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Showing papers by "University of Iowa published in 2015"


Journal ArticleDOI
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

5,668 citations


Journal ArticleDOI
28 Aug 2015-Science
TL;DR: A large-scale assessment suggests that experimental reproducibility in psychology leaves a lot to be desired, and correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
Abstract: Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.

5,532 citations


Journal ArticleDOI
TL;DR: Both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.
Abstract: The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

2,029 citations


Journal ArticleDOI
TL;DR: Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels and there was evidence of a reduction in the rate of cardiovascular events.
Abstract: BackgroundAlirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. MethodsWe conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. ResultsAt week 24, the difference between the alirocumab and placebo ...

1,832 citations


Journal ArticleDOI
08 Sep 2015-JAMA
TL;DR: Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased.
Abstract: Importance Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality. Objective To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers. Design, Setting, Participants Prospective registry of 34 636 infants, 22 to 28 weeks’ gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012. Exposures Extremely preterm birth. Main Outcomes and Measures Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex. Results Use of antenatal corticosteroids increased from 1993 to 2012 (24% [348 of 1431 infants]) to 87% (1674 of 1919 infants];P Conclusions and Relevance Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks’ gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions. Trial Registration clinicaltrials.gov Identifier:NCT00063063.

1,818 citations


Journal ArticleDOI
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

1,656 citations


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +5117 moreInstitutions (314)
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.

1,567 citations


Journal ArticleDOI
TL;DR: Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing technologies, making it well-suited for unsolved problems in genome, transcriptome, and epigenetics research.

1,542 citations


Journal ArticleDOI
TL;DR: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012.

1,030 citations


Journal ArticleDOI
Derrek P. Hibar1, Jason L. Stein2, Jason L. Stein1, Miguel E. Rentería3  +341 moreInstitutions (93)
09 Apr 2015-Nature
TL;DR: In this paper, the authors conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

721 citations


Journal ArticleDOI
Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam  +2134 moreInstitutions (142)
TL;DR: The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays, and no significant deviations are found.
Abstract: Properties of the Higgs boson with mass near 125 GeV are measured in proton-proton collisions with the CMS experiment at the LHC. Comprehensive sets of production and decay measurements are combined. The decay channels include gamma gamma, ZZ, WW, tau tau, bb, and mu mu pairs. The data samples were collected in 2011 and 2012 and correspond to integrated luminosities of up to 5.1 inverse femtobarns at 7 TeV and up to 19.7 inverse femtobarns at 8 TeV. From the high-resolution gamma gamma and ZZ channels, the mass of the Higgs boson is determined to be 125.02 +0.26 -0.27 (stat) +0.14 -0.15 (syst) GeV. For this mass value, the event yields obtained in the different analyses tagging specific decay channels and production mechanisms are consistent with those expected for the standard model Higgs boson. The combined best-fit signal relative to the standard model expectation is 1.00 +/- 0.09 (stat) +0.08 -0.07 (theo) +/- 0.07 (syst) at the measured mass. The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays. No significant deviations are found.

Journal ArticleDOI
TL;DR: The criteria for printing viable and functional scaffolds, scaffolding materials, and 3DP technologies used to print scaffolds for tissue engineering are discussed and could potentially help to meet the demand by patients for tissues and organs without having to wait or rely on donors for transplantation.
Abstract: The current need for organ and tissue replacement, repair, and regeneration for patients is continually growing such that supply is not meeting demand primarily due to a paucity of donors as well as biocompatibility issues leading to immune rejection of the transplant. In order to overcome these drawbacks, scientists have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the ultimate goal of yielding functional tissues or organs. Initial attempts at developing scaffolds were problematic and subsequently inspired an interest in 3D printing as a mode for generating scaffolds. Utilizing three-dimensional printing (3DP) technologies, ECM-like scaffolds can be produced with a high degree of complexity, where fine details can be included at a micrometer level. In this Review, the criteria for printing viable and functional scaffolds, scaffolding materials, and 3DP technologies used to print scaffolds for tissue engineering are discussed. Creating biofunctional scaffolds could potentially help to meet the demand by patients for tissues and organs without having to wait or rely on donors for transplantation.

