Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Search for heavy lepton partners of neutrinos in proton-proton collisions in the context of the type III seesaw mechanism

This is the Pre-print version of the Article. The official publishe version can be accessed from the link below - Copyright @ 2012 ElsevierA search is presented in proton–proton collisions at sqrt(s) = 7TeV for fermionic triplet states expected in type III seesaw models. The search is performed using final states with three isolated charged leptons and an imbalance in transverse momentum. The data, collected with the CMS detector at the LHC, correspond to an integrated luminosity of 4.9 fb−1. No excess of events is observed above the background predicted by the standard model, and the results are interpreted in terms of limits on production cross sections and masses of the heavy partners of the neutrinos in type III seesaw models. Depending on the considered scenarios, lower limits are obtained on the mass of the heavy partner of the neutrino that range from 180 to 210 GeV. These are the first limits on the production of type III seesaw fermionic triplet states reported by an experiment at the LHC.This study is spported by the BMWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MEYS (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); MoER, SF0690030s09 and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); MSI (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MON, RosAtom, RAS and RFBR (Russia); MSTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); ThEP, IPST and NECTEC (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie programme and the European Research Council (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 a 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 Czech Republic; the Council of Science and Industrial Research, India; the Compagnia di San Paolo (Torino); and the HOMING PLUS programme of Foundation for Polish Science, cofinanced from European Union, Regional Development Fund

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Euglenophyta no Parque Estadual Delta do Jacuí, Rio Grande do Sul, Sul do Brasil. 3. Gênero Strombomonas Defl. Euglenophyta in the Jacuí Delta State Park, Rio Grande do Sul State, Southern Brazil. 3. The genus Strombomonas Defl.

Foram identificados 34 táxons específicos e infra-específicos do gênero Strombomonas Defl. resultado do estudo de amostras qualitativas no Parque Estadual Delta do Jacuí, localizado a 29°56'-30°03'S e 51°12'-51°18'W. As amostragens foram realizadas em 25 ambientes aquáticos em abril/1993 e janeiro/1994 e maio/1998 a setembro/1999. Strombomonas borystheniensis, S. ensifera, S. gibberosa, S. girardiana, S. scabra, S. triquetra var. torta e S. verrucosa foram os táxons mais freqüentes na área, ocorrendo em mais de 50% dos locais amostrados, destacando-se S. verrucosa pela ampla distribuição na área do Parque, com a ocorrência em 96% dos locais estudados. Strombomonas chodatti, S. cuneata, S. moreniensis,S. napiformis var. brevicollis são primeiras citações de ocorrência para o Estado e Brasil. S. confortii,S. fluviatilis var. major, S. morenensis, S. scabra var. intermedia e S. scabra var. ovata f. minor ocorrem exclusivamente na América do Sul. São realizadas considerações taxonômicas e ecológicas sobre o gênero, assim como é fornecida sua distribuição nacional e mundial.<br>Thirty four specific and infra-specific taxa of the genus Strombomonas Defl. were identified as the result of the study of qualitative samples from Jacuí Delta State Park, that is located for 29°56'- 30°03'S and 51°12'-51°18'W. Sampling were carried out in 25 stations from April/1993 to January/1994 and May/1998 to September/1999. Strombomonas borystheniensis, S. ensifera, S. gibberosa, S. girardiana, S. scabra, S. triquetra var. torta and S. verrucosa were the most frequent taxa in the area, occuring in more than 50% of the samples, being distinguished S. verrucosa for its wide distribution in the area of the Park, with the occurrence in 96% of the studied places. Strombomonas chodatti, S. cuneata, S. moreniensis and S. napiformis var. brevicollis,were registered for the first time to the State and Brazilian territory. S. confortii, S. fluviatilis var. major, S. morenensis, S. scabra var. intermedia and S. scabra var. ovata f. minor are taxa that occur exclusively in South America. Taxonomic and ecological considerations are supplied as well as its national and world distribution