Structural And Functional Studies On The Interaction Between Alpha2-Antiplasmin And Plasmin
Funder
National Health and Medical Research Council
Funding Amount
$280,400.00
Summary
Fibrinolysis is the process by which the body dissolves clots. In this proposal we aim to investigate how the fibrinolysis inhibitor alpha2-antiplasmin interacts with the clot dissolving protease enzyme plasmin. These data will be useful for developing new approaches to accelerate plasmin-mediated clot breakdown.
An International Randomised Trial Of Low-dose Aspirin To Prevent Recurrent Venous Thromboembolism (INSPIRE)
Funder
National Health and Medical Research Council
Funding Amount
$1,989,986.00
Summary
Patients who develop venous blood clots or pulmonary embolism, without an underyling cause, are at very high risk of recurrence once anticoagulant treatment (warfarin) is discontinued. The international INSPIRE trial is assessing whether low-dose aspirin treatment (a simple and cheap alternative to warfarin) is effective and safe in preventing further blood clots. If proven effective, aspirin could potentially prevent thousands of patients worldwide from experiencing such events.
Low-dose Aspirin To Prevent Recurrent Venous Thromboembolism (ASPIRE) Study: A Multicentre Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,108,600.00
Summary
In approximately one-third of patients who develop deep vein thrombosis or pulmonary embolism, this event is 'unprovoked' . These patients are at very high risk of recurrence once treatment with warfarin is discontinued. Warfarin treatment is very effective to prevent recurrence but is inconvenient because it has to be very closely monitored with blood tests and also causes serious bleeding complications in a significant number of patients. There are currently no other treatments available to pr ....In approximately one-third of patients who develop deep vein thrombosis or pulmonary embolism, this event is 'unprovoked' . These patients are at very high risk of recurrence once treatment with warfarin is discontinued. Warfarin treatment is very effective to prevent recurrence but is inconvenient because it has to be very closely monitored with blood tests and also causes serious bleeding complications in a significant number of patients. There are currently no other treatments available to prevent recurrent thrombosis. Low-dose aspirin treatment offers a simple, inexpensive, and widely practicable alternative to warfarin but has not yet been proven to be effective for preventing recurrent thrombosis. This study will investigate the effectiveness and safety of aspirin to prevent recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism who have completed standard anticoagulation with heparin and warfarin. If proven to be effective, aspirin could potentially prevent thousands of patients from experiencing recurrent venous thromboembolism or fatal pulmonary embolism worldwide and also save millions of dollars in health care costs each year.Read moreRead less
The Molecular Basis For The Increased Incidence Of Thrombosis Associated With The Prothrombin G20210A Gene Polymorphism
Funder
National Health and Medical Research Council
Funding Amount
$213,838.00
Summary
Prothrombin is an important enzyme involved in the formation of blood clots. Recently, a mutation was discovered in the prothrombin gene. This mutation occurs at a frequency of 2% in the normal population but occurs at an increased frequency (6%) in patients with thrombosis and is associated with an increase in the levels of prothombin in the blood. The position of this mutation in the prothrombin gene corresponds to the last residue of the prothrombin mRNA. We have preliminary data to suggest t ....Prothrombin is an important enzyme involved in the formation of blood clots. Recently, a mutation was discovered in the prothrombin gene. This mutation occurs at a frequency of 2% in the normal population but occurs at an increased frequency (6%) in patients with thrombosis and is associated with an increase in the levels of prothombin in the blood. The position of this mutation in the prothrombin gene corresponds to the last residue of the prothrombin mRNA. We have preliminary data to suggest that this mutation results in the prothrombin mRNA being more stable, which in turn allows for the production of more prothrombin protein, leading to an increased risk of developing a blood clot. The aim of this project is to explore the mechanisms leading to the elevated levels of prothrombin observed patients with this mutation.Read moreRead less
The Rane And Spain Routes In The Brain: Functional Studies And Remediation In Dyslexia Subtypes.
Funder
National Health and Medical Research Council
Funding Amount
$374,426.00
Summary
According to a recent DEST report a disturbingly high number of Australian school children are failing to meet a minimum acceptable standard in literacy . Failure to reach these standards is associated with poorer outcomes in mental health and socioeconomic status, greater representation among the prison population and with failure to achieve to true ability. Further, failure to correct these problems may well result in transmission of the problems associated with failed literacy into the next g ....According to a recent DEST report a disturbingly high number of Australian school children are failing to meet a minimum acceptable standard in literacy . Failure to reach these standards is associated with poorer outcomes in mental health and socioeconomic status, greater representation among the prison population and with failure to achieve to true ability. Further, failure to correct these problems may well result in transmission of the problems associated with failed literacy into the next generation. Despite the obvious immense social and personal ramifications and cost, literacy instruction for adults continues to lack a theoretical and research based approach . It is plain that improving population literacy would have significant benefits and it is also plain that early detection, intervention and remediation is desirable. This project brings to bear on these important aims current expertise in the nature of reading, how children learn to read and why some have so much difficulty in doing so, and techniques for determining the neural substrates of the mechanisms involved in reading and learning to read. We will subdivide child readers on the basis of their ability to read words using the letter to sound route or dictionary look-up route. We will use magnetic resonance imaging and spectroscopy to examine which parts of the brain are disrupted and-or disconnected when ability to read in either of these two routes is poor. We will then remediate these poor readers using targetted remediation therapy and re-image them to see whether remediation has altered the way the brain reads.Read moreRead less
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes ....Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and motor activity (often in an attempt to remove the source of the pain). The proposed research aims to characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to examine the brain regions that produce these changes. More specifically, microelectrodes will be used to investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine brain sites that are activated by skin or muscle pain.Read moreRead less
Finding The Optimum Target And Predictors Of Outcome In Deep Brain Stimulation Of Older Patients With Parkinsons Disease
Funder
National Health and Medical Research Council
Funding Amount
$428,392.00
Summary
Parkinson's disease treatment has been revolutionised by the advent of deep brain stimulator surgery. The major benefits come from improved motor function and quality of life. We aim to test the relative benefits of two different targets for brain stimulation and compare their effects on quality of life and cognition. We will also use some of Australia's expertise in brain scanning technology to look for pre-operative predictors of treatment outcomes in this group of older patients with PD.
The amygdala is an area of the brain that is involved in assigning emotional content to sensory information. Disorders of the amygdala lead to a variety of anxiety-related mental disorders such as panic attacks and post-traumatic stress. This grant will study how the NMDA receptor, which plays a central role in memory formation, works in the amygdala. We will determine the functional role of this receptor in the amygdala and how it may be modified by experience.
The Extinction Of Conditioned Fear And Its Implications For Cue Exposure Therapy
Funder
National Health and Medical Research Council
Funding Amount
$322,430.00
Summary
This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavl ....This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavlovian conditioning, subjects (typically rats) are exposed to a signaling relation between an initially neutral stimulus (e.g., a noise) and a feared outcome (e.g., foot shock). When later repeatedly exposed to the initially neutral but now feared stimulus (the noise) in the absence of the feared outcome, the fear reactions it acquired progressively decline until eventually it fails to elicit any such reactions. The fear reactions are said to have been extinguished. There has been significant progress in understanding the psychological processes and neural mechanisms underlying the acquisition of fear reactions, but much less is known about the processes and mechanisms underlying the extinction of these reactions. The project has two general objectives. The first is to determine the conditions of extinction training that promote long-term loss of fear reactions. The second objective is to determine how the brain controls this extinction of learned fear. Achieving these aims will be significant for two reasons. First, it will contribute to understanding the mechanisms by which animals (including people) learn to adjust their behaviour to bring it into line with the current relations that exist between events in the world. Second, it will provide important information about how such adjustment is facilitated or impaired across extinction training and, thereby, contribute towards understanding both the successes and failures of cue exposure therapy for fear-related disorders.Read moreRead less