Journal ArticleDOI
Colm O'Dushlaine1, Lizzy Rossin1, Phil Lee2, Laramie E. Duncan1  +401 moreInstitutions (115)
TL;DR: It is indicated that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders.
Abstract: Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Journal ArticleDOI
TL;DR: The MAVEN spacecraft has eight science instruments (with nine sensors) that measure the energy and particle input from the Sun into the Mars upper atmosphere, the response of the upper atmosphere to that input, and the resulting escape of gas to space as mentioned in this paper.
Abstract: The MAVEN spacecraft launched in November 2013, arrived at Mars in September 2014, and completed commissioning and began its one-Earth-year primary science mission in November 2014 The orbiter’s science objectives are to explore the interactions of the Sun and the solar wind with the Mars magnetosphere and upper atmosphere, to determine the structure of the upper atmosphere and ionosphere and the processes controlling it, to determine the escape rates from the upper atmosphere to space at the present epoch, and to measure properties that allow us to extrapolate these escape rates into the past to determine the total loss of atmospheric gas to space through time These results will allow us to determine the importance of loss to space in changing the Mars climate and atmosphere through time, thereby providing important boundary conditions on the history of the habitability of Mars The MAVEN spacecraft contains eight science instruments (with nine sensors) that measure the energy and particle input from the Sun into the Mars upper atmosphere, the response of the upper atmosphere to that input, and the resulting escape of gas to space In addition, it contains an Electra relay that will allow it to relay commands and data between spacecraft on the surface and Earth


Journal ArticleDOI
TL;DR: The mechanisms and pathways regulating NLRP3 inflammasome activation are reviewed, emerging concepts inNLRP3 complex organization are discussed, and the knowledge gaps hindering a comprehensive understanding of NL RP3 activation are exposed.
Abstract: The NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome is a multiprotein complex that orchestrates innate immune responses to infection and cell stress through activation of caspase-1 and maturation of inflammatory cytokines pro-interleukin-1β (pro-IL-1β) and pro-IL-18. Activation of the inflammasome during infection can be protective, but unregulated NLRP3 inflammasome activation in response to non-pathogenic endogenous or exogenous stimuli can lead to unintended pathology. NLRP3 associates with mitochondria and mitochondrial molecules, and activation of the NLRP3 inflammasome in response to diverse stimuli requires cation flux, mitochondrial Ca(2+) uptake, and mitochondrial reactive oxygen species accumulation. It remains uncertain whether NLRP3 surveys mitochondrial integrity and senses mitochondrial damage, or whether mitochondria simply serve as a physical platform for inflammasome assembly. The structure of the active, caspase-1-processing NLRP3 inflammasome also requires further clarification, but recent studies describing the prion-like properties of ASC have advanced the understanding of how inflammasome assembly and caspase-1 activation occur while raising new questions regarding the propagation and resolution of NLRP3 inflammasome activation. Here, we review the mechanisms and pathways regulating NLRP3 inflammasome activation, discuss emerging concepts in NLRP3 complex organization, and expose the knowledge gaps hindering a comprehensive understanding of NLRP3 activation.

Journal ArticleDOI
Thomas W. Winkler1, Anne E. Justice2, Mariaelisa Graff2, Llilda Barata3  +435 moreInstitutions (106)
TL;DR: In this paper, the authors performed meta-analyses of 114 studies with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium.
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Journal ArticleDOI
TL;DR: In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL.
Abstract: Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death.

