6,309 research outputs found

    Detection and prevention of financial abuse against elders

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    This article is made available through the Brunel Open Access Publishing Fund. Copyright @ The Authors. This article is published under the Creative Commons Attribution (CC BY 3.0) licence. Anyone may reproduce, distribute, translate and create derivative works of this article (for both commercial and non-commercial purposes), subject to full attribution to the original publication and authors. The full terms of this licence may be seen at http://creativecommons.org/licences/ by/3.0/legalcode.Purpose ā€“ This paper reports on banking and finance professionals' decision making in the context of elder financial abuse. The aim was to identify the case features that influence when abuse is identified and when action is taken. Design/methodology/approach ā€“ Banking and finance professionals (n=70) were shown 35 financial abuse case scenarios and were asked to judge how certain they were that the older person was being abused and the likelihood of taking action. Findings ā€“ Three case features significantly influenced certainty of financial abuse: the nature of the financial problem presented, the older person's level of mental capacity and who was in charge of the client's money. In cases where the older person was more confused and forgetful, there was increased suspicion that financial abuse was taking place. Finance professionals were less certain that financial abuse was occurring if the older person was in charge of his or her own finances. Originality/value ā€“ The research findings have been used to develop freely available online training resources to promote professionals' decision making capacity (www.elderfinancialabuse.co.uk). The resources have been advocated for use by Building Societies Association as well as CIFAS, the UK's Fraud Prevention Service.The research reported here was funded by the UK cross council New Dynamicsof Ageing Programme, ESRC Reference No. RES-352-25-0026, with Mary L.M. Gilhooly asPrincipal Investigator. Web-based training tools, developed from the research findings, weresubsequently funded by the ESRC follow-on fund ES/J001155/1 with Priscilla A. Harries asPrincipal Investigator

    Experimental techniques for ductile damage characterisation

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    Ductile damage in metallic materials is caused by the nucleation, growth and coalesce of voids and micro-cracks in the metal matrix when it is subjected to plastic strain. A considerable number of models have been proposed to represent ductile failure focusing on the ultimate failure conditions; however, only some of them study in detail the whole damage accumulation process. The aim of this work is to review experimental techniques developed by various authors to measure the accumulation of ductile damage under tensile loads. The measurement methods reviewed include: stiffness degradation, indentation, microstructure analysis, ultrasonic waves propagation, X-ray tomography and electrical potential drop. Stiffness degradation and indentation techniques have been tested on stainless steel 304L hourglass-shaped samples. A special interest is placed in the Continuum Damage Mechanics approach (CDM) as its equations incorporate macroscopic parameters that can represent directly the damage accumulation measured in the experiments. The other main objective lies in identifying the strengths and weaknesses of each technique for the assessment of materials subjected to different strain-rate and temperature conditions

    Inhibitory Synapse Formation at the Axon Initial Segment

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    The axon initial segment (AIS) is the site of action potential (AP) initiation in most neurons and is thus a critical site in the regulation of neuronal excitability. Normal function within the discrete AIS compartment requires intricate molecular machinery to ensure the proper concentration and organization of voltage-gated and ligand-gated ion channels; in humans, dysfunction at the AIS due to channel mutations is commonly associated with epileptic disorders. In this review, we will examine the molecular mechanisms underlying the formation of the only synapses found at the AIS: synapses containing Ī³-aminobutyric type A receptors (GABAARs). GABAARs are heteropentamers assembled from 19 possible subunits and are the primary mediators of fast synaptic inhibition in the brain. Although the total GABAAR population is incredibly heterogeneous, only one specific GABAAR subtypeā€”the Ī±2-containing receptorā€”is enriched at the AIS. These AIS synapses are innervated by GABAergic chandelier cells, and this inhibitory signaling is thought to contribute to the tight control of AP firing. Here, we will summarize the progress made in understanding the regulation of GABAAR synapse formation, concentrating on post-translational modifications of subunits and on interactions with intracellular proteins. We will then discuss subtype-specific synapse formation, with a focus on synapses found at the AIS, and how these synapses influence neuronal excitation

    Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model

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    Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by Ī³-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the Ī±4 and Ī²3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X mental retardation protein (FMRP) knock-out (Fmr1 KO) mouse. The GABAergic tonic current in dentate gyrus granule cells (DGGCs) from 3- to 5-week-old (p21ā€“35) Fmr1 KO mice was significantly reduced compared to WT mice. Additionally, spontaneous inhibitory post synaptic inhibitory current (sIPSC) amplitudes were increased in DGGCs from Fmr1 KO mice. While sIPSCs decay in both genotypes was prolonged by the prototypic benzodiazepine diazepam, those in Frm1-KO mice were selectively potentiated by RO15-4513. Consistent with this altered pharmacology, modifications in the expression levels and phosphorylation of receptor GABAAR subtypes that mediate tonic inhibition were seen in Fmr1 KO mice. Significantly, exposure to NASs induced a sustained elevation in tonic current in Fmr1 KO mice which was prevented with PKC inhibition. Likewise, exposure reduced elevated membrane excitability seen in the mutant mice. Collectively, our results suggest that NAS act to reverse the deficits of tonic inhibition seen in FXS, and thereby reduce aberrant neuronal hyperexcitability seen in this disorder

    In situ monitoring of the layer height in laser powder bed fusion

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    In situ process monitoring has frequently been cited as an critical requirement in certifying the performance of laser powder bed fusion (LPBF) components for use in high integrity applications. Despite much development in addressing this need, little attention has been been paid to monitoring the layer thickness during the process. In this paper, a laser displacement sensor has been integrated into the build chamber of an LPBF machine, and the height of the top surface layer of a component has been monitored during a build. This has permitted the deposited layer thickness to be measured throughout the build, and the effect on this of a change in processing conditions is characterised. The thermal contraction of the top layer in between successive laser scans has also been evaluated. This demonstrates the potential of utilising laser displacement sensory as a process monitoring tool in LPBF and provides insightful data for implementation in detailed process models

    Factors associated with adherence to antiretroviral therapy in HIV-infected patients in Kathmandu District, Nepal

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    <p><b>Copyright information:</b></p><p>Taken from "Association of oestrogen receptor beta 2 (ERĪ²2/ERĪ²cx) with outcome of adjuvant endocrine treatment for primary breast cancer ā€“ a retrospective study"</p><p>http://www.biomedcentral.com/1471-2407/7/131</p><p>BMC Cancer 2007;7():131-131.</p><p>Published online 18 Jul 2007</p><p>PMCID:PMC1950511.</p><p></p>ses) and dichotomised levels of ERĪ²2 mRNA in the ERĪ± + tamoxifen-treated cohort and (B, 4 events in 29 ERĪ²2 high cases and 12 events in 29 ERĪ²2 low cases). Unbroken green lines represent cases with high levels of ERĪ²2, dotted blue lines represent cases with low levels. In all cases crosses represent censored data and P values are given for Log Rank tests

    The X-ray source population of the globular cluster M15: Chandra high-resolution imaging

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    This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The globular cluster M15 was observed on three occasions with the High Resolution Camera on-board Chandra in 2001 in order to investigate the X-ray source population in the cluster centre. After subtraction of the two bright central sources, four faint sources were identified within 50 arcsec of the core. One of these sources is probably the planetary nebula K648, making this the first positive detection of X-rays from a planetary nebula inside a globular cluster. Another two are identified with UV variables (one previously known), which we suggest are cataclysmic variables (CVs). The nature of the fourth source is more difficult to ascertain, and we discuss whether it is possibly a quiescent soft X-ray transient or also a CV.DCH is grateful to the Academy of Finland and to PPARC for financial support. MBD gratefully acknowledges the support of a Swedish Royal Academy of Sciences (KVA) Research Fellowship. The authors thank Craig Heinke, Bruce Balick and Joel Kastner for valuable comments. The authors also wish to thank Jonathan C. McDowell for useful suggestions, Miriam Krauss at the Chandra HelpDesk, and the anonymous referee for useful comments. DCH is grateful to Panu Muhli for useful comments. This research has made use of NASA's Astrophysics Data System, SAOImage DS9, developed by Smithsonian Astrophysical Observatory, and of the SIMBAD database operated at CDS, Strasbourg, France. Part of this work was based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the Data Archive at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555

