Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Coartem®: the journey to the clinic

Artemisinin, from which the artemether component of Coartem®(artemether/lumefantrine, AL) is derived, is obtained from the plant sweet wormwood (Artemisia annua) which has been used for over 2,000 years as a Chinese herbal remedy. Artemisinin was first identified by Chinese researchers as the active anti-malarial constituent of A. annua and its derivatives were found to be the most potent of all anti-malarial drugs. Artemether acts rapidly, reducing the infecting parasite biomass by approximately 10,000-fold per asexual life cycle. Lumefantrine, the other active constituent of AL, acts over a longer period to eliminate the residual 100-100,000 parasites that remain after artemether is cleared from the body and thus minimizes the risk of recrudescence. The two agents have different modes of action and act at different points in the parasite life cycle and show a synergistic action against Plasmodium falciparum in vitro. The combination of artemether and lumefantrine reduces the risk of resistance developing to either agent, and to date there are no reports of resistance to AL combined therapy in the malaria parasite that infects humans. Following a unique partnership agreement between Chinese authorities and Novartis, the manufacturer of AL, over 20 sponsored clinical studies have been undertaken in various malaria endemic regions and in travellers. These trials have involved more than 3,500 patients (including over 2,000 children), and led to identification of a six-dose, three-day regimen as the optimal dosing strategy for AL in uncomplicated falciparum malaria. AL has consistently shown 28-day polymerase chain (PCR)-corrected cure rates greater than 95% in the evaluable population, meeting WHO recommendations. More recently, Novartis and the Medicines for Malaria Venture have worked in partnership to develop Coartem® Dispersible, a new formulation designed specifically to meet the specific needs of children with malaria. The dispersible tablets have shown similar high response rates to those observed with crushed standard tablets of AL. A partnership agreement between Novartis and WHO has seen over 250 million AL (Coartem®) treatments (75% for children) being distributed to malaria patients in developing countries without profit, supported by training programmes and educational resources

Intravenous pharmacokinetics, oral bioavailability, dose proportionality and in situ permeability of anti-malarial lumefantrine in rats

<p>Abstract</p> <p>Background</p> <p>Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats.</p> <p>Methods</p> <p>A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. <it>In-situ </it>permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC.</p> <p>Results</p> <p>For nominal doses increasing in a 1:2:4 proportion, the C_maxand AUC_0-∞values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the C_maxand the AUC_0-tvalues for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10^-5cm/s) in permeability study.</p> <p>Conclusions</p> <p>The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the <it>in-situ </it>permeability study.</p

Artemisinin-Naphthoquine versus Artemether-Lumefantrine for Uncomplicated Malaria in Papua New Guinean Children: An Open-Label Randomized Trial

