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1.
  • Aad, G, et al. (author)
  • 2015
  • swepub:Mat__t
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2.
  • Aaltonen, T., et al. (author)
  • Combination of CDF and D0 measurements of the W boson helicity in top quark decays
  • 2012
  • In: Physical Review D. - 1550-7998 .- 1550-2368. ; 85:7, s. 071106-
  • Journal article (peer-reviewed)abstract
    • We report the combination of recent measurements of the helicity of the W boson from top quark decay by the CDF and D0 collaborations, based on data samples corresponding to integrated luminosities of 2.7-5.4 fb(-1) of p (p) over bar collisions collected during Run II of the Fermilab Tevatron collider. Combining measurements that simultaneously determine the fractions of W bosons with longitudinal (f(0)) and right-handed (f(+)) helicities, we find f(0) = 0.722 +/- 0.081[+/- 0.062(stat) +/- 0.052(syst)] and f(+) = -0.033 +/- 0.046[+/- 0.034(stat) +/- 0.031(syst)]. Combining measurements where one of the helicity fractions is fixed to the value expected in the standard model, we find f(0) = 0.682 +/- 0.057[+/- 0.035(stat) +/- 0.046(syst)] for fixed f(+) and f(+) = -0.015 +/- 0.035[+/- 0.018(stat) +/- 0.030(syst)] for fixed f(0). The results are consistent with standard model expectations.
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3.
  • Aaltonen, T., et al. (author)
  • Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode
  • 2010
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
  • Journal article (peer-reviewed)abstract
    • We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
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4.
  • Aaltonen, T., et al. (author)
  • Evidence for a Particle Produced in Association with Weak Bosons and Decaying to a Bottom-Antibottom Quark Pair in Higgs Boson Searches at the Tevatron
  • 2012
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 109:7, s. 071804-
  • Journal article (peer-reviewed)abstract
    • We combine searches by the CDF and D0 Collaborations for the associated production of a Higgs boson with a W or Z boson and subsequent decay of the Higgs boson to a bottom-antibottom quark pair. The data, originating from Fermilab Tevatron p (p) over bar collisions at root s = 1.96 TeV, correspond to integrated luminosities of up to 9.7 fb(-1). The searches are conducted for a Higgs boson with mass in the range 100-150 GeV/c(2). We observe an excess of events in the data compared with the background predictions, which is most significant in the mass range between 120 and 135 GeV/c(2). The largest local significance is 3.3 standard deviations, corresponding to a global significance of 3.1 standard deviations. We interpret this as evidence for the presence of a new particle consistent with the standard model Higgs boson, which is produced in association with a weak vector boson and decays to a bottom-antibottom quark pair.
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5.
  • Aaltonen, T., et al. (author)
  • Tevatron Run II combination of the effective leptonic electroweak mixing angle
  • 2018
  • In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:11
  • Journal article (peer-reviewed)abstract
    • Drell-Yan lepton pairs produced in the process p (p) over bar -> l(+)l(-) + X through an intermediate gamma*/Z boson have an asymmetry in their angular distribution related to the spontaneous symmetry breaking of the electroweak force and the associated mixing of its neutral gauge bosons. The CDF and D0 experiments have measured the effective-leptonic electroweak mixing parameter sin(2) theta(lept)(eff) using electron and muon pairs selected from the full Tevatron proton-antiproton data sets collected in 2001-2011, corresponding to 9-10 fb(-1) of integrated luminosity. The combination of these measurements yields the most precise result from hadron colliders, sin(2)theta(lept)(eff) = 0.23148 +/- 0.00033. This result is consistent with, and approaches in precision, the best measurements from electron-positron colliders. The standard model inference of the on-shell electroweak mixing parameter sin(2) theta(W), or equivalently the W-boson mass M-W, using the ZFITTER software package yields sin(2) theta(W) = 0.22324 +/- 0.00033 or equivalently, M-W = 80.367 +/- 0.017 GeV/c(2).
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6.
