Measurement of differential cross sections for Higgs boson production in the diphoton decay channel in pp collisions at √s = 8 TeV

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMA measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at √s = 8TeV. The analysis exploits the H→γγ decay in data corresponding to an integrated luminosity of 19.7fb-1 collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities |η|1/3 and >1/4, the total fiducial cross section is 32±10fbWe acknowledge the enduring support for the construction and operation of the LHC and the CMS detector provided by the following funding agencies: the Austrian Federal Ministry of Science, Research and Economy and the Austrian Science Fund; the Belgian Fonds de la Recherche Scientifique, and Fonds voor Wetenschappelijk Onderzoek; the Brazilian Funding Agencies (CNPq, CAPES, FAPERJ, and FAPESP); the Bulgarian Ministry of Education and Science; CERN; the Chinese Academy of Sciences, Ministry of Science and Technology, and National Natural Science Foundation of China; the Colombian Funding Agency (COLCIENCIAS); the Croatian Ministry of Science, Education and Sport, and the Croatian Science Foundation; the Research Promotion Foundation, Cyprus; the Ministry of Education and Research, Estonian Research Council via IUT23-4 and IUT23- 6 and European Regional Development Fund, Estonia; the Academy of Finland, Finnish Ministry of Education and Culture, and Helsinki Institute of Physics; the Institut National de Physique Nucléaire et de Physique des Particules/CNRS, and Commissariat à l’Énergie Atomique et aux Énergies Alternatives/CEA, France; the Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, and Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany; the General Secretariat for Research and Technology, Greece; the National Scientific Research Foundation, and National Innovation Office, Hungary; the Department of Atomic Energy and the Department of Science and Technology, India; the Institute for Studies in Theoretical Physics and Mathematics, Iran; the Science Foundation, Ireland; the Istituto Nazionale di Fisica Nucleare, Italy; the Ministry of Science, ICT and Future Planning, and National Research Foundation (NRF), Republic of Korea; the Lithuanian Academy of Sciences; the Ministry of Education, and University of Malaya (Malaysia); the Mexican Funding Agencies (CINVESTAV, CONACYT, SEP, and UASLP-FAI); the Ministry of Business, Innovation and Employment, New Zealand; the Pakistan Atomic Energy Commission; the Ministry of Science and Higher Education and the National Science Centre, Poland; the Fundação para a Ciência e a Tecnologia, Portugal; JINR, Dubna; the Ministry of Education and Science of the Russian Federation, the Federal Agency of Atomic Energy of the Russian Federation, Russian Academy of Sciences, and the Russian Foundation for Basic Research; the Ministry of Education, Science and Technological Development of Serbia; the Secretaría de Estado de Investigación, Desarrollo e Innovación and Programa Consolider-Ingenio 2010, Spain; the Swiss Funding Agencies (ETH Board, ETH Zurich, PSI, SNF, UniZH, Canton Zurich, and SER); the Ministry of Science and Technology, Taipei; the Thailand Center of Excellence in Physics, the Institute for the Promotion of Teaching Science and Technology of Thailand, Special Task Force for Activating Research and the National Science and Technology Development Agency of Thailand; the Scientific and Technical Research Council of Turkey, and Turkish Atomic Energy Authority; the National Academy of Sciences of Ukraine, and State Fund for Fundamental Researches, Ukraine; the Science and Technology Facilities Council, UK; the US Department of Energy, and the US National Science Foundation. Individuals have received support from the Marie-Curie program and the European Research Council and EPLANET(European Union); the Leventis Foundation; the A. P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Council of Science and Industrial Research, India; the HOMING PLUS program of the Foun-dation for Polish Science, cofinanced from European Union, Regional Development Fund; the OPUS program of the National Science Center (Poland); the Compagnia di San Paolo (Torino); the Consorzio per la Fisica (Trieste); MIUR project 20108T4XTM (Italy); the Thalis and Aristeia programs cofinanced by EU-ESF and the Greek NSRF; the National PrioritiesResearch Program by QatarNationalResearch Fund; the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University (Thailand); and the Welch Foundation, contract C-184

Search for physics beyond the standard model in dilepton mass spectra in proton-proton collisions at √s=8 TeV

Peer reviewe

Searches for supersymmetry using the M-T2 variable in hadronic events produced in pp collisions at 8 TeV

Peer reviewe

Comparison of Drug Discontinuation, Effectiveness, and Safety Between Clinical Trial Eligible and Ineligible Patients in BADBIR

