Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Geographical variation in therapy for bloodstream infections due to multidrug-resistant enterobacteriaceae: a post hoc analysis of the INCREMENT study

We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ?-lactam/?-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE. The use of BLBLI for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.2) and Turkey (aOR 2.09, 95% CI 1.14-3.81), compared to Spain as a reference. Empirical carbapenems were more likely to be used in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89; 95% CI 1.05-3.39), and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLI for ESBL-E was more likely in sites from Italy. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. A better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.PH is supported by an Australian Postgraduate Award from the University of Queensland. The study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). BGG, JRB, APH and YC also received funds from the COMBACTE-CARE project (grant agreement 115620), Innovative Medicines Initiative (IMI), the European Union's Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles. High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary. The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded. It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses

Measurement of W+W− production in association with one jet in proton–proton collisions at sqrt(s) = 8TeV with the ATLAS detector

The production of W boson pairs in association with one jet in pp collisions at View the MathML sources=8 TeV is studied using data corresponding to an integrated luminosity of 20.3 fb−1 collected by the ATLAS detector during 2012 at the CERN Large Hadron Collider. The cross section is measured in a fiducial phase-space region defined by the presence of exactly one electron and one muon, missing transverse momentum and exactly one jet with a transverse momentum above 25 GeV and a pseudorapidity of |η|<4.5|η|<4.5. The leptons are required to have opposite electric charge and to pass transverse momentum and pseudorapidity requirements. The fiducial cross section is found to be View the MathML sourceσWWfid,1-jet=136±6(stat)±14(syst)±3(lumi) fb. In combination with a previous measurement restricted to leptonic final states with no associated jets, the fiducial cross section of WW production with zero or one jet is measured to be View the MathML sourceσWWfid,≤1-jet=511±9(stat)±26(syst)±10(lumi) fb. The ratio of fiducial cross sections in final states with one and zero jets is determined to be 0.36±0.050.36±0.05. Finally, a total cross section extrapolated from the fiducial measurement of WW production with zero or one associated jet is reported. The measurements are compared to theoretical predictions and found in good agreement

Measurement of the cross section for inclusive isolated-photon production in pp collisions at √s=13TeV using the ATLAS detector

Inclusive isolated-photon production in pp collisions at a centre-of-mass energy of 13TeVis studied with the ATLAS detector at the LHC using a data set with an integrated luminosity of 3.2fb−1. The cross section is measured as a function of the photon transverse energy above 125GeVin different regions of photon pseudorapidity. Next-to-leading-order perturbative QCD and Monte Carlo event-generator predictions are compared to the cross-section measurements and provide an adequate description of the data

Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators

Searches for Higgs boson pair production in the hh→bbττ, γγWW∗, γγbb, bbbb channels with the ATLAS detector

Searches for both resonant and nonresonant Higgs boson pair production are performed in the hh→bbττ, γγWW∗ final states using 20.3  fb−1 of pp collision data at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. No evidence of their production is observed and 95% confidence-level upper limits on the production cross sections are set. These results are then combined with the published results of the hh→γγbb, bbbb analyses. An upper limit of 0.69 (0.47) pb on the nonresonant hh production is observed (expected), corresponding to 70 (48) times the SM gg→hh cross section. For production via narrow resonances, cross-section limits of hh production from a heavy Higgs boson decay are set as a function of the heavy Higgs boson mass. The observed (expected) limits range from 2.1 (1.1) pb at 260 GeV to 0.011 (0.018) pb at 1000 GeV. These results are interpreted in the context of two simplified scenarios of the Minimal Supersymmetric Standard Model

Determination of the ratio of b-quark fragmentation fractions fs/fd in pp collisions at √s = 7 TeV with the ATLAS Detector

With an integrated luminosity of 2.47  fb−1 recorded by the ATLAS experiment at the LHC, the exclusive decays B 0s→J/ψϕ and B0d→J/ψK*0 of B mesons produced in pp collisions at √s=7  TeV are used to determine the ratio of fragmentation fractions fs/fd. From the observed B0s→J/ψϕ and B0d→J/ψK*0 yields, the quantity (fs/fd)[B(B0s→J/ψϕ)/B(B 0d→J/ψK*0)] is measured to be 0.199±0.004(stat)±0.008(syst). Using a recent theory prediction for [B(B0s→J/ψϕ)/B(B0d→J/ψK*0)] yields (fs/fd)=0.240±0.004(stat)±0.010(syst)±0.017(th). This result is based on a new approach that provides a significant improvement of the world average

Dijet Resonance Search with Weak Supervision Using root S=13 TeV pp Collisions in the ATLAS Detector

This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A → BC, for mA ∼ OðTeVÞ, mB; mC ∼ Oð100 GeVÞ and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 ffiffi s p ¼ 13 TeV pp collision dataset of 139 fb−1 recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with mA, mB, and mC. For example, when mA ¼ 3 TeV and mB ≳ 200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on mC. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model boson

Properties of jet fragmentation using charged particles measured with the ATLAS detector in pp collisions at root s=13 TeV

This paper presents a measurement of quantities related to the formation of jets from high-energy quarks and gluons (fragmentation). Jets with transverse momentum 100 GeV 500 MeV and |η| < 2.5 are used to probe the detailed structure of the jet. The fragmentation properties of the more forward and the more central of the two leading jets from each event are studied. The data are unfolded to correct for detector resolution and acceptance effects. Comparisons with parton shower Monte Carlo generators indicate that existing models provide a reasonable description of the data across a wide range of phase space, but there are also significant differences. Furthermore, the data are interpreted in the context of quark- and gluon-initiated jets by exploiting the rapidity dependence of the jet flavor fraction. A first measurement of the charged-particle multiplicity using model-independent jet labels (topic modeling) provides a promising alternative to traditional quark and gluon extractions using input from simulation. The simulations provide a reasonable description of the quark-like data across the jet Pt range presented in -this measurement, but the gluon-like data have systematically fewer charged particles than the simulation