| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Aartsen, M. G., et al.
(författare)
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A Search for Neutrino Emission from Fast Radio Bursts with Six Years of IceCube Data
- 2018
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 857:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a search for coincidence between IceCube TeV neutrinos and fast radio bursts (FRBs). During the search period from 2010 May 31 to 2016 May 12, a total of 29 FRBs with 13 unique locations have been detected in the whole sky. An unbinned maximum likelihood method was used to search for spatial and temporal coincidence between neutrinos and FRBs in expanding time windows, in both the northern and southern hemispheres. No significant correlation was found in six years of IceCube data. Therefore, we set upper limits on neutrino fluence emitted by FRBs as a function of time window duration. We set the most stringent limit obtained to date on neutrino fluence from FRBs with an E-2 energy spectrum assumed, which is 0.0021 GeV cm(-2) per burst for emission timescales up to similar to 10(2) s from the northern hemisphere stacking search.
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| 3. |
- Aartsen, M. G., et al.
(författare)
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All-sky Search for Time-integrated Neutrino Emission from Astrophysical Sources with 7 yr of IceCube Data
- 2017
-
Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 835:2
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Tidskriftsartikel (refereegranskat)abstract
- Since the recent detection of an astrophysical flux of high-energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over 7 yr from 2008 to 2015. The discovery potential of the analysis in the northern sky is now significantly below E(nu)(2)d phi/dE(nu) = 10(-12) TeV cm(-2) s(-1), on average 38% lower than the sensitivity of the previously published analysis of 4 yr exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.
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| 4. |
- Aartsen, M. G., et al.
(författare)
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Astrophysical neutrinos and cosmic rays observed by IceCube
- 2018
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Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 62:10, s. 2902-2930
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Tidskriftsartikel (refereegranskat)abstract
- The core mission of the IceCube neutrino observatory is to study the origin and propagation of cosmic rays. IceCube, with its surface component IceTop, observes multiple signatures to accomplish this mission. Most important are the astrophysical neutrinos that are produced in interactions of cosmic rays, close to their sources and in interstellar space. IceCube is the first instrument that measures the properties of this astrophysical neutrino flux and constrains its origin. In addition, the spectrum, composition, and anisotropy of the local cosmic-ray flux are obtained from measurements of atmospheric muons and showers. Here we provide an overview of recent findings from the analysis of IceCube data, and their implications to our understanding of cosmic rays.
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| 5. |
- Aartsen, M. G., et al.
(författare)
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Constraints on Galactic Neutrino Emission with Seven Years of IceCube Data
- 2017
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 849:1
-
Tidskriftsartikel (refereegranskat)abstract
- The origins of high-energy astrophysical neutrinos remain a mystery despite extensive searches for their sources. We present constraints from seven years of IceCube Neutrino Observatory muon data on the neutrino flux coming from the Galactic plane. This flux is expected from cosmic-ray interactions with the interstellar medium or near localized sources. Two methods were developed to test for a spatially extended flux from the entire plane, both of which are maximum likelihood fits but with different signal and background modeling techniques. We consider three templates for Galactic neutrino emission based primarily on gamma-ray observations and models that cover a wide range of possibilities. Based on these templates and in the benchmark case of an unbroken E-2.5 power-law energy spectrum, we set 90% confidence level upper limits, constraining the possible Galactic contribution to the diffuse neutrino flux to be relatively small, less than 14% of the flux reported in Aartsen et al. above 1 TeV. A stacking method is also used to test catalogs of known high-energy Galactic gamma-ray sources.
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| 6. |
- Aartsen, M. G., et al.
(författare)
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Constraints on Minute-Scale Transient Astrophysical Neutrino Sources
- 2019
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 122:5
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Tidskriftsartikel (refereegranskat)abstract
- High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E-2.5 neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to < 5% of the detected astrophysical flux and the energy released in neutrinos (100 GeV to 10 PeV) by a median bright GRB-like source is < 10(52.5) erg. For a harder E-2.13 neutrino spectrum up to 30% of the flux could be produced by GRBs and the allowed median source energy is < 10(52) erg. A hypothetical population of transient sources has to be more common than 10(-5) Mpc(-3) yr(-1) (5 x 10(-8) Mpc(-3) yr(-1) for the E-2.13 spectrum) to account for the complete astrophysical neutrino flux.
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| 7. |
- Aartsen, M. G., et al.
(författare)
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Detection of the Temporal Variation of the Sun's Cosmic Ray Shadow with the IceCube Detector
- 2019
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Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 872:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the observation of a deficit in the cosmic ray flux from the directions of the Moon and Sun with five years of data taken by the IceCube Neutrino Observatory. Between 2010 May and 2011 May the IceCube detector operated with 79 strings deployed in the glacial ice at the South Pole, and with 86 strings between 2011 May and 2015 May. A binned analysis is used to measure the relative deficit and significance of the cosmic ray shadows. Both the cosmic ray Moon and Sun shadows are detected with high statistical significance (>10σ) for each year. The results for the Moon shadow are consistent with previous analyses and verify the stability of the IceCube detector over time. This work represents the first observation of the Sun shadow with the IceCube detector. We show that the cosmic ray shadow of the Sun varies with time. These results make it possible to study cosmic ray transport near the Sun with future data from IceCube.
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| 8. |
- Aartsen, M. G., et al.
(författare)
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First search for dark matter annihilations in the Earth with the IceCube detector
- 2017
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the first IceCube search for dark matter annihilation in the center of the Earth. Weakly interacting massive particles (WIMPs), candidates for dark matter, can scatter off nuclei inside the Earth and fall below its escape velocity. Over time the captured WIMPs will be accumulated and may eventually self-annihilate. Among the annihilation products only neutrinos can escape from the center of the Earth. Large-scale neutrino telescopes, such as the cubic kilometer IceCube Neutrino Observatory located at the South Pole, can be used to search for such neutrino fluxes. Data from 327 days of detector livetime during 2011/2012 were analyzed. No excess beyond the expected background from atmospheric neutrinos was detected. The derived upper limits on the annihilation rate of WIMPs in the Earth (Gamma(A) = 1.12 x 10(14) s(-1) for WIMP masses of 50 GeV annihilating into tau leptons) and the resulting muon flux are an order of magnitude stronger than the limits of the last analysis performed with data from IceCube's predecessor AMANDA. The limits can be translated in terms of a spin-independent WIMP-nucleon cross section. For a WIMP mass of 50GeV this analysis results in the most restrictive limits achieved with IceCube data.
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| 9. |
- Aartsen, M. G., et al.
(författare)
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Measurement of the multi-TeV neutrino interaction cross-section with IceCube using Earth absorption
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7682, s. 596-600
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Tidskriftsartikel (refereegranskat)abstract
- Neutrinos interact only very weakly, so they are extremely penetrating. The theoretical neutrino-nucleon interaction cross-section, however, increases with increasing neutrino energy, and neutrinos with energies above 40 teraelectronvolts (TeV) are expected to be absorbed as they pass through the Earth. Experimentally, the cross-section has been determined only at the relatively low energies (below 0.4 TeV) that are available at neutrino beams fromaccelerators(1,2). Here we report a measurement of neutrino absorption by the Earth using a sample of 10,784 energetic upward-going neutrino-induced muons. The flux of high-energy neutrinos transiting long paths through the Earth is attenuated compared to a reference sample that follows shorter trajectories. Using a fit to the two-dimensional distribution of muon energy and zenith angle, we determine the neutrino-nucleon interaction cross-section for neutrino energies 6.3-980 TeV, more than an order of magnitude higher than previous measurements. The measured cross-section is about 1.3 times the prediction of the standard model(3), consistent with the expectations for charged-and neutral-current interactions. We do not observe a large increase in the crosssection with neutrino energy, in contrast with the predictions of some theoretical models, including those invoking more compact spatial dimensions(4) or the production of leptoquarks(5). This cross-section measurement can be used to set limits on the existence of some hypothesized beyond-standard-model particles, including leptoquarks.
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| 10. |
- Aartsen, M. G., et al.
(författare)
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Neutrino emission from the direction of the blazar TXS 0506+056 prior to the IceCube-170922A alert
- 2018
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 361:6398, s. 147-151
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Tidskriftsartikel (refereegranskat)abstract
- A high-energy neutrino event detected by IceCube on 22 September 2017 was coincident in direction and time with a gamma-ray flare from the blazar TXS 0506+056. Prompted by this association, we investigated 9.5 years of IceCube neutrino observations to search for excess emission at the position of the blazar. We found an excess of high-energy neutrino events, with respect to atmospheric backgrounds, at that position between September 2014 and March 2015. Allowing for time-variable flux, this constitutes 3.5 sigma evidence for neutrino emission from the direction of TXS 0506+056, independent of and prior to the 2017 flaring episode. This suggests that blazars are identifiable sources of the high-energy astrophysical neutrino flux.
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| 11. |
- Aartsen, M. G., et al.
(författare)
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Neutrino interferometry for high-precision tests of Lorentz symmetry with IceCube
- 2018
-
Ingår i: Nature Physics. - : NATURE PUBLISHING GROUP. - 1745-2473 .- 1745-2481. ; 14:9, s. 961-966
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Tidskriftsartikel (refereegranskat)abstract
- Lorentz symmetry is a fundamental spacetime symmetry underlying both the standard model of particle physics and general relativity. This symmetry guarantees that physical phenomena are observed to be the same by all inertial observers. However, unified theories, such as string theory, allow for violation of this symmetry by inducing new spacetime structure at the quantum gravity scale. Thus, the discovery of Lorentz symmetry violation could be the first hint of these theories in nature. Here we report the results of the most precise test of spacetime symmetry in the neutrino sector to date. We use high-energy atmospheric neutrinos observed at the IceCube Neutrino Observatory to search for anomalous neutrino oscillations as signals of Lorentz violation. We find no evidence for such phenomena. This allows us to constrain the size of the dimension-four operator in the standard-model extension for Lorentz violation to the 10(-28) level and to set limits on higher-dimensional operators in this framework. These are among the most stringent limits on Lorentz violation set by any physical experiment.
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| 12. |
- Aartsen, M. G., et al.
(författare)
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Neutrinos below 100 TeV from the southern sky employing refined veto techniques to IceCube data
- 2020
-
Ingår i: Astroparticle physics. - : ELSEVIER. - 0927-6505 .- 1873-2852. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- Many Galactic sources of gamma rays, such as supernova remnants, are expected to produce neutrinos with a typical energy cutoff well below 100 TeV. For the IceCube Neutrino Observatory located at the South Pole, the southern sky, containing the inner part of the Galactic plane and the Galactic Center, is a particularly challenging region at these energies, because of the large background of atmospheric muons. In this paper, we present recent advancements in data selection strategies for track-like muon neutrino events with energies below 100 TeV from the southern sky. The strategies utilize the outer detector regions as veto and features of the signal pattern to reduce the background of atmospheric muons to a level which, for the first time, allows IceCube searching for point-like sources of neutrinos in the southern sky at energies between 100 GeV and several TeV in the muon neutrino charged current channel. No significant clustering of neutrinos above background expectation was observed in four years of data recorded with the completed IceCube detector. Upper limits on the neutrino flux for a number of spectral hypotheses are reported for a list of astrophysical objects in the southern hemisphere.
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| 13. |
- Aartsen, M. G., et al.
(författare)
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PINGU : a vision for neutrino and particle physics at the South Pole
- 2017
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 44:5
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Tidskriftsartikel (refereegranskat)abstract
- The Precision IceCube Next Generation Upgrade (PINGU) is a proposed low-energy in-fill extension to the IceCube Neutrino Observatory. With detection technology modeled closely on the successful IceCube example, PINGU will provide a 6 Mton effective mass for neutrino detection with an energy threshold of a few GeV. With an unprecedented sample of over 60 000 atmospheric neutrinos per year in this energy range, PINGU will make highly competitive measurements of neutrino oscillation parameters in an energy range over an order of magnitude higher than long-baseline neutrino beam experiments. PINGU will measure the mixing parameters theta(23) and Delta m(32)(2), including the octant of theta(23) for a wide range of values, and determine the neutrino mass ordering at 3 sigma median significance within five years of operation. PINGU's high precision measurement of the rate of nu(T) appearance will provide essential tests of the unitarity of the 3 x 3 PMNS neutrino mixing matrix. PINGU will also improve the sensitivity of searches for low mass dark matter in the Sun, use neutrino tomography to directly probe the composition of the Earth's core, and improve IceCube's sensitivity to neutrinos from Galactic supernovae. Reoptimization of the PINGU design has permitted substantial reduction in both cost and logistical requirements while delivering performance nearly identical to configurations previously studied.
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| 14. |
- Aartsen, M. G., et al.
