Targeting Bone Marrow Lesions To Find Interventions In The Progression Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$467,395.00
Summary
It is essential to elucidate the underlying cause(s) of osteoarthritis because our current level of understanding of this condition has failed to produce effective treatments. Lesions in the bone under the cartilage (BMLs), seen using MRI, have strong potential value for the objective monitoring and management of OA. However, because the nature of BMLs is not well understood, the aim of this application is to perform a comprehensive study of BMLs in OA bone.
The Calcium Channel TRPV4 In Skeletal Development And Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$683,069.00
Summary
We have discovered that mutations in a calcium channel gene, TRPV4, cause an inherited osteoarthritis in the hands and feet. This work suggests that TRPV4 may be important in osteoarthritis and suggests the exciting possibility that modulating TRPV4 activity may provide a new therapeutic approach for arthritis. We will study how and why the mutations disrupt channel function and study mouse models to see if they are more or less susceptible to arthritis.
Modelling TRPV4 Skeletal Disorders Using Human IPSCs
Funder
National Health and Medical Research Council
Funding Amount
$1,171,187.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and new in vitro re-programing technology to induce them to form cartilage cells to produce “disease in a dish” models of human skeletal disorders. These models will allow us to answer questions about how specific mutations cause disease and identify potential therapies
The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.
Preconception Predictors Of Health, Behaviour And Emotional Adjustment At Seven Years
Funder
National Health and Medical Research Council
Funding Amount
$1,170,830.00
Summary
An understanding of the importance of a healthy start to life has underpinned major health policies including Australia’s National Agenda for Early Childhood. The capacity of parents to provide that healthy start has received little study. The present project investigates the extent to which parental lifestyle, social and emotional adjustment prior to conception predictor emotional problems, disruptive behaviour and health in their children at seven years.
An inability to resist a temptation or repeated failures of self-regulation can lead to 'impulsive' and 'compulsive' behaviours that relate to a host of personal and social problems (eg., excessive eating, gambling, and substance use). Despite this, very little research has studied the neural and psychological underpinnings of these behaviours. My research will take advantage of recent innovations and approaches to fill this void and have implications for diagnosis and treatment.
Impact Of A Sleep Intervention In Children With ADHD: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$384,230.00
Summary
Attention deficit hyperactivity disorder (ADHD) affects up to 7.5% of Australian children. Between 50 and 70% of parents also report sleep problems (eg night waking, insomnia) in their child with ADHD. Such sleep problems are associated with poorer child behaviour, concentration, and school attendance as well as poorer parent mental health and work attendance. This randomised controlled trial will determine whether treating sleep problems in children with ADHD can improve these outcomes.
Rates Of Psychosis Onset In A High Risk Population
Funder
National Health and Medical Research Council
Funding Amount
$310,359.00
Summary
Older studies of people at risk of schizophrenia found that about 35% of them developed psychosis within 1 year. However the risk has decreased lately to as low as 10%. They may still become psychotic but take longer to do so, or they may not develop psychosis at all. We need to study this so that those not “at risk” are not needlessly treated. We will follow up “at risk” people and determine their 6 year outcome. We will do scans to see if there are any brain changes associated with psychosis.
Building The Evidence Base For Prevention And Recovery Care Services
Funder
National Health and Medical Research Council
Funding Amount
$365,903.00
Summary
This project involves seven inter-related studies designed to evaluate the appropriateness, effectiveness and efficiency of Victoria's Prevention and Recovery Care Services (PARCS), which are residential services for people with severe mental disorders. The project represents a partnership between universities, PARCS providers, clinical services and the Victorian Government, and will actively engage service users and their carers and other experts
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less