| 1. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 2. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 3. |
- Aprile, E., et al.
(författare)
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Physics reach of the XENON1T dark matter experiment
- 2016
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- The XENON1T experiment is currently in the commissioning phase at the Laboratori Nazionali del Gran Sasso, Italy. In this article we study the experiment's expected sensitivity to the spin-independent WIMP-nucleon interaction cross section, based on Monte Carlo predictions of the electronic and nuclear recoil backgrounds. The total electronic recoil background in 1 tonne fiducial volume and (1, 12) keV electronic recoil equivalent energy region, before applying any selection to discriminate between electronic and nuclear recoils, is (1.80+/-0.15) . 10(-4) (kg.day.keV)(-1), mainly due to the decay of Rn-222 daughters inside the xenon target. The nuclear recoil background in the corresponding nuclear recoil equivalent energy region (4, 50) keV, is composed of (0.6 +/- 0.1) (t.y)(-1) from radiogenic neutrons, (1.8+/-0.3) . 10(-2) (t.y)(-1) from coherent scattering of neutrinos, and less than 0.01 (t.y)(-1) from muon-induced neutrons. The sensitivity of XENON1T is calculated with the Pro file Likelihood Ratio method, after converting the deposited energy of electronic and nuclear recoils into the scintillation and ionization signals seen in the detector. We take into account the systematic uncertainties on the photon and electron emission model, and on the estimation of the backgrounds, treated as nuisance parameters. The main contribution comes from the relative scintillation efficiency L-eff, which affects both the signal from WIMPs and the nuclear recoil backgrounds. After a 2 y measurement in 1 tonne fiducial volume, the sensitivity reaches a minimum cross section of 1.6 . 10(-47) cm(2) at m(chi) = 50 GeV/c(2).
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| 4. |
- Aprile, E., et al.
(författare)
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Effective field theory search for high-energy nuclear recoils using the XENON100 dark matter detector
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:4
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Tidskriftsartikel (refereegranskat)abstract
- We report on weakly interacting massive particles (WIMPs) search results in the XENON100 detector using a nonrelativistic effective field theory approach. The data from science run II (34 kg x 224.6 live days) were reanalyzed, with an increased recoil energy interval compared to previous analyses, ranging from (6.6-240) keV(nr). The data are found to be compatible with the background-only hypothesis. We present 90% confidence level exclusion limits on the coupling constants of WIMP-nucleon effective operators using a binned profile likelihood method. We also consider the case of inelastic WIMP scattering, where incident WIMPs may up-scatter to a higher mass state, and set exclusion limits on this model as well.
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| 5. |
- Aprile, E., et al.
(författare)
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First Dark Matter Search Results from the XENON1T Experiment
- 2017
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 119:18
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Tidskriftsartikel (refereegranskat)abstract
- We report the first dark matter search results from XENON1T, a similar to 2000-kg-target-mass dual-phase (liquid-gas) xenon time projection chamber in operation at the Laboratori Nazionali del Gran Sasso in Italy and the first ton-scale detector of this kind. The blinded search used 34.2 live days of data acquired between November 2016 and January 2017. Inside the (1042 +/- 12)-kg fiducial mass and in the [5, 40] keV(nr) energy range of interest for weakly interacting massive particle (WIMP) dark matter searches, the electronic recoil background was (1.93 +/- 0.25) x 10(-4) events/(kg x day x keV(ee)), the lowest ever achieved in such a dark matter detector. A profile likelihood analysis shows that the data are consistent with the background-only hypothesis. We derive the most stringent exclusion limits on the spin-independent WIMP-nucleon interaction cross section for WIMP masses above 10 GeV/c(2), with a minimum of 7.7 x 10(-47) cm(2) for 35-GeV/c(2) WIMPs at 90% C.L.
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| 6. |
- Aprile, E., et al.
(författare)
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Low-mass dark matter search using ionization signals in XENON100
- 2016
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Ingår i: Physical Review D. - 2470-0010. ; 94:9
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Tidskriftsartikel (refereegranskat)abstract
- We perform a low-mass dark matter search using an exposure of 30 kg x yr with the XENON100 detector. By dropping the requirement of a scintillation signal and using only the ionization signal to determine the interaction energy, we lowered the energy threshold for detection to 0.7 keV for nuclear recoils. No dark matter detection can be claimed because a complete background model cannot be constructed without a primary scintillation signal. Instead, we compute an upper limit on the WIMP-nucleon scattering cross section under the assumption that every event passing our selection criteria could be a signal event. Using an energy interval from 0.7 keV to 9.1 keV, we derive a limit on the spin-independent WIMP-nucleon cross section that excludes WIMPs with a mass of 6 GeV/c(2) above 1.4 x 10(-41) cm(2) at 90% confidence level.
