The first maps of κd - the dust mass absorption coefficient - in nearby galaxies, with DustPedia

The dust mass absorption coefficient, κd is the conversion function used to infer physical dust masses from observations of dust emission. However, it is notoriously poorly constrained, and it is highly uncertain how it varies, either between or within galaxies. Here we present the results of a proof-of-concept study, using the DustPedia data for two nearby face-on spiral galaxies M 74 (NGC 628) and M 83 (NGC 5236), to create the first ever maps of κd in galaxies. We determine κd using an empirical method that exploits the fact that the dust-to-metals ratio of the interstellar medium is constrained by direct measurements of the depletion of gas-phase metals. We apply this method pixel-by-pixel within M 74 and M 83, to create maps of κd. We also demonstrate a novel method of producing metallicity maps for galaxies with irregularly sampled measurements, using the machine learning technique of Gaussian process regression. We find strong evidence for significant variation in κd. We find values of κd at 500 μm spanning the range 0.11-0.25 m^{2 kg^{-1}} in M 74, and 0.15-0.80 m^{2 kg^{-1}} in M 83. Surprisingly, we find that κd shows a distinct inverse correlation with the local density of the interstellar medium. This inverse correlation is the opposite of what is predicted by standard dust models. However, we find this relationship to be robust against a large range of changes to our method - only the adoption of unphysical or highly unusual assumptions would be able to suppress it

Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: an inter-laboratory study.

Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a 'one-stop' test for epidemiological and predictive AST results. Few published comparisons exist for the myriad analytical pipelines used for predicting AMR. To address this, we performed an inter-laboratory study providing sets of participating researchers with identical short-read WGS data from clinical isolates, allowing us to assess the reproducibility of the bioinformatic prediction of AMR between participants, and identify problem cases and factors that lead to discordant results. We produced ten WGS datasets of varying quality from cultured carbapenem-resistant organisms obtained from clinical samples sequenced on either an Illumina NextSeq or HiSeq instrument. Nine participating teams ('participants') were provided these sequence data without any other contextual information. Each participant used their choice of pipeline to determine the species, the presence of resistance-associated genes, and to predict susceptibility or resistance to amikacin, gentamicin, ciprofloxacin and cefotaxime. We found participants predicted different numbers of AMR-associated genes and different gene variants from the same clinical samples. The quality of the sequence data, choice of bioinformatic pipeline and interpretation of the results all contributed to discordance between participants. Although much of the inaccurate gene variant annotation did not affect genotypic resistance predictions, we observed low specificity when compared to phenotypic AST results, but this improved in samples with higher read depths. Had the results been used to predict AST and guide treatment, a different antibiotic would have been recommended for each isolate by at least one participant. These challenges, at the final analytical stage of using WGS to predict AMR, suggest the need for refinements when using this technology in clinical settings. Comprehensive public resistance sequence databases, full recommendations on sequence data quality and standardization in the comparisons between genotype and resistance phenotypes will all play a fundamental role in the successful implementation of AST prediction using WGS in clinical microbiology laboratories

Stabilization of α-conotoxin AuIB: Influences of disulfide connectivity and backbone cyclization

alpha-Conotoxins are peptides isolated from the venom ducts of cone snails that target nicotinic acetylcholine receptors (nAChRs). They are valuable pharmacological tools and have potential applications for treating a range of conditions in humans, including pain. However, like all peptides, conotoxins are susceptible to degradation, and to enhance their therapeutic potential it is important to elucidate the factors contributing to instability and to develop approaches for improving stability. AuIB is a unique member of the alpha-conotoxin family because the nonnative "ribbon'' disulfide isomer exhibits enhanced activity at the nAChR in rat parasympathetic neurons compared with the native "globular'' isomer. Here we show that the ribbon isomer of AuIB is also more resistant to disulfide scrambling, despite having a nonnative connectivity and flexible structure. This resistance to disulfide scrambling does not correlate with overall stability in serum because the ribbon isomer is degraded in human serum more rapidly than the globular isomer. Cyclization via the joining of the N- and C-termini with peptide linkers of four to seven amino acids prevented degradation of the ribbon isomer in serum and stabilized the globular isomers to disulfide scrambling. The linker length used for cyclization strongly affected the relative proportions of the disulfide isomers produced by oxidative folding. Overall, the results of this study provide important insights into factors influencing the stability and oxidative folding of alpha-conotoxin AuIB and might be valuable in the design of more stable antagonists of nAChRs. Antioxid. Redox Signal. 14, 87-95

Research protocol: investigating the feasibility of a group self-management intervention for stroke (the GUSTO study)

