considerable expense of training ambulance paramedics in the skill of RSI, it is proposed that a randomized, controlled trial of RSI in adults with severe head injury be conducted. This trial will compare rapid sequence intubation with standard airway management (no intubation) by ambulance paramedics for major trauma patients with severe head injury. This study will assess differences in patient outcome at 6-months post injury. The study will involve head injury patients treated by paramedics in Victoria.Read moreRead less