Suchergebnisse

The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO. ; The BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the BCFR. CNIO was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish ...

18 pags., 11 figs., 4 tabs. ; The structure of the doubly magic Sn8250132 has been investigated at the ISOLDE facility at CERN, populated both by the β-decay of In132 and β - delayed neutron emission of In133. The level scheme of Sn132 is greatly expanded with the addition of 68 γ transitions and 17 levels observed for the first time in the β decay. The information on the excited structure is completed by new γ transitions and states populated in the β-n decay of In133. Improved delayed neutron emission probabilities are obtained both for In132 and In133. Level lifetimes are measured via the advanced time-delayed βγγ(t) fast-timing method. An interpretation of the level structure is given based on the experimental findings and the particle-hole configurations arising from core excitations both from the N = 82 and Z = 50 shells, leading to positive- and negative-parity particle-hole multiplets. The experimental information provides new data to challenge the theoretical description of Sn132. ; We acknowledge the support of the ISOLDE Collaboration and the ISOLDE technical teams, and by the European Union Horizon 2020 research and innovation programme under Grant Agreement No. 654002. This work was partially funded by the Spanish government via Projects No. FPA2015- 65035-P, No. FPA-64969-P, No. FPA2017-87568-P, and No. RTI2018-098868-B-I00; the Polish National Science Center under Contracts No. UMO-2015/18/E/ST2/00217, No. UMO-2015/18/M/ST2/00523, and No. UMO2019/33/N/ST2/03023; the Portuguese FCT via CERN/FIS-NUC/0004/2015 project; the German BMBF under Contract No. 05P18PKCIA; the Romanian IFA Grant CERN/ISOLDE; and by grants from the U.K. Science and Technology Facilities Council, the Research Foundation Flanders (FWO, Belgium), the Excellence of Science program (EOS, FWO-FNRS, Belgium), and the GOA/2015/010 (BOF KU Leuven). J.B. acknowledges support from the Universidad Complutense de Madrid under the Predoctoral Grant No. CT27/16-CT28/16

According to literature the primary retroperitoneal malignant pathology is rare, representing less than 0.5% of all malignancies. In spite of its low incidence, this pathology often proves challenging in terms of diagnosis and treatment. The most com¬mon retroperitoneal malignancy is represented by lymphoma that accounts for approximately 33 % of the retroperitoneal malignancies. Other frequent retroperitoneal tumors are sarcomas: liposarcomas, leiomyosarcomas and malignant fibrous histiocytoma (in order of incidence). We have analyzed the existing data regarding the most common primary retroperitoneal tumors in order to realize a brief classification and their differential diagnosis considering their clinical, imagistic, histopathological and molecular characteristics. The technological developments that have been made over the years in terms of imaging investigations, as well as in biomelecular and cytogenetic studies have offered new possibilities for of assessing a retroperitoneal mass in order achieve more precise informations that can guide physicians to better distinguish between different types of retroperitoneal tumors and therefore their therapeutical protocol.

Background: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. Objectives: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter <10 (PM10) or <2.5 mu m (PM2.5) and DNA methylation in newborns and children. Methods: We meta-analyzed associations between exposure to PM10 (n=1,949) and PM2.5 (n=1,551) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. Results: Six CpGs were significantly associated [false discovery rate (FDR) <0.05] with prenatal PM10 and 14 with PM2.5 exposure. Two of the PM10-related CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant (p<0.05) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent PM10 exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal PM10 and or PM2.5 exposure, of which two PM10-related DMRs, including H19 and MARCH11, replicated in newborns. Conclusions: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. ; ALSPAC: The UK Medical Research Council and the Wellcome Trust (Grant ref. 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and P.Y. will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristoLac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by a joint grant from the UK Economic & Social and Biotechnology & Biological Sciences Research Councils (Grant ref. ES/N000498/1). ALSPAC was funded by the BBSRC (BBI025751/1 and BB/I025263/1). Air pollution exposure assessment was funded by Public Health England as part of the MRC-PHE Centre for Environment and Health, funded also by the UK Medical Research Council (Grant ref. MR/L01341X/1). This paper does not necessarily reflect the views of Public Health England or the Department of Health. BAMSE was supported by The Swedish Research Council, The Swedish Heart-Lung Foundation, Freemason Child House Foundation in Stockholm, MeDALL (Mechanisms of the Development of ALLergy) a collaborative project conducted within the European Union (grant agreement No. 261357), Centre for Allergy Research, Stockholm County Council (ALE), Swedish Foundation for Strategic Research (SSF) (RBc08-0027), the Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet, The Swedish Research Council Foams, and the Swedish Environment Protection Agency. E.M. is supported by a grant from the European Research Council under the European Union (EU) Horizon 2020 (H2020) research and innovation programme (grant agreement number 757919, TRIBAL). O.G. is supported by Forte (Swedish Research Council for Health, Working Life and Welfare) and The Swedish Society for Medical Research. CHS: This work was supported by NIEHS grants K01ES017801, R01ES022216, and P30ES007048. EARLI: This work was supported by NIH grants R01ES016443, R01ES023780, and R01ES017646 as well as by Autism Speaks (AS 5938). ENVIRONAGE: The ENVIRONAGE birth cohort is funded by the European Research Counsil (ERC-2012-StG.310898) and by funds of the Flemisch Scientific Research Council (FWO, N1516112/G.0.873.11N.10). The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (Grant agreement no. 308610). ZH and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA-Inserm, France) and Association pour la Recherche sur le Cancer (ARC, France). Generation R Study: The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center (MC), Rotterdam, the Erasmus University Rotterdam, Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. The EWAS data was funded by a grant to VWJ from Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project no. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC. V.W.J. also received a grant from Netherlands Organization for Health Research and Development (VIDI 016.136.361) and a Consolidator Grant from the European Research Council (ERC-2014-CoG-648916). J.F.F. has received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no. 633595 (DynaHEALTH). This project received funding from the European Union's Horizon 2020 Research and Innovation Programme (733206, LIFECYCLE). HELIX: The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333 - the HELIX project. R.G. received the grant of the Lithuanian Agency for Science Innovation and Technology (No. 45 31V-66). The Norwegian Mother and Child Cohort Study (MoBa) is supported by the Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS (grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1). INMA: This study was funded by grants from Institut() de Salud Carlos III (Red INMA G03/176), Generalitat de Catalunya-CIRIT 1999SGR 00241, and EU Commission (261357; 211250; 268479). Piccolipiu: The study was approved and initially funded by the Italian National Centre for Disease Prevention and Control (CCM grant 2010) and by the Italian Ministry of Health (art 12 and 12bis Dl.gs.vo 502/92). The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (Grant agreement no: 308610). Z.H. and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA-INSERM, France) and Association pour la Recherche sur le Cancer (ARC, France). Rhea: The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (grant agreement no. 308610). ZH and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA INSERM, France) and Association pour la Recherche sur le Cancer (ARC, France). PRISM: R.J.W. received funding for the PRISM cohort under HL095606 and R01 HL1143396. A.C.J. is supported by R00 ES023450. Project Viva: This Project Viva study was supported by grants from the NIH (NIH R01 HL 111108, R01 NR013945, R01 HD 034568, K24 HD069408, K23 ES022242, P01ES009825, R01AI102960, P30 ES000002) and the U.S. Environmental Protection Agency (EPA) (R832416, RD834798). This publication's contents are solely the responsibility of the grantee and do not necessarily represent the official views of the U.S. Government, the U.S. Department of Health and Human Services or the NIH, or the EPA. Further, the EPA does not endorse the purchase of any commercial products or services mentioned in the publication. MeDALL: The methylation study of MeDALL cohorts was funded by MEDALL, a collaborative project supported by the European Union under the Health Cooperation Work Programme of the 7th Framework Programme (grant agreement no. 261357). The Biobank-Based Integrative Omics Studies (BIOS) Consortium is funded by BBMRI-NL, a research 'infrastructure financed by the Dutch government (NWO 184.021.007). BAMSE: We would like to thank all the families for their participation in the BAMSE study. In addition, we would like to thank E. Haliner, S. Nilsson, and A. Lauber at the BAMSE secretary for invaluable support, as well as Mutation Analysis Facility (MAF) at Karolinska Institutet for genome-wide methylation analysis, and I. Delin for excellent technical assistance. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project b201.4110.

Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding: Bill & Melinda Gates Foundation.

Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies. Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively. Interpretation: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. Funding: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

Altres ajuts europeus: P.A.W. was additionally supported by the European Union Fourth Environment and Climate Framework Programme (Project Number ENV4-CT970586)P.A.W. was additionally supported by the European Union Fourth Environment and Climate Framework Programme (Project Number ENV4-CT970586). ; The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature-trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.

Altres ajuts: This work was in part supported by the Canadian Consortium on Neurodegeneration in Aging (E.R., M.Z.), the ALS Canada-Brain Canada Hudson Grant (J.R., E.R., L.Z.), James Hunter ALS Initiative and the Temerty Family Foundation (L.Z., J.R.), Alzheimer's Society grant #284 (R.F.), Argentine National Research Council (CONICET) (EIS), ALS Canada Clinical Research Fellowship (R.S.), National Institutes of Health (NIH) R35 NS097261, P50 AG016574, P01 NS084974 (RR), P50 AG016574 (N.R.G., D.W.D., J.E.P., B.F.B., R.C.P.), NIH P01 NS084974 (D.W.D.), NIH P01 AG019724 (B.L.M., W.W.S.), JPND PreFrontALS (733051042), JPND RiMOD (733051024), Memorabel-FTD (733050103) (J.C.v-S), the Flemish Government initiated Impulse Program on Networks for Dementia Research (VIND), the Methusalem Excellence Program, the Research Foundation Flanders (FWO) and the University of Antwerp Research Fund (C.V.B., J.v-d-Z.), NIH P01-AG-017586 (V.V.D.), "Investissements d'avenir" ANR-10-IAIHU-06, Assistance Publique-Hôpitaux de Paris (Clinical Research and Development Department), Programme Hospitalier de Recherche Clinique, FTLD-exome RCAOM-12123, the ANR-PRTS PREV-DEMALS project (I.L.B.), an MRC Clinician Scientist Fellowship (MR/M008525/1), the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH), the MRC UK GENFI grant (MR/M023664/1) (J.D.R.), Swedish Research Council (Dnr 521-2010-3134, 529-2014-7504, 2015-02926), Alzheimer foundation Sweden, Brain Foundation Sweden, Swedish FTD Initiative, Swedish Brain Power, Karolinska Institutet doctoral funding, Gamla tjänarinnor, Stohnes foundation, Dementia foundation Sweden and the Stockholm County Council (ALF project) (CG), Ricerca Corrente, Italian Ministry of Health (G.R., G.B., L.B.), a National Health & Medical Research Council of Australia (NHMRC) Boosting Dementia Research Leadership Fellowship (1138223) (C.D.S.), NHMRC Senior Principal Research Fellowship (1079679) (G.M.H.), NHMRC Senior Research Fellowship (1103258) (O.P.), Fondazione CRF Grant 2015.0722, Fondo ...

Within the framework of xenon-based double beta decay experiments, we propose the possibility to improve the background rejection of an electroluminescent Time Projection Chamber (EL TPC) by reducing the diffusion of the drifting electrons while keeping nearly intact the energy resolution of a pure xenon EL TPC. Based on state-of-the-art microscopic simulations, a substantial addition of helium, around 10 or 15 %, may reduce drastically the transverse diffusion down to 2.5 mm/m from the 10.5 mm/m of pure xenon. The longitudinal diffusion remains around 4 mm/m. Light production studies have been performed as well. They show that the relative variation in energy resolution introduced by such a change does not exceed a few percent, which leaves the energy resolution practically unchanged. The technical caveats of using photomultipliers close to an helium atmosphere are also discussed in detail ; The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the Ministerio de Economía y Competitividad of Spain under grants FIS2014-53371-C04, the Severo Ochoa Program SEV-2014-0398 and the María de Maetzu Program MDM-2016-0692; the GVA of Spain under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT and FEDER through the program COMPETE, projects PTDC/FIS-NUC/2525/2014 and UID/FIS/04559/2013; the U.S. Department of Energy under contracts number DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and de-sc0017721 (University of Texas at Arlington); and the University of Texas at Arlington. We acknowledge partial support from the European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreements No. 690575 and 674896

UK Space Agency ; European Research Council ; UK Science & Technology Facilities Council ; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) ; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; U.S. Department of Energy ; U.S. National Science Foundation ; Ministry of Science and Education of Spain ; Science and Technology Facilities Council of the United Kingdom ; Higher Education Funding Council for England ; National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign ; Kavli Institute of Cosmological Physics at the University of Chicago ; Center for Cosmology and Astro-Particle Physics at the Ohio State University ; Mitchell Institute for Fundamental Physics and Astronomy at Texas AM University ; Financiadora de Estudos e Projetos ; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) ; Ministerio da Ciencia, Tecnologia e Inovacao ; Deutsche Forschungsgemeinschaft ; Argonne National Laboratory ; University of California at Santa Cruz ; University of Cambridge ; Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas-Madrid ; University of Chicago ; University College London ; DES-Brazil Consortium ; University of Edinburgh ; Eidgenossische Technische Hochschule (ETH) Zurich ; Fermi National Accelerator Laboratory ; University of Illinois at Urbana-Champaign ; Institut de Ciencies de l'Espai (IEEC/CSIC) ; Institut de Fisica d'Altes Energies ; Lawrence Berkeley National Laboratory ; Ludwig-Maximilians Universitat Munchen ; associated Excellence Cluster Universe ; University of Michigan ; National Optical Astronomy Observatory ; University of Nottingham ; Ohio State University ; University of Pennsylvania ; University of Portsmouth ; SLAC National Accelerator Laboratory ; Stanford University ; University of Sussex ; Texas AM University ; OzDES Membership Consortium ; National Science Foundation ; MINECO ; European Union ; CERCA programme of the Generalitat de Catalunya ; European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) including ERC grant ; Australian Research Council Centre of Excellence for All-sky Astrophysics (CAASTRO) ; U.S. Department of Energy, Office of Science, Office of High Energy Physics ; United States Government ; UK Space Agency: ST/K00283X/1 ; UK Science & Technology Facilities Council: ST/K0090X/1 ; CNPq: 465376/2014-2 ; National Science Foundation: AST-1138766 ; National Science Foundation: AST-1536171 ; MINECO: AYA2015-71825 ; MINECO: ESP2015-66861 ; MINECO: FPA2015-68048 ; MINECO: SEV-2016-0588 ; MINECO: SEV-2016-0597 ; MINECO: MDM-2015-0509 ; European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) including ERC grant: 240672 ; European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) including ERC grant: 291329 ; European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) including ERC grant: 306478 ; Australian Research Council Centre of Excellence for All-sky Astrophysics (CAASTRO): CE110001020 ; U.S. Department of Energy, Office of Science, Office of High Energy Physics: DE-AC02-07CH11359 ; Mock catalogues are a crucial tool in the analysis of galaxy surveys data, both for the accurate computation of covariance matrices, and for the optimization of analysis methodology and validation of data sets. In this paper, we present a set of 1800 galaxy mock catalogues designed to match the Dark Energy Survey Year-1 BAO sample (Crocce et al. 2017) in abundance, observational volume, redshift distribution and uncertainty, and redshift-dependent clustering. The simulated samples were built upon HALOGEN (Avila et al. 2015) halo catalogues, based on a 2LPTdensity field with an empirical halo bias, For each of them, a light-cone is constructed by the superposition of snapshots in the redshift range 0.45 < z < 1.4. Uncertainties introduced by so-called photometric redshifts estimators were modelled with a double-skewed-Gaussian curve fitted to the data. We populate haloes with galaxies by introducing a hybrid halo occupation distribution-halo abundance matching model with two free parameters. These are adjusted to achieve a galaxy bias evolution b(z(ph)) that matches the data at the 1 sigma level in the range 0.6 < z(ph) < 1.0. We further analyse the galaxy mock catalogues and compare their clustering to the data using the angular correlation function w(theta), the comoving transverse separation clustering xi(mu < 0.8)(S-perpendicular to) and the angular power spectrum C-l, finding them in agreement. This is the first large set of three-dimensional {RA,Dec.,z} galaxy mock catalogues able to simultaneously accurately reproduce the photometric redshift uncertainties and the galaxy clustering.

The modelling community has identified challenges for the integration and assessment of lake models due to the diversity of modelling approaches and lakes. In this study, we develop and assess a one-dimensional lake model and apply it to 32 lakes from a global observatory network. The data set included lakes over broad ranges in latitude, climatic zones, size, residence time, mixing regime and trophic level. Model performance was evaluated using several error assessment metrics, and a sensitivity analysis was conducted for nine parameters that governed the surface heat exchange and mixing efficiency. There was low correlation between input data uncertainty and model performance and predictions of temperature were less sensitive to model parameters than prediction of thermocline depth and Schmidt stability. The study provides guidance to where the general model approach and associated assumptions work, and cases where adjustments to model parameterisations and/or structure are required. (c) 2017 Published by Elsevier Ltd. ; Australian Research Council (ARC)Australian Research Council [DP130104078, LP130100756] ; GLM development and funding support for LCB, BDB, CB and MRH was provided by the Australian Research Council (ARC) (grants DP130104078 & LP130100756). Additional contributions from individuals and organisations as well as sources of data, provided from a variety of organisations are summarised in Appendix D. This study was made possible through the sharing of ideas, data and models across the AEMON and GLEON networks as well as discussions and working groups held during AEMON workshops and GLEON meetings. ; Public domain authored by a U.S. government employee

Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, fi nancial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specifi c and cause-specifi c mortality among children under 5 years, and stillbirths by geography over time. ; Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, fi nancial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specifi c and cause-specifi c mortality among children under 5 years, and stillbirths by geography over time.

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype. ; We thank all participating subjects with AS and healthy individuals who provided the DNA and clinical information necessary for this study. This work was in part funded by grants from Arthritis Research UK (19536 and 18797), the NIHR Oxford comprehensive Biomedical Research Centre (immunity and inflammation theme A93081) and NIHR Thames Valley collaborative research network and National Ankylosing Spondylitis Society (UK). SPARCC was established through the support of the Arthritis Society of Canada. Support was received from National Institutes of Health/National Institute of Allergy and Infectious Diseases grant 1U01AI09090-01. This work was supported in part by grant PI12/02587 (Inst. Carlos III, Spain) and by European Union 'Fondos FEDER'. Support was received from Agence Nationale de la Recherche (grant ANR 2010 GEMISA and Investissements d'Avenir programme ANR-11-IDEX-0005-02), the Société Française de Rhumatologie (SFR) and the Arthritis Foundation. M.W. is funded by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. M.A.B. is funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. D.M.E. is funded by an Australian Research Council Future Fellowship (FT130101709). P.I.W.d.B. is funded in part by the Netherlands Organization for Scientific Research (VIDI Vernieuwingsimpuls project 016.126.354) and by the National Institutes of Health (1R01AR062886-1). ; Peer reviewed

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies. ; This work was supported by the Intramural Research Programs of the National Institute of Biomedical Imaging and Bioengineering, the National Heart, Lung, and Blood ...