© 2014 Laman et al. Artemisinin combination therapies (ACTs) with broad efficacy are needed where multiple Plasmodium species are transmitted, especially in children, who bear the brunt of infection in endemic areas. In Papua New Guinea (PNG), artemether-lumefantrine is the first-line treatment for uncomplicated malaria, but it has limited efficacy against P. vivax. Artemisinin-naphthoquine should have greater activity in vivax malaria because the elimination of naphthoquine is slower than that of lumefantrine. In this study, the efficacy, tolerability, and safety of these ACTs were assessed in PNG children aged 0.5–5 y.An open-label, randomized, parallel-group trial of artemether-lumefantrine (six doses over 3 d) and artemisinin-naphthoquine (three daily doses) was conducted between 28 March 2011 and 22 April 2013. Parasitologic outcomes were assessed without knowledge of treatment allocation. Primary endpoints were the 42-d P. falciparum PCR-corrected adequate clinical and parasitologic response (ACPR) and the P. vivax PCR-uncorrected 42-d ACPR. Non-inferiority and superiority designs were used for falciparum and vivax malaria, respectively. Because the artemisinin-naphthoquine regimen involved three doses rather than the manufacturer-specified single dose, the first 188 children underwent detailed safety monitoring. Of 2,542 febrile children screened, 267 were randomized, and 186 with falciparum and 47 with vivax malaria completed the 42-d follow-up. Both ACTs were safe and well tolerated. P. falciparum ACPRs were 97.8% and 100.0% in artemether-lumefantrine and artemisinin-naphthoquine-treated patients, respectively (difference 2.2% [95% CI -3.0% to 8.4%] versus -5.0% non-inferiority margin, p?=?0.24), and P. vivax ACPRs were 30.0% and 100.0%, respectively (difference 70.0% [95% CI 40.9%–87.2%], p&lt;0.001). Limitations included the exclusion of 11% of randomized patients with sub-threshold parasitemias on confirmatory microscopy and direct observation of only morning artemether-lumefantrine dosing.Artemisinin-naphthoquine is non-inferior to artemether-lumefantrine in PNG children with falciparum malaria but has greater efficacy against vivax malaria, findings with implications in similar geo-epidemiologic settings within and beyond Oceania.Australian New Zealand Clinical Trials Registry ACTRN12610000913077.Please see later in the article for the Editors' Summary

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Measurements of jet multiplicity and differential production cross sections of Z+jets events in proton-proton collisions at sqrt(s)=7TeV

Measurements of differential cross sections are presented for the production of a Z boson and at least one hadronic jet in proton-proton collisions at root s = 7 TeV, recorded by the CMS detector, using a data sample corresponding to an integrated luminosity of 4.9 fb(-1). The jet multiplicity distribution is measured for up to six jets. The differential cross sections are measured as a function of jet transverse momentum and pseudorapidity for the four highest transverse momentum jets. The distribution of the scalar sum of jet transverse momenta is also measured as a function of the jet multiplicity. The measurements are compared with theoretical predictions at leading and next-to-leading order in perturbative QCD.Austrian Federal Ministry of Science, Research and EconomyAustrian Science FundBelgian Fonds de la Recherche ScientifiqueFonds