ORCID Profile
0000-0002-9634-3731
Current Organisations
Australian Genomics - Murdoch Children's Research Institute
,
University of Melbourne
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Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.SCHRES.2013.01.023
Abstract: Although schizophrenia is a widespread disorder of unknown aetiology, we have previously shown that muscarinic M4 receptor (CHRM4) expression is decreased in the hippoc us and caudate-putamen from subjects with the disorder, implicating the receptor in its pathophysiology. These findings led us to determine whether variation in the CHRM4 gene sequence was associated with an altered risk of schizophrenia by sequencing the CHRM4 gene from the brains of 76 people with the disorder and 74 people with no history of psychiatric disorders. In addition, because the CHRM4 is a potential target for antipsychotic drug development, we investigated whether variations in CHRM4 sequence were associated with final recorded doses of, and life-time exposure to, antipsychotic drugs. Gene sequencing identified two single nucleotide polymorphisms (SNPs rs2067482 and rs72910092) in the CHRM4 gene. For rs2067482, our data suggested that both genotype (1341C/C p = 0.05) and allele (C p = 0.03) were associated with an increased risk of schizophrenia. In addition, there was a strong trend (p = 0.08) towards an association between CHRM4 sequence and increased lifetime exposure to antipsychotic drugs. Furthermore, there was a trend for people with the C allele to be prescribed benzodiazepines more frequently (p = 0.06) than those with the T allele. These data, albeit on small cohorts, are consistent with genetic variance at rs2067482 contributing to an altered risk of developing schizophrenia which requires more forceful pharmacotherapy to achieve a clinical response.
Publisher: Wiley
Date: 23-08-2021
DOI: 10.1111/JPC.15703
Abstract: Monogenic rare disorders contribute significantly to paediatric morbidity and mortality, and elucidation of the underlying genetic cause may have benefits for patients, families and clinicians. Advances in genomic technology have enabled diagnostic yields of up to 50% in some paediatric cohorts. This has led to an increase in the uptake of genetic testing across paediatric disciplines. This can place an increased burden on paediatricians, who may now be responsible for interpreting and explaining test results to patients. However, genomic results can be complex, and sometimes inconclusive for the ordering paediatrician. Results may also cause uncertainty and anxiety for patients and their families. The paediatrician's genetic literacy and knowledge of genetic principles are therefore critical to inform discussions with families and guide ongoing patient care. Here, we present four hypothetical case vignettes where genomic testing is undertaken, and discuss possible results and their implications for paediatricians and families. We also provide a list of key terms for paediatricians.
Publisher: Elsevier BV
Date: 03-2023
Publisher: Springer Science and Business Media LLC
Date: 07-04-2009
DOI: 10.1007/S11682-009-9067-2
Abstract: With the advent of new therapeutic strategies aimed at reducing β-amyloid (Aβ) burden in the brain to potentially prevent or delay functional and irreversible cognitive loss, there is increased interest in developing agents that allow assessment of Aβ burden in vivo. Molecular neuroimaging techniques such as positron emission tomography (PET), in conjunction with related biomarkers in plasma and cerebrospinal fluid, are proving valuable in the early and differential diagnosis of Alzheimer's disease (AD). (11)C-PiB PET has proven useful in the discrimination of dementias, showing significantly higher PiB retention in grey matter of AD patients when compared with healthy controls or patients with frontotemporal dementia. (11)C-PiB PET also appears to be more accurate than FDG for the diagnosis of AD. Despite apparently underestimating the Aβ burden in the brain, (11)C-PiB PET is an optimal method to differentiate healthy controls from AD, matching histopathological reports in aging and dementia and reflecting the true regional density of Aβ plaques in cortical areas. High striatal Aβ deposition seems to be typical for carriers of familial forms of AD, whilst ApoE ε4 carriers, independent of diagnosis or disease severity, present with higher Aβ burden than non- ε4 carriers. Characterization of the binding properties of PiB has shown that despite binding to other misfolded proteins in vitro, PiB is extremely selective for Aβ at the concentrations achieved during a PET scan. Aβ burden as assessed by PET does not correlate with measures of cognition or cognitive decline in AD. Approximately 30% of apparently healthy older people, and 50-60% of people with mild cognitive impairment, present with cortical (11)C-PiB retention. In these groups, Aβ burden does correlate with episodic memory and rate of memory decline. These observations suggest that Aβ deposition is not part of normal ageing, supporting the hypothesis that Αβ deposition occurs well before the onset of symptoms and is likely to represent preclinical AD. Further longitudinal observations, coupled with different disease-specific tracers and biomarkers are required not only to confirm this hypothesis, but also to better elucidate the role of Αβ deposition in the course of Alzheimer's disease.
