87 research outputs found

    A Comparison of Damage Mechanisms in Scaled Static Indentation Tests on Glass and Carbon Fibre Laminates

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    Treatment for inclusion body myositis

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    Background Inclusion body myositis (IBM) is a late‐onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment. Objectives To assess the effects of treatment for IBM. Search methods On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials. Selection criteria We considered randomised or quasi‐randomised trials, including cross‐over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews. Data collection and analysis We used standard Cochrane methodological procedures. Main results The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta‐1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) ‐0.06, 95% CI ‐0.15 to 0.03) between IFN beta‐1a and placebo (moderate‐quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate‐quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low‐quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta‐analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re‐analysis. Other comparisons were also reported in single trials. An open trial of anti‐T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low‐quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events. Authors' conclusions Trials of interferon beta‐1a and MTX provided moderate‐quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low‐quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures

    A series of three cases of severe Clostridium difficile infection in Australia associated with a binary toxin producing clade 2 ribotype 251 strain

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    Three patients with severe Clostridium difficile infection (CDI) caused by an unusual strain of C. difficile, PCR ribotype (RT) 251, were identified in New South Wales, Australia. All cases presented with severe diarrhoea, two had multiple recurrences and one died following a colectomy. C. difficile RT251 strains were isolated by toxigenic culture. Genetic characterisation was performed using techniques including toxin gene profiling, PCR ribotyping, whole genome sequencing (WGS), in-silico multi-locus-sequence-typing (MLST) and core-genome single nucleotide variant (SNV) analyses. Antimicrobial susceptibility was determined using an agar incorporation method. In vitro toxin production was confirmed by Vero cell cytotoxicity assay and pathogenicity was assessed in a murine model of CDI. All RT251 isolates contained toxin A (tcdA), toxin B (tcdB) and binary toxin (cdtA and cdtB) genes. Core-genome analyses revealed the RT251 strains were clonal, with 0–5 SNVs between isolates. WGS and MLST clustered RT251 in the same evolutionary clade (clade 2) as RT027. Despite comparatively lower levels of in vitro toxin production, in the murine model RT251 infection resembled RT027 infection. Mice showed marked weight loss, severe disease within 48 h post-infection and death. All isolates were susceptible to metronidazole and vancomycin. Our observations suggest C. difficile RT251 causes severe disease and emphasise the importance of ongoing surveillance for new and emerging strains of C. difficile with enhanced virulence

    Assessment of flatness and symmetry of megavoltage x-ray beam with an electronic portal imaging device (EPID)

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    Copyright © 2002 ACPSEM. All rights reserved. The document attached has been archived with permission from the publisher.The input/output characteristics of the Wellhofer BIS 710 electronic portal imaging device (EPID) have been investigated to establish its efficacy for periodic quality assurance (QA) applications. Calibration curves have been determined for the energy fluence incident on the detector versus the pixel values. The effect of the charge coupled device (CCD) camera sampling time and beam parameters (such as beam field size, dose rate, photon energy) on the calibration have been investigated for a region of interest (ROI) around the central beam axis. The results demonstrate that the pixel output is a linear function of the incident exposure, as expected for a video-based electronic portal imaging system. The field size effects of the BIS 710 are similar to that of an ion chamber for smaller field sizes up to 10 x 10 cm2. However, for larger field sizes the pixel value increases more rapidly. Furthermore, the system is slightly sensitive to dose rate and is also energy dependent. The BIS 710 has been used in the current study to develop a QA procedure for measurements of flatness and symmetry of a linac x-ray beam. As a two-dimensional image of the radiation field is obtained from a single exposure of the BIS 710, a technique has been developed to calculate flatness and symmetry from a defined radiation area. The flatness and symmetry values obtained are different from those calculated conventionally from major axes only (inplane, crossplane). This demonstrates that the technique can pick up the "cold" and "hot" spots in the analysed area, providing thus more information about the radiation beam. When calibrated against the water tank measurements, the BIS 710 can be used as a secondary device to monitor the x-ray beam flatness and symmetry.G. Liu, T. van Doorn and E. Beza

    Towards the high-accuracy determination of the 238U fission cross section at the threshold region at CERN - N-TOF

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    The 238U fission cross section is an international standard beyond 2 MeV where the fission plateau starts. However, due to its importance in fission reactors, this cross-section should be very accurately known also in the threshold region below 2 MeV. The 238U fission cross section has been measured relative to the 235U fission cross section at CERN - n-TOF with different detection systems. These datasets have been collected and suitably combined to increase the counting statistics in the threshold region from about 300 keV up to 3 MeV. The results are compared with other experimental data, evaluated libraries, and the IAEA standards

    A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

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    We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

    Rationale, design and methodology of APPROACH-IS II: International study of patient-reported outcomes and frailty phenotyping in adults with congenital heart disease.

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    In recent years, patient-reported outcomes (PROs) have received increasing prominence in cardiovascular research and clinical care. An understanding of the variability and global experience of PROs in adults with congenital heart disease (CHD), however, is still lacking. Moreover, information on epidemiological characteristics and the frailty phenotype of older adults with CHD is minimal. The APPROACH-IS II study was established to address these knowledge gaps. This paper presents the design and methodology of APPROACH-IS II. APPROACH-IS II is a cross-sectional global multicentric study that includes Part 1 (assessing PROs) and Part 2 (investigating the frailty phenotype of older adults). With 53 participating centers, located in 32 countries across six continents, the aim is to enroll 8000 patients with CHD. In Part 1, self-report surveys are used to collect data on PROs (e.g., quality of life, perceived health, depressive symptoms, autonomy support), and explanatory variables (e.g., social support, stigma, illness identity, empowerment). In Part 2, the cognitive functioning and frailty phenotype of older adults are measured using validated assessments. APPROACH-IS II will generate a rich dataset representing the international experience of individuals in adult CHD care. The results of this project will provide a global view of PROs and the frailty phenotype of adults with CHD and will thereby address important knowledge gaps. Undoubtedly, the project will contribute to the overarching aim of improving optimal living and care provision for adults with CHD

    Representational predicaments for employees: Their impact on perceptions of supervisors\u27 individualized consideration and on employee job satisfaction

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    A representational predicament for a subordinate vis-à-vis his or her immediate superior involves perceptual incongruence with the superior about the subordinate\u27s work or work context, with unfavourable implications for the employee. An instrument to measure the incidence of two types of representational predicament, being neglected and negative slanting, was developed and then validated through an initial survey of 327 employees. A subsequent substantive survey with a fresh sample of 330 employees largely supported a conceptual model linking being neglected and negative slanting to perceptions of low individualized consideration by superiors and to low overall job satisfaction. The respondents in both surveys were all Hong Kong Chinese. Two case examples drawn from qualitative interviews illustrate and support the conceptual model. Based on the research findings, we recommend some practical exercises to use in training interventions with leaders and subordinates. © 2013 Copyright Taylor and Francis Group, LLC

    Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

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    A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved
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