Background: Life after stroke can be an ongoing struggle with over half of all survivors reporting unmet emotional and social needs. In the United Kingdom's (UK) national clinical guidelines for stroke, self-management is suggested as one approach which can support long-term needs. In the UK NHS, self-management interventions are delivered in various ways. Regardless of the delivery mechanism, a tailored approach and ways to integrate peer support are advocated. Group delivery offers a platform for peer support and has the potential to remain individualised. However, before the efficacy of a group self-management intervention can be tested, the feasibility must be explored. This research investigates the feasibility of a GroUp Self-management intervention for sTrOke (GUSTO). Methods: A randomised waitlist control design will be used to investigate the feasibility of a group self-management intervention adapted from an existing one-to-one intervention called Bridges. A mixed methods approach will be used. Qualitative work will capture participant experience, while quantitative work will allow preliminary comparison between the intervention and waitlist groups (between subjects) and pre-post intervention measures (within subjects). Interviews will be conducted with stroke survivors and focus groups with family and friends to assess acceptability of the intervention. Discussion: There is a growing interest in group-based self-management interventions for stroke as a method of supporting stroke survivors' ongoing unmet needs. This is an area with limited research to date. This study will inform design of a fully powered trial which would assess the efficacy of a group self-management intervention following stroke. Trial registration: ISRCTN19867168

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Increased consumption of fruit and vegetables for the primary prevention of cardiovascular diseases

There is increasing evidence that high consumption of fruit and vegetables is beneficial for cardiovascular disease (CVD) prevention

Predicting fitness to practise events in international medical graduates who registered as UK doctors via the Professional and Linguistic Assessments Board (PLAB) system: a national cohort study

Background International medical graduates working in the UK are more likely to be censured in relation to fitness to practise compared to home graduates. Performance on the General Medical Council’s (GMC’s) Professional and Linguistic Assessments Board (PLAB) tests and English fluency have previously been shown to predict later educational performance in this group of doctors. It is unknown whether the PLAB system is also a valid predictor of unprofessional behaviour and malpractice. The findings would have implications for regulatory policy. Methods This was an observational study linking data relating to fitness to practise events (referral or censure), PLAB performance, demographic variables and English language competence, as evaluated via the International English Language Test System (IELTS). Data from 27,330 international medical graduates registered with the GMC were analysed, including 210 doctors who had been sanctioned in relation to at least one fitness to practise issue. The main outcome was risk of eventual censure (including a warning). Results The significant univariable educational predictors of eventual censure (versus no censures or referrals) were lower PLAB part 1 (hazard ratio [HR], 0.99; 95% confidence interval, 0.98 to 1.00) and part 2 scores (HR, 0.94; 0.91 to 0.97) at first sitting, multiple attempts at both parts of the PLAB, lower IELTS reading (HR, 0.79; 0.65 to 0.94) and listening scores (HR, 0.76; 0.62 to 0.93) and higher IELTS speaking scores (HR, 1.28; 1.04 to 1.57). Multiple resits at either part of the PLAB and higher IELTS speaking score (HR, 1.49; 1.20 to 1.84) were also independent predictors of censure. We estimated that the proposed limit of four attempts at both parts of the PLAB would reduce the risk in this entire group by only approximately two censures per 5 years in this group of doctors. Conclusions Making the PLAB, or any replacement assessment, more stringent and raising the required standards of English reading and listening may result in fewer fitness to practice events in international medical graduates. However, the number of PLAB resits permitted would have to be further capped to meaningfully impact the risk of sanctions in this group of doctor

Prolonged dopamine signalling in striatum signals proximity and value of distant rewards

Predictions about future rewarding events have a powerful influence on behaviour. The phasic spike activity of dopamine-containing neurons, and corresponding dopamine transients in the striatum, are thought to underlie these predictions, encoding positive and negative reward prediction errors. However, many behaviours are directed towards distant goals, for which transient signals may fail to provide sustained drive. Here we report an extended mode of reward-predictive dopamine signalling in the striatum that emerged as rats moved towards distant goals. These dopamine signals, which were detected with fast-scan cyclic voltammetry (FSCV), gradually increased or—in rare instances—decreased as the animals navigated mazes to reach remote rewards, rather than having phasic or steady tonic profiles. These dopamine increases (ramps) scaled flexibly with both the distance and size of the rewards. During learning, these dopamine signals showed spatial preferences for goals in different locations and readily changed in magnitude to reflect changing values of the distant rewards. Such prolonged dopamine signalling could provide sustained motivational drive, a control mechanism that may be important for normal behaviour and that can be impaired in a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R01 MH060379)National Parkinson Foundation (U.S.)Cure Huntington’s Disease Initiative, Inc. (Grant A-5552)Stanley H. and Sheila G. Sydney Fun

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal