Search for anomalous production of events with three or more leptons in pp collisions at √s = 8TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.A search for physics beyond the standard model in events with at least three leptons is presented. The data sample, corresponding to an integrated luminosity of 19.5fb-1 of proton-proton collisions with center-of-mass energy s=8TeV, was collected by the CMS experiment at the LHC during 2012. The data are divided into exclusive categories based on the number of leptons and their flavor, the presence or absence of an opposite-sign, same-flavor lepton pair (OSSF), the invariant mass of the OSSF pair, the presence or absence of a tagged bottom-quark jet, the number of identified hadronically decaying τ leptons, and the magnitude of the missing transverse energy and of the scalar sum of jet transverse momenta. The numbers of observed events are found to be consistent with the expected numbers from standard model processes, and limits are placed on new-physics scenarios that yield multilepton final states. In particular, scenarios that predict Higgs boson production in the context of supersymmetric decay chains are examined. We also place a 95% confidence level upper limit of 1.3% on the branching fraction for the decay of a top quark to a charm quark and a Higgs boson (t→cH), which translates to a bound on the left- and right-handed top-charm flavor-violating Higgs Yukawa couplings, λtcH and λctH, respectively, of |λtcH|2+|λctH|2<0.21

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Utilization of Dabigatran for Atrial Fibrillation at 3 Tertiary Care Centres

BACKGROUND: The outpatient management of stroke prevention for patients with atrial fibrillation has recently been published and provides insight into the benefits and risks of the new direct-acting oral anti-coagulants. However, real-world use of these agents for hospital inpatients requires additional study. OBJECTIVE: To determine prescribing patterns for dabigatran at 3 Canadian hospitals, specifically adherence with the hospitals’ prescribing restriction limiting dabigatran to patients with nonvalvular atrial fibrillation and creatinine clearance above 30 mL/min (primary outcome) and assessment of age-related prescribing, prescribing of medications with defined contraindications or potential for interaction when given concurrently with dabigatran, and use of risk stratification tools (secondary outcomes). METHODS: A retrospective chart review of patients for whom dabigatran was prescribed from August to October 2011 was performed at 3 hospitals in Toronto, Ontario. Descriptive statistics were used for all outcomes assessed. RESULTS: Overall, dabigatran was prescribed for 69 inpatients, of whom 16 (23%) were new users (dabigatran initiated during hospital admission) and 53 (77%) were prior users (dabigatran prescribed before admission to hospital). Fifty-eight patients (84%; 14 new users and 44 prior users) received dabigatran according to the hospitals’ prescribing restriction. For the remaining 11 patients, dabigatran therapy did not meet prescribing restrictions for use because of valvular disease or presence of prosthetic valve (10 patients [14% of the total sample]) and impaired renal function (1 patient [1%]). Among those whose dabigatran therapy met the prescribing restrictions for use, amiodarone and acetylsalicylic acid were the most common concurrently prescribed medications (17 patients [29%] and 14 patients [24%], respectively). Stroke and bleeding risk were documented for only 27 patients (47%) and 10 patients (17%), respectively. CONCLUSION: At the study hospitals, dabigatran was appropriately prescribed for the indication of nonvalvular atrial fibrillation in patients without renal impairment in most cases. However, greater consideration of cardiac history (including valvular disease and presence of prosthetic valves), drug interactions, and documentation of risks and benefits is warranted. These research findings highlight the importance of and opportunity for pharmacist review and involvement in assessment and selection of patients with indications for anticoagulant therapy, particularly when agents are new to the market

Utilization of Dabigatran for Atrial Fibrillation at 3 Tertiary Care Centres

ABSTRACTBackground: The outpatient management of stroke prevention for patients with atrial fibrillation has recently been published and provides insight into the benefits and risks of the new direct-acting oral anti -coagulants. However, real-world use of these agents for hospital inpatients requires additional study.Objective: To determine prescribing patterns for dabigatran at 3 Canadian hospitals, specifically adherence with the hospitals’ prescribing restriction limiting dabigatran to patients with nonvalvular atrial fibrillation and creatinine clearance above 30 mL/min (primary outcome) and assessment of age-related prescribing, prescribing of medications with defined contraindications or potential for interaction when given concurrently with dabigatran, and use of risk stratification tools (secondary outcomes).Methods: A retrospective chart review of patients for whom dabigatran was prescribed from August to October 2011 was performed at 3 hospitals in Toronto, Ontario. Descriptive statistics were used for all outcomes assessed.Results: Overall, dabigatran was prescribed for 69 inpatients, of whom 16 (23%) were new users (dabigatran initiated during hospital admission) and 53 (77%) were prior users (dabigatran prescribed before admission to hospital). Fifty-eight patients (84%; 14 new users and 44 prior users) received dabigatran according to the hospitals’ prescribing restriction. For the remaining 11 patients, dabigatran therapy did not meet prescribing restrictions for use because of valvular disease or presence of prosthetic valve (10 patients [14% of the total sample]) and impaired renal function (1 patient [1%]). Among those whose dabigatran therapy met the prescribing restrictions for use, amiodarone and acetylsalicylic acid were the most common concurrently prescribed medications (17 patients [29%] and 14 patients [24%], respectively). Stroke and bleeding risk were documented for only 27 patients (47%) and 10 patients (17%), respectively.Conclusion: At the study hospitals, dabigatran was appropriately prescribed for the indication of nonvalvular atrial fibrillation in patients without renal impairment in most cases. However, greater consideration of cardiac history including valvular disease and presence of prosthetic valves), drug interactions, and documentation of risks and benefits is warranted. These research findings highlight the importance of and opportunity for pharmacist review and involvement in assessment and selection of patients with indications for anticoagulant therapy, particularly when agents are new to the market.RÉSUMÉContexte : La publication récente sur la prévention des accidents vasculaires cérébraux (AVC) chez les patients externes atteints de fibrillation auriculaire permet de mieux comprendre les avantages et les risques des nouveaux anticoagulants oraux directs. Cependant, il est nécessaire de faire de plus amples études sur l’utilisation de ces agents en situation réelle chez les patients hospitalisés.Objectif : Déterminer les habitudes de prescription de dabigatran dans trois hôpitaux canadiens, particulièrement en ce qui a trait au respect des restrictions de prescription en vigueur dans les hôpitaux qui limitent le dabigatran aux patients souffrants de fibrillation auriculaire non valvulaire et présentant une clairance de la créatinine supérieure à 30 mL/min (principal paramètre d’évaluation) et à l’évaluation de la prescription en fonction de l’âge du patient, de la prescription de médicaments avec des contre-indications précises ou un potentiel d’interactions médicamenteuses lorsqu’ils sont administrés en concomitance avec du dabigatran et de l’emploi d’outils de stratification du risque (paramètres d’évaluation secondaires).Méthodes : Une analyse rétrospective des dossiers médicaux des patients à qui on avait prescrit du dabigatran entre août et octobre 2011 a été menée dans trois centres hospitaliers de Toronto en Ontario. Des statistiques descriptives ont été employées pour tous les paramètres analysés. Résultats : Dans l’ensemble, on a prescrit du dabigatran à 69 patients hospitalisés. Parmi eux, 16 (23 %) n’en avaient jamais reçu (traitement amorcé pendant l’hospitalisation) et 53 (77 %) en avaient déjà reçu (dabigatran prescrit avant l’hospitalisation). Cinquante-huit patients (84 %; 14 n’en ayant jamais reçu et 44 en ayant déjà reçu) ont reçu du dabigatran selon les restrictions de prescription en vigueur dans les hôpitaux. Pour les 11 patients restants, le traitement par dabigatran ne répondait pas aux restrictions d’utilisation pour cause de valvulopathie ou de présence d’une prothèse valvulaire (10 patients [14 % de l’échantillon total]) ou d’insuffisance rénale (1 patient [1 %]). Au sein du groupe de patients pour lesquels les restrictions d’utilisation ont été respectées,l’amiodarone et l’acide acétylsalicylique étaient les médicaments les plus souvent coprescrits (respectivement, 17 patients [29 %] et 14 patients [24 %]). Le risque d’AVC et d’hémorragie n’était consigné respectivement que pour 27 patients (47 %) et 10 patients (17 %).Conclusion : Dans les hôpitaux de l’étude, le dabigatran était habituellement prescrit de façon appropriée pour l’indication de fibrillation auricu - laire non valvulaire chez des patients ne présentant pas d’insuffisance rénale. Cependant, il est justifié de tenir davantage compte des antécédents cardiaques (notamment les valvulopathies et la présence de prothèses valvulaire), des interactions médicamenteuses ainsi que de la consignation des risques et des avantages. Ces données mettent en relief l’importance et la possibilité de la participation du pharmacien à l’évaluation et à la sélection des patients ayant des indications pour un traitement par anticoagulant ainsi que de son analyse de ces cas, particulièrement lorsque les médicaments sont nouveaux sur le marché

Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK

Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2–3 years, and whether symptoms at 2–3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2–3 years were associated with occupation change. People with lived experience were involved in the study. Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2–3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16–1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2–3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2–3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0–48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0–17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2–3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6–31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04–2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21–1·98] for every point increase in CCI-20). Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2–3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.</p

A search for WWγ\gamma and WZγ\gamma production and constraints on anomalous quartic gauge couplings in pp collisions at s\sqrt{s} = 8 TeV

A search for $WV\gamma$ triple vector boson production is presented based on events containing a $W$ boson decaying to a muon or an electron and a neutrino, a second $V$ ($W$ or $Z$) boson, and a photon. The data correspond to an integrated luminosity of $19.3\text{}\text{}{\mathrm{fb}}^{-1}$ collected in 2012 with the CMS detector at the LHC in $pp$ collisions at $\sqrt{s}=8\text{}\text{}\mathrm{TeV}$. An upper limit of 311 fb on the cross section for the $WV\gamma$ production process is obtained at 95% confidence level for photons with a transverse energy above 30 GeV and with an absolute value of pseudorapidity of less than 1.44. This limit is approximately a factor of 3.4 larger than the standard model predictions that are based on next-to-leading order QCD calculations. Since no evidence of anomalous $WW\gamma \gamma$ or $WWZ\gamma$ quartic gauge boson couplings is found, this paper presents the first experimental limits on the dimension-eight parameter ${f}_{T,0}$ and the $CP$-conserving $WWZ\gamma$ parameters ${\kappa }_{0}^{W}$ and ${\kappa }_{C}^{W}$. Limits are also obtained for the $WW\gamma \gamma$ parameters ${a}_{0}^{W}$ and ${a}_{C}^{W}$