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Showing papers by "University of Ioannina published in 2018"


Journal ArticleDOI
Mary F. Feitosa1, Aldi T. Kraja1, Daniel I. Chasman2, Yun J. Sung1  +296 moreInstitutions (86)
18 Jun 2018-PLOS ONE
TL;DR: In insights into the role of alcohol consumption in the genetic architecture of hypertension, a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions is conducted.
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

1,218 citations


Journal ArticleDOI
TL;DR: In this article, the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry was conducted.
Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future

728 citations


Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Federico Ambrogi1  +2238 moreInstitutions (159)
TL;DR: In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented.
Abstract: Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The b jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV).

454 citations


Journal ArticleDOI
Gail Davies1, Max Lam, Sarah E. Harris1, Joey W. Trampush2  +254 moreInstitutions (79)
TL;DR: In this paper, the authors combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci associated with general cognitive function.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

421 citations


Journal ArticleDOI
TL;DR: It is demonstrated that black-hole solutions appear as a generic feature of this general Einstein-scalar-Gauss-Bonnet theory since a regular horizon and an asymptotically flat solution may be easily constructed under mild assumptions for f(ϕ).
Abstract: We consider a general Einstein-scalar-Gauss-Bonnet theory with a coupling function f(ϕ). We demonstrate that black-hole solutions appear as a generic feature of this theory since a regular horizon and an asymptotically flat solution may be easily constructed under mild assumptions for f(ϕ). We show that the existing no-hair theorems are easily evaded, and a large number of regular black-hole solutions with scalar hair are then presented for a plethora of coupling functions f(ϕ).

419 citations



Journal ArticleDOI
TL;DR: The proposed LSTM-based methodology delivers a significant increase in seizure prediction performance compared to both traditional machine learning techniques and convolutional neural networks that have been previously evaluated in the literature.

374 citations


Journal ArticleDOI
20 Mar 2018-PLOS ONE
TL;DR: A healthy lifestyle pattern could lead to decreased risk for T2DM, and future randomized clinical trials should focus on identifying efficient strategies to modify harmful daily habits and predisposing dietary patterns.
Abstract: Background Type 2 diabetes mellitus (T2DM) is a global epidemic associated with increased health expenditure, and low quality of life. Many non-genetic risk factors have been suggested, but their overall epidemiological credibility has not been assessed. Methods We searched PubMed to capture all meta-analyses and Mendelian randomization studies for risk factors of T2DM. For each association, we estimated the summary effect size, its 95% confidence and prediction interval, and the I2 metric. We examined the presence of small-study effects and excess significance bias. We assessed the epidemiological credibility through a set of predefined criteria. Results We captured 86 eligible papers (142 associations) covering a wide range of biomarkers, medical conditions, and dietary, lifestyle, environmental and psychosocial factors. Adiposity, low hip circumference, serum biomarkers (increased level of alanine aminotransferase, gamma-glutamyl transferase, uric acid and C-reactive protein, and decreased level of adiponectin and vitamin D), an unhealthy dietary pattern (increased consumption of processed meat and sugar-sweetened beverages, decreased intake of whole grains, coffee and heme iron, and low adherence to a healthy dietary pattern), low level of education and conscientiousness, decreased physical activity, high sedentary time and duration of television watching, low alcohol drinking, smoking, air pollution, and some medical conditions (high systolic blood pressure, late menarche age, gestational diabetes, metabolic syndrome, preterm birth) presented robust evidence for increased risk of T2DM. Conclusions A healthy lifestyle pattern could lead to decreased risk for T2DM. Future randomized clinical trials should focus on identifying efficient strategies to modify harmful daily habits and predisposing dietary patterns.

360 citations


Journal ArticleDOI
TL;DR: A more detailed classification of uveitis with the establishment of uniform diagnostic criteria and prospective population based studies would certainly benefit epidemiologic research and clinical practice.
Abstract: Purpose: Uveitis is a common, sight-threatening inflammatory ocular disease and includes multiple heterogeneous clinical entities. The prevalence of various types of uveitis depends upon multiple f...

