Surgery (RMH) - Research Publications
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ItemRegistry of Older South Australians (ROSA): framework and plan(BMJ PUBLISHING GROUP, 2019-06)INTRODUCTION: Australia's ageing population puts significant demands on the aged care and healthcare sectors. To monitor the provision of aged care and healthcare services to older people, each government body has an individual data collection system. Together these systems can be the basis for creating the evidence necessary to support future allocation of resources for our ageing community. The Registry of Older South Australians (ROSA) is a cross-sector multidisciplinary (ie, aged care and healthcare) platform built to address the challenges of monitoring people in aged care settings. This protocol describes the ROSA's framework and plans. METHODS AND ANALYSIS: A registry to capture 16 000 South Australians/year undergoing an aged care eligibility assessment was designed. ROSA will contain information captured by the Commonwealth and South Australian state Health Authority, linked by two data integrating authorities, and housed on a secured data platform. ROSA will contain information on the sociodemographic, health, function, psychological, social, home and safety assessment and concerns characteristics, aged care services, general health services, and mortality of people receiving aged care services. Registered participants will be prospectively monitored until their death and yearly updates of their aged care and healthcare services information will be added to the registry. ETHICS AND DISSEMINATION: ROSA will longitudinally monitor the services provided to a population that puts costly demands on the state healthcare and aged care systems, identify unwanted variation, and underpin future research. ROSA's expected outputs include an annual report, a research agenda that focuses on high burden conditions and potentially economically impactful questions, educational materials, and risk profiling tools. ROSA was approved by the South Australian Department for Health and Ageing HREC (HREC/17/SAH/125) and the Australian Institute of Health and Welfare HREC (EO2018/2/429).
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ItemA novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm(NATURE PORTFOLIO, 2017-05-26)We describe a novel ERBB1/EGFR somatic mutation (p. C329R; c.985 T > C) identified in a patient with JAK2V617F Polycythaemia Vera (PV). This substitution affects a conserved cysteine residue in EGFR domain 2 and leads to the formation of a ligand-independent covalent receptor dimer, associated with increased transforming potential. Aberrant signalling from the EGFRC329R receptor is cell type-dependent and in the TF1.8 erythroid cell line expression of this mutant suppresses EPO-induced differentiation. Clonal analysis shows that the dominant JAK2V617F-positive clone in this PV patient harbors EGFRC329R, thus this mutation may contribute to clonal expansion. Somatic mutations affecting other ERBB and related receptor tyrosine kinases are observed in myeloproliferative neoplasms (MPN), and we show elevated EGFR levels in MPN samples, consistent with previous reports. Thus activation of this group of receptors, via multiple mechanisms, may contribute to clonal growth and survival of the JAK2V617F disease clone in MPN.
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ItemSynergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation(AMER ASSOC ADVANCEMENT SCIENCE, 2016-06)The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region. We identify a narrow megafaunal extinction phase 12,280 ± 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts.