320 research outputs found

    Withernam: A Legal Practical Joke of Sir Thomas More

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    Awareness of the need for safe storage of Methadone at home is not improved by the use of protocols on recording information giving

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    <p>Abstract</p> <p>Background</p> <p>Methadone is a synthetic, narcotic analgesic used in the treatment of drug misuse. Tragedies involving children being poisoned by the accidental ingestion of methadone are no longer a rare occurrence. Following an audit of the effectiveness of the provision and recall of information to patients attending an NHS Methadone Clinic a protocol was introduced to ensure that staff documented the provision of such information and patients gave a written confirmation that they had received the information.</p> <p>Methods</p> <p>The study was undertaken in the setting of an NHS methadone clinic with the aim of re- auditing the storage of methadone at home following the introduction of the new protocols. 174 patients completed an anonymous questionnaire regarding where they store methadone at home and whether they recall being given advice about safe storage. Community pharmacists were contacted by telephone to assess the level of advice given to methadone patients regarding safety.</p> <p>Results</p> <p>Only 49 (28.2%) patients recalled being given advice about safe storage, 24 (13.8%) recalled that information was provided by clinic staff. 170 (97.7%) patients regard methadone as being dangerous. (28.2%). Methadone is most commonly stored in a cupboard (37.9%). All methadone is dispensed in a bottle with a child resistant cap on it. All patients reported they stored their methadone in the original bottle provided by the pharmacist.</p> <p>Conclusion</p> <p>Recall of information on safety issues is very poor. Provision of written as well as verbal information is needed. The use of printed safety information cards which patients can take away for future reference may be of use. It is the responsibility of health professionals to ensure they provide information and advice to methadone users on the safe storage of their methadone at home.</p

    Being a quantitative interviewer: qualitatively exploring interviewers' experiences in a longitudinal cohort study

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    <p>Abstract</p> <p>Background</p> <p>Many studies of health outcomes rely on data collected by interviewers administering highly-structured (quantitative) questionnaires to participants. Little appears to be known about the experiences of such interviewers. This paper explores interviewer experiences of working on a longitudinal study in New Zealand (the Prospective Outcomes of injury Study - POIS). Interviewers administer highly-structured questionnaires to participants, usually by telephone, and enter data into a secure computer program. The research team had expectations of interviewers including: consistent questionnaire administration, timeliness, proportions of potential participants recruited and an empathetic communication style. This paper presents results of a focus group to qualitatively explore with the team of interviewers their experiences, problems encountered, strategies, support systems used and training.</p> <p>Methods</p> <p>A focus group with interviewers involved in the POIS interviews was held; it was audio-recorded and transcribed. The analytical method was thematic, with output intended to be descriptive and interpretive.</p> <p>Results</p> <p>Nine interviewers participated in the focus group (average time in interviewer role was 31 months). Key themes were: 1) the positive aspects of the quantitative interviewer role (i.e. relationships and resilience, insights gained, and participants' feedback), 2) difficulties interviewers encountered and solutions identified (i.e. stories lost or incomplete, forgotten appointments, telling the stories, acknowledging distress, stories reflected and debriefing and support), and 3) meeting POIS researcher expectations (i.e. performance standards, time-keeping, dealing exclusively with the participant and maintaining privacy).</p> <p>Conclusions</p> <p>Interviewers demonstrated great skill in the way they negotiated research team expectations whilst managing the relationships with participants. Interviewers found it helpful to have a research protocol in place in the event of sensitive situations - this appeared to alleviate the pressure on interviewers to carry the burden of responsibility. Interviewers are employed to scientifically gather quantitative data, yet their effectiveness relies largely on their humanity. We propose that the personal connection generated between the interviewers and participants was important, and enabled successful follow-up rates for the study. The enjoyment of these relationships was crucial to interviewers and helped balance the negative aspects of their role. Our results suggest that experienced quantitative interviewers endeavour, as do many qualitative researchers, to carefully and respectfully negotiate the requirements of the interview within a relationship they form with participants: being sensitive to the needs of participants and respectful of their wishes - and establishing an ethical relationship.</p

    The dynastic history of the Hoysala kings.

