979 research outputs found

    Response to: "Renal biopsies should be performed whenever treatment strategies depend on renal involvement"

    Get PDF
    We thank Chemouny et al for their letter and concur with their conclusions. As we state (1): “A positive biopsy for AAV is helpful when considering an initial diagnosis or recurrent disease.” In our view, renal biopsy is important to establish diagnosis and may also provide an indication of prognostic trajectory and although existing classification systems need further validation, changes like glomerular sclerosis have obvious adverse prognostic value for patients with AAV (2-4). The Delphi process, for the scope of the current recommendations, identified the role of biopsy at both diagnosis and follow-up as an important item for update. Histopathological evidence of vasculitis, such as pauci-immune glomerulonephritis or necrotising vasculitis in any organ, remains the gold standard for diagnostic purposes. The likely diagnostic yield varies and is dependent on the organ targeted and in patients with GPA with renal involvement can be as high as 91.5% from renal biopsy (5). As Chemouny and colleagues have demonstrated, a renal biopsy was definitive in determining their management decisions. However during follow-up when relapses occur, it may be prudent to consider judicious use of further kidney biopsy during suspected renal relapse since the cause for acute kidney injury may be due to another cause other than AAV (6). Kind regards, M Yates, C Mukhtyar and DR Jayne on behalf of co-authors

    Predicting the effect of voids on mechanical properties of woven composites.

    Get PDF
    An accurate yet easy to use methodology for determining the effective mechanical properties of woven fabric reinforced composites is presented. The approach involves generating a representative unit cell geometry based on randomly selected 2D orthogonal slices from a 3D X-ray micro-tomographic scan. Thereafter, the finite element mesh is generated from this geometry. Analytical and statistical micromechanics equations are then used to calculate effective input material properties for the yarn and resin regions within the FE mesh. These analytical expressions account for the effect of resin volume fraction within the yarn (due to infiltration during curing) as well as the presence of voids within the composite. The unit cell model is then used to evaluate the effective properties of the composite.DelPHE 780 Project funded by UK Department of International Development (DFID), through British Council managed DelPHE scheme

    Bearing performance and damage characteristics of rein-infused thermoplastic 3D woven composites bolted joints

    Get PDF
    This paper presents a comprehensive study on the single-bolt single-shear (SBSS) and double-bolt single shear (DBSS) lap joint performance of resin-infused thermoplastic 3D fibre-reinforced composite (FRC) in on-axis (0°and 90°) and off-axis (45°) configurations. The bearing performance and failure mechanisms are compared with thermoset 3D-FRC. The resin-infused thermoplastic 3D-FRC bolted joint shows improved bearing performance in terms of higher ultimate bearing strength, stiffness loss strength, and reduced damage severity than its thermoset counterpart. Additionally, this paper presents a detailed study on the intermediate and final failure mechanisms, obtained from scanning electron microscopy of the interrupted and ultimate bearing tests, to understand damage progression in SBSS and BDSS lap joints at the submicron level. The major damage characteristics of a thermoplastic 3D-FRC bolted joint include plastic deformation and plastic kinking at the hole front tip, which improve the bearing capacity and reduce stress concentration, damage severity, and its deleterious effects

    Effectiveness of e-learning in continuing medical education for occupational physicians

    Get PDF
    Background Within a clinical context e-learning is comparable to traditional approaches of continuing medical education (CME). However, the occupational health context differs and until now the effect of postgraduate e-learning among occupational physicians (OPs) has not been evaluated

    Bounds for Lepton Flavor Violation and the Pseudoscalar Higgs in the General Two Higgs Doublet Model using g2g-2 muon factor

    Full text link
    Current experimental data from the g2g-2 muon factor, seems to show the necessity of physics beyond the Standard Model (SM), since the difference between SM and experimental predictions is 2.6σ\sigma . In the framework of the General Two Higgs Doublet Model (2HDM), we calculate the muon anomalous magnetic moment to get lower and upper bounds for the Flavour Changing (FC) Yukawa couplings in the leptonic sector. We also obtain lower bounds for the mass of the pseudoscalar Higgs (mA0m_{A^0}) as a function of the parameters of the model.Comment: 12 pages, RevTex4, 5 figures. Improved presentation, updated experimental data, amplified analysis, new figures added. Subbmited to Phys. Rev.

    Snapshot PCR surveillance for SARS-CoV-2 in hospital staff in England

    Get PDF
    Background: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. / Methods: Cross-sectional ‘snapshot’ survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. / Findings: Point prevalence of SARS-CoV-2 carriage across the sites was 2.0% (23/1152 participants), median cycle threshold value 35.70 (IQR:32.42–37.57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3.46, 95%CI 1.38–8.67; p = 0.008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. / Interpretation: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests. / Funding: Public Health England

    Integrated analysis of microRNA and mRNA expression and association with HIF binding reveals the complexity of microRNA expression regulation under hypoxia.

    Get PDF
    BACKGROUND: In mammalians, HIF is a master regulator of hypoxia gene expression through direct binding to DNA, while its role in microRNA expression regulation, critical in the hypoxia response, is not elucidated genome wide. Our aim is to investigate in depth the regulation of microRNA expression by hypoxia in the breast cancer cell line MCF-7, establish the relationship between microRNA expression and HIF binding sites, pri-miRNA transcription and microRNA processing gene expression. METHODS: MCF-7 cells were incubated at 1% Oxygen for 16, 32 and 48 h. SiRNA against HIF-1α and HIF-2α were performed as previously published. MicroRNA and mRNA expression were assessed using microRNA microarrays, small RNA sequencing, gene expression microarrays and Real time PCR. The Kraken pipeline was applied for microRNA-seq analysis along with Bioconductor packages. Microarray data was analysed using Limma (Bioconductor), ChIP-seq data were analysed using Gene Set Enrichment Analysis and multiple testing correction applied in all analyses. RESULTS: Hypoxia time course microRNA sequencing data analysis identified 41 microRNAs significantly up- and 28 down-regulated, including hsa-miR-4521, hsa-miR-145-3p and hsa-miR-222-5p reported in conjunction with hypoxia for the first time. Integration of HIF-1α and HIF-2α ChIP-seq data with expression data showed overall association between binding sites and microRNA up-regulation, with hsa-miR-210-3p and microRNAs of miR-27a/23a/24-2 and miR-30b/30d clusters as predominant examples. Moreover the expression of hsa-miR-27a-3p and hsa-miR-24-3p was found positively associated to a hypoxia gene signature in breast cancer. Gene expression analysis showed no full coordination between pri-miRNA and microRNA expression, pointing towards additional levels of regulation. Several transcripts involved in microRNA processing were found regulated by hypoxia, of which DICER (down-regulated) and AGO4 (up-regulated) were HIF dependent. DICER expression was found inversely correlated to hypoxia in breast cancer. CONCLUSIONS: Integrated analysis of microRNA, mRNA and ChIP-seq data in a model cell line supports the hypothesis that microRNA expression under hypoxia is regulated at transcriptional and post-transcriptional level, with the presence of HIF binding sites at microRNA genomic loci associated with up-regulation. The identification of hypoxia and HIF regulated microRNAs relevant for breast cancer is important for our understanding of disease development and design of therapeutic interventions
    corecore