Journal ArticleDOI
Emanuele Di Angelantonio1, Stephen Kaptoge1, David Wormser1, Peter Willeit1, Adam S. Butterworth1, Narinder Bansal1, Linda M. O’Keeffe1, Pei Gao1, Angela M. Wood1, Stephen Burgess1, Daniel F. Freitag1, Lisa Pennells1, Sanne A.E. Peters2, Carole L. Hart3, Lise Lund Håheim4, Richard F. Gillum5, Børge G. Nordestgaard6, Bruce M. Psaty7, Bu B. Yeap8, Matthew Knuiman8, Paul J. Nietert9, Jussi Kauhanen10, Jukka T. Salonen11, Lewis H. Kuller12, Leon A. Simons13, Yvonne T. van der Schouw2, Elizabeth Barrett-Connor14, Randi Selmer15, Carlos J. Crespo16, Beatriz L. Rodriguez17, W. M. Monique Verschuren, Veikko Salomaa18, Kurt Svärdsudd19, Pim van der Harst20, Cecilia Björkelund21, Lars Wilhelmsen21, Robert B. Wallace22, Hermann Brenner23, Philippe Amouyel24, Elizabeth L M Barr25, Hiroyasu Iso26, Altan Onat27, Maurizio Trevisan28, Ralph B. D'Agostino29, Cyrus Cooper30, Cyrus Cooper31, Maryam Kavousi32, Lennart Welin, Ronan Roussel33, Ronan Roussel34, Frank B. Hu35, Shinichi Sato, Karina W. Davidson36, Barbara V. Howard37, Maarten J.G. Leening32, Annika Rosengren21, Marcus Dörr38, Dorly J. H. Deeg39, Stefan Kiechl, Coen D.A. Stehouwer40, Aulikki Nissinen18, Simona Giampaoli41, Chiara Donfrancesco41, Daan Kromhout42, Jackie F. Price43, Annette Peters, Tom W. Meade44, Edoardo Casiglia45, Debbie A Lawlor46, John Gallacher47, Dorothea Nagel48, Oscar H. Franco32, Gerd Assmann, Gilles R. Dagenais, J. Wouter Jukema49, Johan Sundström19, Mark Woodward50, Eric J. Brunner51, Kay-Tee Khaw1, Nicholas J. Wareham52, Eric A. Whitsel53, Inger Njølstad54, Bo Hedblad55, Sylvia Wassertheil-Smoller56, Gunnar Engström55, Wayne D. Rosamond53, Elizabeth Selvin57, Naveed Sattar3, Simon G. Thompson1, John Danesh1 
University of Cambridge1, Utrecht University2, University of Glasgow3, University of Oslo4, Howard University5, Copenhagen University Hospital6, University of Washington7, University of Western Australia8, Medical University of South Carolina9, University of Eastern Finland10, Analytical Services11, University of Pittsburgh12, University of New South Wales13, University of California, San Diego14, Norwegian Institute of Public Health15, Portland State University16, University of Hawaii17, National Institutes of Health18, Uppsala University19, University Medical Center Groningen20, University of Gothenburg21, University of Iowa22, German Cancer Research Center23, Pasteur Institute24, Baker IDI Heart and Diabetes Institute25, Osaka University26, Istanbul University27, City College of New York28, Boston University29, University of Oxford30, University of Southampton31, Erasmus University Rotterdam32, French Institute of Health and Medical Research33, Paris Diderot University34, Harvard University35, Columbia University Medical Center36, MedStar Health37, Greifswald University Hospital38, VU University Amsterdam39, Maastricht University Medical Centre40, Istituto Superiore di Sanità41, Wageningen University and Research Centre42, University of Edinburgh43, University of London44, University of Padua45, University of Bristol46, Cardiff University47, Ludwig Maximilian University of Munich48, Leiden University Medical Center49, University of Sydney50, University College London51, Medical Research Council52, University of North Carolina at Chapel Hill53, University of Tromsø54, Lund University55, Albert Einstein College of Medicine56, Johns Hopkins University57
07 Jul 2015-JAMA
TL;DR: Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
Abstract: IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Journal ArticleDOI
TL;DR: Boys were less sedentary and more active than girls at all ages, and overweight/obese participants were less active than their normal weight counterparts from age seven onwards.
Abstract: Physical activity and sedentary behaviour in youth have been reported to vary by sex, age, weight status and country. However, supporting data are often self-reported and/or do not encompass a wide range of ages or geographical locations. This study aimed to describe objectively-measured physical activity and sedentary time patterns in youth. The International Children’s Accelerometry Database (ICAD) consists of ActiGraph accelerometer data from 20 studies in ten countries, processed using common data reduction procedures. Analyses were conducted on 27,637 participants (2.8–18.4 years) who provided at least three days of valid accelerometer data. Linear regression was used to examine associations between age, sex, weight status, country and physical activity outcomes. Boys were less sedentary and more active than girls at all ages. After 5 years of age there was an average cross-sectional decrease of 4.2 % in total physical activity with each additional year of age, due mainly to lower levels of light-intensity physical activity and greater time spent sedentary. Physical activity did not differ by weight status in the youngest children, but from age seven onwards, overweight/obese participants were less active than their normal weight counterparts. Physical activity varied between samples from different countries, with a 15–20 % difference between the highest and lowest countries at age 9–10 and a 26–28 % difference at age 12–13. Physical activity differed between samples from different countries, but the associations between demographic characteristics and physical activity were consistently observed. Further research is needed to explore environmental and sociocultural explanations for these differences.