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| 7. |
- Aprile, E., et al.
(författare)
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Material radioassay and selection for the XENON1T dark matter experiment
- 2017
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:12
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Tidskriftsartikel (refereegranskat)abstract
- The XENON1T dark matter experiment aims to detect weakly interactingmassive particles (WIMPs) through low-energy interactions with xenon atoms. To detect such a rare event necessitates the use of radiopure materials to minimize the number of background events within the expected WIMP signal region. In this paper we report the results of an extensive material radioassay campaign for the XENON1T experiment. Using gamma-ray spectroscopy and mass spectrometry techniques, systematic measurements of trace radioactive impurities in over one hundred samples within a wide range of materials were performed. The measured activities allowed for stringent selection and placement of materials during the detector construction phase and provided the input for XENON1T detection sensitivity estimates through Monte Carlo simulations.
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| 8. |
- Aprile, E., et al.
(författare)
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Online Rn-222 removal by cryogenic distillation in the XENON100 experiment
- 2017
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:6
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Tidskriftsartikel (refereegranskat)abstract
- We describe the purification of xenon from traces of the radioactive noble gas radon using a cryogenic distillation column. The distillation column was integrated into the gas purification loop of the XENON100 detector for online radon removal. This enabled us to significantly reduce the constant Rn-222 background originating from radon emanation. After inserting an auxiliary 222Rn emanation source in the gas loop, we determined a radon reduction factor of R > 27 (95% C.L.) for the distillation column by monitoring the Rn-222 activity concentration inside the XENON100 detector.
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| 9. |
- Aprile, E., et al.
(författare)
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Removing krypton from xenon by cryogenic distillation to the ppq level
- 2017
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:5
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Tidskriftsartikel (refereegranskat)abstract
- The XENON1T experiment aims for the direct detection of dark matter in a detector filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the beta-emitter Kr-85 which is present in the xenon. For XENON1T a concentration of natural krypton in xenon Kr-nat/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10(-15) mol/mol) is required. In this work, the design, construction and test of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4 . 10(5) with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of natKr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN.
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| 10. |
- Aprile, E., et al.
(författare)
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Results from a calibration of XENON100 using a source of dissolved radon-220
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 95:7
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Tidskriftsartikel (refereegranskat)abstract
- A Rn-220 source is deployed on the XENON100 dark matter detector in order to address the challenges in calibration of tonne-scale liquid noble element detectors. We show that the Pb-212 beta emission can be used for low-energy electronic recoil calibration in searches for dark matter. The isotope spreads throughout the entire active region of the detector, and its activity naturally decays below background level within a week after the source is closed. We find no increase in the activity of the troublesome Rn-222 background after calibration. Alpha emitters are also distributed throughout the detector and facilitate calibration of its response to Rn-222. Using the delayed coincidence of Rn-220-Po-216, we map for the first time the convective motion of particles in the XENON100 detector. Additionally, we make a competitive measurement of the half-life of Po-212, t(1/2) = (293.9 +/- (1.0)(stat) +/- (0.6)(sys)) ns.
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| 11. |
- Aprile, E., et al.
(författare)
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Search for bosonic super-WIMP interactions with the XENON100 experiment
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:12
-
Tidskriftsartikel (refereegranskat)abstract
- We present results of searches for vector and pseudoscalar bosonic super-weakly interacting massive particles (WIMPs), which are dark matter candidates with masses at the keV-scale, with the XENON100 experiment. XENON100 is a dual-phase xenon time projection chamber operated at the Laboratori Nazionali del Gran Sasso. A profile likelihood analysis of data with an exposure of 224.6 live days x34 kg showed no evidence for a signal above the expected background. We thus obtain new and stringent upper limits in the (8-125) keV/c(2) mass range, excluding couplings to electrons with coupling constants of g(ae) > 3 x 10(-13) for pseudo-scalar and alpha'/alpha > 2 x 10(-28) for vector super-WIMPs, respectively. These limits are derived under the assumption that super-WIMPs constitute all of the dark matter in our galaxy.
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| 12. |
- Aprile, E., et al.
(författare)
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Search for Electronic Recoil Event Rate Modulation with 4 Years of XENON100 Data
- 2017
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 118:10
-
Tidskriftsartikel (refereegranskat)abstract
- We report on a search for electronic recoil event rate modulation signatures in the XENON100 data accumulated over a period of 4 yr, from January 2010 to January 2014. A profile likelihood method, which incorporates the stability of the XENON100 detector and the known electronic recoil background model, is used to quantify the significance of periodicity in the time distribution of events. There is a weak modulation signature at a period of 431(-14)(+16) day in the low energy region of (2.0-5.8) keV in the single scatter event sample, with a global significance of 1.9 sigma; however, no other more significant modulation is observed. The significance of an annual modulation signature drops from 2.8 sigma, from a previous analysis of a subset of this data, to 1.8 sigma with all data combined. Single scatter events in the low energy region are thus used to exclude the DAMA/LIBRA annual modulation as being due to dark matter electron interactions via axial vector coupling at 5.7 sigma.