Publisher: Springer Science and Business Media LLC
Date: 21-07-2023
DOI: 10.1007/S00439-023-02587-5
Abstract: Genomics research related to Indigenous people has been at worst exploitative and at best, retrospectively on a journey to improve effective engagement of Indigenous in iduals and communities. Genomics can positively impact all stages of clinical management, and to improve genomic effectiveness researchers aggregate genomic data from erse global sub-populations, such as shared ancestry groupings, as people within these groupings will have a greater proportion of shared DNA traits. While genomics is already being used worldwide to improve lives, its utility and effectiveness has not been maximized for in iduals with Indigenous ancestry. Several large datasets of human genetic variation have been made publicly available, of which the most widely used is the Genome Aggregation Database (gnomAD), but none of these databases currently contain any population-specific data for Indigenous populations. There are many reasons why Indigenous people have been largely left out of genomics research and, because of this, miss out on the benefits offered. It is also clear that if research is to be effective, it needs to be done ‘with’ and not ‘on’ Indigenous communities. This systematic review of the literature regarding Indigenous peoples (in high income countries) and genomics aims to review the existing literature and identify areas of strength and weakness in study design and conduct, focusing on the effectiveness of Indigenous community engagement.
Publisher: AMPCo
Date: 11-2019
DOI: 10.5694/MJA2.50397
Publisher: AMPCo
Date: 30-03-2019
DOI: 10.5694/MJA2.50032
Publisher: Wiley
Date: 07-07-2007
Publisher: BMJ
Date: 06-02-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-05-2007
DOI: 10.1212/01.WNL.0000261919.22630.EA
Abstract: To compare brain beta-amyloid (Abeta) burden measured with [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias. Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio. Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus osterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis. Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.
Publisher: MDPI AG
Date: 28-10-2022
DOI: 10.3390/JPM12111781
Abstract: Reproductive genetic carrier screening (RGCS) provides people with information about their chance of having children with autosomal recessive or X-linked genetic conditions, enabling informed reproductive decision-making. RGCS is recommended to be offered to all couples during preconception or in early pregnancy. However, cost and a lack of awareness may prevent access. To address this, the Australian Government funded Mackenzie’s Mission—the Australian Reproductive Genetic Carrier Screening Project. Mackenzie’s Mission aims to assess the acceptability and feasibility of an easily accessible RGCS program, provided free of charge to the participant. In study Phase 1, implementation needs were mapped, and key study elements were developed. In Phase 2, RGCS is being offered by healthcare providers educated by the study team. Reproductive couples who provide consent are screened for over 1200 genes associated with serious, childhood-onset genetic conditions. Those with an increased chance result are provided comprehensive genetic counseling support. Reproductive couples, recruiting healthcare providers, and study team members are also invited to complete surveys and/or interviews. In Phase 3, a mixed-methods analysis will be undertaken to assess the program outcomes, psychosocial implications and implementation considerations alongside an ongoing bioethical analysis and a health economic evaluation. Findings will inform the implementation of an ethically robust RGCS program.
Publisher: Springer Science and Business Media LLC
Date: 14-09-2023
Publisher: Springer Science and Business Media LLC
Date: 02-08-2018
Publisher: Springer Science and Business Media LLC
Date: 11-05-2023
DOI: 10.1038/S41431-023-01373-1
Abstract: Fears of genetic discrimination in life insurance continue to deter some Australians from genetic testing. In July 2019, the life insurance industry introduced a partial, self-regulated moratorium restricting the use of genetic results in underwriting, applicable to policies up to certain limits (eg AUD$500,000 for death cover). We administered an online survey to consumers who had taken, or been offered, clinical genetic testing for adult-onset conditions, to gather views and experiences about the moratorium and the use of genetic results in life insurance, including its regulation. Most respondents ( n = 367) had undertaken a genetic test (89%), and had a positive test result (76% n = 243/321). Almost 30% ( n = 94/326) reported testing after 1 July 2019. Relatively few respondents reported knowing about the moratorium (16% n = 54/340) or that use of genetic results in life insurance underwriting is legal (17% n = 60/348). Only 4% ( n = 14/350) consider this practice should be allowed. Some respondents reported ongoing difficulties accessing life insurance products, even after the moratorium. Further, discrimination concerns continue to affect some consumers’ decision-making about having clinical testing and applying for life insurance products, despite the Moratorium being in place. Most respondents (88% n = 298/340) support the introduction of legislation by the Australian government to regulate this issue. Despite the introduction of a partial moratorium in Australia, fears of genetic discrimination persist, and continue to deter people from genetic testing. Consumers overwhelmingly consider life insurers should not be allowed to use genetic results in underwriting, and that federal legislation is required to regulate this area.
