Transcribing your own qualitative data

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Radiotherapy-related insufficiency fractures and bone mineral density: what is the connection?

Background: Radiotherapy-related insufficiency fractures (RRIFs) represent a common, burdensome consequence of pelvic radiotherapy. Their underlying mechanisms remain unclear, and data on the effect of osteoporosis are contradictor y, with limited studies assessing bone mineral density (BMD) by dual-energy x-ray absor ptiometry (DXA). Methods: BMD by DXA (Hologic) scan and fracture risk following pelvic R RIF were retrospectively assessed in 39 patients (median age 68 years) a t a tertiary cancer centre. Patient characteristics and treatment history are presented narratively; correlations were explored using univariate regression analyses. Results: Additional cancer treatments included chemotherapy (n = 31), surgery (n = 20) and brachytherapy (n = 19). Median interval between initiation of radiotherapy and RR IF was 11 (7.5–20.8) and that between RRIF and DXA 3 was (1–6) mon ths. Three patients had normal BMD, 16 had osteopenia and 16 osteoporosis, followin g World Health Organization classification. Four patients were –2). Median 10-year risk for hip and major osteoporotic fract ure was 3.1% (1.5–5.7) and 11.5% (7.1–13.8), respectively. Only 33.3% of patients had high fracture risk (hip fracture >4% and/or major osteoporotic >20%), and 31% fell abov e the intervention threshold per National Osteoporosis Guidelines Group (NOGG) gui dance (2017). Higher BMD was predicted by lower pelvic radiotherapy dose (only in L3 and L4), concomitant chemotherapy and higher body mass index. Conclusion: At the time of RRIF, most patients did not have osteoporosis, some had normal BMD and overall had low fracture risk. Whilst low BMD is a prob able risk factor, it is unlikely to be the main mechanism underlying RRIFs, and further studies are required to understand the predictive value of BMD

eHydrogenation: electrochemical Hydrogen-free hydrogenation

Hydrogenation reactions are staple transformations commonly used across scientific fields to synthesise pharmaceuticals, natural products, and various functional materials. However, the vast majority of these reactions require the use of a toxic and costly catalyst leading to unpractical, hazardous and often functionally limited conditions. Herein, we report a new, general, practical, efficient, mild and high-yielding hydrogen-free electrochemical method for the reduction of alkene, alkyne, nitro and azido groups. Finally, this method has been applied to deuterium labelling

Automatically Comparing Memory Consistency Models

A memory consistency model (MCM) is the part of a programming language or computer architecture specification that defines which values can legally be read from shared memory locations. Because MCMs take into account various optimisations employed by archi- tectures and compilers, they are often complex and counterintu- itive, which makes them challenging to design and to understand. We identify four tasks involved in designing and understanding MCMs: generating conformance tests, distinguishing two MCMs, checking compiler optimisations, and checking compiler mappings. We show that all four tasks are instances of a general constraint-satisfaction problem to which the solution is either a program or a pair of programs. Although this problem is intractable for automatic solvers when phrased over programs directly, we show how to solve analogous constraints over program executions, and then construct programs that satisfy the original constraints. Our technique, which is implemented in the Alloy modelling framework, is illustrated on several software- and architecture-level MCMs, both axiomatically and operationally defined. We automatically recreate several known results, often in a simpler form, including: distinctions between variants of the C11 MCM; a failure of the ‘SC-DRF guarantee’ in an early C11 draft; that x86 is ‘multi-copy atomic’ and Power is not; bugs in common C11 compiler optimisations; and bugs in a compiler mapping from OpenCL to AMD-style GPUs. We also use our technique to develop and validate a new MCM for NVIDIA GPUs that supports a natural mapping from OpenCL

Mixed-size concurrency: ARM, POWER, C/C++11, and SC

Previous work on the semantics of relaxed shared-memory concurrency has only considered the case in which each load reads the data of exactly one store. In practice, however, multiprocessors support mixed-size accesses, and these are used by systems software and (to some degree) exposed at the C/C++ language level. A semantic foundation for software, therefore, has to address them. We investigate the mixed-size behaviour of ARMv8 and IBM POWER architectures and implementations: by experiment, by developing semantic models, by testing the correspondence between these, and by discussion with ARM and IBM staff. This turns out to be surprisingly subtle, and on the way we have to revisit the fundamental concepts of coherence and sequential consistency, which change in this setting. In particular, we show that adding a memory barrier between each instruction does not restore sequential consistency. We go on to extend the C/C++11 model to support nonatomic mixed-size memory accesses, and prove the standard compilation scheme from C11 atomics to POWER remains sound. This is a necessary step towards semantics for real-world shared-memory concurrent code, beyond litmus tests

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus 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. METHODS: In 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. FINDINGS: Between 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). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets 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 4,261 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 signalling and cytokine-cytokine pathways, for which relevant therapies exist