Effect of prolonged treatment with phosphodiesterase-5-inhibitors on endothelial dysfunction in vascular diseases and vascular risk conditions: A systematic review analysis and meta-analysis of randomized double-blind placebo-controlled trials.

OBJECTIVE To challenge the argument that continuous use of phosphodiesterase-5-selective inhibitors may reduce endothelial cell dysfunction in patients with vascular diseases or vascular risk conditions. DESIGN This study included systematic reviews and meta-analysis of randomized double-blind placebo-controlled trials dealing with the prolonged use of phosphodiesterase-5-selective inhibitors. The risk of bias and quality of trials were assessed by the Cochrane algorithm. Fixed or random effect models, standardised mean differences and heterogeneity were estimated in the study. DATA SOURCES Systematic search for randomized double-blind placebo-controlled trials was done in PubMed, Scopus, CINAHL, Science direct and the Cochrane Library. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomized double-blind placebo-controlled trials reporting measures of endothelial cell dysfunction and/or endothelial cell activation were included. RESULTS On the whole, 469 subjects were allocated to the phosphodiesterase-5-selective inhibitor group, while 463 were assigned to the placebo group in 13 randomized double-blind placebo-controlled trials. Flow-mediated dilation of the brachial artery was found to improve after the administration of phosphodiesterase-5-selective inhibitors (P < 0.0001). The results were questioned by the elevated and uncorrectable heterogeneity (I2 = 92%) and the asymmetry of the funnel plot suggested a publication bias. Phosphodiesterase-5-selective inhibitors have no effect on endothelial cell dysfunction, as assessed in the resistance vessels by digital arterial tonometry. The blood level of endothelin-1 was observed to be decreased in phosphodiesterase-5-selective inhibitors arm (P = 0.03), although the effect disappeared once the publication bias and heterogeneity were corrected. The effect of phosphodiesterase-5-selective inhibitors on biomarkers of endothelial cell activation was found to be inconsistent. CONCLUSIONS The results on the benefits of a prolonged use of phosphodiesterase-5-selective inhibitors, with the objective of lowering endothelial cell dysfunction in patients with vascular diseases or vascular risk conditions are not convincing. This is because of the overall low quality of evidence, giving an unclear scientific support to this treatment. Systematic review registration: PROSPERO registration: CRD42017055399

Testicular Cancer in Infertile Men With and Without Testicular Microlithiasis: A Systematic Review and Meta-Analysis of Case-Control Studies

Background: An association between testicular microlithiasis (TM) and both carcinoma in situ (CIS) of the testis and testicular germ cell tumors (TGCTs) has been reported. Furthermore, TM seems to be significantly more prevalent in men with male-factor infertility, representing itself a risk factor for TGCT. Nevertheless, the evidence of the association of TM with a higher prevalence of testicular cancer in infertile men remains inconclusive. The aim of this study was to systematically evaluate whether, and to what extent, TM is associated to a significantly higher prevalence of testicular cancer in infertile males.Methods: A thorough search of MEDLINE, SCOPUS, CINAHL, WEB OF SCIENCE, and Cochrane Library databases was carried out to identify case-control studies comparing the prevalence of testicular cancer in infertile men with and without TM. Methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. In the absence of heterogeneity, odds ratios (ORs) with 95% confidence intervals (CIs) for testicular cancer were combined using a fixed effect model. Funnel plots and trim-and-fill analysis were used to assess publication bias.Results: Eight studies met the inclusion criteria and provided information on 180 infertile men with TM and 5,088 infertile men without TM. The pooled OR indicated that the presence of TM is associated with a ~18-fold higher odd for testicular cancer (pooled OR:18.11, 95%CI: 8.09, 40.55; P &lt; 0.0001). No heterogeneity among the studies was observed (Pfor heterogeneity = 0.99, I2 = 0%). At the sensitivity analysis, similar pooled ORs and 95%CIs were generated with the exclusion of each study, indicating the high degree of stability of the results. The funnel plot revealed a possible publication bias and the trim-and-fill test detected two putative missing studies. Nevertheless, even when the pooled estimate was adjusted for publication bias, there was a still significantly higher odd for testicular cancer in the TM group (adjusted pooled OR: 16.42, 95%CI: 7.62, 35.37; P &lt; 0.0001).Conclusions: In infertile men the presence of TM is associated to an ~18-fold higher prevalence of testicular cancer. Longitudinal studies are warranted to elucidate whether this cross-sectional association actually reflects a higher susceptibility of infertile men with TM to develop testicular cancer over time

Erectile dysfunction in hyperuricemia: A prevalence meta‐analysis and meta‐regression study

AbstractBackgroundWhether and to what extent an association exists between hyperuricemia and erectile dysfunction (ED) has not yet been fully determined.ObjectiveTo define pooled prevalence estimates and correlates of erectile dysfunction in men with hyperuricemic disorders.Materials and methodsA thorough search of Medline, Scopus, and Cochrane Library databases was performed. Data were combined using random‐effects models and the between‐study heterogeneity was assessed by Cochrane's Q and I2 tests. A funnel plot was used to assess publication bias.ResultsOverall, 8 studies included gave information about 85,406 hyperuricemic men, of whom 5023 complained of erectile dysfunction, resulting in a pooled erectile dysfunction prevalence estimate of 33% (95% Confidence Interval: 13–52%; I² = 99.9%). The funnel plot suggested the presence of a publication bias. At the meta‐regression analyses, among the available covariates that could affect estimates, only type 2 diabetes mellitus was significantly associated with a higher prevalence of erectile dysfunction (β = 0.08; 95% Confidence Interval: 0.01, 0.15, p = 0.025). At the sub‐group analysis, the pooled erectile dysfunction prevalence decreased to 4% (95% Confidence Interval: 0%–8%) when only the largest studies with the lowest prevalence of type 2 diabetes mellitus were included and increased up to 50% (95% Confidence Interval: 17%–84%) when the analysis was restricted to studies enrolling smaller series with higher prevalence of type 2 diabetes mellitus.ConclusionsA not negligible proportion of men with hyperuricemia can complain of erectile dysfunction. While a pathogenetic contribution of circulating uric acid in endothelial dysfunction cannot be ruled out, the evidence of a stronger association between hyperuricemia and erectile dysfunction in type 2 diabetes mellitus points to hyperuricemia as a marker of systemic dysmetabolic disorders adversely affecting erectile function

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurement of the correlation between the polar angles of leptons from top quark decays in the helicity basis at √s = 7 TeV using the ATLAS detector

A measurement of the correlations between the polar angles of leptons from the decay of pair-produced t and t̄ quarks in the helicity basis is reported, using proton-proton collision data collected by the ATLAS detector at the LHC. The dataset corresponds to an integrated luminosity of 4.6  fb−¹ at a center-of-mass energy of √s = 7  TeV collected during 2011. Candidate events are selected in the dilepton topology with large missing transverse momentum and at least two jets. The angles θ1 and θ2 between the charged leptons and the direction of motion of the parent quarks in the tt̄ rest frame are sensitive to the spin information, and the distribution of cosθ1 ⋅ cosθ2 is sensitive to the spin correlation between the t and t̄ quarks. The distribution is unfolded to parton level and compared to the next-to-leading order prediction. A good agreement is observed

Search for massive, long-lived particles using multitrack displaced vertices or displaced lepton pairs in pp collisions at √s = 8 TeV with the ATLAS detector

Many extensions of the Standard Model posit the existence of heavy particles with long lifetimes. This article presents the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles. This analysis uses a data sample of proton-proton collisions at √s=8  TeV corresponding to an integrated luminosity of 20.3  fb−1 collected in 2012 by the ATLAS detector operating at the Large Hadron Collider. No events are observed in any of the signal regions, and limits are set on model parameters within supersymmetric scenarios involving R-parity violation, split supersymmetry, and gauge mediation. In some of the search channels, the trigger and search strategy are based only on the decay products of individual long-lived particles, irrespective of the rest of the event. In these cases, the provided limits can easily be reinterpreted in different scenarios

Measurement of the CP-violating phase ϕs and the Bs0 meson decay width difference with Bs0 → J/ψϕ decays in ATLAS