Publisher: Springer Science and Business Media LLC
Date: 22-02-2019
Publisher: Springer Science and Business Media LLC
Date: 06-06-2023
DOI: 10.1038/S41431-023-01395-9
Abstract: Genetic risk information for medically actionable conditions has relevance for patients’ blood relatives. However, cascade testing uptake in at-risk families is %, and the burden of contacting relatives is a significant barrier to dissemination of risk information. Health professionals (HPs) could notify at-risk relatives directly, with patients’ consent. This practice is supported by international literature, including strong public support. However, there is little exploration of the Australian public’s views about this issue. We surveyed Australian adults using a consumer research company. Respondents were provided a hypothetical scenario and asked about views and preferences regarding direct contact by HPs. 1030 members of the public responded, with median age 45 y and 51% female. The majority would want to be told about genetic risk for conditions that can be prevented/treated early (85%) and contacted directly by a HP (68%). Most preferred a letter that included specific information about the genetic condition in the family (67%) and had no privacy concerns about HPs sending a letter using contact details provided by a relative (85%). A minority ( 5%) had significant privacy concerns, mostly about use of personal contact information. Concerns included ensuring information was not shared with third parties. Almost 50% would prefer that a family member contacted them before the letter was sent, while about half did not prefer this or were unsure. The Australian public supports (and prefers) direct notification of relatives at risk of medically actionable genetic conditions. Guidelines would assist with clarifying clinicians’ discretion in this area.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.ATHORACSUR.2008.04.085
Abstract: The plasma protein apolipoprotein E (APOE) is a risk factor for degenerative cognitive decline manifested by mild cognitive impairment and later by Alzheimer's disease. Patients undergoing coronary artery bypass grafting (CABG) are known to have a high prevalence of preexisting cognitive impairment and postoperative cognitive dysfunction. Because both mild cognitive impairment and Alzheimer's disease generally occur in elderly in iduals, the age group that commonly present for CABG, we investigated if the APOE epsilon4 allele was associated with patients manifesting preexisting cognitive impairment and postoperative cognitive dysfunction. The DNA of 282 patients who had undergone neuropsychologic testing before and 3 and 12 months after CABG was analyzed for APOE genotype. Patients were classified as having preexisting cognitive impairment if cognitive function was decreased in two or more tests compared with a healthy control group. Postoperative cognitive dysfunction was defined as a decrease in two or more tests compared with the group mean baseline score. The APOE epsilon4 allele was found in 83 (29.4%) patients. Although preexisting cognitive impairment was present in 105 (37.2%) and postoperative cognitive dysfunction in 33 (12%) and 31 (11%) at 3 and 12 months postoperatively, there was no relationship with the presence of the APOE epsilon4 allele or any of the six genotypes. Preexisting cognitive impairment and postoperative cognitive dysfunction are not associated with APOE epsilon4 genotype, suggesting that cognitive impairment both before and after CABG may not be associated with degenerative cognitive decline.
