216 research outputs found

    Perceptions of sex offenders with intellectual disability: a comparison of forensic staff and the general public

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    Background. Existing literature suggests that individuals with intellectual disability are not always held accountable for their actions and forensic staff are unlikely to report their sexually harmful behaviour. Method. This research explores how categorisation of an offender as having intellectual disability and the framing of an offence as planned or opportunistic, impacts upon ratings of risk, blame and intent by forensic staff and the general public. The impact of pre-existing attitudes towards sex offenders upon these ratings was also considered. Results. Differences are identified between participants’ ratings when the offender is categorised as having an intellectual disability. More positive attitudes are associated with lower ratings of several factors. Conclusions. Individuals with overly positive attitudes towards sex offenders could underestimate the risk posed by sex offenders with intellectual disability. These results are important to consider alongside the NHS Transforming Care Agenda

    Carbon Black Exposure Induces Alterations in Mitochondrial Morphology in Human Lung Cells: A Software-Based Quantitative Analysis

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    Nanoparticulates of pure carbon, carbon black (CB), are a common atmospheric pollutant in industrialized and heavily populated areas. They are produced primarily via combustion of fossil fuels, and represent a significant health hazard. They are known to worsen asthma and bronchitis when inhaled and to cause inflammation, heart dysfunction, and oxidative stress when incorporated into other organs. The key focal point of this work was to examine markers of stress signaling and cellular dysfunction when human bronchial epithelial cells (16HBE14o-) were exposed to CB particles ranging in size from 70 nm and averaging 130 nm in diameter. BrdU incorporation and DAPI staining studies revealed a 24-hour CB exposure (25 ug/ml and higher) to reduce rates of cell division and to significantly elevate percentages of cells exhibiting apoptotic nuclear morphology. Chronic exposure (24 days) of cells to low doses of CB (5 ug/ml) revealed a significant impact upon both cell division and survival. A central marker for stress signaling in these lung cells was elevation of reactive oxygen species, which rose within 12 hours of CB exposure, consistent with stress signals that induce mitochondrial apoptosis. Sirtuin 1, a stress regulated protein deacetylase in the cytosol, whose levels are known to be destabilized by ROS elevation in stressed cells, displayed no significant change following CB exposure at varied doses. Analysis of mitochondrial dynamics via fluorescence microscopy revealed clear changes in organization and morphology. HBE cells were treated with varying doses of CB, fixed, and analyzed via immunocytochemistry. Mitochondria were labelled using a Tom20 antibody conjugate (Alexa488), while microtubules were assessed with phalloidin (Alexa594). Using software developed in MatLab, mitochondria were analyzed for changes in mitochondrial size and localization. Significant changes were identified with regard to an increase in mitochondrial size, and strong trends were observed in an increased localization preference for the perinuclear region. A discussion of the link between elevated ROS levels and mitochondrial behavior will be discussed

    Dualism in action

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    We know what one dualist account of human action looks like, because Descartes gave us one. I want to explore the extent ot which presnet-day accounts of physical action are vulnerable to the charges that may be made against Descartes's dualist account. I once put forward an account of human action, and I have always maintained that my view about the basic shape of a correct ‘theory of aciton’ can be combined with a thoroughgoing opposition to dualism. But the possibility of the combination has been doubted and it will remain doubtful until we have a better understanding of what makes an account objectionably dualistic. In this paper, I hope to deflect some of the criticims aimed what I shall call my account, and to show that when they are turned onto their proper path their actual target is some physicalist accounts

    Phenotypic convergence of Menkes and Wilson disease.

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    Menkes disease is an X-linked multisystem disorder with epilepsy, kinky hair, and neurodegeneration caused by mutations in the copper transporter ATP7A. Other ATP7A mutations have been linked to juvenile occipital horn syndrome and adult-onset hereditary motor neuropathy.1,2 About 5%-10% of the patients present with "atypical Menkes disease" characterized by longer survival, cerebellar ataxia, and developmental delay.2 The intracellular copper transport is regulated by 2 P type ATPase copper transporters ATP7A and ATP7B. These proteins are expressed in the trans-Golgi network that guides copper to intracellular compartments, and in copper excess, it relocates copper to the plasma membrane to pump it out from the cells.3ATP7B mutations cause Wilson disease with dystonia, ataxia, tremor, and abnormal copper accumulation in the brain, liver, and other organs.4

    Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations.