    Analyzing the mechanisms that facilitate the subtype-specific assembly of Ī³-aminobutyric acid type A receptors

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    Impaired inhibitory signaling underlies the pathophysiology of many neuropsychiatric and neurodevelopmental disorders including autism spectrum disorders and epilepsy. Neuronal inhibition is regulated by synaptic and extrasynaptic Ī³-aminobutyric acid type A receptors (GABAARs), which mediate phasic and tonic inhibition, respectively. These two GABAAR subtypes differ in their function, ligand sensitivity, and physiological properties. Importantly, they contain different Ī± subunit isoforms: synaptic GABAARs contain the Ī±1ā€“3 subunits whereas extrasynaptic GABAARs contain the Ī±4ā€“6 subunits. While the subunit composition is critical for the distinct roles of synaptic and extrasynaptic GABAAR subtypes in inhibition, the molecular mechanism of the subtype-specific assembly has not been elucidated. To address this issue, we purified endogenous Ī±1- and Ī±4-containing GABAARs from adult murine forebrains and examined their subunit composition and interacting proteins using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and quantitative analysis. We found that the Ī±1 and Ī±4 subunits form separate populations of GABAARs and interact with distinct sets of binding proteins. We also discovered that the Ī²3 subunit, which co-purifies with both the Ī±1 and Ī±4 subunits, has different levels of phosphorylation on serines 408 and 409 (S408/9) between the two receptor subtypes. To understand the role S408/9 plays in the assembly of Ī±1- and Ī±4-containing GABAARs, we examined the effects of S408/9A (alanine) knock-in mutation on the subunit composition of the two receptor subtypes using LC-MS/MS and quantitative analysis. We discovered that the S408/9A mutation results in the formation of novel Ī±1Ī±4-containing GABAARs. Moreover, in S408/9A mutants, the plasma membrane expression of the Ī±4 subunit is increased whereas its retention in the endoplasmic reticulum is reduced. These findings suggest that S408/9 play a critical role in determining the subtype-specific assembly of GABAARs, and thus the efficacy of neuronal inhibition

    Parenthood and pregnancy in Australians receiving treatment for end-stage kidney disease: protocol of a national study of perinatal and parental outcomes through population record linkage.

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    INTRODUCTION:Achieving parenthood is challenging in individuals receiving renal replacement therapy (RRT; dialysis or kidney transplantation) for end-stage kidney disease. Decision-making regarding parenthood in RRT recipients should be underpinned by robust data, yet there is limited data on parental factors that drive adverse health outcomes. Therefore, we aim to investigate the perinatal risks and outcomes in parents receiving RRT. METHODS AND ANALYSIS:This is a multijurisdictional probabilistic data linkage study of perinatal, hospital, birth, death and renal registers from 1991 to 2013 from New South Wales, Western Australia, South Australia and the Australian Capital Territory. This study includes all babies born ā‰„20 weeks' gestation or 400 g birth weight captured through mandated data collection in the perinatal data sets. Through linkage with the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry, babies exposed to RRT (and their parents) will be compared with babies who have not been exposed to RRT (and their parents) to determine obstetric and fetal outcomes, birth rates and fertility rates. One of the novel aspects of this study is the method that will be used to link fathers receiving RRT to the mothers and their babies within the perinatal data sets, using the birth register, enabling the identification of family units. The linked data set will be used to validate the parenthood events directly reported to ANZDATA. ETHICS AND DISSEMINATION:Ethics approval was obtained from Human Research Ethics Committees (HREC) and Aboriginal HREC in each jurisdiction. Findings of this study will be disseminated at scientific conferences and in peer-reviewed journals in tabular and aggregated forms. De-identified data will be presented and individual patients will not be identified. We will aim to present findings to relevant stakeholders (eg, patients, clinicians and policymakers) to maximise translational impact of research findings
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