They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid ....They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid bodies (EB) - EB-derived cells, fetal pancreas and adult pancreas duct cells, will be employed to screen for and identify novel growth-differentiation factors and to optimise parameters for creating B cells in vitro or (re) generating B cells in vivo. Genetic constructs allowing regulated expression of fluorescently-tagged marker genes and growth-transcription factors will be introduced into cultured cells or transgenic mice to enable progenitor B cells to be tracked and isolated. Progenitor B cells will be typed with panels of known novel markers molecules at the gene and protein level, and gene expression profiles of tissue yielding B cells will be analysed across time to reveal further candidate markers. Molecules and methods effective in mouse systems will be applied to human ES cell-derived or pancreatic duct cells. The capacity to progenitor cells or insulin-secreting cells to ameliorate diabetes when transplanted into the testis, under the kidney capsule or into the pancreas of mouse models would represent proof-of-concept. Functional B cells derived from human ERS cells or pancreas duct cells, or growth factors that regenerate B cells in vivo, could together with appropriate immunotherapy restore B-cell function in people with type 1 diabetes.Read moreRead less
Expectations And Barriers In The Ambulance Service And Palliative Care Interface
Funder
National Health and Medical Research Council
Funding Amount
$49,916.00
Summary
There are over 6000 paramedics in Australia. The ambulance service is faced with palliative care on a daily basis throughout the country. Their involvement in palliative care is diverse and may include response to end of life calls, response to aid home care, response to manage acute events, providing health transport and collaborating with other care givers. The nature of this involvement, and the broader policy, operational, clinical and social implications has not been researched in Australia ....There are over 6000 paramedics in Australia. The ambulance service is faced with palliative care on a daily basis throughout the country. Their involvement in palliative care is diverse and may include response to end of life calls, response to aid home care, response to manage acute events, providing health transport and collaborating with other care givers. The nature of this involvement, and the broader policy, operational, clinical and social implications has not been researched in Australia. This study will survey paramedics across two states to describe their involvement in palliative care, and the issues and challenges associated with provision of this service.Read moreRead less
Oxygen To Relieve Dyspnoea In Non-hypoxaemic Patients With End-stage Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$445,658.00
Summary
Chronic heart failure is a cause of suffering and a major cause of death in the Australian community. Patients who have chronic heart failure suffer from a range of symptoms that severely impacts every aspect of their life. One of the most common and distressing symptoms is breathlessness. As people with heart failure near death, their breathlessness may worsen not only in terms of its frequency, but also in its intensity. This worsening of symptoms is a source of great distress, both to patient ....Chronic heart failure is a cause of suffering and a major cause of death in the Australian community. Patients who have chronic heart failure suffer from a range of symptoms that severely impacts every aspect of their life. One of the most common and distressing symptoms is breathlessness. As people with heart failure near death, their breathlessness may worsen not only in terms of its frequency, but also in its intensity. This worsening of symptoms is a source of great distress, both to patients as well as their carers and family. Breathlessness is also the most common cause of admission to hospital for patients. A key strategy for managing this distressing symptom in the home is the supply of oxygen. However, due to a lack of scientific evidence for the benefit of home oxygen for people with heart failure, who do not necessarily have low levels of oxygen, it is very difficult for clinicians to access this therapy for their patients. This study seeks to assess if a specific breathlessness action plan alone or if the addition of either oxygen or air can relieve this distressing symptom. The scientific evaluation of these strategies will assist in improving the palliative care of people with chronic heart failure.Read moreRead less
Burden Of Disease&cost Effectiveness Of Intervention Options:informing Policy Choices & Health System Reform In Thailand
Funder
National Health and Medical Research Council
Funding Amount
$787,978.00
Summary
This research project aims to improve the scientific basis for health services provision in Thailand by filling important gaps in knowledge about the causes of disease and the possibility of effectively intervening to reduce them. Since the accuracy of the routine death registration system in Thailand is unknown, it cannot be confidently used to guide policy. The team will evaluate how accurately causes of death are being recorded, both in urban and rural areas. It will also calculate how much d ....This research project aims to improve the scientific basis for health services provision in Thailand by filling important gaps in knowledge about the causes of disease and the possibility of effectively intervening to reduce them. Since the accuracy of the routine death registration system in Thailand is unknown, it cannot be confidently used to guide policy. The team will evaluate how accurately causes of death are being recorded, both in urban and rural areas. It will also calculate how much disease and injury in Thailand is being caused by major risk factors, such as tobacco and unsafe sex. Using this information the team will evaluate the effectiveness of the major interventions to reduces diseases and injuries from risk factors that are affordable and applicable in the Thai context.Read moreRead less
Early Intervention To Prevent Childhood Obesity Among A Disadvantaged Population: A Home-based Randomised Controlled Tri
Funder
National Health and Medical Research Council
Funding Amount
$675,082.00
Summary
This intervention research will conduct a randomised controlled trial, of a community-based early childhood home visiting intervention designed to improve family and behavioural risk factors for childhood obesity and overweight. This intervention which will be developed in collaboration with the Health Promotion Unit, Child and Family Health Nurses, university academic experts and mothers in the community promises to deliver significant health and social benefits, in particular, preventing early ....This intervention research will conduct a randomised controlled trial, of a community-based early childhood home visiting intervention designed to improve family and behavioural risk factors for childhood obesity and overweight. This intervention which will be developed in collaboration with the Health Promotion Unit, Child and Family Health Nurses, university academic experts and mothers in the community promises to deliver significant health and social benefits, in particular, preventing early onset of childhood obesity. It will result in a series of recommendations for policies and practical methods for promoting healthy feeding and physical activity of infants under two years of age with particular application to families who are socially and economically disadvantaged. These policies and practical methods for preventing childhood obesity could be used across Australia.Read moreRead less
Chimeric Virus-like Particles (VLPs) Displaying H1, H3 And H5 Haemagglutinins - Construction And Immunogenicity
Funder
National Health and Medical Research Council
Funding Amount
$207,543.00
Summary
Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can b ....Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can be produced containing each of the three most important HA types _ H1 and H3 that are currently circulating in man, and H5 (avian) that is considered a pandemic threat. VLPs will be tested for their ability to induce neutralizing antibody and cellular immune responses in mice, and for their ability to protect ferrets from influenza infection. If successful, the HA-VLP system would provide a method for the rapid production of new influenza vaccines using large-scale fermentation technology as for hepatitis B and many other vaccines, rather than eggs or cell culture as used for current influenza vaccines.Read moreRead less
Improving Identification And Treatment Of Early-onset Behaviour Disorders In Children
Funder
National Health and Medical Research Council
Funding Amount
$498,869.00
Summary
Most mental health problems begin in childhood and adolescence. Of these, oppositional-defiant and conduct problems in childhood are the most common precursor of all types of adult mental health problems. These children are the most common referral to child mental health clinics but little is known about which of these children will go in which direction i.e., good health, chronic antisocial behaviour, depression and anxiety, substance abuse, the psychoses. Progress in more accurately defining s ....Most mental health problems begin in childhood and adolescence. Of these, oppositional-defiant and conduct problems in childhood are the most common precursor of all types of adult mental health problems. These children are the most common referral to child mental health clinics but little is known about which of these children will go in which direction i.e., good health, chronic antisocial behaviour, depression and anxiety, substance abuse, the psychoses. Progress in more accurately defining subgroups of these children would have huge implications for early intervention for mental health problems in our community. This project proposes the first large scale analysis of genetic distributions through to behavioural and treatment factors that characterise and differentiate a large representative sample of children with conduct problems. The project will test a model of child psychopathology that links genotype, via environmental risk and emotion processing problems, to an improved diagnostic-phenotypic model for treatment of the major childhood disorder. Clinical research activities will be structured into three intersecting arms: first, identifying the genetic and behavioural subtypes of early-onset conduct problems; second, innovative treatments for these children, and third, the dissemination of findings to these children and their families via the health care system. The research will build new collaborations between established and internationally recognised clinical research teams in childhood mental health, biological psychiatry, genetics and the Child and Adolescent Mental Health Statewide Network (CAMHSNET). CAMHSNET have specific responsibilities to NSW Health for expert advice and input on the development of child mental health services directions, dissemination, training, and effectiveness research.Read moreRead less
Self Adjuvanting CTL-Based Influenza Vaccines For Human Use
Funder
National Health and Medical Research Council
Funding Amount
$214,842.00
Summary
This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recog ....This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recognised by specific receptors on the surface of dendritic cells and also causes their maturation, a step which is essential for recognition by the immune system of potential pathogens. The technology to design and assemble these new vaccines is already.Read moreRead less
Assessment Of Alpha-galactosylceramide As A Novel Adjuvant For Pandemic Influenza: A Virua Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$220,042.00
Summary
The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, ....The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, however there are no commercially available avian influenza vaccines available. Moreover, recent evidence suggests current vaccines strategies may be less than effective. This proposal aims to evaluate the efficacy of a novel vaccine strategy that promotes immune protection against a potential pandemic influenza strain.Read moreRead less