voor Wetenschappelijk OnderzoekConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Bulgarian Ministry of Education and ScienceCERNChinese Academy of SciencesMinistry of Science and TechnologyNational Natural ScienceFoundationofChinaColombian FundingAgency (COLCIENCIAS)Croatian Ministry of Science, Education, and SportCroatian Science FoundationResearch Promotion Foundation, CyprusMinistry of Education and Research, EstoniaEstonian Research Council, EstoniaEuropean Regional Development Fund, EstoniaAcademy of FinlandFinnish Ministry of Education and CultureHelsinki Institute of PhysicsInstitut National de Physique Nucleaire et de Physique des Particules / CNRS, FranceCommissariat a l&apos;Energie Atomique et aux Energies Alternatives / CEA, FranceBundesministerium fur Bildung und Forschung, GermanyDeutsche Forschungsgemeinschaft, GermanyHelmholtz-Gemeinschaft Deutscher Forschungs zentren, GermanyGeneral Secretariat for Research and Technology, GreeceNational Scientific Research Foundation, HungaryNational Innovation Office, HungaryDepartment of Atomic Energy, IndiaDepartment of Science and Technology, IndiaInstitute for Studies in Theoretical Physics and Mathematics, IranScience Foundation, IrelandIstituto Nazionale di Fisica Nucleare, ItalyKorean Ministry of Education, Science and Technology, Republic of KoreaWorld Class University program of NRF, Republic of KoreaLithuanian Academy of SciencesMinistry of Education, and University of Malaya (Malaysia)Mexican Funding Agency (CINVESTAV)Mexican Funding Agency (CONACYT)Mexican Funding Agency (SEP)Mexican Funding Agency (UASLP-FAI)Ministry of Business, Innovation and Employment, New ZealandPakistan Atomic Energy CommissionMinistry of Science and Higher Education, PolandNational Science Centre, PolandFundacao para a Cienciaea Tecnologia, PortugalJINR, DubnaMinistry of Education and Science of the Russian FederationFederal Agency of Atomic Energy of the Russian FederationRussian Academy of SciencesRussian Foundation for Basic ResearchMinistry of Education, Science and Technological Development of SerbiaSecretaria de Estado de Investigacion, Desarrollo e Innovacion and Programa Consolider-Ingenio, SpainSwiss Funding Agency (ETH Board)Swiss Funding Agency (ETH Zurich)Swiss Funding Agency (PSI)Swiss Funding Agency (SNF)Swiss Funding Agency (UniZH)Swiss Funding Agency (Canton Zurich)Swiss Funding Agency (SER)Ministry of Science and Technology, TaipeiThailand Center of Excellence in PhysicsInstitute for the Promotion of Teaching Science andTechnologyofThailandSpecialTaskForceforActivating ResearchNational Science and Technology Development Agency of ThailandScientific and Technical Research Council of TurkeyTurkish Atomic Energy AuthorityNational Academy of Sciences of Ukraine, UkraineState Fund for Fundamental Researches, UkraineScience and Technology Facilities Council, United KingdomU.S. Department of EnergyU.S. National Science FoundationMarie Curie programEuropean Research CouncilEPLANET (European Union)Leventis FoundationA. P. Sloan FoundationAlexander von Humboldt FoundationBelgian Federal Science Policy OfficeFonds pour la Formation a la Recherche dans l&apos;Industrie et dans l&apos;Agriculture (FRIA-Belgium)Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium)Ministry of Education, Youth and Sports (MEYS) of the Czech RepublicCouncil ofScienceandIndustrialResearch, IndiaHOMINGPLUS