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| 13. |
- Aprile, E., et al.
(författare)
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Search for magnetic inelastic dark matter with XENON100
- 2017
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :10
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first search for dark matter-induced delayed coincidence signals in a dual-phase xenon time projection chamber, using the 224.6 live days of the XENON100 science run II. This very distinct signature is predicted in the framework of magnetic inelastic dark matter which has been proposed to reconcile the modulation signal reported by the DAMA/LIBRA collaboration with the null results from other direct detection experiments. No candidate event has been found in the region of interest and upper limits on the WIMP's magnetic dipole moment are derived. The scenarios proposed to explain the DAMA/LIBRA modulation signal by magnetic inelastic dark matter interactions of WIMPs with masses of 58.0 GeV/c(2) and 122.7 GeV/c(2) are excluded at 3.3 sigma and 9.3 sigma, respectively.
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| 14. |
- Aprile, E., et al.
(författare)
-
Search for two-neutrino double electron capture of Xe-124 with XENON100
- 2017
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Ingår i: Physical Review C. - 2469-9985. ; 95:2
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Tidskriftsartikel (refereegranskat)abstract
- Two-neutrino double electron capture is a rare nuclear decay where two electrons are simultaneously captured from the atomic shell. For Xe-124 this process has not yet been observed and its detection would provide a new reference for nuclear matrix element calculations. We have conducted a search for two-neutrino double electron capture from the K shell of 124Xe using 7636 kg d of data from the XENON100 dark matter detector. Using a Bayesian analysis we observed no significant excess above background, leading to a lower 90% credibility limit on the half-life T-1/2 > 6.5 x 10(20) yr. We have also evaluated the sensitivity of the XENON1T experiment, which is currently being commissioned, and found a sensitivity of T-1/2 > 6.1 x 10(22) yr after an exposure of 2 t yr.
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| 15. |
- Aprile, E., et al.
(författare)
-
Search for WIMP inelastic scattering off xenon nuclei with XENON100
- 2017
-
Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first constraints on the spin-dependent, inelastic scattering cross section of weakly interacting massive particles (WIMPs) on nucleons from XENON100 data with an exposure of 7.64 x 10(3) kg . days. XENON100 is a dual-phase xenon time projection chamber with 62 kg of active mass, operated at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy and designed to search for nuclear recoils from WIMP-nucleus interactions. Here we explore inelastic scattering, where a transition to a low-lying excited nuclear state of Xe-129 is induced. The experimental signature is a nuclear recoil observed together with the prompt deexcitation photon. We see no evidence for such inelastic WIMP-Xe-129 interactions. A profile likelihood analysis allows us to set a 90% C.L. upper limit on the inelastic, spin-dependent WIMP-nucleon cross section of 3.3 x 10(-38) cm(2) at 100 GeV/c(2). This is the most constraining result to date, and sets the pathway for an analysis of this interaction channel in upcoming, larger dual-phase xenon detectors.
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| 16. |
- Aprile, E., et al.
(författare)
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Signal yields of keV electronic recoils and their discrimination from nuclear recoils in liquid xenon
- 2018
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 97:9
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Tidskriftsartikel (refereegranskat)abstract
- We report on the response of liquid xenon to low energy electronic recoils below 15 keV from beta decays of tritium at drift fields of 92 V/cm, 154 V/cm and 366 V/cm using the XENON100 detector. A data-to-simulation fitting method based on Markov Chain Monte Carlo is used to extract the photon yields and recombination fluctuations from the experimental data. The photon yields measured at the two lower fields are in agreement with those from literature; additional measurements at a higher field of 366 V/cm are presented. The electronic and nuclear recoil discrimination as well as its dependence on the drift field and photon detection efficiency are investigated at these low energies. The results provide new measurements in the energy region of interest for dark matter searches using liquid xenon.
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| 17. |
- Aprile, E., et al.
(författare)
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The XENON1T dark matter experiment
- 2017
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:12
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Tidskriftsartikel (refereegranskat)abstract
- The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2t liquid xenon inventory, 2.0t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented.
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| 18. |
- Karyotaki, Eirini, et al.