Publisher: Springer Science and Business Media LLC
Date: 07-04-2020
Publisher: Humana Press
Date: 2010
DOI: 10.1007/978-1-60761-756-3_5
Abstract: Autophagy is a cellular quality control process by which cytoplasmic constituents including proteins, protein aggregates, organelles, and invading pathogens can be delivered to lysosomes for degradation. Autophagy is activated in response to changes in the internal status of the cell and/or changes in the extracellular environment. It is therefore essential for the maintenance of cellular homeostasis and for an efficient response to cellular stresses. As such autophagy has been implicated either in the pathogenesis, or response to a wide variety of diseases, bacterial, and viral infections, and ageing.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.ATHORACSUR.2009.07.003
Abstract: Decreased cognitive function associated with coronary artery bypass graft surgery is common. These deficits may be similar to the cognitive dysfunction seen in the spectrum of mild cognitive impairment to Alzheimer's disease, which are believed to result from the accumulation of amyloid beta (Abeta) peptide in the brain. We measured cognition both before and after coronary artery bypass graft surgery and assayed Abeta levels to investigate whether the cognitive dysfunction of cardiac surgery was associated with Abeta levels. The plasma of 332 patients, who had undergone neuropsychological testing before and 3 and 12 months after coronary artery bypass graft surgery, was analyzed for Abeta(42) and Abeta(40). Patients were classified as having preexisting cognitive impairment if cognitive function was decreased in two or more tests compared with a healthy control group, and postoperative cognitive dysfunction was defined as a decline in two or more tests compared with the group mean baseline score. Preexisting cognitive impairment was present in 117 patients (35.2%), and postoperative cognitive dysfunction was present in 40 (12%) at 3 months and 41 (13%) at 12 months after surgery. Both plasma Abeta(42) and Abeta(40) levels assessed before the surgery were significantly lower in patients who later had postoperative cognitive dysfunction at 3 months. Decreased preoperative plasma levels of Abeta(42) and Abeta(40) in patients who exhibit postoperative cognitive dysfunction at 3 months suggest that postoperative cognitive dysfunction at this time may share a common mechanism with mild cognitive impairment and Alzheimer's disease. This process may be exacerbated by anesthesia.
Publisher: Elsevier BV
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 06-01-2021
DOI: 10.1038/S41431-020-00782-W
Abstract: The complexities of the informed consent process for participating in research in genomic medicine are well-documented. Inspired by the potential for Dynamic Consent to increase participant choice and autonomy in decision-making, as well as the opportunities for ongoing participant engagement it affords, we wanted to trial Dynamic Consent and to do so developed our own web-based application (web app) called CTRL (control). This paper documents the design and development of CTRL, for use in the Australian Genomics study: a health services research project building evidence to inform the integration of genomic medicine into mainstream healthcare. Australian Genomics brought together a multi-disciplinary team to develop CTRL. The design and development process considered user experience security and privacy the application of international standards in data sharing IT, operational and ethical issues. The CTRL tool is now being offered to participants in the study, who can use CTRL to keep personal and contact details up to date make consent choices (including indicate preferences for return of results and future research use of biological s les, genomic and health data) follow their progress through the study complete surveys, contact the researchers and access study news and information. While there are remaining challenges to implementing Dynamic Consent in genomic research, this study demonstrates the feasibility of building such a tool, and its ongoing use will provide evidence about the value of Dynamic Consent in large-scale genomic research programs.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 12-2019
DOI: 10.1200/PO.19.00019
Abstract: The ALLOCATE study was designed as a pilot to demonstrate the feasibility and clinical utility of real-time targeted molecular profiling of patients with recurrent or advanced ovarian cancer for identification of potential targeted therapies. A total of 113 patients with ovarian cancer of varying histologies were recruited from two tertiary hospitals, with 99 patient cases suitable for prospective analysis. Targeted molecular and methylation profiling of fresh biopsy and archived tumor s les were performed by screening for mutations or copy-number variations in 44 genes and for promoter methylation of BRCA1 and RAD51C. Somatic genomic or methylation events were identified in 85% of all patient cases, with potentially actionable events with defined targeted therapies (including four resistance events) detected in 60% of all patient cases. On the basis of these findings, six patients received molecularly guided therapy, three patients had unsuspected germline cancer–associated BRCA1/ 2 mutations and were referred for genetic counseling, and two intermediate differentiated (grade 2) serous ovarian carcinomas were reclassified as low grade, leading to changes in clinical management. Additionally, secondary reversion mutations in BRCA1/ 2 were identified in fresh biopsy s les of two patients, consistent with clinical platinum oly (ADP-ribose) polymerase inhibitor resistance. Timely reporting of results if molecular testing is done at disease recurrence, as well as early referral for patients with platinum-resistant cancers, were identified as factors that could improve the clinical utility of molecular profiling. ALLOCATE molecular profiling identified known genomic and methylation alterations of the different ovarian cancer subtypes and was deemed feasible and useful in routine clinical practice. Better patient selection and access to a wider range of targeted therapies or clinical trials will further enhance the clinical utility of molecular profiling.
