Characterizing Scales of Genetic Recombination and Antibiotic Resistance in Pathogenic Bacteria Using Topological Data Analysis

Pathogenic bacteria present a large disease burden on human health. Control of these pathogens is hampered by rampant lateral gene transfer, whereby pathogenic strains may acquire genes conferring resistance to common antibiotics. Here we introduce tools from topological data analysis to characterize the frequency and scale of lateral gene transfer in bacteria, focusing on a set of pathogens of significant public health relevance. As a case study, we examine the spread of antibiotic resistance in Staphylococcus aureus. Finally, we consider the possible role of the human microbiome as a reservoir for antibiotic resistance genes.Comment: 12 pages, 6 figures. To appear in AMT 2014 Special Session on Advanced Methods of Interactive Data Mining for Personalized Medicin

Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation

OBJECTIVES: To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care. DESIGN: Systematic review of current evidence and economic modelling. DATA SOURCES: Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing self-monitoring versus standard clinical care in people with different clinical conditions. Self-monitoring included both self-management (patients conducted the tests and adjusted their treatment according to an algorithm) and self-testing (patients conducted the tests, but received treatment recommendations from a clinician). Various point-of-care coagulometers were considered. RESULTS: 26 RCTs (8763 participants) were included. Both self-management and self-testing were as safe as standard care in terms of major bleeding events (RR 1.08, 95% CI 0.81 to 1.45, p=0.690, and RR 0.99, 95% CI 0.80 to 1.23, p=0.92, respectively). Self-management was associated with fewer thromboembolic events (RR 0.51, 95% CI 0.37 to 0.69, p </= 0.001) and with a borderline significant reduction in all-cause mortality (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) than standard care. Self-testing resulted in a modest increase in time in therapeutic range compared with standard care (weighted mean difference, WMD 4.4%, 95% CI 1.71 to 7.18, p=0.02). Total health and social care costs over 10 years were pound7324 with standard care and pound7326 with self-monitoring (estimated quality adjusted life year, QALY gain was 0.028). Self-monitoring was found to have approximately 80% probability of being cost-effective compared with standard care applying a ceiling willingness-to-pay threshold of pound20,000 per QALY gained. Within the base case model, applying the pooled relative effect of thromboembolic events, self-management alone was highly cost-effective while self-testing was not. CONCLUSIONS: Self-monitoring appears to be a safe and cost-effective option. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013004944

What do young athletes implicitly understand about psychological skills?

One reason sport psychologists teach psychological skills is to enhance performance in sport; but the value of psychological skills for young athletes is questionable because of the qualitative and quantitative differences between children and adults in their understanding of abstract concepts such as mental skills. To teach these skills effectively to young athletes, sport psychologists need to appreciate what young athletes implicitly understand about such skills because maturational (e.g., cognitive, social) and environmental (e.g., coaches) factors can influence the progressive development of children and youth. In the present qualitative study, we explored young athletes’ (aged 10–15 years) understanding of four basic psychological skills: goal setting, mental imagery, self-talk, and relaxation. Young athletes (n = 118: 75 males and 43 females) completed an open-ended questionnaire to report their understanding of these four basic psychological skills. Compared with the older youth athletes, the younger youth athletes were less able to explain the meaning of each psychological skill. Goal setting and mental imagery were better understood than self-talk and relaxation. Based on these findings, sport psychologists should consider adapting interventions and psychoeducational programs to match young athletes’ age and developmental level

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

SN 2018bsz: a Type I superluminous supernova with aspherical circumstellar material