A measurement of the Bs0 decay parameters in the Bs0 → J/ψϕ channel using an integrated luminosity of 14.3 fb−1 collected by the ATLAS detector from 8 TeV pp collisions at the LHC is presented. The measured parameters include the CP -violating phase ϕs, the decay width Γs and the width difference between the mass eigenstates ΔΓs. The values measured for the physical parameters are statistically combined with those from 4.9 fb−1 of 7 TeV data, leading to the following: ϕ s =−0.090±0.078(stat.)±0.041(syst.)rad ΔΓ s =0.085±0.011(stat.)±0.007(syst.)ps −1 Γ s =0.675±0.003(stat.)±0.003(syst.)ps −1 In the analysis the parameter ΔΓs is constrained to be positive. Results for ϕs and ΔΓs are also presented as 68% and 95% likelihood contours in the ϕs-ΔΓs plane. Also measured in this decay channel are the transversity amplitudes and corresponding strong phases. All measurements are in agreement with the Standard Model predictions

Measurement of the differential cross-section of highly boosted top quarks as a function of their transverse momentum in s =8 TeV proton-proton collisions using the ATLAS detector

The differential cross-section for pair production of top quarks with high transverse momentum is measured in 20.3  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The measurement is performed for tt¯ events in the lepton+jets channel. The cross-section is reported as a function of the hadronically decaying top quark transverse momentum for values above 300 GeV. The hadronically decaying top quark is reconstructed as an anti-kt jet with radius parameter R=1.0 and identified with jet substructure techniques. The observed yield is corrected for detector effects to obtain a cross-section at particle level in a fiducial region close to the event selection. A parton-level cross-section extrapolated to the full phase space is also reported for top quarks with transverse momentum above 300 GeV. The predictions of a majority of next-to-leading-order and leading-order matrix-element Monte Carlo generators are found to agree with the measured cross-sections.- We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, HGF, and MPG, Germany; GSRT, Greece; RGC, Hong Kong SAR, China; ISF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW and NCN, Poland; FCT, Portugal; MNE/IFA, Romania; MES of Russia and NRC KI, Russian Federation; JINR; MESTD, Serbia; MSSR, Slovakia; ARRS and MIZS, Slovenia; DST/NRF, South Africa; MINECO, Spain; SRC and Wallenberg Foundation, Sweden; SERI, SNSF and Cantons of Bern and Geneva, Switzerland; MOST, Taiwan; TAEK, Turkey; STFC, United Kingdom; DOE and NSF, United States of America. In addition, individual groups and members have received support from BCKDF, the Canada Council, CANARIE, CRC, Compute Canada, FQRNT, and the Ontario Innovation Trust, Canada; EPLANET, ERC, FP7, Horizon 2020 and Marie Sklodowska-Curie Actions, European Union; Investissements d'Avenir Labex and Idex, ANR, Region Auvergne and Fondation Partager le Savoir, France; DFG and AvH Foundation, Germany; Herakleitos, Thales and Aristeia programmes co-financed by EU-ESF and the Greek NSRF; BSF, GIF and Minerva, Israel; BRF, Norway; the Royal Society and Leverhulme Trust, United Kingdom. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) an

Measurement of the production cross-section of a single top quark in association with a W boson at 8 TeV with the ATLAS experiment

The cross-section for the production of a single top quark in association with a W boson in proton-proton collisions at s√=8TeV is measured. The dataset corresponds to an integrated luminosity of 20.3 fb−1, collected by the ATLAS detector in 2012 at the Large Hadron Collider at CERN. Events containing two leptons and one central b-jet are selected. The W t signal is separated from the backgrounds using boosted decision trees, each of which combines a number of discriminating variables into one classifier. Production of W t events is observed with a significance of 7.7σ. The cross-section is extracted in a profile likelihood fit to the classifier output distributions. The W t cross-section, inclusive of decay modes, is measured to be 23.0 ± 1.3(stat.)− 3.5+ 3.2(syst.)±1.1(lumi.) pb. The measured cross-section is used to extract a value for the CKM matrix element |Vtb| of 1.01 ± 0.10 and a lower limit of 0.80 at the 95% confidence level. The cross-section for the production of a top quark and a W boson is also measured in a fiducial acceptance requiring two leptons with pT> 25 GeV and |η| 20 GeV and |η|  20 GeV, including both W t and top-quark pair events as signal. The measured value of the fiducial cross-section is 0.85 ± 0.01(stat.)− 0.07+ 0.07(syst.)±0.03(lumi.) pb