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Neurosteroid Mediated Protection After Birth: Approaches For Maximising Protective Steroid Levels In The Neonatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$450,703.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the ....Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the fetal brain and levels rise further in response to fetal stress. The placenta contributes steroid precursors that help maintain these high neurosteroid levels. This placenta-fetal brain interaction comprises an internal mechanism that protects the fetal brain from adverse events during pregnancy. At birth, however, there is a dramatic decline in neurosteroid concentrations in the brain after the loss of the placental precursor supply. The fall in concentrations is even greater in animals that are born growth restricted. This suggests that newborns, particularly those from compromised pregnancies, are at increased risk of brain damage due to low neurosteroid levels. We believe that certain commonly used steroid therapies may also lower steroid levels in the brain and result in increased vulnerability to brain damage during birth or in the early neonatal period. Alternatively, we propose that replacement of neurosteroid precursors in the newborn may raise brain neurosteroid levels and protect against brain damage. In the proposed studies we will evaluate treatments that can raise the concentration of steroids and determine the best strategy for reducing brain injury following complications during pregnancy, at birth and during the early newborn period. This work will determine the best therapeutic approaches for maximising neurosteroid-induced brain protection and for reducing the risk of brain damage.Read moreRead less
Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Tra ....Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Travel (AT). There is an opportunity to promote AT as part of an integrated transport strategy, and to develop tools for the robust evaluation of AT impacts to inform future investment strategies. This proposal will provide our partner organisation Transport for New South Wales (with the knowledge required to achieve this.
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Photochemical Design of Microstructured Aerospace Materials. Commercial aviation and shipping spend over US$300 billion on fuel and emit almost 3 billion tonnes of carbon dioxide annually at an enormous environmental cost. This project will provide the material chemistry innovation basis for the production of drag reduction surfaces that can be applied to enable a more effective airflow over an aircraft, thus reducing fuel consumption. Critically, the material design approach will not only deliv ....Photochemical Design of Microstructured Aerospace Materials. Commercial aviation and shipping spend over US$300 billion on fuel and emit almost 3 billion tonnes of carbon dioxide annually at an enormous environmental cost. This project will provide the material chemistry innovation basis for the production of drag reduction surfaces that can be applied to enable a more effective airflow over an aircraft, thus reducing fuel consumption. Critically, the material design approach will not only deliver a high performance coating for the production of drag reduction surfaces, but allow these surfaces to be tailored to specific application profiles including UV resistance and anti-fouling properties. The project will place an Australian company at the forefront of drag reduction technologyRead moreRead less
Integrating Attribute Decision Heuristics into Travel Choice Models that accommodate Risk Attitude and Perceptual Conditioning. This proposal has the specific objective of integrating two disconnected literatures that are having a major influence on the behavioural and statistical performance of discrete choice models in travel choice modelling. These fields are attribute processing strategies and the conditioning of the marginal utility of attributes by risk attitude and perceptual conditioning ....Integrating Attribute Decision Heuristics into Travel Choice Models that accommodate Risk Attitude and Perceptual Conditioning. This proposal has the specific objective of integrating two disconnected literatures that are having a major influence on the behavioural and statistical performance of discrete choice models in travel choice modelling. These fields are attribute processing strategies and the conditioning of the marginal utility of attributes by risk attitude and perceptual conditioning. These two major developments have not been jointly integrated into a behaviourally richer representation of choice making. Given the encouraging evidence from both literatures, the research will determine more precisely the benefits in terms of improved estimates of willingness to pay for specific attributes and also increased predictive power. Read moreRead less
Funding on the line: public transport financing and property value capture. This project aims to develop property value capture schemes that would provide alternative funding for public transport infrastructure. It plans to model the timing and spatial patterns of property value uplift from recent investments in rail, busways and ferries in Queensland and New South Wales. It then intends to conduct a survey of Australian stakeholders and discrete choice modelling to determine willingness-to-pay. ....Funding on the line: public transport financing and property value capture. This project aims to develop property value capture schemes that would provide alternative funding for public transport infrastructure. It plans to model the timing and spatial patterns of property value uplift from recent investments in rail, busways and ferries in Queensland and New South Wales. It then intends to conduct a survey of Australian stakeholders and discrete choice modelling to determine willingness-to-pay. This data is then expected to be used to develop an institutionally, legally and politically feasible scheme for implementation in Australia, focused on cases including extension to the Gold Coast light rail network.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101793