Importance: Patients with psoriasis enrolled in clinical trials of biologics may not be representative of the real-world population. There is evidence that patients ineligible for such trials have a greater risk of serious adverse events (SAEs), but the effect on drug discontinuation and effectiveness are unknown.Objective: To determine whether (1) drug discontinuation, (2) effectiveness, and (3) rates of SAEs differ in patients with psoriasis categorized as eligible or ineligible for clinical trials.Design, Setting, and Participants: An observational study using 157 dermatology centers in the United Kingdom and Republic of Ireland was carried out wherein we applied the eligibility criteria of clinical trials of biologic therapies for psoriasis to patients who were being followed up in the British Association of Dermatologists Biologic Interventions Register (BADBIR) and being prescribed biologics as part of standard clinical care. Patients with psoriasis registered to BADBIR who were taking etanercept (enbrel only; n = 1509), adalimumab (n = 4000), and ustekinumab (n = 1627) with at least 1 follow-up visit. Eligibility criteria were extracted from phase 3 licensing trials for etanercept, adalimumab, and ustekinumab for the treatment of moderate to severe psoriasis. Patients in BADBIR with a missing baseline Psoriasis Area and Severity Index (PASI) or baseline PASI value less than 10 (etanercept) or less than 12 (adalimumab; ustekinumab) but who would otherwise be eligible were investigated separately. Eligibility categories applied to BADBIR included: eligible, ineligible, insufficient baseline PASI only, and missing baseline PASI only.Main Outcomes and Measures: (1) Drug discontinuation: cumulative incidence at 12 months by stop reason per eligibility category and drug; (2) effectiveness: linear regression of absolute change in PASI from baseline to 6 and 12 months; and (3) SAEs: incidence rate ratio (IRR) at 12 months between eligibility categories per drug.Results: The mean (SD) age of the 7136 patients included in the analysis was 45 (13) years and 2924 (41%) were women and 4212 (59%) were men. Of 7136 patients, 839 (56%) etanercept, 2219 (56%) adalimumab, and 754 (46%) ustekinumab registrations were categorized as eligible. The most common reasons for ineligibility were diabetes (etanercept, 143 [9%]; ustekinumab, 201 [12%]) and nonchronic plaque psoriasis (adalimumab, 157 [4%]). Patients categorized as ineligible (etanercept, 367 [24%]; adalimumab, 282 [7%]; ustekinumab, 394 [24%]) achieved a smaller absolute change in PASI after 6 and 12 months (adalimumab, ustekinumab), and had significantly higher rates of SAEs compared with the eligible category (etanercept: IRR, 1.9; 95% CI, 1.4-2.6; adalimumab: IRR, 2.0; 95% CI, 1.5-2.6; ustekinumab: IRR, 2.8; 95% CI, 2.1-3.8). No significant differences in drug discontinuation were observed between categories.Conclusions and Relevance: Clinical trial effectiveness and safety outcomes are not representative of real-world patients in BADBIR patients categorized as ineligible for such trials.</p

Measurement of the W+W− cross section in pp collisions at s√=7 TeV and limits on anomalous WWγ and WWZ couplings

A measurement of W+W− production in pp collisions at s√=7 TeV is presented. The data were collected with the CMS detector at the LHC, and correspond to an integrated luminosity of 4.92±0.11 fb−1. The W+W− candidates consist of two oppositely charged leptons, electrons or muons, accompanied by large missing transverse energy. The W+W− production cross section is measured to be 52.4±2.0 (stat.)±4.5 (syst.)±1.2 (lum.) pb. This measurement is consistent with the standard model prediction of 47.0±2.0 pb at next-to-leading order. Stringent limits on the WWγ and WWZ anomalous triple gauge-boson couplings are set

No Differences in Hippocampal Volume between Carriers and Non-Carriers of the ApoE ε4 and ε2 Alleles in Young Healthy Adolescents

Alleles of the apolipoprotein E (ApoE) gene are known to modulate the genetic risk for developing late-onset Alzheimer's disease (AD) and have been associated with hippocampal volume differences in AD. However, the effect of these alleles on hippocampal volume in younger subjects has yet to be clearly established. Using a large cohort of more than 1,400 adolescents, this study found no hippocampal volume or hippocampal asymmetry differences between carriers and non-carriers of the ApoE ε4 or ε2 alleles, nor dose-dependent effects of either allele, suggesting that regionally specific effects of these alleles may only become apparent in later life

Tract based spatial statistic reveals no differences in white matter microstructural organization between carriers and non-carriers of the APOE ε4 and ε2 alleles in young healthy adolescents