(författare)
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Internet-Based Cognitive Behavioral Therapy for Depression : A Systematic Review and Individual Patient Data Network Meta-analysis
- 2021
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:4, s. 361-371
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Forskningsöversikt (refereegranskat)abstract
- IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire-9 (PHQ-9) scores.RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
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| 19. |
- Kessler, Jan H., et al.
(författare)
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Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes
- 2010
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 12:1, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- Cytotoxic T lymphocytes (CTLs) recognize peptides presented by HLA class I molecules on the cell surface. The C terminus of these CTL epitopes is considered to be produced by the proteasome. Here we demonstrate that the cytosolic endopeptidases nardilysin and thimet oligopeptidase (TOP) complemented proteasome activity. Nardilysin and TOP were required, either together or alone, for the generation of a tumor-specific CTL epitope from PRAME, an immunodominant CTL epitope from Epstein-Barr virus protein EBNA3C, and a clinically important epitope from the melanoma protein MART-1. TOP functioned as C-terminal trimming peptidase in antigen processing, and nardilysin contributed to both the C-terminal and N-terminal generation of CTL epitopes. By broadening the antigenic peptide repertoire, nardilysin and TOP strengthen the immune defense against intracellular pathogens and cancer.
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| 20. |
- Mendieta-Leiva, Glenda, et al.
(författare)
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EpIG-DB: A database of vascular epiphyte assemblages in the Neotropics
- 2020
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Ingår i: Journal of Vegetation Science. - : Wiley. - 1100-9233 .- 1654-1103. ; 31, s. 518-528
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Tidskriftsartikel (refereegranskat)abstract
- Vascular epiphytes are a diverse and conspicuous component of biodiversity in tropical and subtropical forests. Yet, the patterns and drivers of epiphyte assemblages are poorly studied in comparison with soil-rooted plants. Current knowledge about diversity patterns of epiphytes mainly stems from local studies or floristic inventories, but this information has not yet been integrated to allow a better understanding of large-scale distribution patterns. EpIG-DB, the first database on epiphyte assemblages at the continental scale, resulted from an exhaustive compilation of published and unpublished inventory data from the Neotropics. The current version of EpIG-DB consists of 463,196 individual epiphytes from 3,005 species, which were collected from a total of 18,148 relevés (host trees and ‘understory’ plots). EpIG-DB reports the occurrence of ‘true’ epiphytes, hemiepiphytes and nomadic vines, including information on their cover, abundance, frequency and biomass. Most records (97%) correspond to sampled host trees, 76% of them aggregated in forest plots. The data is stored in a TURBOVEG database using the most up-to-date checklist of vascular epiphytes. A total of 18 additional fields were created for the standardization of associated data commonly used in epiphyte ecology (e.g. by considering different sampling methods). EpIG-DB currently covers six major biomes across the whole latitudinal range of epiphytes in the Neotropics but welcomes data globally. This novel database provides, for the first time, unique biodiversity data on epiphytes for the Neotropics and unified guidelines for future collection of epiphyte data. EpIG-DB will allow exploration of new ways to study the community ecology and biogeography of vascular epiphytes.
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| 21. |
- Stitziel, Nathan O., et al.
(författare)
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Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease
- 2016
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
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| 22. |
- Treydte, Kerstin, et al.
(författare)
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Recent human-induced atmospheric drying across Europe unprecedented in the last 400 years
- 2024
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Ingår i: NATURE GEOSCIENCE. - 1752-0894 .- 1752-0908. ; 17, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- The vapor pressure deficit reflects the difference between how much moisture the atmosphere could and actually does hold, a factor that fundamentally affects evapotranspiration, ecosystem functioning, and vegetation carbon uptake. Its spatial variability and long-term trends under natural versus human-influenced climate are poorly known despite being essential for predicting future effects on natural ecosystems and human societies such as crop yield, wildfires, and health. Here we combine regionally distinct reconstructions of pre-industrial summer vapor pressure deficit variability from Europe's largest oxygen-isotope network of tree-ring cellulose with observational records and Earth system model simulations with and without human forcing included. We demonstrate that an intensification of atmospheric drying during the recent decades across different European target regions is unprecedented in a pre-industrial context and that it is attributed to human influence with more than 98% probability. The magnitude of this trend is largest in Western and Central Europe, the Alps and Pyrenees region, and the smallest in southern Fennoscandia. In view of the extreme drought and compound events of the recent years, further atmospheric drying poses an enhanced risk to vegetation, specifically in the densely populated areas of the European temperate lowlands. The atmosphere has dried across most regions of Europe in recent decades, a trend that can be attributed primarily to human impacts, according to tree ring records spanning 400 years and Earth system model simulations.
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| 23. |
- Webb, Thomas R., et al.
(författare)
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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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