314 citations


Journal ArticleDOI
TL;DR: In this paper, the performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016.
Abstract: The CMS muon detector system, muon reconstruction software, and high-level trigger underwent significant changes in 2013–2014 in preparation for running at higher LHC collision energy and instantaneous luminosity. The performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016. The measured performance parameters, including spatial resolution, efficiency, and timing, are found to meet all design specifications and are well reproduced by simulation. Despite the more challenging running conditions, the modified muon system is found to perform as well as, and in many aspects better than, previously. We dedicate this paper to the memory of Prof. Alberto Benvenuti, whose work was fundamental for the CMS muon detector.

303 citations



Journal ArticleDOI
TL;DR: These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.
Abstract: Background:The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through d

Journal ArticleDOI
Valérie Turcot1, Yingchang Lu2, Yingchang Lu3, Heather M. Highland4  +486 moreInstitutions (129)
TL;DR: Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index that confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
Abstract: Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2240 moreInstitutions (157)
TL;DR: In this article, a measurement of the H→ττ signal strength is performed using events recorded in proton-proton collisions by the CMS experiment at the LHC in 2016 at a center-of-mass energy of 13TeV.

Journal ArticleDOI
TL;DR: This Special Report presents a description of Geant4-DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path…) and shows that the most recent sets of physics models available in Geant 4-DNA enable more accurate simulation of stopping powers, dose point kernels, and W-values in liquidWater.
Abstract: This Special Report presents a description of Geant4-DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path…). These example applications are included in the Geant4 Monte Carlo toolkit and are available in open access. Each application is described and comparisons to recent international recommendations are shown (e.g., ICRU, MIRD), when available. The influence of physics models available in Geant4-DNA for the simulation of electron interactions in liquid water is discussed. Thanks to these applications, the authors show that the most recent sets of physics models available in Geant4-DNA (the so-called "option4" and "option 6" sets) enable more accurate simulation of stopping powers, dose point kernels, and W-values in liquid water, than the default set of models ("option 2") initially provided in Geant4-DNA. They also serve as reference applications for Geant4-DNA users interested in TS simulations.

Journal ArticleDOI
TL;DR: These are the first direct limits for N mass above 500 GeV and the first limits obtained at a hadron collider for N masses below 40 Ge V.
Abstract: A search for a heavy neutral lepton N of Majorana nature decaying into a W boson and a charged lepton is performed using the CMS detector at the LHC. The targeted signature consists of three prompt charged leptons in any flavor combination of electrons and muons. The data were collected in proton-proton collisions at a center-of-mass energy of 13 TeV, with an integrated luminosity of 35.9 fb^(−1). The search is performed in the N mass range between 1 GeV and 1.2 TeV. The data are found to be consistent with the expected standard model background. Upper limits are set on the values of |V_(eN)|^2and |V_(μN)|^2, where V_(lN) is the matrix element describing the mixing of N with the standard model neutrino of flavor l. These are the first direct limits for N masses above 500 GeV and the first limits obtained at a hadron collider for N masses below 40 GeV.

Journal ArticleDOI
TL;DR: Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts and population-wide strategies to tackle obesity are challenged, challenging the concept of 'metabolically healthy obesity.
Abstract: EPIC-CVD has been supported by the European Union Framework 7 (HEALTH-F2-2012-279233), the European Research Council (268834), the UK Medical Research Council (G0800270 and MR/L003120/1), the British Heart Foundation (SP/09/002 and RG/08/014 and RG13/13/30194), and the UK National Institute of Health Research. EPIC Asturias was also supported by the Regional Government of Asturias. EPIC-Greece is also supported by the Hellenic Health Foundation. EPIC- Heidelberg was also supported by the German Cancer Aid, German Cancer Research Centre, German Federal Ministry of Education and Research. EPIC-Oxford was also supported by the UK Medical Research Council (MR/M012190/1) and Cancer Research UK (570/A16491). EPIC-Ragusa was also supported by the Sicilian Government, AIRE ONLUS Ragusa, and AVIS Ragusa. EPIC-Turin was supported also by the Compagnia di San Paolo and the Human Genetics Foundation-Torino (HuGeF).

Journal ArticleDOI
TL;DR: In this paper, the existence of regular black-hole solutions with scalar hair was investigated in the context of the Einstein-scalar-Gauss-Bonnet theory, with a general coupling function between the scalar field and the quadratic Gauss Bonnet term.
Abstract: In the context of the Einstein-scalar-Gauss-Bonnet theory, with a general coupling function between the scalar field and the quadratic Gauss-Bonnet term, we investigate the existence of regular black-hole solutions with scalar hair. Based on a previous theoretical analysis, which studied the evasion of the old and novel no-hair theorems, we consider a variety of forms for the coupling function (exponential, even and odd polynomial, inverse polynomial, and logarithmic) that, in conjunction with the profile of the scalar field, satisfy a basic constraint. Our numerical analysis then always leads to families of regular, asymptotically flat black-hole solutions with nontrivial scalar hair. The solution for the scalar field and the profile of the corresponding energy-momentum tensor, depending on the value of the coupling constant, may exhibit a nonmonotonic behavior, an unusual feature that highlights the limitations of the existing no-hair theorems. We also determine and study in detail the scalar charge, horizon area, and entropy of our solutions.

Journal ArticleDOI
27 Feb 2018-BMJ
TL;DR: Most CIN2 lesions, particularly in young women (<30 years), regress spontaneously, and active surveillance, rather than immediate intervention, is justified, especially among young women who are likely to adhere to monitoring.
Abstract: Objective To estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols. Design Systematic review and meta-analysis. Data sources Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016. Eligibility criteria Studies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months. Data synthesis Two reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I2 statistics. Main outcome measures Rates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months). Results 36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I2=77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I2=82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I2=90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I2=0%), 23% (two studies, 226/938 women, 20% to 26%; I2=97%), and 11% (three studies, 163/1033 women, 5% to 19%; I2=67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%. Conclusions Most CIN2 lesions, particularly in young women ( Systematic review registration PROSPERO 2014: CRD42014014406.

Journal ArticleDOI
Carolina Medina-Gomez1, John P. Kemp2, John P. Kemp3, Katerina Trajanoska1, Jian'an Luan4, Alessandra Chesi5, Tarunveer S. Ahluwalia6, Tarunveer S. Ahluwalia7, Dennis O. Mook-Kanamori8, Annelies C. Ham1, Fernando Pires Hartwig9, Daniel S. Evans10, Raimo Joro11, Ivana Nedeljkovic1, Hou-Feng Zheng12, Hou-Feng Zheng13, Hou-Feng Zheng14, Kun Zhu15, Kun Zhu16, Mustafa Atalay11, Ching-Ti Liu17, Maria Nethander18, Linda Broer1, Gudmar Porleifsson19, Benjamin H. Mullin16, Benjamin H. Mullin15, Samuel K. Handelman20, Mike A. Nalls21, Leon Eyrich Jessen6, Denise H. M. Heppe1, J. Brent Richards13, Carol A. Wang15, Bo L. Chawes6, Katharina E. Schraut22, Najaf Amin1, Nicholas J. Wareham4, David Karasik23, Nathalie van der Velde24, Nathalie van der Velde1, M. Arfan Ikram1, Babette S. Zemel5, Yanhua Zhou17, Christian J. Carlsson6, Yongmei Liu25, Fiona E. McGuigan26, Cindy G. Boer1, Klaus Bønnelykke6, Stuart H. Ralston22, John A Robbins27, John P. Walsh15, John P. Walsh16, M. Carola Zillikens1, Claudia Langenberg4, Ruifang Li-Gao8, Frances M K Williams28, Tamara B. Harris21, Kristina Åkesson26, Rebecca D. Jackson29, Gunnar Sigurdsson30, Martin den Heijer31, Martin den Heijer8, Bram C. J. van der Eerden1, Jeroen van de Peppel1, Tim D. Spector28, Craig E. Pennell15, Bernardo L. Horta9, Janine F. Felix1, Jing Hua Zhao4, Scott Wilson16, Scott Wilson28, Scott Wilson15, Renée de Mutsert8, Hans Bisgaard6, Unnur Styrkarsdottir19, Vincent W. V. Jaddoe1, Eric S. Orwoll32, Timo A. Lakka11, Robert A. Scott4, Struan F.A. Grant33, Mattias Lorentzon18, Cornelia M. van Duijn1, James F. Wilson22, Kari Stefansson19, Bruce M. Psaty34, Bruce M. Psaty35, Douglas P. Kiel, Claes Ohlsson18, Evangelia E. Ntzani36, Andre J. van Wijnen37, Vincenzo Forgetta13, Mohsen Ghanbari1, Mohsen Ghanbari38, John G. Logan39, Graham R. Williams39, J. H. Duncan Bassett39, Peter I. Croucher40, Evangelos Evangelou36, Evangelos Evangelou39, André G. Uitterlinden1, Cheryl L. Ackert-Bicknell41, Jonathan H Tobias2, David M. Evans3, David M. Evans2, Fernando Rivadeneira1 
TL;DR: TB-BMD is revealed as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments and their effect can be captured throughout the life course.
Abstract: Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2357 moreInstitutions (197)
TL;DR: In this article, a low-mass search for resonances decaying into pairs of jets is performed using proton-proton collision data collected at s√=13 TeV corresponding to an integrated luminosity of up to 36 fb−1.
Abstract: Searches for resonances decaying into pairs of jets are performed using proton-proton collision data collected at s√=13 TeV corresponding to an integrated luminosity of up to 36 fb−1. A low-mass search, for resonances with masses between 0.6 and 1.6 TeV, is performed based on events with dijets reconstructed at the trigger level from calorimeter information. A high-mass search, for resonances with masses above 1.6 TeV, is performed using dijets reconstructed offline with a particle-flow algorithm. The dijet mass spectrum is well described by a smooth parameterization and no evidence for the production of new particles is observed. Upper limits at 95% confidence level are reported on the production cross section for narrow resonances with masses above 0.6 TeV. In the context of specific models, the limits exclude string resonances with masses below 7.7 TeV, scalar diquarks below 7.2 TeV, axigluons and colorons below 6.1 TeV, excited quarks below 6.0 TeV, color-octet scalars below 3.4 TeV, W′ bosons below 3.3 TeV, Z′ bosons below 2.7 TeV, Randall-Sundrum gravitons below 1.8 TeV and in the range 1.9 to 2.5 TeV, and dark matter mediators below 2.6 TeV. The limits on both vector and axial-vector mediators, in a simplified model of interactions between quarks and dark matter particles, are presented as functions of dark matter particle mass and coupling to quarks. Searches are also presented for broad resonances, including for the first time spin-1 resonances with intrinsic widths as large as 30% of the resonance mass. The broad resonance search improves and extends the exclusions of a dark matter mediator to larger values of its mass and coupling to quarks.

Journal ArticleDOI
TL;DR: Physical activity is associated with a lower risk of several cancers, but only colon and breast cancer associations were supported by strong or highly suggestive evidence, respectively.
Abstract: Objective To provide an overview of the breadth and validity of claimed associations between physical activity and risk of developing or dying from cancer. Design Umbrella review. Data sources We searched Medline, Embase, Cochrane Database and Web of Science. Eligibility criteria for selecting studies Systematic reviews about physical activity and cancer incidence and cancer mortality in different body sites among general population. Results We included 19 reviews covering 22 cancer sites, 26 exposure-outcome pairs meta-analyses and 541 original studies. Physical activity was associated with lower risk of seven cancer sites (colon, breast, endometrial, lung, oesophageal, pancreas and meningioma). Only colon (a protective association with recreational physical activity) and breast cancer (a protective association with overall physical activity) were supported by strong evidence and highly suggestive evidence, respectively. Evidence from endometrial, lung, oesophageal, pancreas and meningioma presented hints of uncertainty and bias in the literature ( eg, not reaching P values -6 ) showing large between-study heterogeneity and/or not demonstrating a definite direction for the effect when 95% prediction intervals were considered. Four of the 26 meta-analyses showed small study effects and 4 showed excess significance. Conclusion Physical activity is associated with a lower risk of several cancers, but only colon and breast cancer associations were supported by strong or highly suggestive evidence, respectively. Evidence from other cancer sites was less consistent, presenting hints of uncertainty and/or bias.