program of Foundation for Polish ScienceEuropean UnionRegional Development FundCompagnia di San Paolo (Torino)Consorzio per la Fisica (Trieste)MIUR (Italy)Thalis and Aristeia programsEU-ESFGreekNSRFNationalPrioritiesResearchProgram by Qatar National Research FundYerevan Phys Inst, Yerevan 375036, ArmeniaInst Hochenergiephys OeAW, Vienna, AustriaNatl Ctr Particle &High Energy Phys, Minsk, ByelarusUniv Antwerp, Antwerp, BelgiumVrije Univ Brussel, Brussels, BelgiumUniv Libre Bruxelles, Brussels, BelgiumUniv Ghent, B-9000 Ghent, BelgiumCatholic Univ Louvain, Louvain La Neuve, BelgiumUniv Mons, B-7000 Mons, BelgiumCtr Brasileiro Pesquisas Fis, Rio De Janeiro, BrazilUniv Estado Rio de Janeiro, BR-20550011 Rio De Janeiro, BrazilUniv Estadual Paulista, Sao Paulo, BrazilUniv Fed ABC, Sao Paulo, BrazilInst Nucl Energy Res, Sofia, BulgariaUniv Sofia, BU-1126 Sofia, BulgariaInst High Energy Phys, Beijing 100039, Peoples R ChinaPeking Univ, State Key Lab Nucl Phys &Technol, Beijing 100871, Peoples R ChinaUniv Los Andes, Bogota, ColombiaUniv Split, Fac Elect Engn, Mech Engn &Naval Architecture, Split, CroatiaUniv Split, Fac Sci, Split, CroatiaRudjer Boskovic Inst, Zagreb, CroatiaUniv Cyprus, CY-1678 Nicosia, CyprusCharles Univ Prague, Prague, Czech RepublicAcad Sci Res &Technol Arab Republ Egypt, Egyptian Network High Energy Phys, Cairo, EgyptNICPB, Tallinn, EstoniaUniv Helsinki, Dept Phys, Helsinki, FinlandHelsinki Inst Phys, Helsinki, FinlandLappeenranta Univ Technol, Lappeenranta, FinlandCEA Saclay, DSM IRFU, F-91191 Gif Sur Yvette, FranceEcole Polytech, IN2P3 CNRS, Lab Leprince Ringuet, Palaiseau, FranceUniv Strasbourg, Univ Haute Alsace Mulhouse, Inst Puridisciplinaire Hubert Curien, CNRS IN2P3, Strasbourg, FranceCtr Calcul Inst Natl Phys Nucl &Phys Particules, CNRS IN2P3, Villeurbanne, FranceUniv Lyon 1, Univ Lyon, Inst Phys Nucl Lyon, CNRS IN2P3, F-69622 Villeurbanne, FranceTbilisi State Univ, Inst High Energy Phys &Informatizat, GE-380086 Tbilisi, Rep of GeorgiaRWTH Aachen Univ I, Inst Phys, Aachen, GermanyRWTH Aachen Univ III, Phys Inst A, Aachen, GermanyRWTH Aachen Univ III, Phys Inst B, Aachen, GermanyDESY, Hamburg, GermanyUniv Hamburg, Hamburg, GermanyInst Expt Kernphys, Karlsruhe, GermanyNCSR Demokritos, Inst Nucl &Particle Phys, Aghia Paraskevi, GreeceUniv Athens, Athens, GreeceUniv Ioannina, GR-45110 Ioannina, GreeceWigner Res Ctr Phys, Budapest, HungaryInst Nucl Res ATOMKI, Debrecen, HungaryUniv Debrecen, Debrecen, HungaryNatl Inst Sci Educ &Res, Bhubaneswar, Orissa, IndiaPanjab Univ, Chandigarh 160014, IndiaUniv Delhi, Delhi 110007, IndiaSaha Inst Nucl Phys, Kolkata, IndiaBhabha Atom Res Ctr, Mumbai 400085, Maharashtra, IndiaTata Inst Fundamental Res, Mumbai 400005, Maharashtra, IndiaInst Res Fundamental Sci IPM, Tehran, IranUniv Coll Dublin, Dublin 2, IrelandIst Nazl Fis Nucl, Sez Bari, I-70126 Bari, ItalyUniv Bari, Bari, ItalyPolitecn Bari, Bari, ItalyIst Nazl Fis Nucl, Sez Bologna, I-40126 Bologna, ItalyUniv Bologna, Bologna, ItalyIst Nazl Fis Nucl, Sez Catania, I-95129 Catania, ItalyUniv Catania, Catania, ItalyCSFNSM, Catania, ItalyIst Nazl Fis Nucl, Sez Firenze, I-50125 Florence, ItalyUniv Florence, Florence, ItalyIst Nazl Fis Nucl, Lab Nazl Frascati, I-00044 Frascati, ItalyIst Nazl Fis Nucl, Sez Genova, I-16146 Genoa, ItalyUniv Genoa, Genoa, ItalyIst Nazl Fis Nucl, Sez Milano Bicocca, I-20133 Milan, ItalyUniv Milano