Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

SummaryBackgroundStaphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.MethodsIn this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.FindingsBetween Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% CI −7·0 to 4·3; hazard ratio 0·96, 0·68–1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3–4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).InterpretationAdjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.FundingUK National Institute for Health Research Health Technology Assessment.

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The increased use of Residual Hardware Devices (RHDs) in medicine combined with antimicrobial resistant-bacteria make it critical to reduce the number of RHD associated osteomyelitic infections. This paper proposes a surface treatment based on ionic emission to create an antibiotic environment that can significantly reduce RHD associated infections. The Kirby-Bauer agar gel diffusion technique was adopted to examine the antimicrobial efficacy of eight metals and their ionic forms against seven microbes commonly associated with osteomyelitis. Silver ions (Ag(+)) showed the most significant bactericidal efficacy. A second set of experiments, designed to identify the best configuration and operational parameters for Ag(+) based RHDs addressed current and ionic concentrations by identifying and optimizing parameters including amperage, cathode and anode length, separation between anode and cathode, and surface charge density. The system demonstrated an unparalleled efficacy. The concept was then implemented during in vitro testing of an antimicrobial hip implant, RHD.

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For two bamboo products, bamboo in its natural form (the culm) and in an industrial form (as a panel), the environmental impact was determined and compared to alternatives. This comparison was made using a model that uses data from Life Cycle Assessment (LCA), based on the use of these products in the Netherlands. The consequences of the application of bamboo culm in the building process of 5 bamboo building projects in Western Europe were also analysed.

Characterization of prior austenite grain size is important for understanding the microstructure-property relationships in steels. The prior austenite grain size plays an important role in defining the microstructural scale of low-temperature phases and the mechanical properties (e.g., strength, ductility, fracture toughness, etc.) of steels in the final product form. Moreover, in several failure analyses, the cracks are observed to propagate along the prior austenite grain boundaries (PAGBs). The delineation of PAGBs in steels of new composition can be quite challenging, as the response to a particular etching protocol is very sensitive to the chemical composition of steel. The objective of this study was to establish a methodology to delineate PAGBs in AF9628, a newly developed low-alloy high-performance steel. Several different etchants and etching techniques from the literature were evaluated. These methods were unsuccessful or had limited success in revealing PAGBs in AF9628. However, swab etching with a solution of 100 ml saturated aqueous picric acid and 0.5 g sodium dodecyl benzene sulfonate worked remarkably well for delineating the PAGBs in this steel. This etchant was found to have high selectivity, revealing PAGBs preferentially over packet, block, and sub-block boundaries.

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