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Sökning: WFRF:(Mancuso A. P.)

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4.
  • Aprile, E., et al. (författare)
  • Double-weak decays of 124Xe and 136Xe in the XENON1T and XENONnT experiments
  • 2022
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 106:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present results on the search for two-neutrino double-electron capture (2νECEC) of 124Xe and neutrinoless double-β decay (0νββ) of 136Xe in XENON1T. We consider captures from the K shell up to the N shell in the 2νECEC signal model and measure a total half-life of T2νECEC1/2=(1.1±0.2stat±0.1sys)×1022yr with a 0.87 kg yr isotope exposure. The statistical significance of the signal is 7.0σ. We use XENON1T data with 36.16 kg yr of 136Xe exposure to search for 0νββ. We find no evidence of a signal and set a lower limit on the half-life of T0νββ1/2>1.2×1024 yr at 90%CL. This is the best result from a dark matter detector without an enriched target to date. We also report projections on the sensitivity of XENONnT to 0νββ. Assuming a 275 kg yr 136Xe exposure, the expected sensitivity is T0νββ1/2>2.1×1025 yr at 90%CL, corresponding to an effective Majorana mass range of ⟨mββ⟩<(0.19–0.59)eV/c2.
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  • Aprile, E., et al. (författare)
  • Effective Field Theory and Inelastic Dark Matter Results from XENON1T
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • In this work we expand on the XENON1T nuclear recoil searches and study the individual signals of Dark Matter interactions from operators up to dimension-eight in a Chiral Effective Field Theory (ChEFT) as well as a model of inelastic Dark Matter using data from the two science runs of the detector totalling 1 tonne*year exposure. For these analyses we extended the region of interest from [4.9, 40.9]keVnr to [4.9, 54.4]keVnr to enhance our sensitivity for signals that peak at nonzero energies. We show that the data is consistent with a background only hypothesis, with small excesses in the models which peak between 20 and 50keVnr, obtaining a maximum local discovery significance of 1.7 for the VVs ChEFT model for a WIMP mass of 70GeV/c2, and 1.8 for an iDM particle of 50GeV/c2 with a mass splitting of 100keV/c2. For each model we report 90% confidence level upper limits. We also report limits on three benchmark models of WIMP interaction using ChEFT for which we investigate the effect of isospin breaking interactions, reporting up to 6 orders of magnitude weaker limits with respect to the isospin conserving case driven by cancellations in the expected rate.
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6.
  • Aprile, E., et al. (författare)
  • Emission of single and few electrons in XENON1T and limits on light dark matter
  • 2022
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 106:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Delayed single- and few-electron emissions plague dual-phase time projection chambers, limiting their potential to search for light-mass dark matter. This paper examines the origins of these events in the XENON1T experiment. Characterization of the intensity of delayed electron backgrounds shows that the resulting emissions are correlated, in time and position, with high-energy events and can effectively be vetoed. In this work we extend previous S2-only analyses down to a single electron. From this analysis, after removing the correlated backgrounds, we observe rates <30 events/(electron×kg×day) in the region of interest spanning 1 to 5 electrons. We derive 90% confidence upper limits for dark matter-electron scattering, first direct limits on the electric dipole, magnetic dipole, and anapole interactions, and bosonic dark matter models, where we exclude new parameter space for dark photons and solar dark photons.
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  • Aprile, E., et al. (författare)
  • An approximate likelihood for nuclear recoil searches with XENON1T data
  • 2022
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The XENON collaboration has published stringent limits on specific dark matter – nucleon recoil spectra from dark matter recoiling on the liquid xenon detector target. In this paper, we present an approximate likelihood for the XENON1T 1 t-year nuclear recoil search applicable to any nuclear recoil spectrum. Alongside this paper, we publish data and code to compute upper limits using the method we present. The approximate likelihood is constructed in bins of reconstructed energy, profiled along the signal expectation in each bin. This approach can be used to compute an approximate likelihood and therefore most statistical results for any nuclear recoil spectrum. Computing approximate results with this method is approximately three orders of magnitude faster than the likelihood used in the original publications of XENON1T, where limits were set for specific families of recoil spectra. Using this same method, we include toy Monte Carlo simulation-derived binwise likelihoods for the upcoming XENONnT experiment that can similarly be used to assess the sensitivity to arbitrary nuclear recoil signatures in its eventual 20 t-year exposure.
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  • Aprile, E., et al. (författare)
  • Application and modeling of an online distillation method to reduce krypton and argon in XENON1T
  • 2022
  • Ingår i: Progress of Theoretical and Experimental Physics. - : Oxford University Press (OUP). - 2050-3911. ; 2022:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A novel online distillation technique was developed for the XENON1T dark matter experiment to reduce intrinsic background components more volatile than xenon, such as krypton or argon, while the detector was operating. The method is based on a continuous purification of the gaseous volume of the detector system using the XENON1T cryogenic distillation column. A krypton-in-xenon concentration of (360 +/- 60) ppq was achieved. It is the lowest concentration measured in the fiducial volume of an operating dark matter detector to date. A model was developed and fitted to the data to describe the krypton evolution in the liquid and gas volumes of the detector system for several operation modes over the time span of 550 days, including the commissioning and science runs of XENON1T. The online distillation was also successfully applied to remove Ar-37 after its injection for a low-energy calibration in XENON1T. This makes the usage of Ar-37 as a regular calibration source possible in the future. The online distillation can be applied to next-generation liquid xenon time projection chamber experiments to remove krypton prior to, or during, any science run. The model developed here allows further optimization of the distillation strategy for future large-scale detectors.
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  • Aprile, E., et al. (författare)
  • Material radiopurity control in the XENONnT experiment
  • 2022
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The selection of low-radioactive construction materials is of the utmost importance for rare-event searches and thus critical to the XENONnT experiment. Results of an extensive radioassay program are reported, in which material samples have been screened with gamma-ray spectroscopy, mass spectrometry, and 222Rn emanation measurements. Furthermore, the cleanliness procedures applied to remove or mitigate surface contamination of detector materials are described. Screening results, used as inputs for a XENONnT Monte Carlo simulation, predict a reduction of materials background (∼∼17%) with respect to its predecessor XENON1T. Through radon emanation measurements, the expected 222Rn activity concentration in XENONnT is determined to be 4.2 (+0.5−0.7) μBq/kg, a factor three lower with respect to XENON1T. This radon concentration will be further suppressed by means of the novel radon distillation system.
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10.
  • Aprile, E., et al. (författare)
  • Search for New Physics in Electronic Recoil Data from XENONnT
  • 2022
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 129:16
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3)  events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.
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  • Meyer, H., et al. (författare)
  • Overview of physics results from MAST
  • 2009
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 49:10, s. 104017-
  • Tidskriftsartikel (refereegranskat)abstract
    • Several improvements to the MAST plant and diagnostics have facilitated new studies advancing the physics basis for ITER and DEMO, as well as for future spherical tokamaks (STs). Using the increased heating capabilities P-NBI <= 3.8 MW H-mode at I-P = 1.2 MA was accessed showing that the energy confinement on MAST scales more weakly with I-P and more strongly with B-t than in the ITER IPB98(y, 2) scaling. Measurements of the fuel retention of shallow pellets extrapolate to an ITER particle throughput of 70% of its original designed total throughput capacity. The anomalous momentum diffusion, chi(phi), is linked to the ion diffusion, chi(i), with a Prandtl number close to P-phi approximate to chi(phi)/chi(i) approximate to 1, although chi(i) approaches neoclassical values. New high spatial resolution measurements of the edge radial electric field, E-r, show that the position of steepest gradients in electron pressure and E-r (i.e. shearing rate) are coincident, but their magnitudes are not linked. The T-e pedestal width on MAST scales with root beta(ped)(pol) rather than rho(pol). The edge localized mode (ELM) frequency for type-IV ELMs, new in MAST, was almost doubled using n = 2 resonant magnetic perturbations from a set of four external coils (n = 1, 2). A new internal 12 coil set (n <= 3) has been commissioned. The filaments in the inter-ELM and L-mode phase are different from ELM filaments, and the characteristics in L-mode agree well with turbulence calculations. A variety of fast particle driven instabilities were studied from 10 kHz saturated fishbone like activity up to 3.8 MHz compressional Alfven eigenmodes. Fast particle instabilities also affect the off-axis NBI current drive, leading to fast ion diffusion of the order of 0.5 m(2) s(-1) and a reduction in the driven current fraction from 40% to 30%. EBW current drive start-up is demonstrated for the first time in a ST generating plasma currents up to 55 kA. Many of these studies contributed to the physics basis of a planned upgrade to MAST.
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  • Aprile, E., et al. (författare)
  • Excess electronic recoil events in XENON1T
  • 2020
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 102:7
  • Tidskriftsartikel (refereegranskat)abstract
    • We report results from searches for new physics with low-energy electronic recoil data recorded with the XENONIT detector. With an exposure of 0.65 tonne-years and an unprecedentedly low background rate of 76 +/- 2(stat) events/(tonne x year x keV) between 1 and 30 keV, the data enable one of the most sensitive searches for solar axions, an enhanced neutrino magnetic moment using solar neutrinos, and bosonic dark matter. An excess over known backgrounds is observed at low energies and most prominent between 2 and 3 keV. The solar axion model has a 3.4 sigma significance, and a three-dimensional 90% confidence surface is reported for axion couplings to electrons, photons, and nucleons. This surface is inscribed in the cuboid defined by g(ae) < 3.8 x 10(-12), g(ae)g(an)(eff) < 4.8 x 10(-18), and g(ae)g(a gamma) < 7.7 x 10(-22) GeV-1, and excludes either g(ae) = 0 or g(ae)g(a gamma) = g(ae)ge(an)(eff), = 0. The neutrino magnetic moment signal is similarly favored over background at 3.2 sigma, and a confidence interval of mu(nu) is an element of (1.4, 2.9) x 10(-11) mu(B) (90% C.L.) is reported. Both results are in strong tension with stellar constraints. The excess can also be explained by beta decays of tritium at 3.2 sigma significance with a corresponding tritium concentration in xenon of (6.2 +/- 2.0) x 10(-25) mol/mol. Such a trace amount can neither be confirmed nor excluded with current knowledge of its production and reduction mechanisms. The significances of the solar axion and neutrino magnetic moment hypotheses arc decreased to 2.0 sigma and 0.9 sigma, respectively, if an unconstrained tritium component is included in the fitting. With respect to bosonic dark matter, the excess favors a monoenergetic peak at (2.3 +/- 0.2) keV (68% C.L.) with a 3.0 sigma global (4.0 sigma local) significance over background. This analysis sets the most restrictive direct constraints to date on pseudoscalar and vector bosonic dark matter for most masses between 1 and 210 keV/c(2). We also consider the possibility that Ar-37 may be present in the detector, yielding a 2.82 keV peak from electron capture. Contrary to tritium, the Ar-37 concentration can be tightly constrained and is found to be negligible.
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  • Aprile, E., et al. (författare)
  • Projected WIMP sensitivity of the XENONnT dark matter experiment
  • 2020
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • XENONnT is a dark matter direct detection experiment, utilizing 5.9 t of instrumented liquid xenon, located at the INFN Laboratori Nazionali del Gran Sasso. In this work, we predict the experimental background and project the sensitivity of XENONnT to the detection of weakly interacting massive particles (WIMPs). The expected average differential background rate in the energy region of interest, corresponding to (1, 13) keV and (4, 50) keV for electronic and nuclear recoils, amounts to 12.3 +/- 0.6 (keV t y)(-1) and (2.2 +/- 0.5) x 10(-3 )(keV t y)(-1), respectively, in a 4t fiducial mass. We compute unified confidence intervals using the profile construction method, in order to ensure proper coverage. With the exposure goal of 20 t y, the expected sensitivity to spin-independent WIMP-nucleon interactions reaches a cross-section of 1.4 x 10(-48) cm(2) for a 50 GeV/c(2) mass WIMP at 90% confidence level, more than one order of magnitude beyond the current best limit, set by XENON1T. In addition, we show that for a 50 GeV/c(2) WIMP with cross-sections above 2.6 x 10(-48) cm(2) (5.0 x 10(-48) cm(2)) the median XENONnT discovery significance exceeds 3 sigma (5 sigma). The expected sensitivity to the spin-dependent WIMP coupling to neutrons (protons) reaches 2.2 x 10(-43) cm(2) (6.0 x 10(-42) cm(2)).
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  • Aprile, E., et al. (författare)
  • Search for Coherent Elastic Scattering of Solar B-8 Neutrinos in the XENON1T Dark Matter Experiment
  • 2021
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 126:9
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on a search for nuclear recoil signals from solar B-8 neutrinos elastically scattering off xenon nuclei in XENON1T data, lowering the energy threshold from 2.6 to 1.6 keV. We develop a variety of novel techniques to limit the resulting increase in backgrounds near the threshold. No significant B-8 neutrinolike excess is found in an exposure of 0.6 t x y. For the first time, we use the nondetection of solar neutrinos to constrain the light yield from 1-2 keV nuclear recoils in liquid xenon, as well as nonstandard neutrino-quark interactions. Finally, we improve upon world-leading constraints on dark matter-nucleus interactions for dark matter masses between 3 and 11 GeV c(-2) by as much as an order of magnitude.
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17.
  • Aprile, E., et al. (författare)
  • Search for inelastic scattering of WIMP dark matter in XENON1T
  • 2021
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 103:6
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the results of a search for the inelastic scattering of weakly interacting massive particles (WIMPs) in the XENON1T dark matter experiment. Scattering off Xe-129 is the most sensitive probe of inelastic WIMP interactions, with a signature of a 39.6 keV deexcitation photon detected simultaneously with the nuclear recoil. Using an exposure of 0.83 tonne-years, we find no evidence of inelastic WIMP scattering with a significance of more than 2 sigma. A profile-likelihood ratio analysis is used to set upper limits on the cross section of WIMP-nucleus interactions. We exclude new parameter space for WIMPs heavier than 100 GeV/c(2), with the strongest upper limit of 3.3 x 10(-39) cm(2) for 130 GeV/c(2) WIMPs at 90% confidence level.
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  • Wang, Anqi, et al. (författare)
  • Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
  • 2023
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
  • Tidskriftsartikel (refereegranskat)abstract
    • The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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21.
  • Altavilla, R., et al. (författare)
  • Anticoagulation After Stroke in Patients With Atrial Fibrillation: To Bridge or Not With Low-Molecular-Weight Heparin?
  • 2019
  • Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:8, s. 2093-2100
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.
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  • Jentschel, M., et al. (författare)
  • EXILL - a high-efficiency, high-resolution setup for gamma-spectroscopy at an intense cold neutron beam facility
  • 2017
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • In the EXILL campaign a highly efficient array of high purity germanium (HPGe) detectors was operated at the cold neutron beam facility PF1B of the Institut Laue-Langevin (ILL) to carry out nuclear structure studies, via measurements of gamma-rays following neutron-induced capture and fission reactions. The setup consisted of a collimation system producing a pencil beam with a thermal capture equivalent flux of about 10(8) ns(-1)cm(2) at the target position and negligible neutron halo. The targetwas surrounded by an array of eight to ten anti-Compton shielded EXOGAMClover detectors, four to six anti-Compton shielded large coaxial GASP detectors and two standard Clover detectors. For a part of the campaign the array was combined with 16 LaBr3:(Ce) detectors from the FATIMA collaboration. The detectorswere arranged in an array of rhombicuboctahedron geometry, providing the possibility to carry out very precise angular correlation and directional-polarization correlation measurements. The triggerless acquisition system allowed a signal collection rate of up to 6 x 10(5) Hz. The data allowed to set multi-fold coincidences to obtain decay schemes and in combination with the FATIMA array of LaBr3:(Ce) detectors to analyze half-lives of excited levels in the pico-to microsecond range. Precise energy and efficiency calibrations of EXILL were performed using standard calibration sources of Ba-133, Co-60 and Eu-152 as well as data from the reactions Al-27(n, gamma)Al-28 and Cl-35(n,gamma)Cl-36 in the energy range from 30 keV up to 10MeV.
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  • Paciaroni, M., et al. (författare)
  • Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: Time to initiation of oral anticoagulant therapy and outcomes
  • 2018
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background—In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results—HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions—In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability. © 2018 The Authors.
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  • Paciaroni, M., et al. (författare)
  • Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema The ALESSA Score Study
  • 2017
  • Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 48:3, s. 726-732
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purposes-This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods-The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age 80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results-The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions-In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.
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25.
  • Giustozzi, M., et al. (författare)
  • Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation
  • 2020
  • Ingår i: Stroke. - 0039-2499. ; 51:8, s. 2347-2354
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 Georg Thieme Verlag. All rights reserved.