Publisher: SAGE Publications
Date: 03-06-2014
DOI: 10.1111/IJS.12301
Abstract: Globally, stroke and dementia are leading causes of disability and mortality. More than one third of stroke patients will develop dementia, but mechanisms are unclear. The study aims to establish whether brain volume change is associated with poststroke dementia, and to elucidate potential causal mechanisms, including genetic markers, amyloid deposition and vascular risk factors. An understanding of whether – and in whom – stroke is neurodegenerative is critical for the strategic use of potential disease-modifying therapies. That stroke patients will exhibit greater brain volume loss than comparable cohorts of stroke-free controls and that those who develop dementia will exhibit greater brain volume loss than those who do not. Advanced brain imaging techniques are used to longitudinally measure brain volume and cortical thickness in 135 stroke patients. Concurrent neuropsychological testing will correlate clinical profile with these measures. Primary imaging end-point is brain volume change between three-months and three-years poststroke primary clinical outcome is the presence of dementia at three-years. We will examine the correlations with the following variables: dementia subtype physical activity levels behavioral dysfunction as measured by patient and caregiver-reported scales structural and functional brain connectivity disruption apolipoprotein E and specific neuropsychological test scores. Magnetic resonance imaging markers of structural brain aging and performance on neuropsychological tests are powerful predictors of dementia. We need to understand the trajectory of regional brain volume change and cognitive decline in patients after stroke. This will allow future risk stratification for prognostic counseling, service planning, and early therapeutic intervention.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Elsevier BV
Date: 08-2020
Publisher: Wiley
Date: 06-2010
Abstract: The primary constituent of the amyloid plaque, beta-amyloid (Abeta), is thought to be the causal "toxic moiety" of Alzheimer's disease. However, despite much work focused on both Abeta and its parent protein, amyloid precursor protein (APP), the functional roles of APP and its cleavage products remain to be fully elucidated. Protein-protein interaction networks can provide insight into protein function, however, high-throughput data often report false positives and are in frequent disagreement with low-throughput experiments. Moreover, the complexity of the CNS is likely to be under represented in such databases. Therefore, we curated the published work characterizing both APP and Abeta to create a protein interaction network of APP and its proteolytic cleavage products, with annotation, where possible, to the level of APP binding domain and isoform. This is the first time that an interactome has been refined to domain level, essential for the interpretation of APP due to the presence of multiple isoforms and processed fragments. Gene ontology and network analysis were used to identify potentially novel functional relationships among interacting proteins.
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 07-12-2007
Publisher: Springer Science and Business Media LLC
Date: 04-03-2009
DOI: 10.1038/MP.2008.28
Abstract: Schizophrenia is widely acknowledged as being a syndrome, consisting of an undefined number of diseases probably with differing pathologies. Although studying a syndrome makes the identification of an underlying pathology more difficult neuroimaging, neuropsychopharmacological and post-mortem brain studies all implicate muscarinic acetylcholine receptors (CHRM) in the pathology of the disorder. We have established that the CHRM1 is selectively decreased in the dorsolateral prefrontal cortex of subjects with schizophrenia. To expand this finding, we wanted to ascertain whether decreased cortical CHRMs might (1) define a subgroup of schizophrenia and/or (2) be related to CHRM1 genotype. We assessed cortical [(3)H]pirenzepine binding and sequenced the CHRM1 in 80 subjects with schizophrenia and 74 age sex-matched control subjects. Kernel density estimation showed that [(3)H]pirenzepine binding in BA9 ided the schizophrenia, but not control, cohort into two distinct populations. One of the schizophrenia cohorts, comprising 26% of all subjects with the disorder, had a 74% reduction in mean cortical [(3)H]pirenzepine binding compared to controls. We suggest that these in iduals make up 'muscarinic receptor-deficit schizophrenia' (MRDS). The MRDS could not be separated from other subjects with schizophrenia by CHRM1 sequence, gender, age, suicide, duration of illness or any particular drug treatment. Being able to define a subgroup within schizophrenia using a central biological parameter is a pivotal step towards understanding the biochemistry underlying at least one form of the disorder and may represent a biomarker that can be used in neuroimaging.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2021
DOI: 10.1186/S12910-021-00634-2
Abstract: The use of genetic test results in risk-rated insurance is a significant concern internationally, with many countries banning or restricting the use of genetic test results in underwriting. In Australia, life insurers’ use of genetic test results is legal and self-regulated by the insurance industry (Financial Services Council (FSC)). In 2018, an Australian Parliamentary Inquiry recommended that insurers’ use of genetic test results in underwriting should be prohibited. In 2019, the FSC introduced an industry self-regulated moratorium on the use of genetic test results. In the absence of government oversight, it is critical that the impact, effectiveness and appropriateness of the moratorium is monitored. Here we describe the protocol of our government-funded research project, which will serve that critical function between 2020 and 2023. A realist evaluation framework was developed for the project, using a context-mechanism-outcome (CMO) approach, to systematically assess the impact of the moratorium for a range of stakeholders. Outcomes which need to be achieved for the moratorium to accomplish its intended aims were identified, and specific data collection measures methods were developed to gather the evidence from relevant stakeholder groups (consumers, health professionals, financial industry and genetic research community) to determine if aims are achieved. Results from each arm of the study will be analysed and published in peer-reviewed journals as they become available. The A-GLIMMER project will provide essential monitoring of the impact and effectiveness of the self-regulated insurance moratorium. On completion of the study (3 years) a Stakeholder Report will be compiled. The Stakeholder Report will synthesise the evidence gathered in each arm of the study and use the CMO framework to evaluate the extent to which each of the outcomes have been achieved, and make evidence-based recommendations to the Australian federal government, life insurance industry and other stakeholders.
Publisher: BMJ
Date: 20-09-2021
DOI: 10.1136/JMEDGENET-2021-107989
Abstract: In 2019, the Australian life insurance industry introduced a partial moratorium (ban) limiting the use of genetic test results in life insurance underwriting. The moratorium is industry self-regulated and applies only to policies below certain financial limits (eg, $500 000 of death cover). We surveyed Australian health professionals (HPs) who discuss genetic testing with patients, to assess knowledge of the moratorium reported patient experiences since its commencement and HP views regarding regulation of genetic discrimination (GD) in Australia. Between April and June 2020, 166 eligible HPs responded to the online survey. Of these, 86% were aware of the moratorium, but % had attended related training/information sessions. Only 16% answered all knowledge questions correctly, yet 69% believed they had sufficient knowledge to advise patients. Genetics HPs’ awareness and knowledge were better than non-genetics HPs’ (p .05). There was some reported decrease in patients delaying/declining testing after the moratorium’s introduction, however, 42% of HPs disagreed that patients were more willing to have testing post-moratorium. Although many (76%) felt the moratorium resolved some GD concerns, most (88%) still have concerns, primarily around self-regulation, financial limits and the moratorium’s temporary nature. Almost half (49%) of HPs reported being dissatisfied with the moratorium as a solution to GD. The majority (95%) felt government oversight is required, and 93% felt specific Australian legislation regarding GD is required. While the current Australian moratorium is considered a step forward, most HPs believe it falls short of an adequate long-term regulatory solution to GD in life insurance.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.SCHRES.2012.02.011
Abstract: It has been reported that people with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism of the cholinergic muscarinic M1 receptor (CHRM1) perform less well on the Wisconsin Card Sorting Test than those who are heterozygous. We investigated whether CHRM1 sequence is associated with impaired executive function, a common problem in schizophrenia. We sequenced the CHRM1 using peripheral DNA from 97 people with schizophrenia who completed the Wisconsin Card Sorting Test, a verbal fluency test and the National Adult Reading Test. Clinical severity was assessed using the Positive and Negative Syndrome Scale. To determine whether CHRM1 sequence affected receptor expression, we used post-mortem data, from another cohort, to investigate associations between CHRM1 sequence and mRNA levels. On the Wisconsin Card Sorting Test, 267C/C participants with schizophrenia made more perseverative errors (p<0.05) and perseverative responses (p<0.05) than 267C/A participants. Genotype had no effect on verbal fluency (p=0.8) or National Adult Reading test (p=0.62). Cortical CHRM1 mRNA levels did not vary with gene sequence (p=0.409). The clinical study supports the proposal that CHRM1 sequence is associated with alterations in some aspects of executive function. However, the post-mortem study indicates this is not simply due to altered expression at the level of mRNA, suggesting this sequence alteration may affect the functionality of the CHRM1.