Bicocca, Milan, ItalyIst Nazl Fis Nucl, Sez Napoli, I-80125 Naples, ItalyUniv Naples Federico II, Naples, ItalyUniv Basilicata Potenza, Naples, ItalyUniv G Marconi Roma, Naples, ItalyIst Nazl Fis Nucl, Sez Padova, Padua, ItalyUniv Padua, Padua, ItalyUniv Trento, Padua, ItalyIst Nazl Fis Nucl, Sez Pavia, I-27100 Pavia, ItalyUniv Pavia, I-27100 Pavia, ItalyIst Nazl Fis Nucl, Sez Perugia, I-06100 Perugia, ItalyUniv Perugia, I-06100 Perugia, ItalyIst Nazl Fis Nucl, Sez Pisa, Pisa, ItalyUniv Pisa, Pisa, ItalyScuola Normale Super Pisa, Pisa, ItalyIst Nazl Fis Nucl, Sez Roma, Rome, ItalyUniv Rome, Rome, ItalyIst Nazl Fis Nucl, Sez Torino, I-10125 Turin, ItalyUniv Turin, Turin, ItalyUniv Piemonte Orientale Novara, Turin, ItalyIst Nazl Fis Nucl, Sez Trieste, Trieste, ItalyUniv Trieste, Trieste, ItalyKangwon Natl Univ, Chunchon, South KoreaKyungpook Natl Univ, Daegu, South KoreaChonbuk Natl Univ, Jeonju 561756, South KoreaChonnam Natl Univ, Inst Univ &Elementary Particles, Kwangju, South KoreaKorea Univ, Seoul, South KoreaUniv Seoul, Seoul, South KoreaSungkyunkwan Univ, Suwon, South KoreaVilnius Univ, Vilnius, LithuaniaUniv Malaya, Natl Ctr Particle Phys, Kuala Lumpur, MalaysiaCtr Invest &Estudios Avanzados, IPN, Mexico City, DF, MexicoUniv Iberoamer, Mexico City, DF, MexicoBenemerita Univ Autonoma Puebla, Puebla, MexicoUniv Autonoma San Luis Potosi, San Luis Potosi, MexicoUniv Auckland, Auckland 1, New ZealandUniv Canterbury, Christchurch 1, New ZealandQuaid I Azam Univ, Natl Ctr Phys, Islamabad, PakistanNatl Ctr Nucl Res, Otwock, PolandUniv Warsaw, Fac Phys, Inst Expt Phys, Warsaw, PolandLab Instrumentacao &Fis Expt Particulas, Lisbon, PortugalJoint Inst Nucl Res, Dubna, RussiaPetersburg Nucl Phys Inst, St Petersburg, RussiaRussian Acad Sci, Inst Nucl Res, Moscow 117312, RussiaInst Theoret &Expt Phys, Moscow 117259, RussiaPN Lebedev Phys Inst, Moscow 117924, RussiaMoscow MV Lomonosov State Univ, Skobeltsyn Inst Nucl Phys, Moscow, RussiaInst High Energy Phys, State Res Ctr Russian Federat, Protvino, RussiaUniv Belgrade, Fac Phys, Belgrade 11001, SerbiaVinca Inst Nucl Sci, Belgrade, SerbiaCIEMAT, E-28040 Madrid, SpainUniv Autonoma Madrid, Madrid, SpainUniv Oviedo, Oviedo, SpainUniv Cantabria, CSIC, IFCA, E-39005 Santander, SpainCERN, European Org Nucl Res, CH-1211 Geneva, SwitzerlandPaul Scherrer Inst, Villigen, SwitzerlandETH, Inst Particle Phys, Zurich, SwitzerlandUniv Zurich, Zurich, SwitzerlandNatl Cent Univ, Chungli 32054, TaiwanNatl Taiwan Univ, Taipei 10764, TaiwanChulalongkorn Univ, Fac Sci, Dept Phys, Bangkok, ThailandCukurova Univ, Adana, TurkeyMiddle E Tech Univ, Dept Phys, TR-06531 Ankara, TurkeyBogazici Univ, Istanbul, TurkeyIstanbul Tech Univ, TR-80626 Istanbul, TurkeyKharkov Phys &Technol Inst, Natl Sci Ctr, UA-310108 Kharkov, UkraineUniv Bristol, Bristol, Avon, EnglandRutherford Appleton Lab, Didcot OX11 0QX, Oxon, EnglandUniv London Imperial Coll Sci Technol &Med, London, EnglandBrunel Univ, Uxbridge UB8 3PH, Middx, EnglandBaylor Univ, Waco, TX 76798 USAUniv Alabama, Tuscaloosa, AL USABoston Univ, Boston, MA 02215 USABrown Univ, Providence, RI 02912 USAUniv Calif Davis, Davis, CA 95616 USAUniv Calif Los Angeles, Los Angeles, CA USAUniv Calif Riverside, Riverside, CA 92521 USAUniv Calif San Diego, La Jolla, CA 92093 USAUniv Calif Santa Barbara, Santa Barbara, CA 93106 USACALTECH, Pasadena, CA 91125 USACarnegie Mellon Univ, Pittsburgh, PA 15213 USAUniv Colorado, Boulder, CO 80309 USACornell Univ, Ithaca, NY USAFairfield Univ, Fairfield, CT 06430 USAFermilab Natl Accelerator Lab, Batavia, IL 60510 USAUniv Florida, Gainesville, FL USAFlorida Int Univ, Miami, FL 33199 USAFlorida State Univ, Tallahassee, FL 32306 USAFlorida Inst Technol, Melbourne, FL 32901 USAUniv Illinois, Chicago, IL USAUniv Iowa, Iowa City, IA USAJohns Hopkins Univ, Baltimore, MD USAUniv Kansas, Lawrence, KS 66045 USAKansas State Univ, Manhattan, KS 66506 USALawrence Livermore Natl Lab, Livermore, CA USAUniv Maryland, College Pk, MD 20742 USAMIT, Cambridge, MA 02139 USAUniv Minnesota, Minneapolis, MN USAUniv Mississippi, Oxford, MS USAUniv Nebraska, Lincoln, NE USASUNY Buffalo, Buffalo, NY 14260 USANortheastern Univ, Boston, MA 02115 USANorthwestern Univ, Evanston, IL USAUniv Notre Dame, Notre Dame, IN 46556 USAOhio State Univ, Columbus, OH 43210 USAPrinceton Univ, Princeton, NJ 08544 USAUniv Puerto Rico, Mayaguez, PR USAPurdue Univ, W Lafayette, IN 47907 USAPurdue Univ Calumet, Hammond, LA USARice Univ, Houston, TX USAUniv Rochester, Rochester, NY 14627 USARockefeller Univ, New York, NY 10021 USARutgers State Univ, Piscataway, NJ USAUniv Tennessee, Knoxville, TN USATexas A&amp;M Univ, College Stn, TX USATexas Tech Univ, Lubbock, TX 79409 USAVanderbilt Univ, Nashville, TN 37235 USAUniv Virginia, Charlottesville, VA USAWayne State Univ, Detroit, MI USAUniv Wisconsin, Madison, WI 53706 USAVienna Univ Technol, A-1040 Vienna, AustriaUniv Haute Alsace Mulhouse, Univ Strasbourg, Inst Pluridisciplinaire Hubert Curien, CNRS IN2P3, Strasbourg, FranceUniv Estadual Campinas, Campinas, SP, BrazilSuez Univ, Suez, EgyptCairo Univ, Cairo, EgyptFayoum Univ, Al Fayyum, EgyptBritish Univ Egypt, Cairo, EgyptAin Shams Univ, Cairo, EgyptUniv Haute Alsace, Mulhouse, FranceBrandenburg Tech Univ Cottbus, Cottbus, GermanyInst Nucl Res, ATOMKI, H-4001 Debrecen, HungaryEotvos Lorand Univ, Budapest, HungaryVisva Bharati Univ, Santini Ketan, W Bengal, IndiaKing Abdulaziz Univ, Jeddah 21413, Saudi ArabiaUniv Ruhuna, Matara, Sri LankaIsfahan Univ Technol, Esfahan, IranSharif Univ Technol, Tehran, IranIslamic Azad Univ, Plasma Phys Res Ctr, Sci &Res Branch, Tehran, IranIst Nazl Fis Nucl, Lab Nazl Legnaro, I-35020 Legnaro, ItalyUniv Siena, I-53100 Siena, ItalyCNRS, IN2P3, Paris, FranceUniv Michoacana, Morelia, Michoacan, MexicoSt Petersburg State Polytech Univ, St Petersburg, RussiaUniv Rome, Fac Ingn, Rome, ItalyIst Nazl Fis Nucl, Scuola Normale &Sez, Pisa, ItalyAlbert Einstein Ctr Fundamental Phys, Bern, SwitzerlandGaziosmanpasa Univ, Tokat, TurkeyAdiyaman Univ, Adiyaman, TurkeyCag Univ, Mersin, TurkeyMersin Univ, Mersin, TurkeyIzmir Inst Technol, Izmir, TurkeyOzyegin Univ, Istanbul, TurkeyMarmara Univ, Istanbul, TurkeyKafkas Univ, Kars, TurkeyMimar Sinan Univ, Istanbul, TurkeyUniv Southampton, Sch Phys &Astron, Southampton, Hants, EnglandArgonne Natl Lab, Argonne, IL 60439 USAErzincan Univ, Erzincan, TurkeyYildiz Tekn Univ, Istanbul, TurkeyTexas A&amp;M Univ, Doha, QatarUniv Estadual Paulista, Instituto de Física Teórica (IFT), Sao Paulo, BrazilEstonian Research Council, Estonia: IUT23-4Estonian Research Council, Estonia: IUT23-6MIUR (Italy): 20108T4XT

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

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.AMSUNY DownstatePsychiatry and Behavioral SciencesInstitute for Genomics in HealthN/