The apolipoprotein E (APOE) ε4 allele is the best established genetic risk factor for Alzheimer's disease (AD) and has been previously associated with alterations in structural gray matter and changes in functional brain activity in healthy middle-aged individuals and older non-demented subjects. In order to determine the neural mechanism by which APOE polymorphisms affect white matter (WM) structure, we investigated the diffusion characteristics of WM tracts in carriers and non-carriers of the APOE ε4 and ε2 alleles using an unbiased whole brain analysis technique (Tract Based Spatial Statistics) in a healthy young adolescent (14 years) cohort. A large sample of healthy young adolescents (n = 575) were selected from the European neuro imaging-genetics IMAGEN study with available APOE status and accompanying diffusion imaging data. MR Diffusion data was acquired on 3T systems using 32 diffusion-weighted (DW) directions and 4 non-DW volumes (b-value = 1,300 s/mm&lt;sup&gt;2&lt;/sup&gt; and isotropic resolution of 2.4×2.4×2.4 mm). No significant differences in WM structure were found in diffusion indices between carriers and non-carriers of the APOE ε4 and ε2 alleles, and dose-dependent effects of these variants were not established, suggesting that differences in WM structure are not modulated by the APOE polymorphism. In conclusion, our results suggest that microstructural properties of WM structure are not associated with the APOE ε4 and ε2 alleles in young adolescence, suggesting that the neural effects of these variants are not evident in 14-year-olds and may only develop later in life.</p

RASGRF2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neuron activity and dopamine release

[ES]La activación de las neuronas dopaminérgicas mesolímbicas es importante para el refuerzo inducido por fármacos, aunque los factores genéticos subyacentes siguen siendo poco conocidos. En un reciente metaanálisis de asociación de todo el genoma de la ingesta de alcohol, identificamos una sugerente asociación del SNP rs26907 en el gen del factor liberador de nucleótidos de guanina específico de ras 2 (RASGRF2), que codifica una proteína que media la activación dependiente de Ca2+ de la vía ERK. Realizamos una caracterización funcional de este gen en relación con los fenotipos relacionados con el alcohol y la función de la dopamina mesolímbica tanto en ratones como en humanos adolescentes. La ingesta y la preferencia de etanol disminuyeron en los ratones Rasgrf2-/- en comparación con los controles WT. En consecuencia, la liberación de dopamina inducida por etanol en el cuerpo estriado ventral se redujo en ratones Rasgrf2-/-. El registro de neuronas de dopamina en el área tegmental ventral reveló una excitabilidad reducida en ausencia de Ras-GRF2, probablemente debido a la falta de inhibición de la corriente de potasio IA por parte de ERK. Este déficit proporcionó una explicación para la liberación alterada de dopamina, presumiblemente relacionada con una activación deficiente de las neuronas de dopamina que se activan. El análisis de neuroimagen funcional de una tarea de incentivo-retraso monetario en 663 adolescentes reveló una asociación significativa de la actividad estriada ventral durante la anticipación de la recompensa con un haplotipo RASGRF2 que contiene rs26907, el SNP asociado con la ingesta de alcohol en nuestro metaanálisis anterior. Este hallazgo sugiere un vínculo entre el haplotipo RAGRF2 y la sensibilidad a la recompensa, un factor de riesgo conocido para la adicción al alcohol y las drogas. De hecho, el seguimiento de estos mismos chicos a los 16 años reveló una asociación entre este haplotipo y el número de episodios de consumo de alcohol. En conjunto, estos datos combinados de animales y humanos indican un papel de RASGRF2 en la regulación de la actividad de las neuronas dopaminérgicas mesolímbicas, la respuesta de recompensa y el uso y abuso de alcohol.[EN]The firing of mesolimbic dopamine neurons is important for drug-induced reinforcement, although underlying genetic factors remain poorly understood. In a recent genome-wide association metaanalysis of alcohol intake, we identified a suggestive association of SNP rs26907 in the ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) gene, encoding a protein that mediates Ca2+-dependent activation of the ERK pathway. We performed functional characterization of this gene in relation to alcohol-related phenotypes and mesolimbic dopamine function in both mice and adolescent humans. Ethanol intake and preference were decreased in Rasgrf2−/− mice relative to WT controls. Accordingly, ethanol-induced dopamine release in the ventral striatum was blunted in Rasgrf2−/− mice. Recording of dopamine neurons in the ventral tegmental area revealed reduced excitability in the absence of Ras-GRF2, likely because of lack of inhibition of the IA potassium current by ERK. This deficit provided an explanation for the altered dopamine release, presumably linked to impaired activation of dopamine neurons firing. Functional neuroimaging analysis of a monetary incentive–delay task in 663 adolescent boys revealed significant association of ventral striatal activity during reward anticipation with a RASGRF2 haplotype containing rs26907, the SNP associated with alcohol intake in our previous metaanalysis. This finding suggests a link between the RASGRF2 haplotype and reward sensitivity, a known risk factor for alcohol and drug addiction. Indeed, follow-up of these same boys at age 16 y revealed an association between this haplotype and number of drinking episodes. Together, these combined animal and human data indicate a role for RASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse.Este trabajo fue apoyado por subvenciones del FIS (Fondo de Investigación Sanitaria) [PS09/01979]; RTICC (Red Temática de Investigación Cooperativa en Cáncer) [RD06/0020/000], y JCYL (Junta de Castilla y León) [SA044A08 y GR93]

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely