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  • Justice, A. E., et al. (författare)
  • Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
  • 2017
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
  • Abbasi, R., et al. (författare)
  • Extending the Search for Neutrino Point Sources with IceCube above the Horizon
  • 2009
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:22, s. Article ID: 221102-
  • Tidskriftsartikel (refereegranskat)abstract
    • Point source searches with the IceCube neutrino telescope have been restricted to one hemisphere, due to the exclusive selection of upward going events as a way of rejecting the atmospheric muon background. We show that the region above the horizon can be included by suppressing the background through energy-sensitive cuts. This improves the sensitivity above PeV energies, previously not accessible for declinations of more than a few degrees below the horizon due to the absorption of neutrinos in Earth. We present results based on data collected with 22 strings of IceCube, extending its field of view and energy reach for point source searches. No significant excess above the atmospheric background is observed in a sky scan and in tests of source candidates. Upper limits are reported, which for the first time cover point sources in the southern sky up to EeV energies.
  • Ederle, Joerg, et al. (författare)
  • Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
  • 2010
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X. ; 375:9719, s. 985-997
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
  • Saunois, M., et al. (författare)
  • The global methane budget 2000–2012
  • 2016
  • Ingår i: Earth System Science Data. - : COPERNICUS GESELLSCHAFT MBH. - 1866-3508 .- 1866-3516. ; 8:2, s. 697-751
  • Tidskriftsartikel (refereegranskat)abstract
    • The global methane (CH4) budget is becoming an increasingly important component for managing realistic pathways to mitigate climate change. This relevance, due to a shorter atmospheric lifetime and a stronger warming potential than carbon dioxide, is challenged by the still unexplained changes of atmospheric CH4 over the past decade. Emissions and concentrations of CH4 are continuing to increase, making CH4 the second most important human-induced greenhouse gas after carbon dioxide. Two major difficulties in reducing uncertainties come from the large variety of diffusive CH4 sources that overlap geographically, and from the destruction of CH4 by the very short-lived hydroxyl radical (OH). To address these difficulties, we have established a consortium of multi-disciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate research on the methane cycle, and producing regular (∼ biennial) updates of the global methane budget. This consortium includes atmospheric physicists and chemists, biogeochemists of surface and marine emissions, and socio-economists who study anthropogenic emissions. Following Kirschke et al. (2013), we propose here the first version of a living review paper that integrates results of top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models, inventories and data-driven approaches (including process-based models for estimating land surface emissions and atmospheric chemistry, and inventories for anthropogenic emissions, data-driven extrapolations). For the 2003–2012 decade, global methane emissions are estimated by top-down inversions at 558 Tg CH4 yr−1, range 540–568. About 60 % of global emissions are anthropogenic (range 50–65 %). Since 2010, the bottom-up global emission inventories have been closer to methane emissions in the most carbon-intensive Representative Concentrations Pathway (RCP8.5) and higher than all other RCP scenarios. Bottom-up approaches suggest larger global emissions (736 Tg CH4 yr−1, range 596–884) mostly because of larger natural emissions from individual sources such as inland waters, natural wetlands and geological sources. Considering the atmospheric constraints on the top-down budget, it is likely that some of the individual emissions reported by the bottom-up approaches are overestimated, leading to too large global emissions. Latitudinal data from top-down emissions indicate a predominance of tropical emissions (∼ 64 % of the global budget, < 30° N) as compared to mid (∼ 32 %, 30–60° N) and high northern latitudes (∼ 4 %, 60–90° N). Top-down inversions consistently infer lower emissions in China (∼ 58 Tg CH4 yr−1, range 51–72, −14 %) and higher emissions in Africa (86 Tg CH4 yr−1, range 73–108, +19 %) than bottom-up values used as prior estimates. Overall, uncertainties for anthropogenic emissions appear smaller than those from natural sources, and the uncertainties on source categories appear larger for top-down inversions than for bottom-up inventories and models. The most important source of uncertainty on the methane budget is attributable to emissions from wetland and other inland waters. We show that the wetland extent could contribute 30–40 % on the estimated range for wetland emissions. Other priorities for improving the methane budget include the following: (i) the development of process-based models for inland-water emissions, (ii) the intensification of methane observations at local scale (flux measurements) to constrain bottom-up land surface models, and at regional scale (surface networks and satellites) to constrain top-down inversions, (iii) improvements in the estimation of atmospheric loss by OH, and (iv) improvements of the transport models integrated in top-down inversions. The data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (http://doi.org/10.3334/CDIAC/GLOBAL_METHANE_BUDGET_2016_V1.1) and the Global Carbon Project.
  • Soda, T., et al. (författare)
  • International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic)
  • 2019
  • Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer. - 0940-1334 .- 1433-8491. ; 270:7, s. 921-932
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.
  • Aartsen, M. G., et al. (författare)
  • Determining neutrino oscillation parameters from atmospheric muon neutrino disappearance with three years of IceCube DeepCore data
  • 2015
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 91:7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a measurement of neutrino oscillations via atmospheric muon neutrino disappearance with three years of data of the completed IceCube neutrino detector. DeepCore, a region of denser IceCube instrumentation, enables the detection and reconstruction of atmospheric muon neutrinos between 10 and 100 GeV, where a strong disappearance signal is expected. The IceCube detector volume surrounding DeepCore is used as a veto region to suppress the atmospheric muon background. Neutrino events are selected where the detected Cherenkov photons of the secondary particles minimally scatter, and the neutrino energy and arrival direction are reconstructed. Both variables are used to obtain the neutrino oscillation parameters from the data, with the best fit given by Delta m(32)(2) = 2.72(-0.20)(+0.19) x 10(-3) eV(2) and sin(2)theta(23) = 0.53(-0.12)(+0.09) (normal mass ordering assumed). The results are compatible, and comparable in precision, to those of dedicated oscillation experiments.
  • Aartsen, M. G., et al. (författare)
  • Energy reconstruction methods in the IceCube neutrino telescope
  • 2014
  • Ingår i: Journal of Instrumentation. - 1748-0221 .- 1748-0221. ; 9, s. P03009-
  • Tidskriftsartikel (refereegranskat)abstract
    • Accurate measurement of neutrino energies is essential to many of the scientific goals of large-volume neutrino telescopes. The fundamental observable in such detectors is the Cherenkov light produced by the transit through a medium of charged particles created in neutrino interactions. The amount of light emitted is proportional to the deposited energy, which is approximately equal to the neutrino energy for v(e) and v(mu) charged-current interactions and can be used to set a lower bound on neutrino energies and to measure neutrino spectra statistically in other channels. Here we describe methods and performance of reconstructing charged-particle energies and topologies from the observed Cherenkov light yield, including techniques to measure the energies of uncontained muon tracks, achieving average uncertainties in electromagnetic-equivalent deposited energy of similar to 15% above 10 TeV.
  • Aartsen, M. G., et al. (författare)
  • Probing the origin of cosmic rays with extremely high energy neutrinos using the IceCube Observatory
  • 2013
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11
  • Tidskriftsartikel (refereegranskat)abstract
    • We have searched for extremely high energy neutrinos using data taken with the IceCube detector between May 2010 and May 2012. Two neutrino-induced particle shower events with energies around 1 PeV were observed, as reported previously. In this work, we investigate whether these events could originate from cosmogenic neutrinos produced in the interactions of ultrahigh energy cosmic rays with ambient photons while propagating through intergalactic space. Exploiting IceCube's large exposure for extremely high energy neutrinos and the lack of observed events above 100 PeV, we can rule out the corresponding models at more than 90% confidence level. The model-independent quasidifferential 90% C. L. upper limit, which amounts to E-2 phi(nu e)+(nu mu)+(nu tau) = 1.2 x 10(-7) GeV cm(-2) s(-1) sr(-1) at 1 EeV, provides the most stringent constraint in the energy range from 10 PeV to 10 EeV. Our observation disfavors strong cosmological evolution of the highest energy cosmic-ray sources such as the Fanaroff-Riley type II class of radio galaxies.
  • Aartsen, M. G., et al. (författare)
  • Searches for small-scale anisotropies from neutrino point sources with three years of IceCube data
  • 2015
  • Ingår i: Astroparticle physics. - 0927-6505 .- 1873-2852. ; 66, s. 39-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, IceCube found evidence for a diffuse signal of astrophysical neutrinos in an energy range of similar to 60 TeV to the PeV-scale [1]. The origin of those events, being a key to understanding the origin of cosmic rays, is still an unsolved question. So far, analyses have not succeeded to resolve the diffuse signal into point-like sources. Searches including a maximum-likelihood-ratio test, based on the reconstructed directions and energies of the detected down- and up-going neutrino candidates, were also performed on IceCube data leading to the exclusion of bright point sources. In this paper, we present two methods to search for faint neutrino point sources in three years of IceCube data, taken between 2008 and 2011. The first method is an autocorrelation test, applied separately to the northern and southern sky. The second method is a multipole analysis, which expands the measured data in the northern hemisphere into spherical harmonics and uses the resulting expansion coefficients to separate signal from background. With both methods, the results are consistent with the background expectation with a slightly more sparse spatial distribution, corresponding to an underfluctuation. Depending on the assumed number of sources, the resulting upper limit on the flux per source in the northern hemisphere for an E-2 energy spectrum ranges from similar to 1.5. 10(-8) GeV/cm(2) s(-1), in the case of one assumed source, to similar to 4. 10(-10) GeV/cm(2) s(-1), in the case of 3500 assumed sources.
  • Abbasi, R., et al. (författare)
  • An absence of neutrinos associated with cosmic-ray acceleration in gamma-ray bursts
  • 2012
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 484:7394, s. 351-354
  • Tidskriftsartikel (refereegranskat)abstract
    • Very energetic astrophysical events are required to accelerate cosmic rays to above 10(18) electronvolts. GRBs (c-ray bursts) have been proposed as possible candidate sources(1-3). In the GRB 'fireball' model, cosmic-ray acceleration should be accompanied by neutrinos produced in the decay of charged pions created in interactions between the high-energy cosmic-ray protons and gamma-rays(4). Previous searches for such neutrinos found none, but the constraints were weak because the sensitivity was at best approximately equal to the predicted flux(5-7). Here we report an upper limit on the flux of energetic neutrinos associated with GRBs that is at least a factor of 3.7 below the predictions(4,8-10). This implies either that GRBs are not the only sources of cosmic rays with energies exceeding 10(18) electronvolts or that the efficiency of neutrino production is much lower than has been predicted.
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