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    The object of the Thesis is to demonstrate from all available sources the origin, rise, prosperity and decline of the Hoysala dynasty, and to explain its sudden disappearance, into which questions no sufficient investigation has hitherto been made. The information has been derived from the very numerous inscriptions in Old Kannada, Sanskrit, Tamil and Telugu, available both in published and unpublished form; from various literary sources in each of the above-mentioned languages; from Persian chronicles, including the valuable Eutuh us balatin of' Isami never before investigated from the point of view of hysorean history; and from the works of Arabic geographers. Attention has been paid to legendary and semi-legendary material, largely collected by Europeans during the nineteenth century and existing for the most part in unpublished form. The whole political history of the dynasty has been illuminated by a thorough geographical investigation of the limits of the kingdom throughout the period of three centuries, and the thesis is illustrated by a series of maps, which facilitate a Knowledge of the extent of Hoysa4.a power and influence to a greater degree of precision than has been possible hitherto in the case of any Hindu dynasty. The main body of the thesis describes the origin of the family from the chiefs of a hill-tribe, obscure but enjoying certain natural advantages; its early rise at the expense of neighbouring dynasties; its prowess against the Cola, and its period of apprenticeship under the Calukya; its subsequent hostility towards and successes against the latter and against his successor the Kalacuri; and its eventual triumph during the ascendancy of the Yadava. A aeries of reverses than led to an aberration under Ballala II, consisting in the commencemeit of a series of interferences in the affairs of the southern Cola and Paridya kingdoms, which, apparently confirming, in fact undermined the stability of the Hoysala empire. A civil war between the sons of Somesvara stimulated the decline & vain attempts were made by Ballala III to stave off the disruption of his kingdom before a sudden blow at the hands of the Muslims made it a suitable object for the ambitions of the Hindi Vijayanagara family. The thesis is accompanied by a brief description of the administrative methods employed during the period, together with lists of officials, which, it is hope, will enable the epigraphic material which is constantly being discovered to be thereby more easily dated, collated and utilized. Throughout the thesis further light is thrown on the political history of twenty contemporary dynasties

    Disentangling Holocene Climate Change and Human Impact from Palaeoenvironmental Records from the Scottish West Coast

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    Phases of rapid climate change throughout the early to mid Holocene coincide with regional human population expansion in Scotland and North-West Europe. Palaeoenvironmental signals of climate and anthropogenically driven vegetation changes can therefore be difficult to separate. To identify whether it is possible to distinguish potential signatures of anthropogenic clearance and agricultural activities from climatic drivers of landscape change in the early to mid Holocene in the region, two topographically contrasting sites on the Isle of Skye and the Isle of Bute were investigated. A multiproxy approach including pollen, spore, microcharcoal, loss on ignition and particle size analyses was adopted to investigate changes in vegetation and climate. There are subtle indications that the 8200 cal BP climate event had an effect on the vegetation composition at both sites. Signals of anthropogenic woodland clearance are apparent early in the sequence at Peat Hill (Bute), indicated by a peak in Poaceae (grass) cereal-type (7–14%) at 8592–8793 cal BP, alongside a decrease in arboreal pollen, which could not be associated with a regional episode of climate change. Early to mid Holocene vegetation changes at Lyndale House (Skye) occur alongside regional changes in precipitation and sea level and therefore cannot be readily separated. Continuous declines in arboreal pollen from ca. 5000 cal BP at Lyndale House indicates the onset of widespread clearance on Skye via felling and sustained grazing pressures

    Outcomes linked to eligibility for stem cell transplantation trials in diffuse cutaneous systemic sclerosis

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    Objectives: The aim of this study was to explore outcomes in a cohort of diffuse cutaneous systemic sclerosis (dcSSc) patients fulfilling eligibility criteria for stem cell transplantation (SCT) studies but receiving standard immunosuppression. Methods: From a large single-centre dcSSc cohort (n = 636), patients were identified using the published SCT trials’ inclusion criteria. Patients meeting the trials’ exclusion criteria were excluded. Results: Of the 227 eligible patients, 214 met the inclusion criteria for ASTIS, 82 for SCOT and 185 for the UPSIDE trial, and 66 were excluded based on age > 65 years, low DLco, pulmonary hypertension or creatinine clearance <40ml/min. The mean follow-up time was 12 years (SD 7). Among the eligible patients, 103 (45.4%) died. Survival was 96% at 2-, 88% at 5-, 73% at 10- and 43% at 20 years. Compared with this ‘SCT-eligible’ cohort, those patients who would have been excluded from SCT trials had a worse long-term survival (97% at 2-, 77% at 5-, 52% at 10- and 15% at 20 years, log rank p< 0.001). Excluded patients also had a significantly worse long-term event free survival. Hazard of death was higher in patients with higher age at onset (HR 1.05, p< 0.001), higher ESR at baseline (HR 1.01, p= 0.025) and males (HR 2.12, p= 0.008). Conclusion: SCT inclusion criteria identify patients with poor outcome despite current best practice treatment. Patients meeting the inclusion criteria for SCT but who would have been excluded from the trials because of age, pulmonary hypertension, poor kidney function or DLco <40%, had worse outcomes

    Why people attend science festivals : interests, motivations and self-reported benefits of public engagement with research

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    As a form of public engagement, science festivals have rapidly expanded in size and number over recent years. However, as with other domains of informal public engagement that are not linked to policy outcomes, existing research does not fully address science festivals’ impacts and popularity.This study adduces evidence from surveys and focus groups to elucidate the perspectives of visitors at a large UK science festival. Results show that visitors value the opportunities science festivals afford to interact with scientific researchers and to encounter different types of science engagement aimed at adults, children and families. The most significant self-reported impact of attending a science festival was the development of increased interest and curiosity about new areas of scientific knowledge within a socially stimulating and enjoyable setting

    TGFβ activation primes canonical Wnt signaling through the downregulation of AXIN2

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    OBJECTIVES: Aberrant activation of Wnt signaling has been observed in systemic sclerosis (SSc) affected tissues. This study aimed to determine the role of transforming growth factor (TGF)β in driving the increased Wnt signaling, through modulation of AXIN2, a critical regulator of Wnt canonical pathway. METHODS: Canonical Wnt signaling activation was analyzed by TOPFlash TCF/LEF promoter assays. AXIN2 was evaluated in vitro by analysis of AXIN2 primary/mature transcripts expression and decay, TβRI blockade, siRNA-mediated TTP-1 depletion and through XAV-939-mediated AXIN2 stabilisation. In vivo, Axin2 mRNA and protein expression was determined in skin and lung biopsies from TβRIIΔk-fib transgenic mice and littermate controls. RESULTS: SSc fibroblasts display increased response to canonical Wnt ligands despite basal levels of Wnt signaling comparable to healthy control (HC) fibroblasts in vitro. Notably, we show that SSc fibroblasts express reduced basal expression of AXIN2, which is caused by endogenous TGFβ-dependent increase of AXIN2 mRNA decay. Accordingly, we observed that TGFβ decreased AXIN2 expression both in vitro in HC fibroblasts and in vivo, employing TβRIIΔk-fib transgenic mice. Additionally, we demonstrate by AXIN2 loss and gain of function experiments, that the TGFβ-induced increased response to Wnt activation characteristic of SSc fibroblasts is dependent on reduced AXIN2 bioavailability. CONCLUSIONS: This study highlights the importance of reduced AXIN2 bioavailability in mediating the increased canonical Wnt response observed in SSc fibroblasts. This novel mechanism extends our understanding of the processes involved in Wnt/β-catenin-driven pathology and supports the rationale for targeting the TGFβ pathway to regulate the aberrant Wnt signaling observed during fibrosis. This article is protected by copyright. All rights reserved

    Integrated analysis of dermal blister fluid proteomics and genome-wide skin gene expression in systemic sclerosis: an observational study

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    Background: Skin fibrosis is a hallmark feature of systemic sclerosis. Skin biopsy transcriptomics and blister fluid proteomics give insight into the local environment of the skin. We have integrated these modalities with the aim of developing a surrogate for the modified Rodnan skin score (mRSS), using candidate genes and proteins from the skin and blister fluid as anchors to identify key analytes in the plasma. Methods: In this single-centre, prospective observational study at the Royal Free Campus, University College London, London, UK, transcriptional and proteomic analyses of blood and skin were performed in a cohort of patients with systemic sclerosis (n=52) and healthy controls (n=16). Weighted gene co-expression network analysis was used to explore the association of skin transcriptomics data, clinical traits, and blister fluid proteomic results. Candidate hub analytes were identified as those present in both blister and skin gene sets (modules), and which correlated with plasma (module membership >0·7 and gene significance >0·6). Hub analytes were confirmed using RNA transcript data obtained from skin biopsy samples from patients with early diffuse cutaneous systemic sclerosis at 12 months. Findings: We identified three modules in the skin, and two in blister fluid, which correlated with a diagnosis of early diffuse cutaneous systemic sclerosis. From these modules, 11 key hub analytes were identified, present in both skin and blister fluid modules, whose transcript and protein levels correlated with plasma protein concentrations, mRSS, and showed statistically significant correlation on repeat transcriptomic samples taken at 12 months. Multivariate analysis identified four plasma analytes as correlates of mRSS (COL4A1, COMP, SPON1, and TNC), which can be used to differentiate disease subtype. Interpretation: This unbiased approach has identified potential biological candidates that might be drivers of local skin pathogenesis in systemic sclerosis. By focusing on measurable analytes in the plasma, we generated a promising composite plasma protein biomarker that could be used for assessment of skin severity, case stratification, and as a potential outcome measure for clinical trials and practice. Once fully validated, the biomarker score could replace a clinical score such as the mRSS, which carries substantial variability. Funding: GlaxoSmithKline and UK Medical Research Council
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