Journal ArticleDOI
TL;DR: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.
Abstract: Background: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)– associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. Methods: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. Results: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups.

Journal ArticleDOI
Daniel I. Swerdlow1, David Preiss2, Karoline Kuchenbaecker3, Michael V. Holmes1, Jorgen Engmann1, Tina Shah1, Reecha Sofat1, Stefan Stender4, Paul C. D. Johnson2, Robert A. Scott5, Maarten Leusink6, Niek Verweij, Stephen J. Sharp5, Yiran Guo7, Claudia Giambartolomei1, Christina Chung1, Anne Peasey1, Antoinette Amuzu8, KaWah Li7, Jutta Palmen1, Philip N. Howard1, Jackie A. Cooper1, Fotios Drenos1, Yun Li1, Gordon D.O. Lowe2, John Gallacher9, Marlene C. W. Stewart9, Ioanna Tzoulaki10, Sarah G. Buxbaum4, Daphne L. van der A4, Nita G. Forouhi5, N. Charlotte Onland-Moret4, Yvonne T. van der Schouw4, Renate B. Schnabel11, Jaroslav A. Hubacek12, Ruzena Kubinova13, Migle Baceviciene14, Abdonas Tamosiunas13, Andrzej Pajak15, Romanvan Topor-Madry15, Urszula Stepaniak15, Sofia Malyutina15, Damiano Baldassarre16, Bengt Sennblad17, Elena Tremoli16, Ulf de Faire18, Fabrizio Veglia19, Ian Ford2, J. Wouter Jukema20, Rudi G. J. Westendorp20, Gert J. de Borst4, Pim A. de Jong4, Ale Algra, Wilko Spiering, Anke H. Maitland-van der Zee6, Olaf H. Klungel6, Anthonius de Boer6, Pieter A. Doevendans, Charles B. Eaton21, Jennifer G. Robinson22, David Duggan23, John Kjekshus24, John R. Downs25, Antonio M. Gotto, Anthony C Keech, Roberto Marchioli, Gianni Tognoni26, Peter S. Sever, Neil R Poulter, David D. Waters, Terje R. Pedersen, Pierre Amarenco, Haruo Nakamura, John J.V. McMurray2, James Lewsey3, Daniel I. Chasman27, Paul M. Ridker27, Aldo P. Maggioni28, Luigi Tavazzi28, Kausik K. Ray29, Sreenivasa Rao Kondapally Seshasai29, JoAnn E. Manson27, Jackie F. Price9, Peter H. Whincup30, Richard W Morris1, Debbie A Lawlor31, George Davey Smith31, Yoav Ben-Shlomo31, Pamela J. Schreiner32, Myriam Fornage33, David S. Siscovick34, Mary Cushman35, Meena Kumari1, Nicholas J. Wareham5, W M Monique Verschuren4, Susan Redline36, Sanjay R. Patel36, John C. Whittaker32, Anders Hamsten17, Joseph A.C. Delaney37, Caroline Dale38, Tom R. Gaunt30, Andrew Wong1, Diana Kuh1, Rebecca Hardy1, Sekar Kathiresan, Berta Almoguera Castillo7, Pim van der Harst, Eric J. Brunner1, Anne Tybjærg-Hansen4, Michael Marmot1, Ronald M. Krauss39, Michael Y. Tsai26, Josef Coresh40, Ron C. Hoogeveen40, Bruce M. Psaty34, Leslie A. Lange40, Hakon Hakonarson7, Frank Dudbridge8, Steve E. Humphries1, Philippa J. Talmud1, Mika Kivimäki1, Nicholas J. Timpson31, Claudia Langenberg5, Folkert W. Asselbergs, Mikhail Voevoda15, Martin Bobak1, Hynek Pikhart1, James G. Wilson40, Alexander P. Reiner40, Brendan J. Keating7, Aroon D. Hingorani1, Naveed Sattar2 
TL;DR: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.

Journal ArticleDOI
TL;DR: Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients.
Abstract: BackgroundBetween-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth. MethodsWe studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%). ResultsOverall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and su...

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TL;DR: This study suggests ELS may shape the development of brain areas involved with emotion processing and regulation in similar ways, and differences in the amygdala and hippocampus may be a shared diathesis for later negative outcomes related to ELS.

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TL;DR: The idea is that blood flow to the contracting muscle links oxygen in the atmosphere with the contracting muscles where it is consumed in order to link oxygen with the muscle, and the vasodilating factors in the muscle are responsible for these very high flows.
Abstract: This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them We highlight the very high muscle blood flow responses to exercise discovered in the 1980s We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans At this time, no one dominant dilator mechanism accounts for exercise hyperemia Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans

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TL;DR: In this paper, a meta-analysis of 67 flood disaster case studies (1997-2013) was conducted to identify demographic characteristics, socioeconomic status, and health as the leading empirical drivers of social vulnerability to damaging flood events.
Abstract: A leading challenge in measuring social vulnerability to hazards is for output metrics to better reflect the context in which vulnerability occurs. Through a meta-analysis of 67 flood disaster case studies (1997–2013), this paper profiles the leading drivers of social vulnerability to floods. The results identify demographic characteristics, socioeconomic status, and health as the leading empirical drivers of social vulnerability to damaging flood events. However, risk perception and coping capacity also featured prominently in the case studies, yet these factors tend to be poorly reflected in many social vulnerability indicators. The influence of social vulnerability drivers varied considerably by disaster stage and national setting, highlighting the importance of context in understanding social vulnerability precursors, processes, and outcomes. To help tailor quantitative indicators of social vulnerability to flood contexts, the article concludes with recommendations concerning temporal context, measurability, and indicator interrelationships.

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Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam2  +2802 moreInstitutions (215)
04 Jun 2015-Nature
TL;DR: In this paper, the branching fractions of the B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) were observed.
Abstract: The standard model of particle physics describes the fundamental particles and their interactions via the strong, electromagnetic and weak forces. It provides precise predictions for measurable quantities that can be tested experimentally. The probabilities, or branching fractions, of the strange B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) are especially interesting because of their sensitivity to theories that extend the standard model. The standard model predicts that the B-s(0)->mu(+)mu(-) and B-0 ->mu(+)mu(-) decays are very rare, with about four of the former occurring for every billion B-s(0) mesons produced, and one of the latter occurring for every ten billion B-0 mesons(1). A difference in the observed branching fractions with respect to the predictions of the standard model would provide a direction in which the standard model should be extended. Before the Large Hadron Collider (LHC) at CERN2 started operating, no evidence for either decay mode had been found. Upper limits on the branching fractions were an order of magnitude above the standard model predictions. The CMS (Compact Muon Solenoid) and LHCb(Large Hadron Collider beauty) collaborations have performed a joint analysis of the data from proton-proton collisions that they collected in 2011 at a centre-of-mass energy of seven teraelectronvolts and in 2012 at eight teraelectronvolts. Here we report the first observation of the B-s(0)->mu(+)mu(-) decay, with a statistical significance exceeding six standard deviations, and the best measurement so far of its branching fraction. Furthermore, we obtained evidence for the B-0 ->mu(+)mu(-) decay with a statistical significance of three standard deviations. Both measurements are statistically compatible with standard model predictions and allow stringent constraints to be placed on theories beyond the standard model. The LHC experiments will resume taking data in 2015, recording proton-proton collisions at a centre-of-mass energy of 13 teraelectronvolts, which will approximately double the production rates of B-s(0) and B-0 mesons and lead to further improvements in the precision of these crucial tests of the standard model.

Journal ArticleDOI
24 Sep 2015
TL;DR: Both the prevention of AIS and the treatment of its direct underlying cause are not possible, because the definite aetiology and aetiopathogenetic mechanisms that underlie AIS are still unclear.
Abstract: Adolescent idiopathic scoliosis (AIS) is the most common form of structural spinal deformities that have a radiological lateral Cobb angle - a measure of spinal curvature - of ≥10(°). AIS affects between 1% and 4% of adolescents in the early stages of puberty and is more common in young women than in young men. The condition occurs in otherwise healthy individuals and currently has no recognizable cause. In the past few decades, considerable progress has been made towards understanding the clinical patterns and the three-dimensional pathoanatomy of AIS. Advances in biomechanics and technology and their clinical application, supported by limited evidence-based research, have led to improvements in the safety and outcomes of surgical and non-surgical treatments. However, the definite aetiology and aetiopathogenetic mechanisms that underlie AIS are still unclear. Thus, at present, both the prevention of AIS and the treatment of its direct underlying cause are not possible.

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TL;DR: The expected accuracy of ne and issues in the interpretation of the electrostatic wave spectrum are described and described.
Abstract: The twin Van Allen Probe spacecraft, launched in August 2012, carry identical scientific payloads. The Electric and Magnetic Field Instrument Suite and Integrated Science suite includes a plasma wave instrument (Waves) that measures three magnetic and three electric components of plasma waves in the frequency range of 10 Hz to 12 kHz using triaxial search coils and the Electric Fields and Waves triaxial electric field sensors. The Waves instrument also measures a single electric field component of waves in the frequency range of 10 to 500 kHz. A primary objective of the higher-frequency measurements is the determination of the electron density ne at the spacecraft, primarily inferred from the upper hybrid resonance frequency fuh. Considerable work has gone into developing a process and tools for identifying and digitizing the upper hybrid resonance frequency in order to infer the electron density as an essential parameter for interpreting not only the plasma wave data from the mission but also as input to various magnetospheric models. Good progress has been made in developing algorithms to identify fuh and create a data set of electron densities. However, it is often difficult to interpret the plasma wave spectra during active times to identify fuh and accurately determine ne. In some cases, there is no clear signature of the upper hybrid band, and the low-frequency cutoff of the continuum radiation is used. We describe the expected accuracy of ne and issues in the interpretation of the electrostatic wave spectrum.

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Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam2  +2119 moreInstitutions (141)
29 May 2015
TL;DR: In this paper, a search for particle dark matter (DM), extra dimensions, and unparticles using events containing a jet and an imbalance in transverse momentum was conducted at the LHC.
Abstract: Results are presented from a search for particle dark matter (DM), extra dimensions, and unparticles using events containing a jet and an imbalance in transverse momentum. The data were collected by the CMS detector in proton-proton collisions at the LHC and correspond to an integrated luminosity of 19.7 fb$^{-1}$ at a centre-of-mass energy of 8 TeV. The number of observed events is found to be consistent with the standard model prediction. Limits are placed on the DM-nucleon scattering cross section as a function of the DM particle mass for spin-dependent and spin-independent interactions. Limits are also placed on the scale parameter $M_\mathrm{D}$ in the ADD model of large extra dimensions, and on the unparticle model parameter $\Lambda_\mathrm{U}$. The constraints on ADD models and unparticles are the most stringent limits in this channel and those on the DM-nucleon scattering cross section are an improvement over previous collider results.