(författare)
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Search for annihilating dark matter in the Sun with 3 years of IceCube data
- 2017
-
Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:3
-
Tidskriftsartikel (refereegranskat)abstract
- We present results from an analysis looking for darkmatter annihilation in the Sun with the IceCube neutrino telescope. Gravitationally trapped dark matter in the Sun's core can annihilate into Standard Model particles making the Sun a source of GeV neutrinos. IceCube is able to detect neutrinos with energies > 100 GeV while its low-energy infill array DeepCore extends this to >10GeV. This analysis uses data gathered in the austral winters between May 2011 and May 2014, corresponding to 532 days of livetime when the Sun, being below the horizon, is a source of up-going neutrino events, easiest to discriminate against the dominant background of atmospheric muons. The sensitivity is a factor of two to four better than previous searches due to additional statistics and improved analysis methods involving better background rejection and reconstructions. The resultant upper limits on the spin-dependent dark matter-proton scattering cross section reach down to 1.46 x 10(-5) pb for a dark matter particle of mass 500GeV annihilating exclusively into tau(+)tau(-) particles. These are currently the most stringent limits on the spin-dependent dark matter-proton scattering cross section for WIMP masses above 50GeV.
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| 15. |
- Aartsen, M. G., et al.
(författare)
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The IceCube Neutrino Observatory : instrumentation and online systems
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
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| 16. |
- Aartsen, M. G., et al.
(författare)
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Very high-energy gamma-ray follow-up program using neutrino triggers from IceCube
- 2016
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- We describe and report the status of a neutrino-triggered program in IceCube that generates real-time alerts for gamma-ray follow-up observations by atmospheric-Cherenkov telescopes (MAGIC and VERITAS). While IceCube is capable of monitoring the whole sky continuously, high-energy gamma-ray telescopes have restricted fields of view and in general are unlikely to be observing a potential neutrino-flaring source at the time such neutrinos are recorded. The use of neutrino-triggered alerts thus aims at increasing the availability of simultaneous multi-messenger data during potential neutrino flaring activity, which can increase the discovery potential and constrain the phenomenological interpretation of the high-energy emission of selected source classes (e. g. blazars). The requirements of a fast and stable online analysis of potential neutrino signals and its operation are presented, along with first results of the program operating between 14 March 2012 and 31 December 2015.
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| 17. |
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| 18. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 19. |
- Garrappa, S., et al.
(författare)
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Investigation of Two Fermi-LAT Gamma-Ray Blazars Coincident with High-energy Neutrinos Detected by IceCube
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 880:2
-
Tidskriftsartikel (refereegranskat)abstract
- After the identification of the gamma-ray blazar TXS 0506+056 as the first compelling IceCube neutrino source candidate, we perform a systematic analysis of all high-energy neutrino events satisfying the IceCube realtime trigger criteria. We find one additional known gamma-ray source, the blazar GB6 J1040+0617, in spatial coincidence with a neutrino in this sample. The chance probability of this coincidence is 30% after trial correction. For the first time, we present a systematic study of the gamma-ray flux, spectral and optical variability, and multiwavelength behavior of GB6 J1040+0617 and compare it to TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the Fermi-Large Area Telescope gamma-ray band, being in an active state around the arrival of IceCube-170922A, but in a low state during the archival IceCube neutrino flare in 2014/15. In both cases the spectral shape is statistically compatible (<= 2 sigma) with the average spectrum showing no indication of a significant relative increase of a high-energy component. While the association of GB6 J1040+0617 with the neutrino is consistent with background expectations, the source appears to be a plausible neutrino source candidate based on its energetics and multiwavelength features, namely a bright optical flare and modestly increased gamma-ray activity. Finding one or two neutrinos originating from gamma-ray blazars in the given sample of high-energy neutrinos is consistent with previously derived limits of neutrino emission from gamma-ray blazars, indicating the sources of the majority of cosmic high-energy neutrinos remain unknown.
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| 20. |
- Grasselli, Giacomo, et al.
(författare)
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ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
- 2023
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Ingår i: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
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Tidskriftsartikel (refereegranskat)abstract
- The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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| 21. |
- Jackson, Victoria E, et al.
(författare)
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Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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| 22. |
- Kankare, E., et al.