Publisher: Cold Spring Harbor Laboratory
Date: 29-05-2021
DOI: 10.1101/2021.05.25.21257683
Abstract: In 2019, the Australian life insurance industry introduced a partial moratorium (ban) limiting the use of genetic test results in life insurance underwriting. The moratorium is industry self-regulated and applies only to policies below certain financial limits (eg AUD$500,000 of life cover). We surveyed Australian health professionals (HPs) who discuss genetic testing with patients, to assess knowledge of the moratorium reported patient experiences since its commencement and HP views regarding regulation of genetic discrimination (GD) in Australia. Between April-June 2020, 166 eligible HPs responded to the online survey. Of these, 86% were aware of the moratorium, but % had attended related training/information sessions. Only 16% answered all knowledge questions correctly, yet 69% believed they had sufficient knowledge to advise patients. Genetics HPs’ awareness and knowledge were better than non-genetics HPs’ (p .05). There was some reported decrease in patients delaying/declining testing after the moratorium’s introduction, however 42% of HPs disagreed that patients were more willing to have testing post-moratorium. Although many (76%) felt the moratorium resolved some GD concerns, most (88%) still have concerns, primarily around self-regulation, financial limits and the moratorium’s temporary nature. Almost half (49%) of HPs reported being dissatisfied with the moratorium as a solution to GD. The majority (95%) felt government oversight is required, and 93% felt specific Australian legislation regarding GD is required. While the current Australian moratorium is considered a step forward, most HPs believe it falls short of an adequate long-term regulatory solution to GD in life insurance.
Publisher: MDPI AG
Date: 21-06-2021
DOI: 10.3390/MPS4020042
Abstract: (1) Background: Genomic precision medicine (PM) utilises people’s genomic data to inform the delivery of preventive and therapeutic health care. PM has not been well-established for use with people of Aboriginal and Torres Strait Islander ancestry due to the paucity of genomic data from these communities. We report the development of a new protocol using co-design methods to enhance the potential use of PM for Aboriginal Australians. (2) Methods: This iterative qualitative study consists of five main phases. Phase-I will ensure appropriate governance of the project and establishment of a Project Advisory Committee. Following an initial consultation with the Aboriginal community, Phase-II will invite community members to participate in co-design workshops. In Phase-III, the Chief Investigators will participate in co-design workshops and document generated ideas. The notes shall be analysed thematically in Phase-IV with Aboriginal community representatives, and the summary will be disseminated to the communities. In Phase-V, we will evaluate the co-design process and adapt our protocol for the use in partnership with other communities. (3) Discussion: This study protocol represents a crucial first step to ensure that PM research is relevant and acceptable to Aboriginal Australians. Without fair access to PM, the gap in health outcome between Aboriginal and non-Aboriginal Australians will continue to widen.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2021
Publisher: MDPI AG
Date: 02-06-2023
Abstract: Genetic risk information has relevance for patients’ blood relatives. However, cascade testing uptake in at-risk families is %. International research supports direct notification of at-risk relatives by health professionals (HPs), with patient consent. However, HPs express concerns about the privacy implications of this practice. Our privacy analysis, grounded in a clinically relevant hypothetical scenario, considers the types of personal information involved in direct notification of at-risk relatives and the application of Australian privacy regulations. It finds that collecting relatives’ contact details, and using those details (with patient consent) to notify relatives of possible genetic risk, does not breach Australian privacy law, providing that HPs adhere to regulatory requirements. It finds the purported “right to know” does not prevent disclosure of genetic information to at-risk relatives. Finally, the analysis confirms that the discretion available to HPs does not equate to a positive duty to warn at-risk relatives. Thus, direct notification of a patient’s at-risk relatives regarding medically actionable genetic information, with patient consent, is not a breach of Australian privacy regulations, providing it is conducted in accordance with the applicable principles set out. Clinical services should consider offering this service to patients where appropriate. National guidelines would assist with the clarification of the discretion for HPs.
Publisher: Springer Science and Business Media LLC
Date: 28-07-2022
DOI: 10.1038/S41431-022-01150-6
Abstract: Australian life insurance companies can legally use genetic test results in underwriting, which can lead to genetic discrimination. In 2019, the Financial Services Council (Australian life insurance industry governing body) introduced a partial moratorium restricting the use of genetic testing in underwriting policies ≤ $500,000 (active 2019–2024). Health professionals (HPs), especially clinical geneticists and genetic counsellors, often discuss the implications of genetic testing with patients, and provide critical insights into the effectiveness of the moratorium. Using a sequential explanatory mixed methods design, we interviewed 23 Australian HPs, who regularly discuss genetic testing with patients and had previously completed an online survey about genetic testing and life insurance. Interviews explored views and experiences about the moratorium, and regulation, in greater depth. Interview transcripts were analysed using thematic analysis. Two key themes emerged from views expressed by HPs during interviews (about matters reported to or observed by them): 1) benefits of the moratorium, and 2) concerns about the moratorium. While HPs reported that the moratorium reassures some consumers, concerns include industry self-regulation, uncertainty created by the temporary time period, and the inadequacy of the moratorium’s financial limits for patients’ financial needs. Although a minority of HPs felt the current industry self-regulated moratorium is an adequate solution to genetic discrimination, the vast majority (19/23) expressed concern with industry self-regulation and most felt government regulation is required to adequately protect consumers. HPs in Australia are concerned about the adequacy of the FSC moratorium with regards to consumer protections, and suggest government regulation is required.