  • Aaltonen, T., et al. (author)
  • Combination of CDF and D0 W-Boson mass measurements
  • 2013
  • In: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:5, s. 052018-
  • Journal article (peer-reviewed)abstract
    • We summarize and combine direct measurements of the mass of the W boson in root s = 1.96 TeV proton-antiproton collision data collected by CDF and D0 experiments at the Fermilab Tevatron Collider. Earlier measurements from CDF and D0 are combined with the two latest, more precise measurements: a CDF measurement in the electron and muon channels using data corresponding to 2.2 fb(-1) of integrated luminosity, and a D0 measurement in the electron channel using data corresponding to 4.3 fb(-1) of integrated luminosity. The resulting Tevatron average for the mass of the W boson is M-W = 80387 +/- 16 MeV. Including measurements obtained in electron-positron collisions at LEP yields the most precise value of M-W = 80385 +/- 15 MeV.
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7.
  • Aaltonen, T., et al. (author)
  • Combination of measurements of the top-quark pair production cross section from the Tevatron Collider
  • 2014
  • In: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:7
  • Journal article (peer-reviewed)abstract
    • We combine six measurements of the inclusive top-quark pair (t(sic)) production cross section (sigma(t)(sic)) from data collected with the CDF and D0 detectors at the Fermilab Tevatron with proton-antiproton collisions at root s = 1.96 TeV. The data correspond to integrated luminosities of up to 8.8 fb(-1). We obtain a value of sigma tt = 7.60 +/- 0.41 pb for a top-quark mass of m(t) = 172.5 GeV. The contributions to the uncertainty are 0.20 pb from statistical sources, 0.29 pb from systematic sources, and 0.21 pb from the uncertainty on the integrated luminosity. The result is in good agreement with the standard model expectation of 7.35(-0.33)(+0.28) pb at next-to-next-to-leading order and next-to-next-to leading logarithms in perturbative QCD.
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8.
  • Aaltonen, T., et al. (author)
  • Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron
  • 2018
  • In: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 120:4
  • Journal article (peer-reviewed)abstract
    • The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of root s = 1.96 TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is A(FB)(t (t) over bar) = 0.128 +/- 0.025. The combined inclusive and differential asymmetries are consistent with recent standard model predictions.
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9.
  • Aaltonen, T., et al. (author)
  • Higgs boson studies at the Tevatron
  • 2013
  • In: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:5, s. 052014-
  • Journal article (peer-reviewed)abstract
    • We combine searches by the CDF and D0 Collaborations for the standard model Higgs boson with mass in the range 90-200 GeV/c(2) produced in the gluon-gluon fusion, WH, ZH, t (t) over barH, and vector boson fusion processes, and decaying in the H -> b (b) over bar, H -> W+W-, H -> ZZ, H -> tau(+)tau(-), and H -> gamma gamma modes. The data correspond to integrated luminosities of up to 10 fb(-1) and were collected at the Fermilab Tevatron in p (p) over bar collisions at root s = 1.96 TeV. The searches are also interpreted in the context of fermiophobic and fourth generation models. We observe a significant excess of events in the mass range between 115 and 140 GeV/c(2). The local significance corresponds to 3.0 standard deviations at m(H) = 125 GeV/c(2), consistent with the mass of the Higgs boson observed at the LHC, and we expect a local significance of 1.9 standard deviations. We separately combine searches for H -> b (b) over bar, H -> W+W-, H -> tau(+)tau(-), and H -> gamma gamma. The observed signal strengths in all channels are consistent with the presence of a standard model Higgs boson with a mass of 125 GeV/c(2).
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10.
  • Aaltonen, T., et al. (author)
  • Observation of s-Channel Production of Single Top Quarks at the Tevatron
  • 2014
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 112:23
  • Journal article (peer-reviewed)abstract
    • We report the first observation of single-top-quark production in the s channel through the combination of the CDF and D0 measurements of the cross section in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The measured cross section is sigma(s) = 1.29(-0.24)(+0.26) pb. The probability of observing a statistical fluctuation of the background to a cross section of the observed size or larger is 1.8 x 10(-10), corresponding to a significance of 6.3 standard deviations for the presence of an s-channel contribution to the production of single-top quarks.
