161 research outputs found

    A comparative analysis of Patient-Reported Expanded Disability Status Scale tools.

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    BACKGROUND: Patient-Reported Expanded Disability Status Scale (PREDSS) tools are an attractive alternative to the Expanded Disability Status Scale (EDSS) during long term or geographically challenging studies, or in pressured clinical service environments. OBJECTIVES: Because the studies reporting these tools have used different metrics to compare the PREDSS and EDSS, we undertook an individual patient data level analysis of all available tools. METHODS: Spearman's rho and the Bland-Altman method were used to assess correlation and agreement respectively. RESULTS: A systematic search for validated PREDSS tools covering the full EDSS range identified eight such tools. Individual patient data were available for five PREDSS tools. Excellent correlation was observed between EDSS and PREDSS with all tools. A higher level of agreement was observed with increasing levels of disability. In all tools, the 95% limits of agreement were greater than the minimum EDSS difference considered to be clinically significant. However, the intra-class coefficient was greater than that reported for EDSS raters of mixed seniority. The visual functional system was identified as the most significant predictor of the PREDSS-EDSS difference. CONCLUSION: This analysis will (1) enable researchers and service providers to make an informed choice of PREDSS tool, depending on their individual requirements, and (2) facilitate improvement of current PREDSS tools.University of Southampton and National Institute of Health Research (NIHR)

    A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

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    Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms

    A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

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    Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Meeting abstrac

    Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV

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    A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe

    Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

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    A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

    Evidence for Top Quark Production in Nucleus-Nucleus Collisions

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    Peer reviewe

    Observation of the B-s(0) -> X(3872)phi Decay

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    Using a data sample of proton-proton collisions at root s = 13 TeV, corresponding to an integrated luminosity of 140 fb(-1) collected by the CMS experiment in 2016-2018, the B-s(0) -> X(3872)phi decay is observed. Decays into J/psi pi(+)pi(-) and K+K- are used to reconstruct, respectively, the X(3872) and phi. The ratio of the product of branching fractions B[B-s(0) -> X(3872)phi]B[X(3872) -> J/psi pi(+)pi(-)] to the product B[B-s(0) ->psi(2S)phi]B[psi(2S) -> J/psi pi(+)pi(-)] is measured to be [2.21 +/- 0.29(stat) +/- 0.17(syst)]%. The ratio B[B-s(0) -> X(3872)phi]/B[B-0 -> X(3872)K-0] is found to be consistent with one, while the ratio B[B-s(0) -> X(3872)phi]/B[B+-> X(3872)K+] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B-0 and B(0)s meson decays compared to B+. The reported observation may shed new light on the nature of the X(3872) particle.Peer reviewe

    Observation of a New Excited Beauty Strange Baryon Decaying to Ξb- π+π-

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    The Ξb-π+π- invariant mass spectrum is investigated with an event sample of proton-proton collisions at s=13 TeV, collected by the CMS experiment at the LHC in 2016-2018 and corresponding to an integrated luminosity of 140 fb-1. The ground state Ξb- is reconstructed via its decays to J/ψΞ- and J/ψΛK-. A narrow resonance, labeled Ξb(6100)-, is observed at a Ξb-π+π- invariant mass of 6100.3±0.2(stat)±0.1(syst)±0.6(Ξb-) MeV, where the last uncertainty reflects the precision of the Ξb- baryon mass. The upper limit on the Ξb(6100)- natural width is determined to be 1.9 MeV at 95% confidence level. The low Ξb(6100)- signal yield observed in data does not allow a measurement of the quantum numbers of the new state. However, following analogies with the established excited Ξc baryon states, the new Ξb(6100)- resonance and its decay sequence are consistent with the orbitally excited Ξb- baryon, with spin and parity quantum numbers JP=3/2-
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