Journal ArticleDOI
TL;DR: In this paper, an updated extended compilation of distinct (but possibly correlated) $fensuremath{\sigma}}{8}(z)$ redshift space distortion (RSD) data published between 2006 and 2018 is presented.
Abstract: We construct an updated extended compilation of distinct (but possibly correlated) $f{\ensuremath{\sigma}}_{8}(z)$ redshift space distortion (RSD) data published between 2006 and 2018. It consists of 63 datapoints and is significantly larger than previously used similar data sets. After fiducial model correction we obtain the best fit ${\mathrm{\ensuremath{\Omega}}}_{0m}\ensuremath{-}{\ensuremath{\sigma}}_{8}$ $\mathrm{\ensuremath{\Lambda}}\mathrm{CDM}$ parameters and show that they are at a $5\ensuremath{\sigma}$ tension with the corresponding $\text{Planck}15/\mathrm{\ensuremath{\Lambda}}\mathrm{CDM}$ values. Introducing a nontrivial covariance matrix correlating randomly 20% of the RSD datapoints has no significant effect on the above tension level. We show that the tension disappears (becomes less than $1\ensuremath{\sigma}$) when a subsample of the 20 most recently published data is used. A partial cause for this reduced tension is the fact that more recent data tend to probe higher redshifts (with higher errorbars) where there is degeneracy among different models due to matter domination. Allowing for a nontrivial evolution of the effective Newton's constant as ${G}_{\mathrm{eff}}(z)/{G}_{\mathrm{N}}=1+{g}_{a}{(\frac{z}{1+z})}^{2}\ensuremath{-}{g}_{a}{(\frac{z}{1+z})}^{4}$ (${g}_{a}$ is a parameter) and fixing a $\text{Planck}15/\mathrm{\ensuremath{\Lambda}}\mathrm{CDM}$ background we find ${g}_{a}=\ensuremath{-}0.91\ifmmode\pm\else\textpm\fi{}0.17$ from the full $f{\ensuremath{\sigma}}_{8}$ data set while the 20 earliest and 20 latest datapoints imply ${g}_{a}=\ensuremath{-}{1.28}_{\ensuremath{-}0.26}^{+0.28}$ and ${g}_{a}=\ensuremath{-}0.4{3}_{\ensuremath{-}0.41}^{+0.46}$ respectively. Thus, the more recent $f{\ensuremath{\sigma}}_{8}$ data appear to favor GR in contrast to earlier data. Finally, we show that the parametrization $f{\ensuremath{\sigma}}_{8}(z)=\ensuremath{\lambda}{\ensuremath{\sigma}}_{8}\mathrm{\ensuremath{\Omega}}(z{)}^{\ensuremath{\gamma}}/(1+z{)}^{\ensuremath{\beta}}$ provides an excellent fit to the solution of the growth equation for both GR (${g}_{a}=0$) and modified gravity (${g}_{a}\ensuremath{ e}0$).

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2314 moreInstitutions (196)
TL;DR: A statistical combination of several searches for the electroweak production of charginos and neutralinos is presented in this article, where a targeted analysis requiring three or more charged leptons (electrons or muons) is presented, focusing on the challenging scenario in which the difference in mass between the two least massive neutralino is approximately equal to the mass of the Z boson.
Abstract: A statistical combination of several searches for the electroweak production of charginos and neutralinos is presented. All searches use proton-proton collision data at $ \sqrt{s}=13 $ TeV, recorded with the CMS detector at the LHC in 2016 and corresponding to an integrated luminosity of 35.9 fb$^{−1}$. In addition to the combination of previous searches, a targeted analysis requiring three or more charged leptons (electrons or muons) is presented, focusing on the challenging scenario in which the difference in mass between the two least massive neutralinos is approximately equal to the mass of the Z boson. The results are interpreted in simplified models of chargino-neutralino or neutralino pair production. For chargino-neutralino production, in the case when the lightest neutralino is massless, the combination yields an observed (expected) limit at the 95% confidence level on the chargino mass of up to 650 (570) GeV, improving upon the individual analysis limits by up to 40 GeV. If the mass difference between the two least massive neutralinos is approximately equal to the mass of the Z boson in the chargino-neutralino model, the targeted search requiring three or more leptons obtains observed and expected exclusion limits of around 225 GeV on the second neutralino mass and 125 GeV on the lightest neutralino mass, improving the observed limit by about 60 GeV in both masses compared to the previous CMS result. In the neutralino pair production model, the combined observed (expected) exclusion limit on the neutralino mass extends up to 650–750 (550–750) GeV, depending on the branching fraction assumed. This extends the observed exclusion achieved in the individual analyses by up to 200 GeV. The combined result additionally excludes some intermediate gaps in the mass coverage of the individual analyses.

Journal ArticleDOI
TL;DR: In this article, the authors exhaustively review the experimental and computational works in the literature dealing with the optical properties and electronic structure of transition metal nitrides (TMN) spanning over three decades of time and employing all the available growth techniques.
Abstract: The nitrides of most of the group IVb-Vb-VIb transition metals (TiN, ZrN, HfN, VN, NbN, TaN, MoN, WN) constitute the unique category of conductive ceramics. Having substantial electronic conductivity, exceptionally high melting points and covering a wide range of work function values, they were considered for a variety of electronic applications, which include diffusion barriers in metallizations of integrated circuits, Ohmic contacts on compound semiconductors, and thin film resistors, since early eighties. Among them, TiN and ZrN are recently emerging as significant candidates for plasmonic applications. So the possible plasmonic activity of the rest of transition metal nitrides (TMN) emerges as an important open question. In this work, we exhaustively review the experimental and computational (mostly ab initio) works in the literature dealing with the optical properties and electronic structure of TMN spanning over three decades of time and employing all the available growth techniques. We critically evaluate the optical properties of all TMN and we model their predicted plasmonic response. Hence, we provide a solid understanding of the intrinsic (e.g. the valence electron configuration of the constituent metal) and extrinsic (e.g. point defects and microstructure) factors that dictate the plasmonic performance. Based on the reported optical spectra, we evaluate the quality factors for surface plasmon polariton and localized surface plasmon for various TMN and critically compare them to each other. We demonstrate that, indeed TiN and ZrN along with HfN are the most well-performing plasmonic materials in the visible range, while VN and NbN may be viable alternatives for plasmonic devices in the blue, violet and near UV ranges, albeit in expense of increased electronic loss. Furthermore, we consider the alloyed ternary TMN and by critical evaluation and comparison of the reported experimental and computational works, we identify the emerging optimal tunable plasmonic conductors among the immense number of alloying combinations.

Journal ArticleDOI
Antonio J. Vallejo-Vaz1, Martina De Marco1, C. Stevens1, Asif Akram, Tomáš Freiberger2, G. Kees Hovingh, John J.P. Kastelein, Pedro Mata, Frederick J. Raal3, Raul D. Santos4, Handrean Soran5, Gerald F. Watts6, Marianne Abifadel7, Carlos A. Aguilar-Salinas, Mutaz Alkhnifsawi, Fahad Alkindi8, Fahad Alnouri, Rodrigo Alonso, Khalid Al-Rasadi9, Ahmad Al-Sarraf, T.F. Ashavaid, Christoph J. Binder10, Martin Prøven Bogsrud11, Mafalda Bourbon, Eric Bruckert12, Krzysztof Chlebus13, Pablo Corral, Olivier S. Descamps, Ronen Durst14, Marat V. Ezhov, Zlatko Fras15, Jacques Genest16, Urh Groselj15, Mariko Harada-Shiba, Meral Kayıkçıoğlu17, Katarina Lalic18, Carolyn S.P. Lam19, Gustavs Latkovskis20, Ulrich Laufs, Evangelos Liberopoulos21, Jie Lin22, Vincent Maher, Nelson Majano, A. David Marais23, Winfried März24, Erkin M. Mirrakhimov25, André R. Miserez26, Olena Mitchenko27, Hapizah Nawawi28, Børge G. Nordestgaard29, György Paragh30, Zaneta Petrulioniene31, Belma Pojskic, Arman Postadzhiyan32, Ashraf Reda, Željko Reiner33, Wilson E Sadoh34, Amirhossein Sahebkar35, Abdullah Shehab36, Aleksander B Shek, Mario Stoll, Ta-Chen Su37, Tavintharan Subramaniam38, Andrey V. Susekov27, Phivos Symeonides, Myra Tilney39, Brian Tomlinson40, Thanh-Huong Truong41, Alexandros D. Tselepis21, Anne Tybjærg-Hansen29, Alejandra Vázquez-Cárdenas42, Margus Viigimaa43, Branislav Vohnout44, Elisabeth Widen45, Shizuya Yamashita46, Maciej Banach47, Dan Gaita, Lixin Jiang, Lennart Nilsson48, Lourdes Ella G. Santos49, Heribert Schunkert50, Lale Tokgozoglu51, Josip Car52, Alberico L. Catapano53, Kausik K. Ray1 
Imperial College London1, Central European Institute of Technology2, University of the Witwatersrand3, University of São Paulo4, University of Manchester5, University of Western Australia6, Saint Joseph's University7, Hamad Medical Corporation8, Sultan Qaboos University9, Medical University of Vienna10, Oslo University Hospital11, Institute of Chartered Accountants of Nigeria12, Gdańsk Medical University13, Hebrew University of Jerusalem14, Ljubljana University Medical Centre15, McGill University Health Centre16, Ege University17, University of Belgrade18, National University of Singapore19, University of Latvia20, University of Ioannina21, Capital Medical University22, National Health Laboratory Service23, Heidelberg University24, Kyrgyz State Medical Academy25, University of Basel26, Academy of Medical Sciences, United Kingdom27, Universiti Teknologi MARA28, University of Copenhagen29, University of Debrecen30, Vilnius University31, Sofia Medical University32, University of Zagreb33, University of Benin34, Mashhad University of Medical Sciences35, United Arab Emirates University36, National Taiwan University37, Khoo Teck Puat Hospital38, University of Malta39, The Chinese University of Hong Kong40, National Institutes of Health41, Universidad Autónoma de Guadalajara42, Tallinn University of Technology43, Slovak Medical University44, University of Helsinki45, Osaka University46, Medical University of Łódź47, Linköping University48, University of the Philippines49, Technische Universität München50, Hacettepe University51, Nanyang Technological University52, University of Milan53
TL;DR: FH is a recognised public health concern, with overall suboptimal identification and under-treatment, and efforts and initiatives to improve FH knowledge and management are underway, but support from health authorities and better funding are greatly needed.

