Rapidly giving intravenous fluid to prevent or treat shock (fluid resuscitation) is one of the commonest treatments given to critically ill patients. Current guidelines recommend crystalloid solutions but it is unknown whether any particular crystalloid is better than others. This trial will determine whether the use of one of two crystalloid fluids, saline or PlasmaLyte, reduces the risk of organ injuries, such as kidney failure, and improves patients chances of surviving critically illness.
Development of new methods to measure in vivo properties of human body tissues. This project will develop new methods of noninvasively measuring the viscoelastic properties of soft tissues in live humans, using a novel magnetic resonance elastography technique. These methods will be applied to study the operation of the human muscle-tendon system, differences in neck muscle properties with age and gender and to measure the properties of the human brain, kidney and liver in vivo. These techniques ....Development of new methods to measure in vivo properties of human body tissues. This project will develop new methods of noninvasively measuring the viscoelastic properties of soft tissues in live humans, using a novel magnetic resonance elastography technique. These methods will be applied to study the operation of the human muscle-tendon system, differences in neck muscle properties with age and gender and to measure the properties of the human brain, kidney and liver in vivo. These techniques may be useful in diagnosing soft tissue disease or injury which are currently difficult to detect using standard imaging techniques. It will also explain how the muscle-tendon unit moves during normal motion in live humans.Read moreRead less
The Role Of Nuclear Architecture In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$561,966.00
Summary
The goal of the proposed research is to understand how dynamic changes to the chromatin genome packaging network, interact with the DNA damage response and gene expression machinery, to repair damaged DNA and the impact this has on cancer biology. To do so we are combining cutting edge molecular biology techniques with innovative novel microscopy methods developed by our research team, that far exceed the spatiotemporal resolution currently used to study chromatin biology.
Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less
Novel methods for detecting changes in soft tissue microstructure and biomechanical properties using multi-modality MR imaging. This project will lead to novel methods for studying the internal structure of the soft tissues of the body, such as muscles and brain tissue, and how this is affected by mechanical loading and disease states. The project will thoroughly validate these new methods. This will not only provide new techniques for research use, but lead to improved diagnostic techniques in ....Novel methods for detecting changes in soft tissue microstructure and biomechanical properties using multi-modality MR imaging. This project will lead to novel methods for studying the internal structure of the soft tissues of the body, such as muscles and brain tissue, and how this is affected by mechanical loading and disease states. The project will thoroughly validate these new methods. This will not only provide new techniques for research use, but lead to improved diagnostic techniques in the future.Read moreRead less
How Replication Stress Activates The Mitotic Telomere DNA Damage Response To Kill Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$486,467.00
Summary
We discovered a novel mechanism linking stress during DNA replication to difficulties with the cell division process, and identified how this turns on DNA damage response signals from the chromosome ends (i.e. “telomeres”). We have further identified that we can exploit this mechanism to kill cancer cells. In this project we will explore this newly discovered mechanism and identify how it can be targeted for therapeutic purposes.
Long-term Nerve Damage In Cancer Survivors: Identification Of Risk Factors And Optimal Assessment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$850,172.00
Summary
Nerve damage following chemotherapy treatment leads to early treatment cessation and long-lasting disability, developing with commonly used chemotherapies. There is a critical need to understand the mechanisms, optimize clinical assessment and develop interventions to prevent nerve damage. This project is designed to detect the impact of long-term nerve damage in cancer survivors and develop a risk profile based on clinical, neurophysiological and genetic factors.
Haemodynamic investigation of flow diverter stents for the treatment of intracranial aneurysms. This project will explore the engineering of a flow diverter, an endovascular device for the treatment of brain aneurysms. The project will determine the optimal design of new types of flow diverters, which in turn could improve the effectiveness of treatments, thus reducing the associated costs of cerebral haemorrhage and stroke.
X-ray Micro-tomography Validation of HRCT-Based Airway Measurements. This project brings together a newly emergent modality of microscopy in the form of 3D X-ray micro-tomography (XRMT) along with leading-edge image analysis to develop breakthrough science in respiratory research aimed at improving the reliability of high resolution computed tomography (HRCT). The project will develop novel 3D lung image segmentation protocols, a stereotactic registration program allowing 3D matching of XRCT and ....X-ray Micro-tomography Validation of HRCT-Based Airway Measurements. This project brings together a newly emergent modality of microscopy in the form of 3D X-ray micro-tomography (XRMT) along with leading-edge image analysis to develop breakthrough science in respiratory research aimed at improving the reliability of high resolution computed tomography (HRCT). The project will develop novel 3D lung image segmentation protocols, a stereotactic registration program allowing 3D matching of XRCT and HRCT data sets, and a validation protocol for quantitative HRCT analysis of airway disease. These outcomes will allow wider application of HRCT to non-invasively follow the dynamics of pulmonary function.Read moreRead less
In-vivo detection of airway injury and disease using phase contrast X-ray velocimetry. Currently diagnosis of lung disease, a major cause of death in humans, is based on clinical symptoms that do not usually manifest until the disease is well advanced. This project will develop a novel imaging technique, X-ray velocimetry, to detect changes in tissue before symptoms arise, potentially leading to strategies for managing lung diseases.