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11.
  • Aaltonen, T., et al. (author)
  • Tevatron Combination of Single-Top-Quark Cross Sections and Determination of the Magnitude of the Cabibbo-Kobayashi-Maskawa Matrix Element V-tb
  • 2015
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 115:15
  • Journal article (peer-reviewed)abstract
    • We present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The t-channel cross section is measured to be sigma(t) = 2.25(-0.31)(+0.29) pb. We also present the combinations of the two-dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s + t channel cross section measurement resulting in sigma(s+t) = 3.30(-0.40)(+0.52) pb, without assuming the standard model value for the ratio sigma(s)/sigma(t). The resulting value of the magnitude of the top-to-bottom quark coupling is vertical bar V-tb vertical bar = 1.02(-0.05)(+0.06), corresponding to vertical bar V-tb vertical bar > 0.92 at the 95% C. L.
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12.
  • Aaltonen, T., et al. (author)
  • Tevatron Constraints on Models of the Higgs Boson with Exotic Spin and Parity Using Decays to Bottom-Antibottom Quark Pairs
  • 2015
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 114:15
  • Journal article (peer-reviewed)abstract
    • Combined constraints from the CDF and D0 Collaborations on models of the Higgs boson with exotic spin J and parity P are presented and compared with results obtained assuming the standard model value J(P) = 0(+). Both collaborations analyzed approximately 10 fb(-1) of proton-antiproton collisions with a center-of-mass energy of 1.96 TeV collected at the Fermilab Tevatron. Two models predicting exotic Higgs bosons with J(P) = 0(-) and J(P) = 2(+) are tested. The kinematic properties of exotic Higgs boson production in association with a vector boson differ from those predicted for the standard model Higgs boson. Upper limits at the 95% credibility level on the production rates of the exotic Higgs bosons, expressed as fractions of the standard model Higgs boson production rate, are set at 0.36 for both the J(P) = 0(-) hypothesis and the J(P) = 2(+) hypothesis. If the production rate times the branching ratio to a bottom-antibottom pair is the same as that predicted for the standard model Higgs boson, then the exotic bosons are excluded with significances of 5.0 standard deviations and 4.9 standard deviations for the J(P) = 0(-) and J(P) = 2(+) hypotheses, respectively.
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16.
  • Hibar, D. P., et al. (author)
  • Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
  • 2018
  • In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
  • Journal article (peer-reviewed)abstract
    • Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d='0.293; P=1.71 × 10 '21), left fusiform gyrus (d='0.288; P=8.25 × 10 '21) and left rostral middle frontal cortex (d='0.276; P=2.99 × 10 '19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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18.
  • de Heus, R. A. A., et al. (author)
  • Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension
  • 2019
  • In: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 8:10
  • Journal article (peer-reviewed)abstract
    • Background-Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results-Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop >= 20/>= 10 mm Hg after 1 minute of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2 +/- 8.2 years and mean Mini-Mental State Examination score was 20.4 +/- 3.8. Baseline blood pressure was 137.8 +/- 14.0/77.0 +/- 8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by -7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo (P<0.001). Across the 78-week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI] 1.1 [0.8-1.5], P 0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7 +/- 13.8% versus 7.3 +/- 11.6%). OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions-This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease.
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19.
  • Dyer, A. H., et al. (author)
  • Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
  • 2020
  • In: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
  • Journal article (peer-reviewed)abstract
    • Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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20.
  • Landén, Mikael, 1966, et al. (author)
  • Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
  • 2021
  • In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5124-5139
  • Journal article (peer-reviewed)abstract
    • Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
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21.
  • Lawlor, B., et al. (author)
  • Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
  • 2018
  • In: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 15:9
  • Journal article (peer-reviewed)abstract
    • Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated antiinflammatory and anti-tau activity in preclinical studies, properties that could have diseasemodifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged > 50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of >= 12 and < 27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease +/- specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADASCog 12 on placebo was 0.79 (95% CI, -0.07 +/- 1.64) at 13 weeks, 6.41 (5.33 +/- 7.49) at 52 weeks, and 9.63 (8.33 +/- 10.93) at 78 weeks and on nilvadipine was 0.88 (0.02 +/- 1.74) at 13 weeks, 5.75 (4.66 +/- 6.85) at 52 weeks, and 9.41 (8.09 +/- 10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease.
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26.
  • Abramowicz, H., et al. (author)
  • Conceptual design report for the LUXE experiment
  • 2021
  • In: European Physical Journal-Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 230:11, s. 2445-2560
  • Journal article (peer-reviewed)abstract
    • This Conceptual Design Report describes LUXE (Laser Und XFEL Experiment), an experimental campaign that aims to combine the high-quality and high-energy electron beam of the European XFEL with a powerful laser to explore the uncharted terrain of quantum electrodynamics characterised by both high energy and high intensity. We will reach this hitherto inaccessible regime of quantum physics by analysing high-energy electron-photon and photon-photon interactions in the extreme environment provided by an intense laser focus. The physics background and its relevance are presented in the science case which in turn leads to, and justifies, the ensuing plan for all aspects of the experiment: Our choice of experimental parameters allows (i) field strengths to be probed where the coupling to charges becomes non-perturbative and (ii) a precision to be achieved that permits a detailed comparison of the measured data with calculations. In addition, the high photon flux predicted will enable a sensitive search for new physics beyond the Standard Model. The initial phase of the experiment will employ an existing 40 TW laser, whereas the second phase will utilise an upgraded laser power of 350 TW. All expectations regarding the performance of the experimental set-up as well as the expected physics results are based on detailed numerical simulations throughout.
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27.
  • Browne, F., et al. (author)
  • Pairing Forces Govern Population of Doubly Magic Ca-54 from Direct Reactions
  • 2021
  • In: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 126:25
  • Journal article (peer-reviewed)abstract
    • Direct proton-knockout reactions of Sc-55 at similar to 220 MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of Ca-54 were investigated through -ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological intemucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the Sc-55 ground state with states in Ca-54. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of Sc-55, valence proton removals populated predominantly the ground state of Ca-54. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.
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28.
  • Chelban, V., et al. (author)
  • PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation
  • 2019
  • In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:2, s. 225-240
  • Journal article (peer-reviewed)abstract
    • Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
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29.
  • Abercrombie, Daniel, et al. (author)
  • Dark Matter benchmark models for early LHC Run-2 Searches : Report of the ATLAS/CMS Dark Matter Forum
  • 2020
  • In: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 27
  • Journal article (peer-reviewed)abstract
    • This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.
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30.
  • D'Avanzo, F, et al. (author)
  • Mucopolysaccharidoses Differential Diagnosis by Mass Spectrometry-Based Analysis of Urine Free Glycosaminoglycans-A Diagnostic Prediction Model
  • 2023
  • In: Biomolecules. - : MDPI AG. - 2218-273X. ; 13:3
  • Journal article (peer-reviewed)abstract
    • Impaired glycosaminoglycans (GAGs) catabolism may lead to a cluster of rare metabolic and genetic disorders called mucopolysaccharidoses (MPSs). Each subtype is caused by the deficiency of one of the lysosomal hydrolases normally degrading GAGs. Affected tissues accumulate undegraded GAGs in cell lysosomes and in the extracellular matrix, thus leading to the MPS complex clinical phenotype. Although each MPS may present with recognizable signs and symptoms, these may often overlap between subtypes, rendering the diagnosis difficult and delayed. Here, we performed an exploratory analysis to develop a model that predicts MPS subtypes based on UHPLC-MS/MS measurement of a urine free GAG profile (or GAGome). We analyzed the GAGome of 78 subjects (38 MPS, 37 healthy and 3 with other MPS symptom-overlapping disorders) using a standardized kit in a central-blinded laboratory. We observed several MPS subtype-specific GAGome changes. We developed a multivariable penalized Lasso logistic regression model that attained 91.2% balanced accuracy to distinguish MPS type II vs. III vs. any other subtype vs. not MPS, with sensitivity and specificity ranging from 73.3% to 91.7% and from 98.4% to 100%, depending on the predicted subtype. In conclusion, the urine GAGome was revealed to be useful in accurately discriminating the different MPS subtypes with a single UHPLC-MS/MS run and could serve as a reliable diagnostic test for a more rapid MPS biochemical diagnosis.
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31.
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32.
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33.
  • Hauber, Ernst, et al. (author)
  • DEBRIS FLOW FANS AND PERMAFROST LANDFORMS ON SVALBARD (NORWAY): TERRESTRIAL ANALOGUES FOR MARTIAN MID-LATITUDE PERIGLACIAL LANDSCAPES.
  • 2010
  • In: 41st Lunar and Planetary Science Conference. ; :1922
  • Conference paper (peer-reviewed)abstract
    • Many young landforms on Mars that were probably formed by exogenic processes show a latitude- dependent geographic distribution. They include surface mantling, lobate debris aprons, lineated valley fill, and concentric crater fill, viscous flow features, gullies, and patterned ground. Collectively, these landforms are hypothesized to represent the surface records of Martian ice ages that were induced by astronomical forcing and associated climate changes. Previous studies often considered just one of the features in isolation (e.g., gullies), without taking into account the geomorphologic context. A more comprehensive investigation of the full assemblage of landforms (landscape analysis), however, has the potential to reduce the ambiguity in interpreting landforms (the problem of equifinality, e.g., in the case of pingos), and to reveal the evolution of the climatic environment in more detail. Here we present permafrost landforms of Svalbard (Norway) as useful terrestrial analogues for the suite of possible periglacial landforms that are typically found at mid-latitudes on Mars. We build on our previous investigations of gullies and fans, and include a number of classical periglacial landforms (patterned ground, rock glaciers, pingos) that all have close morphological analogues on Mars. Based on this comparison, we propose an evolutionary scenario which helps to understand the sequential formation of the Martian landforms into their present state.
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34.
  • Hauber, Ernst, et al. (author)
  • MORPHOMETRY OF ALLUVIAL FANS IN A POLAR DESERT (SVALBARD, NORWAY): IMPLICATIONS FOR INTERPRETING MARTIAN FANS.
  • 2009
  • In: 40th Lunar and Planetary Science Conference. ; :1648
  • Conference paper (peer-reviewed)abstract
    • Alluvial fan-like landforms have been identified on Mars. Since alluvial fans are recorders of processes that are sensitive to climatic conditions, the investigation of possible Martian fans can reveal information about the planet`s climate. In lieu of direct observations of active depositional processes on Martian fans, comparisons with terrestrial analogues can constrain models of Martian fan formation derived from remote sensing data. Since present-day Mars is cold and dry, alluvial fans formed in cold deserts should be considered as useful analogues. The probably closest climatic analogue to Mars on Earth are the Antarctic Dry Valleys , but polar deserts can also be found in the Arctic. We report on our field work in summer 2008 and a simultaneous flight campaign with an airborne version (HRSC-AX) of the High Resolution Stereo Camera (HRSC) onboard Mars Express. The results are compared with measurements of Martian fans, based on HRSC DEM.
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35.
  • Hauber, Ernst, et al. (author)
  • Svalbard (Norway) as a terrestrial analogue for Martian landforms: Results on
  • 2009
  • In: EPSC Abstracts. European Planetary Science Congress. ; 4, EPSC2009-772
  • Conference paper (peer-reviewed)abstract
    • Small alluvial fan-like landforms have been observed on Mars in association with recent gullies. Such fans are relatively small (km-scale) when compared to large alluvial fans on Mars, which can reach dimensions of tens of kilometers. The small fans are part of an erosion-transportsedimentation system (alcove-channel-apron). Morphologically very similar systems can be studied on Svalbard (Norway), which is a cold and dry polar desert and, therefore, a potentially useful terrestrial analogue for Mars` climate and climaterelated landforms. Here we give an update on our field work in summer 2008 and a simultaneous flight campaign with an airborne version (HRSCAX) of the High Resolution Stereo Camera (HRSC) onboard Mars Express. We also present very preliminary results from the field campaign in summer 2009.
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36.
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37.
  • Johnsson, Andreas, 1977, et al. (author)
  • THE ORIGIN OF STRIPE-LIKE PATTERNS ON MARTIAN GULLY SLOPES; USING SVALBARD ADVENT VALLEY AS A MARS ANALOGUE.
  • 2010
  • In: 41st Lunar and Planetary Science Conference. ; :1665
  • Conference paper (other academic/artistic)abstract
    • Stripes are a common slope features in polar regions on Earth were active layer processes (freezing/thawing and gelifluction) occur. Their origin is most likely polygenic and closely related to frost crack plygons and sorted circles with the addition of a gravitational component. Stripes are either sorted or unsorted. Features resembling stripes have been observed on slopes on Mars with or without association with polygons. Due to the current temperature and pressure regime on Mars soil moisture and active layer processes are not likely to occur. However, in recent HiRISE images stripelike patterns can be observed in proximity to gullies . Stripe width typically ranges from ~50 cm to 1.5 m, and their orientation is consistently down slope, although it can not be excluded that it sometimes slightly deviates from the steepest topographic gradient. In our study we have examined sorted and nonsorted stripes on slopes in Svalbard in order to test the working hypothesis of an cryoturbation origin for the martian stripe-like patterns. In doing so we compare their morphological characteristics, settings, and slope to those on Mars.
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38.
  • Machiela, Mitchell J., et al. (author)
  • Characterization of Large Structural Genetic Mosaicism in Human Autosomes
  • 2015
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
  • Journal article (peer-reviewed)abstract
    • Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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39.
  • Nagel, G., et al. (author)
  • Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2010
  • In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 119:3, s. 753-765
  • Journal article (peer-reviewed)abstract
    • So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded.
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40.
  • Reiss, Dennis, et al. (author)
  • MORPHOLOGIC AND MORPHOMETRIC COMPARISION OF GULLIES ON SVALBARD AND MARS.
  • 2009
  • In: 40th Lunar and Planetary Science Conference. ; :2362
  • Conference paper (other academic/artistic)abstract
    • The morphology of gullies on Mars indi-cates that they were formed by the action of water. How-ever, it is not clear what the dominant gully forming process is. On Earth, gullies might have formed by the processes of overland flow or debris flows, or a combination of both. In this work we compare the morphologic and morphometric observations and measurements (slopes, depth-width ratios and sinuosities) of Martian gullies with terrestrial analogs from Svalbard, Norway, in order to constrain the formation process (fluvial and/or debris flow).
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41.
  • Reiss, Dennis, et al. (author)
  • TERRESTRIAL GULLIES ON SVALBARD AS PLANETARY ANALOGS FOR MARS
  • 2010
  • In: 41st Lunar and Planetary Science Conference. ; :2492
  • Conference paper (other academic/artistic)abstract
    • Martian gullies resemble terrestrial gul-lies, which are formed by a combination of processes includ-ing mass wasting, overland flow and debris flows. The gullies on Mars show several morphologic features such as braided channels, multiple terraces, point bars and cutbanks, which indicate that fluvial processes were involved in their formation. However, it remains unclear whether fluvial processes or debris flows are dominating the formation of gullies on Mars. Debris flows are viscous slurry flows with water and fines as the interstitial fluid. The flowing mix-tures of fines, clastic debris and water has a relatively low water content (≤ 30 % water by weight). Stream flows and hyperconcentrated flows have a high water content and relatively low sediment supply (≥ 30 % water by weight). The morphologies of debris flows fans show typical fea-tures such as levées, lobes, snouts and debris plugs, which are not observed from purely fluvial processes. In this work we compare the morphology of terrestrial gully analogs from Svalbard with Martian gullies in order to constrain which formation process might be dominant on Mars, i.e. fluvial and/or debris flow processes.
