Shuffling of mobile genetic elements (MGEs) in successful healthcare-associated MRSA (HA-MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) CC22 SCCmecIV is a successful hospital-associated (HA-) MRSA, widespread throughout the world, and now the dominant clone in UK hospitals. We have recently shown that MRSA CC22 is a particularly fit clone, and it rose to dominance in a UK hospital at the same time as it began acquiring an increased range of antibiotic resistances. These resistances were not accumulated by individual CC22 isolates, but appear to shuffle frequently between isolates of the MRSA CC22 population. Resistances are often encoded on mobile genetic elements (MGEs) that include plasmids, transposons, bacteriophage and S. aureus pathogenicity islands (SaPIs). Using multi-strain whole genome microarrays, we show that there is enormous diversity of MGE carried within a MRSA CC22 SCCmecIV population, even among isolates from the same hospital and time period. MGE profiles were so variable that they could be used to track the spread of variant isolates within the hospital. We exploited this to show that the majority of patients colonised with MRSA at hospital admission that subsequently became infected were infected with their own colonising isolate. Our studies reveal MGE spread, stability, selection and clonal adaptation to the healthcare setting may be key to the success of HA-MRSA clones, presumably by allowing rapid adaptation to antibiotic exposure and new hosts

Implications of eocene-age philippine sea and forearc basalts for initiation and early history of the izu-bonin-mariana arc

Whole-rock isotope ratio (Hf, Nd, Pb, Sr) and trace element data for basement rocks at ocean drilling Sites U1438, 1201 and 447 immediately west of the KPR (Kyushu-Palau Ridge) are compared to those of FAB (forearc basalts) previously interpreted to be the initial products of IBM subduction volcanism. West-of-KPR basement basalts (drill sites U1438, 1201, 447) and FAB occupy the same Hf-Nd and Pb-Pb isotopic space and share distinctive source characteristics with εHf mostly >16.5 and up to εHf =19.8, which is more radiogenic than most Indian mid-ocean ridge basalts (MORB). Lead isotopic ratios are depleted, with ²⁰⁶Pb/²⁰⁴Pb = 17.8-18.8 accompanying relatively high ²⁰⁸Pb/²⁰⁴Pb, indicating an Indian-MORB source unlike that of West Philippine Basin plume basalts. Some Sr isotopes show affects of seawater alteration, but samples with ⁸⁷Sr/⁸⁶Sr8.0 appear to preserve magmatic compositions and also indicate a common source for west-of-KPR basement and FAB. Trace element ratios resistant to seawater alteration (La/Yb, Lu/Hf, Zr/Nb, Sm/Nd) in west-of-KPR basement are generally more depleted than normal MORB and so also appear similar to FAB. At Site U1438, only andesite sills intruding sedimentary rocks overlying the basement have subduction-influenced geochemical characteristics (εNd ∼6.6, εHf ∼13.8, La/Yb > 2.5, Nd/Hf ∼9). The key characteristic that unites drill site basement rocks west of KPR and FAB is the nature of their source, which is more depleted in lithophile trace elements than average MORB but with Hf, Nd, and Pb isotope ratios that are common in MORB. The lithophile element-depleted nature of FAB has been linked to initiation of IBM subduction in the Eocene, but Sm-Nd model ages and errorchron relationships in Site U1438 basement indicate that the depleted character of the rocks is a regional characteristic that was produced well prior to the time of subduction initiation and persists today in the source of modern IBM arc volcanic rocks with Sm/Nd>0.34 and εNd ∼9.0

A current perspective on cancer immune therapy: Step‑by‑step approach to constructing the magic bullet

Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers. While early scientists, such as Coley, elicited an unselective but effective response against cancer, the search for selectivity pushed immunotherapy to the side in favor of drugs focused on targeting cancer cells. Fortunately, the modern era would revive the importance of the immune system in battling cancer by releasing the brakes or checkpoints (anti-CTLA-4 and anti-PD-1/PD-L1) that have been holding the immune system at bay. However, there are still many hurdles to overcome before immunotherapy becomes a universal cancer therapy. For example, we discuss how the redundant and complex nature of the immune system can impede tumor elimination by teeter tottering between different polarization states: one eliciting anti-cancer effects while the other promoting cancer growth and invasion. In addition, we highlight the incapacity of the immune system to choose between a fight or repair action with respect to tumor growth. Finally we combine these concepts to present a new way to think about the immune system and immune tolerance, by introducing two new metaphors, the “push the accelerator” and “repair the car” metaphors, to explain the current limitations associated with cancer immunotherapyThis work was supported by NIH R00 CA154605 and Louisiana Board of Regents LEQSF(2016-17)-RD-C-14 (H.L.M.), a Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain (B.S.Jr) and a Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY (B.S.Jr)

Display of probability densities for data from a continuous distribution

Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

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

Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system

Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined and the possibility of confounding factors has not been excluded. Patients aged 6-19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis & Reporting System (2001-2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20 586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10 000 patient-years. No increased risk was found during MPH exposed compared to non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53-1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17-9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events prior to the first prescription of MPH, which may be due to an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment

Percentile reference values for anthropometric body composition indices in European children from the IDEFICS study

INTRODUCTION: To characterise the nutritional status in children with obesity or wasting conditions, European anthropometric reference values for body composition measures beyond the body mass index (BMI) are needed. Differentiated assessment of body composition in children has long been hampered by the lack of appropriate references. OBJECTIVES: The aim of our study is to provide percentiles for body composition indices in normal weight European children, based on the IDEFICS cohort (Identification and prevention of Dietary-and lifestyle-induced health Effects in Children and infantS). METHODS: Overall 18 745 2.0-10.9-year-old children from eight countries participated in the study. Children classified as overweight/obese or underweight according to IOTF (N = 5915) were excluded from the analysis. Anthropometric measurements (BMI (N = 12 830); triceps, subscapular, fat mass and fat mass index (N = 11 845-11 901); biceps, suprailiac skinfolds, sum of skinfolds calculated from skinfold thicknesses (N = 8129-8205), neck circumference (N = 12 241); waist circumference and waist-to-height ratio (N = 12 381)) were analysed stratified by sex and smoothed 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentile curves were calculated using GAMLSS. RESULTS: Percentile values of the most important anthropometric measures related to the degree of adiposity are depicted for European girls and boys. Age-and sex-specific differences were investigated for all measures. As an example, the 50th and 99th percentile values of waist circumference ranged from 50.7-59.2 cm and from 51.3-58.7 cm in 4.5-to < 5.0-year-old girls and boys, respectively, to 60.6-74.5 cm in girls and to 59.9-76.7 cm in boys at the age of 10.5-10.9 years. CONCLUSION: The presented percentile curves may aid a differentiated assessment of total and abdominal adiposity in European children