We present a spectroscopic analysis of the most nearby Type I superluminous supernova (SLSN-I), SN 2018bsz. The photometric evolution of SN 2018bsz has several surprising features, including an unusual pre-peak plateau and evidence for rapid formation of dust ≳200 d post-peak. We show here that the spectroscopic and polarimetric properties of SN 2018bsz are also unique. While its spectroscopic evolution closely resembles SLSNe-I, with early O II absorption and C II P Cygni profiles followed by Ca, Mg, Fe, and other O features, a multi-component Hα profile appearing at ∼30 d post-maximum is the most atypical. The Hα is at first characterised by two emission components, one at ∼+3000 km s−1 and a second at ∼ − 7500 km s−1, with a third, near-zero-velocity component appearing after a delay. The blue and central components can be described by Gaussian profiles of intermediate width (FWHM ∼ 2000–6000 km s−1), but the red component is significantly broader (FWHM ≳ 10 000 km s−1) and Lorentzian. The blue Hα component evolves towards a lower-velocity offset before abruptly fading at ∼ + 100 d post-maximum brightness, concurrently with a light curve break. Multi-component profiles are observed in other hydrogen lines, including Paβ, and in lines of Ca II and He I. Spectropolarimetry obtained before (10.2 d) and after (38.4 d) the appearance of the H lines shows a large shift on the Stokes Q – U plane consistent with SN 2018bsz undergoing radical changes in its projected geometry. Assuming the supernova is almost unpolarised at 10.2 d, the continuum polarisation at 38.4 d reaches P ∼ 1.8%, implying an aspherical configuration. We propose that the observed evolution of SN 2018bsz can be explained by highly aspherical, possibly disk-like, circumstellar material (CSM) with several emitting regions. After the supernova explosion, the CSM is quickly overtaken by the ejecta, but as the photosphere starts to recede, the different CSM regions re-emerge, producing the peculiar line profiles. Based on the first appearance of Hα, we can constrain the distance of the CSM to be less than ∼6.5 × 1015 cm (430 AU), or even lower (≲87 AU) if the pre-peak plateau is related to an eruption that created the CSM. The presence of CSM has been inferred previously for other SLSNe-I, both directly and indirectly. However, it is not clear whether the rare properties of SN 2018bsz can be generalised for SLSNe-I, for example in the context of pulsational pair instability, or whether they are the result of an uncommon evolutionary path, possibly involving a binary companion

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

A nearby super-luminous supernova with a long pre-maximum & "plateau" and strong C II features

Context. Super-luminous supernovae (SLSNe) are rare events defined as being significantly more luminous than normal terminal stellar explosions. The source of the additional power needed to achieve such luminosities is still unclear. Discoveries in the local Universe (i.e. z < 0.1) are scarce, but afford dense multi-wavelength observations. Additional low-redshift objects are therefore extremely valuable. Aims. We present early-time observations of the type I SLSN ASASSN-18km/SN 2018bsz. These data are used to characterise the event and compare to literature SLSNe and spectral models. Host galaxy properties are also analysed. Methods. Optical and near-IR photometry and spectroscopy were analysed. Early-time ATLAS photometry was used to constrain the rising light curve. We identified a number of spectral features in optical-wavelength spectra and track their time evolution. Finally, we used archival host galaxy photometry together with H II region spectra to constrain the host environment. Results. ASASSN-18km/SN 2018bsz is found to be a type I SLSN in a galaxy at a redshift of 0.0267 (111 Mpc), making it the lowest-redshift event discovered to date. Strong C II lines are identified in the spectra. Spectral models produced by exploding a Wolf-Rayet progenitor and injecting a magnetar power source are shown to be qualitatively similar to ASASSN-18km/SN 2018bsz, contrary to most SLSNe-I that display weak or non-existent C II lines. ASASSN-18km/SN 2018bsz displays a long, slowly rising, red “plateau” of >26 days, before a steeper, faster rise to maximum. The host has an absolute magnitude of –19.8 mag (r), a mass of M⋆ = 1.5−0.33+0.08 × 109 M⊙, and a star formation rate of = 0.50−0.19+2.22 M⊙ yr −1. A nearby H II region has an oxygen abundance (O3N2) of 8.31 ± 0.01 dex