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42.
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43.
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44.
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45.
  • Bieber, A., et al. (author)
  • Access to community care for people with dementia and their informal carers : Case vignettes for a European comparison of structures and common pathways to formalcare [Zugang zu professioneller Unterstützung für Menschen mit Demenz und ihre Angehörigen: Fallvignetten für den europäischen Vergleich von Strukturen und Zugangswegen zu professioneller Pflege]
  • 2018
  • In: Zeitschrift für Gerontologie und Geriatrie (Print). - : Springer Science and Business Media LLC. - 0948-6704 .- 1435-1269. ; 51:5, s. 530-536
  • Journal article (peer-reviewed)abstract
    • BackgroundPeople with dementia and their informal carers often do not receive appropriate professional support or it is not received at the right time.ObjectivesDescription and comparison of common pathways to formal community dementia care in eight European countries as a part of the transnational Actifcare project.Materials and methodsThe German team was responsible for creating an individual case scenario as a starting point. The research teams in Ireland, Italy, the Netherlands, Norway, Portugal, Sweden, and the United Kingdom were then asked to describe a common pathway to formal dementia care by writing their own vignette using the provided individual case scenario.ResultsA transnational qualitative content analysis was used to identify the following categories as being the most important: involved professionals, dementia-specific and team-based approaches, proactive roles, and financial aspects. General practitioners (GPs) are described as being the most important profession supporting the access to formal care in all the involved countries. In some countries other professionals take over responsibility for the access procedure. Dementia-specific approaches are rarely part of standard care; team-based approaches have differing significances in each of the countries. Informal carers are mainly proactive in seeking formal care. The Nordic countries demonstrate how financial support enhances access to the professional system.ConclusionEnhanced cooperation between GPs and other professions might optimize access to formal dementia care. Team-based approaches focusing on dementia care should be developed further. Informal carers should be supported and relieved in their role. Financial barriers remain which should be further investigated and reduced.
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46.
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47.
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48.
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49.
  • Boretzky, K., et al. (author)
  • NeuLAND: The high-resolution neutron time-of-flight spectrometer for R 3 B at FAIR
  • 2021
  • In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 1014
  • Journal article (peer-reviewed)abstract
    • NeuLAND (New Large-Area Neutron Detector) is the next-generation neutron detector for the R3B (Reactions with Relativistic Radioactive Beams) experiment at FAIR (Facility for Antiproton and Ion Research). NeuLAND detects neutrons with energies from 100 to 1000 MeV, featuring a high detection efficiency, a high spatial and time resolution, and a large multi-neutron reconstruction efficiency. This is achieved by a highly granular design of organic scintillators: 3000 individual submodules with a size of 5 × 5 × 250 cm3 are arranged in 30 double planes with 100 submodules each, providing an active area of 250 × 250 cm2 and a total depth of 3 m. The spatial resolution due to the granularity together with a time resolution of σt≤ 150 ps ensures high-resolution capabilities. In conjunction with calorimetric properties, a multi-neutron reconstruction efficiency of 50% to 70% for four-neutron events will be achieved, depending on both the emission scenario and the boundary conditions allowed for the reconstruction method. We present in this paper the final design of the detector as well as results from test measurements and simulations on which this design is based.
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50.
  • Carland, Corinne, et al. (author)
  • Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases
  • 2023
  • In: Clinical Proteomics. - : BMC. - 1542-6416 .- 1559-0275. ; 20:1
  • Journal article (peer-reviewed)abstract
    • Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance.Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins.Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F).Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.
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