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2008.02.008
Abstract: Approximately 30% of healthy persons aged over 75 years show Abeta deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between Abeta burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and cognitive tests were performed on 34 elderly participants (age 73+/-6) from the longitudinal Melbourne Healthy Aging Study (MHAS). Subjects were classified as being cognitively 'stable' or 'declining' by an independent behavioural neurologist based on clinical assessment and serial word-list recall scores from the preceding 6-10 years. Decline was calculated from the slope of the word-list recall scores. Abeta burden was quantified using Standardized Uptake Value normalized to cerebellar cortex. Ten subjects were clinically classified as declining. At the time of the PET scans, three of the declining subjects had mild cognitive impairment, one had AD, and six were declining but remained within the normal range for age on cognitive tests. Declining subjects were much more likely to show cortical PiB binding than stable subjects (70% vs. 17%, respectively). Neocortical Abeta burden correlated with word-list recall slopes (r=-0.78) and memory function (r=-0.85) in the declining group. No correlations were observed in the stable group. Abeta burden correlated with incident memory impairment and the rate of memory decline in the non-demented ageing population. These observations suggest that neither memory decline nor Abeta deposition are part of normal ageing and likely represent preclinical AD. Further longitudinal observations are required to confirm this hypothesis.
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1080/00313020601024052
Abstract: Considerable heterogeneity of morphology and disease outcome exists within breast cancers (BC), which likely reflects variable molecular pathogeneses within this broad clinical group. To evaluate the underlying genomic alterations associated with familial, early-onset BC (EOBC) phenotypes, in order to improve the management of this disease. Using hierarchical clustering of morphological and immunophenotypical parameters, 116 EOBC were stratified into six groups. Conventional and array-based comparative genomic hybridisation was used to analyse the genomic alterations. Specific areas of genomic imbalance were associated with in idual phenotypes. The largest phenotypical group was high grade, oestrogen receptor and HER-2 negative. This group contained the majority of BRCA1 germline mutation-associated tumours and commonly showed loss of chromosomal regions 5cent-5q13, 5q14-22 and 4q28-32. High mitotic rate, an important indicator of tumour cell proliferation and poor prognosis, was associated with gain of 19p, mapped within 7 Mb of the telomere. This region contains the candidate oncogene CDC34, the protein product of which is involved in ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor, p27Kip1. Phenotype-based analysis can be used to determine the genetic changes important in subtypes of BC. Further, the different morphological phenotypes could act as a cost-effective surrogate for genotypical stratification to facilitate optimal management of this disease.
Publisher: Wiley
Date: 10-02-2021
DOI: 10.1111/JPC.15382
Abstract: Genomic testing for a genetic diagnosis is becoming standard of care for many children, especially those with a syndromal intellectual disability. While previously this type of specialised testing was performed mainly by clinical genetics teams, it is increasingly being ‘mainstreamed’ into standard paediatric care. With the introduction of a new Medicare rebate for genomic testing in May 2020, this type of testing is now available for paediatricians to order, in consultation with clinical genetics. Children must be aged less than 10 years with facial dysmorphism and multiple congenital abnormalities or have global developmental delay or moderate to severe intellectual disability. This rebate should increase the likelihood of a genetic diagnosis, with accompanying benefits for patient management, reproductive planning and diagnostic certainty. Similar to the introduction of chromosomal microarray into mainstream paediatrics, this genomic testing will increase the number of genetic diagnoses, however, will also yield more variants of uncertain significance, incidental findings, and negative results. This paper aims to guide paediatricians through the process of genomic testing, and represents the combined expertise of educators, clinical geneticists, paediatricians and genomic pathologists around Australia. Its purpose is to help paediatricians navigate choosing the right genomic test, consenting patients and understanding the possible outcomes of testing.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Springer Science and Business Media LLC
Date: 22-05-2023
Publisher: Elsevier BV
Date: 11-2021
Location: Australia
No related grants have been discovered for Tiffany Boughtwood.