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    PURPOSE: Mitochondrial disorders are a common cause of inherited metabolic disease and can be due to mutations affecting mitochondrial DNA or nuclear DNA. The current diagnostic approach involves the targeted resequencing of mitochondrial DNA and candidate nuclear genes, usually proceeds step by step, and is time consuming and costly. Recent evidence suggests that variations in mitochondrial DNA sequence can be obtained from whole-exome sequence data, raising the possibility of a comprehensive single diagnostic test to detect pathogenic point mutations. METHODS: We compared the mitochondrial DNA sequence derived from off-target exome reads with conventional mitochondrial DNA Sanger sequencing in 46 subjects. RESULTS: Mitochondrial DNA sequences can be reliably obtained using three different whole-exome sequence capture kits. Coverage correlates with the relative amount of mitochondrial DNA in the original genomic DNA sample, heteroplasmy levels can be determined using variant and total read depths, and-providing there is a minimum read depth of 20-fold-rare sequencing errors occur at a rate similar to that observed with conventional Sanger sequencing. CONCLUSION: This offers the prospect of using whole-exome sequence in a diagnostic setting to screen not only all protein coding nuclear genes but also all mitochondrial DNA genes for pathogenic mutations. Off-target mitochondrial DNA reads can also be used to assess quality control and maternal ancestry, inform on ethnic origin, and allow genetic disease association studies not previously anticipated with existing whole-exome data sets

    Advancing cluster randomised trials in children’s therapy: a survey of the acceptability of trial behaviours to therapists and parents

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    Background Randomised controlled trials of non-pharmacological interventions in children’s therapy are rare. This is, in part, due to the challenges of the acceptability of common trial designs to therapists and service users. This study investigated the acceptability of participation in cluster randomised controlled trials to therapists and service users. Methods A national electronic survey of UK occupational therapists, physiotherapists, speech and language therapists, service managers, and parents of children who use their services. Participants were recruited by NHS Trusts sharing a link to an online questionnaire with children’s therapists in their Trust and with parents via Trust social media channels. National professional and parent networks also recruited to the survey. We aimed for a sample size of 325 therapists, 30 service managers, and 60 parents. Trial participation was operationalised as three behaviours undertaken by both therapists and parents: agreeing to take part in a trial, discussing a trial, and sharing information with a research team. Acceptability of the behaviours was measured using an online questionnaire based on the Theoretical Framework of Acceptability constructs: affective attitude, self-efficacy, and burden. The general acceptability of trials was measured using the acceptability constructs of intervention coherence and perceived effectiveness. Data were collected from June to September 2020. Numerical data were analysed using descriptive statistics and textual data by descriptive summary. Results A total of 345 survey responses were recorded. Following exclusions, 249 therapists and 40 parents provided data which was 69.6% (289/415) of the target sample size. It was not possible to track the number of people invited to take the survey nor those who viewed, but did not complete, the online questionnaire for calculation of response rates. A completion rate (participants who completed the last page of the survey divided by the participants who completed the first, mandatory, page of the survey) of 42.9% was achieved. Of the three specified trial behaviours, 140/249 (56.2%) therapists were least confident about agreeing to take part in a trial. Therapists (135/249, 52.6%) reported some confidence they could discuss a trial with a parent and child at an appointment. One hundred twenty of 249 (48.2%) therapists reported confidence in sharing information with a research team through questionnaires and interviews or sharing routine health data. Therapists (140/249, 56.2%) felt that taking part in the trial would take a lot of effort and resources. Support and resources, confidence with intervention allocation, and sense of control and professional autonomy over clinical practice were factors that positively affected the acceptability of trials. Of the 40 parents, twelve provided complete data. Most parents (18/40, 45%) agreed that it was clear how trials improve children’s therapies and outcomes and that a cluster randomised trial made sense to them in their therapy situation (12/29, 30%). Conclusions Using trials to evaluate therapy interventions is, in principle, acceptable to therapists, but their willingness to participate in trials is variable. The willingness to participate may be particularly influenced by their views related to the burden associated with trials, intervention allocation, and professional autonomy
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