(författare)
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Search for transient optical counterparts to high-energy IceCube neutrinos with Pan-STARRS1
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 626
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Tidskriftsartikel (refereegranskat)abstract
- In order to identify the sources of the observed diffuse high-energy neutrino flux, it is crucial to discover their electromagnetic counterparts. To increase the sensitivity of detecting counterparts of transient or variable sources by telescopes with a limited field of view, IceCube began releasing alerts for single high-energy (E-v > 60 TeV) neutrino detections with sky localisation regions of order 1 degrees radius in 2016. We used Pan-STARRS1 to follow-up five of these alerts during 2016-2017 to search for any optical transients that may be related to the neutrinos. Typically 10-20 faint m(ip1) less than or similar to 22.5 mag) extragalactic transients are found within the Pan-STARRS1 footprints and are generally consistent with being unrelated field supernovae (SNe) and AGN. We looked for unusual properties of the detected transients, such as temporal coincidence of explosion epoch with the IceCube timestamp, or other peculiar light curve and physical properties. We found only one transient that had properties worthy of a specific follow-up. In the Pan-STARRS1 imaging for IceCube-160427A (probability to be of astrophysical origin of similar to 50%), we found a SN PS16cgx, located at 10.0' from the nominal IceCube direction. Spectroscopic observations of PS16cgx showed that it was an H-poor SN at redshift z = 0.2895 +/- 0.0001. The spectra and light curve resemble some high-energy Type Ic SNe, raising the possibility of a jet driven SN with an explosion epoch temporally coincident with the neutrino detection. However, distinguishing Type Ia and Type Ic SNe at this redshift is notoriously difficult. Based on all available data we conclude that the transient is more likely to be a Type Ia with relatively weak Sin absorption and a fairly normal rest-frame r-band light curve. If, as predicted, there is no high-energy neutrino emission from Type Ia SNe, then PS16cgx must be a random coincidence, and unrelated to the IceCube-160427A. We find no other plausible optical transient for any of the five IceCube events observed down to a 5 sigma limiting magnitude of mip1 approximate to 22 mag, between 1 day and 25 days after detection.
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| 23. |
- Kern, Wolfgang, et al.
(författare)
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Multicenter prospective evaluation of diagnostic potential of flow cytometric aberrancies in myelodysplastic syndromes by the ELN iMDS flow working group
- 2023
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Ingår i: Cytometry Part B - Clinical Cytometry. - : Wiley. - 1552-4949 .- 1552-4957. ; 104:1, s. 51-65
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myelodysplastic syndromes (MDS) represent a diagnostic challenge. This prospective multicenter study was conducted to evaluate pre-defined flow cytometric markers in the diagnostic work-up of MDS and chronic myelomonocytic leukemia (CMML). Methods: Thousand six hundred and eighty-two patients with suspected MDS/CMML were analyzed by both cytomorphology according to WHO 2016 criteria and flow cytometry according to ELN recommendations. Flow cytometric readout was categorized ‘non-MDS’ (i.e. no signs of MDS/CMML and limited signs of MDS/CMML) and ‘in agreement with MDS’ (i.e., in agreement with MDS/CMML). Results: Flow cytometric readout categorized 60% of patients in agreement with MDS, 28% showed limited signs of MDS and 12% had no signs of MDS. In 81% of cases flow cytometric readouts and cytomorphologic diagnosis correlated. For high-risk MDS, the level of concordance was 92%. A total of 17 immunophenotypic aberrancies were found independently related to MDS/CMML in ≥1 of the subgroups of low-risk MDS, high-risk MDS, CMML. A cut-off of ≥3 of these aberrancies resulted in 80% agreement with cytomorphology (20% cases concordantly negative, 60% positive). Moreover, >3% myeloid progenitor cells were significantly associated with MDS (286/293 such cases, 98%). Conclusion: Data from this prospective multicenter study led to recognition of 17 immunophenotypic markers allowing to identify cases ‘in agreement with MDS’. Moreover, data emphasizes the clinical utility of immunophenotyping in MDS diagnostics, given the high concordance between cytomorphology and the flow cytometric readout. Results from the current study challenge the application of the cytomorphologically defined cut-off of 5% blasts for flow cytometry and rather suggest a 3% cut-off for the latter.
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| 24. |
- Levy, Rebecca C., et al.
