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.
We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less
Improving eyewitness identification accuracy using free-report lineups. There is major national and community interest in the successful conduct of criminal investigations. This research addresses the accuracy of eyewitness identification tests. Specifically, we investigate whether developing lineup procedures that separate out witnesses who are unsure of their response will prevent erroneous identifications. Progress on this issue makes an important contribution to decisions about the ideal lin ....Improving eyewitness identification accuracy using free-report lineups. There is major national and community interest in the successful conduct of criminal investigations. This research addresses the accuracy of eyewitness identification tests. Specifically, we investigate whether developing lineup procedures that separate out witnesses who are unsure of their response will prevent erroneous identifications. Progress on this issue makes an important contribution to decisions about the ideal lineup procedure, thereby preventing innocent people from being prosecuted and perpetrators being free to re-offend. Additionally the international collaboration on the project will increase the visibility of Australian social science research and provide crucial development opportunities for young Australian scientists.Read moreRead less
Identifying the bad guy with deadlined confidence judgments. There is major interest in the successful conduct of criminal investigations. Identity tests are commonly used in such investigations, but eyewitness decision accuracy is still unacceptably low. While eyewitness memory research has already contributed significantly to the development of procedures that improve the diagnosticity of identification decisions, our proposal offers radical new alternatives that can significantly improve diag ....Identifying the bad guy with deadlined confidence judgments. There is major interest in the successful conduct of criminal investigations. Identity tests are commonly used in such investigations, but eyewitness decision accuracy is still unacceptably low. While eyewitness memory research has already contributed significantly to the development of procedures that improve the diagnosticity of identification decisions, our proposal offers radical new alternatives that can significantly improve diagnosticity. In refining and evaluating these alternatives we will boost the profile of Australian science research and provide rich international training environments for young Australian and overseas scientists.Read moreRead less
Interviewing eyewitnesses: Enhancing output quantity and diagnosing accuracy. Although there has been general international agreement that open-ended police interviews (e.g., the Cognitive Interview) enhance output quantity and accuracy, it is also well documented that police investigators often depart from these procedures in order to probe for additional information. An approach to eyewitness interviewing that allows police to elicit greater detail while able to assess likely accuracy not only ....Interviewing eyewitnesses: Enhancing output quantity and diagnosing accuracy. Although there has been general international agreement that open-ended police interviews (e.g., the Cognitive Interview) enhance output quantity and accuracy, it is also well documented that police investigators often depart from these procedures in order to probe for additional information. An approach to eyewitness interviewing that allows police to elicit greater detail while able to assess likely accuracy not only has the potential to be widely adopted but would also provide a major breakthrough in the investigation of crimes and other incidents where interview data are so critical. This in turn would further enhance the profile of Australian (and UK) forensic science.Read moreRead less
Uncovering the processes underlying human category learning. There is a pervasive belief that complex tasks can somehow be learned via a 'smart' implicit or procedural learning mechanism, which operates independently of memory and attention. This idea has important implications for our understanding of cognition. If true, there seems little point in providing explicit instruction in such tasks, and efforts to do so are, at best, wasted time and, at worst, detrimental to the learning process. Th ....Uncovering the processes underlying human category learning. There is a pervasive belief that complex tasks can somehow be learned via a 'smart' implicit or procedural learning mechanism, which operates independently of memory and attention. This idea has important implications for our understanding of cognition. If true, there seems little point in providing explicit instruction in such tasks, and efforts to do so are, at best, wasted time and, at worst, detrimental to the learning process. This project will provide much-needed scrutiny of this idea and will help not only to re-orient our understanding of how we deal with complex information, but will also highlight issues about data interpretation that are fundamental for the research and wider communities.Read moreRead less
I am a molecular geneticist with a main research focus in the identification and characterisation of genes and molecular pathways involved in intellectual disability and epilepsy.
Eyewitness identification: Metacognitive influences on choosing behaviour. There is major national and community interest in the successful conduct of criminal investigations. This research addresses the two most significant problems associated with the conduct of eyewitness identification tests: mistaken identifications of innocent suspects and failure to identify guilty suspects when they are present in the lineup. Progress on the latter problem - which results in offenders avoiding detection ....Eyewitness identification: Metacognitive influences on choosing behaviour. There is major national and community interest in the successful conduct of criminal investigations. This research addresses the two most significant problems associated with the conduct of eyewitness identification tests: mistaken identifications of innocent suspects and failure to identify guilty suspects when they are present in the lineup. Progress on the latter problem - which results in offenders avoiding detection - would be a major contribution with national impact. As well as the obvious implications for the conduct of lineups, the international collaboration on the project will increase the visibility of Australian social science research and provide crucial development opportunities for young Australian scientists.Read moreRead less
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
Can attentional re-training reduce food cravings and consumption? This project aims to determine the impact of a procedure involving the re-training of attention to food cues on food cravings and food intake. Results will advance our understanding of food cravings and contribute to interventions aimed at curbing unwanted cravings and (over) consumption.