1,926 research outputs found

    Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.

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    Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 10(5) bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines

    An Integrative Design Framework for New Service Development

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    Service innovation is focused on customer value creation. At its core, customer-centric service innovation in an increasingly digital world is technology-enabled, human-centered, and process-oriented. This requires a cross-disciplinary, holistic approach to new service design and development (NSD). This paper proposes a new service strategy-aligned integrative design framework for NSD. It correlates the underlying theories and principles of disparate but interrelated aspects of service design thinking: service strategy, concept, design, experience and architecture into a coherent framework for NSD, consistent with the service brand value. Application of the framework to NSD is envisioned to be iterative and holistic, accentuated on continuous organizational and customer learning. The preliminary framework's efficacy is illustrated using a simplified telecom case example. © Springer International Publishing Switzerland 2014

    Isolated and dynamical horizons and their applications

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    Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

    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

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    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

    A search for the decay modes B+/- to h+/- tau l

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    We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

    Evidence for an excess of B -> D(*) Tau Nu decays

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    Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg

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

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    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

    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

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    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

    Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

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    We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page
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