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2291 moreInstitutions (195)
TL;DR: In this paper, a search for the direct electroweak production of charginos and neutralinos in signatures with either two or more leptons (electrons or muons) of the same electric charge, or with three or more hadronically decaying tau-leptons.
Abstract: Results are presented from a search for the direct electroweak production of charginos and neutralinos in signatures with either two or more leptons (electrons or muons) of the same electric charge, or with three or more leptons, which can include up to two hadronically decaying tau leptons. The results are based on a sample of proton-proton collision data collected at $ \sqrt{s}=13 $ TeV, recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb$^{−1}$. The observed event yields are consistent with the expectations based on the standard model. The results are interpreted in simplified models of supersymmetry describing various scenarios for the production and decay of charginos and neutralinos. Depending on the model parameters chosen, mass values between 180 GeV and 1150 GeV are excluded at 95% CL. These results significantly extend the parameter space probed for these particles in searches at the LHC. In addition, results are presented in a form suitable for alternative theoretical interpretations.

Journal ArticleDOI
TL;DR: A pilot version checklist with Preferred Reporting Items for OoSRs (PRIO-harms) to promote a more balanced reporting of benefits and harms in Oo SRs of health care interventions and will assist overview authors to improve completeness and transparency of research reporting.

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2340 moreInstitutions (198)
TL;DR: A measurement of the inelastic proton-proton cross section with the CMS detector at a center-of-mass energy of $ \sqrt{s}=13 $ TeV is presented in this paper.
Abstract: A measurement of the inelastic proton-proton cross section with the CMS detector at a center-of-mass energy of $ \sqrt{s}=13 $ TeV is presented. The analysis is based on events with energy deposits in the forward calorimeters, which cover pseudorapidities of −6.6 4.1 GeV and/or M$_{Y}$ > 13 GeV, where M$_{X}$ and M$_{Y}$ are the masses of the diffractive dissociation systems at negative and positive pseudorapidities, respectively. The results are compared with those from other experiments as well as to predictions from high-energy hadron-hadron interaction models.

Journal ArticleDOI
Albert M. Sirunyan1, Robin Erbacher2, Wagner Carvalho3, Maciej Górski  +2272 moreInstitutions (151)
TL;DR: The first observation of electroweak production of same-sign W boson pairs in proton-proton collisions was reported in this article, where the data sample corresponds to an integrated luminosity of 359 fb^(−1) collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC Events are selected by requiring exactly two leptons (electrons or muons) of the same charge, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass.
Abstract: The first observation of electroweak production of same-sign W boson pairs in proton-proton collisions is reported The data sample corresponds to an integrated luminosity of 359 fb^(−1) collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC Events are selected by requiring exactly two leptons (electrons or muons) of the same charge, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass The observed significance of the signal is 55 standard deviations, where a significance of 57 standard deviations is expected based on the standard model The ratio of measured event yields to that expected from the standard model at leading order is 090 ± 022 A cross section measurement in a fiducial region is reported Bounds are given on the structure of quartic vector boson interactions in the framework of dimension-8 effective field theory operators and on the production of doubly charged Higgs bosons