(författare)
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Outflows from Super Star Clusters in the Central Starburst of NGC 253
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 912:1
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Tidskriftsartikel (refereegranskat)abstract
- Young massive clusters play an important role in the evolution of their host galaxies, and feedback from the high-mass stars in these clusters can have profound effects on the surrounding interstellar medium. The nuclear starburst in the nearby galaxy NGC 253 at a distance of 3.5 Mpc is a key laboratory in which to study star formation in an extreme environment. Previous high-resolution (1.9 pc) dust continuum observations from the Atacama Large Millimeter/submillimeter Array (ALMA) discovered 14 compact, massive super star clusters (SSCs) still in formation. We present here ALMA data at 350 GHz with 28 mas (0.5 pc) resolution. We detect blueshifted absorption and redshifted emission (P-Cygni profiles) toward three of these SSCs in multiple lines, including CS 7-6 and (HCN)-C-13 4-3, which represent direct evidence for previously unobserved outflows. The mass contained in these outflows is a significant fraction of the cluster gas masses, which suggests we are witnessing a short but important phase. Further evidence of this is the finding of a molecular shell around the only SSC visible at near-IR wavelengths. We model the P-Cygni line profiles to constrain the outflow geometry, finding that the outflows must be nearly spherical. Through a comparison of the outflow properties with predictions from simulations, we find that none of the available mechanisms completely explains the observations, although dust-reprocessed radiation pressure and O star stellar winds are the most likely candidates. The observed outflows will have a very substantial effect on the clusters' evolution and star formation efficiency.
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| 25. |
- Merid, Simon Kebede, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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| 26. |
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| 27. |
- Papousek, Ilona, et al.
(författare)
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Serotonin Transporter Genotype (5-HTTLPR) and Electrocortical Responses Indicating the Sensitivity to Negative Emotional Cues
- 2013
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Ingår i: Emotion. - : AMER PSYCHOLOGICAL ASSOC. - 1528-3542 .- 1931-1516. ; 13:6, s. 1173-1181
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Tidskriftsartikel (refereegranskat)abstract
- Growing literature indicates that emotional reactivity and regulation are strongly linked to genetic modulation of serotonergic neurotransmission. However, until now, most studies have focused on the relationship between genotypic markers, in particular the serotonin transporter-linked polymorphic region (5-HTTLPR), and neural structures using MRI. The current study aimed to bridge the gap between the relevant MRI literature on the effects of the 5-HTTLPR genotype and the research tradition focusing on transient lateralized changes of electrocortical activity in the prefrontal cortex using electroencephalography (EEG). Lateral shifts of EEG alpha asymmetry in response to an aversive film consisting of scenes of real injury and death were assessed in healthy participants (n = 165). To evaluate the specificity of the 5-HTTLPR effect, participants were also tested for the COMT Val158Met polymorphism which is linked to dopamine inactivation. While viewing the film, individuals homozygous for the 5-HTTLPR short allele displayed a clear lateral shift of dorsolateral frontal activity to the right, which was virtually absent in participants carrying the long allele. The heightened electrocortical response to the aversive stimulation and its direction indicates a greater propensity of s/s homozygotes to experience withdrawal oriented affect in response to negative emotion cues in the environment. Moreover, together with previous research the findings support the notion of a link between the serotonergic system and self-regulation related to avoidance motivation, and a link between the dopaminergic system and self-regulation related to approach motivation.
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| 28. |
- Reiser, Eva M., et al.
(författare)
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Prefrontal-posterior coupling while observing the suffering of other people, and the development of intrusive memories
- 2014
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Ingår i: Psychophysiology. - : WILEY. - 0048-5772 .- 1469-8986. ; 51:6, s. 546-555
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Tidskriftsartikel (refereegranskat)abstract
- Witnessing the suffering of others, for instance, in hospital emergency rooms but also through televised images in news or reality programs, may be associated with the occurrence of later intrusive memories. The factors contributing to why some people develop intrusive memories and others do not are still poorly understood. N = 121 healthy women were exposed to film scenes showing the suffering of dying, severely injured, and mourning people while their EEG was recorded. Individuals showing greater decreases of functional coupling between prefrontal and posterior cortices (greater decreases of EEG beta coherences) reported more intrusive memories of the witnessed events. This was shown for intrusions in the short term (immediately after viewing the film) as well as in the medium term (intrusive memories over 1 week). The findings illuminate brain mechanisms involved in the encoding of information in ways that make intrusive memories more likely.
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| 29. |
- van der Velden, Vincent H.J., et al.
(författare)
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Flow cytometric analysis of myelodysplasia : Pre-analytical and technical issues—Recommendations from the European LeukemiaNet
- 2023
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Ingår i: Cytometry Part B - Clinical Cytometry. - : Wiley. - 1552-4949 .- 1552-4957. ; 104:1, s. 15-26
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Tidskriftsartikel (refereegranskat)abstract
- Background: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures. Methods: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group. Results: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies. Conclusions: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice.
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