Funder
Australian Research Council
Funding Amount
$423,038.00
Summary
Quantifying and managing the network impacts of transport sharing services. This project aims to address the challenge of effectively modelling multiple transport sharing services (e.g., ridesharing and parking sharing) in a multimodal network, and efficiently operating these services, and incentivising people to use them. The project expects to generate new knowledge in shared transport by developing an innovative approach to systematically reproducing and optimising network impacts of sharing ....Quantifying and managing the network impacts of transport sharing services. This project aims to address the challenge of effectively modelling multiple transport sharing services (e.g., ridesharing and parking sharing) in a multimodal network, and efficiently operating these services, and incentivising people to use them. The project expects to generate new knowledge in shared transport by developing an innovative approach to systematically reproducing and optimising network impacts of sharing services on travel choices, sharing demand-supply matching patterns, movement trajectory features and traffic dynamics. Expected outcomes include new models and strategies to improve decision support for transport planners and operators. This should provide significant benefits for human mobility and city sustainability.Read moreRead less
Travel time budget analysis from multi-day and multi-year data. This research will investigate whether people have stable budgets for daily travel time and travel cost expenditure. Stable budgets have enormous implications for how various transport policies and investments are likely to affect the way people choose to travel and will likely change various policy and investment decisions related to transport.
Chemical listening devices: Novel sensors targeting the clandestine manufacture and transport of illicit drugs and explosives. There can be no doubt that protecting Australia's borders from the dual threats of terrorism and illicit drugs is of paramount importance to continuation of our well-being and way of life. Our chemical sensors are simple hand-held or remote chemical listening sensors, which will have the ability to sense the presence of characteristic chemical vapours associated with exp ....Chemical listening devices: Novel sensors targeting the clandestine manufacture and transport of illicit drugs and explosives. There can be no doubt that protecting Australia's borders from the dual threats of terrorism and illicit drugs is of paramount importance to continuation of our well-being and way of life. Our chemical sensors are simple hand-held or remote chemical listening sensors, which will have the ability to sense the presence of characteristic chemical vapours associated with explosives and illicit drugs. The simplicity and low cost of the chemical listening allows for installation at key locations -e.g. transport hubs, shipping containers, airports etc as well as placement within clandestine drug laboratories.Read moreRead less
Integrating network modelling with observed choice data for multi-criteria optimisation of complex car share systems: cost, mobility and transit usage. This project will develop methods to determine an efficient car share system, which includes optimal location, one-way car sharing, and how carshare influences the broader transport system. By adopting such new comprehensive methods, the overall transport system will benefit through potential improvements in public transit usage.
Neuroactive Steroids In The Developing Brain: Potential For Preventing Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown tha ....Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown that protective neuroactive steroids are present in very large amounts in the fetal brain. Steroids produced by the placenta are converted to these neuroactive products by enzymes in the brain leading to the high levels that are seen during fetal life. Certain adverse conditions during pregnancy as well as preterm birth may cause marked changes in the balance of steroids that could increase susceptibility to brain injury. We have found that areas of the brain, where damage most often occurs, normally contain the highest amount of protective steroids, but only in late pregnancy. This suggests that disturbances that lower steroid production in these areas could contribute to the death of cells, particularly in mid-pregnancy and after premature birth. In the proposed studies, we will examine whether a toxic balance of steroids develops following adverse events in pregnancy as well as the areas of the brain where this is most pronounced. We will examine the changes in the expression of enzymes that can potentially cause the accumulation of protective steroids in the brain. We will then examine treatments that can raise the concentration of steroids and determine which combination of steroids best reduces cell death and brain injury following complications during pregnancy. The findings of this work will indicate the best therapeutic approach that may be adopted to modify the concentration of certain steroids so as to reduce the risk of brain damage in the fetus and neonate.Read moreRead less