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26.
  • Lloyd, B., et al. (författare)
  • Overview of physics results from MAST
  • 2007
  • Ingår i: Nuclear Fusion. - 0029-5515 .- 1741-4326. ; 47:10, s. S658-S667
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial advances have been made on the Mega AmpÚre Spherical Tokamak (MAST). The parameter range of the MAST confinement database has been extended and it now also includes pellet-fuelled discharges. Good pellet retention has been observed in H-mode discharges without triggering an ELM or an H/L transition during peripheral ablation of low speed pellets. Co-ordinated studies on MAST and DIII-D demonstrate a strong link between the aspect ratio and the beta scaling of H-mode energy confinement, consistent with that obtained when MAST data were merged with a subset of the ITPA database. Electron and ion ITBs are readily formed and their evolution has been investigated. Electron and ion thermal diffusivities have been reduced to values close to the ion neoclassical level. Error field correction coils have been used to determine the locked mode threshold scaling which is comparable to that in conventional aspect ratio tokamaks. The impact of plasma rotation on sawteeth has been investigated and the results have been well-modelled using the MISHKA-F code. Alfvén cascades have been observed in discharges with reversed magnetic shear. Measurements during off-axis NBCD and heating are consistent with classical fast ion modelling and indicate efficient heating and significant driven current. Central electron Bernstein wave heating has been observed via the O-X-B mode conversion process in special magnetically compressed plasmas. Plasmas with low pedestal collisionality have been established and further insight has been gained into the characteristics of filamentary structures at the plasma edge. Complex behaviour of the divertor power loading during plasma disruptions has been revealed by high resolution infra-red measurements.
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27.
  • Echelmeier, A., et al. (författare)
  • Segmented flow generator for serial crystallography at the European X-ray free electron laser
  • 2020
  • Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported. 
  •  
28.
  • Conti, David, V, et al. (författare)
  • Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
  • 2021
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
  •  
29.
  • Paciaroni, M., et al. (författare)
  • Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes
  • 2020
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.
  •  
30.
  • Abdelhameed, A. H., et al. (författare)
  • First results on sub-GeV spin-dependent dark matter interactions with Li-7
  • 2019
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 79:7
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, we want to highlight the potential of lithium as a target for spin-dependent dark matter search in cryogenic experiments, with a special focus on the low-mass region of the parameter space. We operated a prototype detector module based on a Li2MoO4 target crystal in an above-ground laboratory. Despite the high background environment, the detector sets a competitive limit on spin-dependent interactions of dark matter particles with protons and neutrons for masses between 1.5 GeV/c(2).
  •  
31.
  • Lambert, J-C, et al. (författare)
  • Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease
  • 2013
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 18:4, s. 461-470
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 x 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and A beta plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma A beta 42/A beta 40 ratio (best signal, P=5.4 x 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
  •  
32.
  • Abdelhameed, A. H., et al. (författare)
  • Cryogenic characterization of a LiAlO2 crystal and new results on spin-dependent dark matter interactions with ordinary matter: CRESST Collaboration
  • 2020
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:9
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, a first cryogenic characterization of a scintillating LiAlO2 single crystal is presented. The results achieved show that this material holds great potential as a target for direct dark matter search experiments. Three different detector modules obtained from one crystal grown at the Leibniz-Institut fur Kristallzuchtung (IKZ) have been tested to study different properties at cryogenic temperatures. Firstly, two 2.8 g twin crystals were used to build different detector modules which were operated in an above-ground laboratory at the Max Planck Institute for Physics (MPP) in Munich, Germany. The first detector module was used to study the scintillation properties of LiAlO2 at cryogenic temperatures. The second achieved an energy threshold of (213.02 +/- 1.48) eV which allows setting a competitive limit on the spin-dependent dark matter particle-proton scattering cross section for dark matter particle masses between 350 MeV/c2 and 1.50 GeV/c2. Secondly, a detector module with a 373 g LiAlO2 crystal as the main absorber was tested in an underground facility at the Laboratori Nazionali del Gran Sasso (LNGS): from this measurement it was possible to determine the radiopurity of the crystal and study the feasibility of using this material as a neutron flux monitor for low-background experiments.
  •  
33.
  • Paciaroni, M., et al. (författare)
  • Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study
  • 2017
  • Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 6:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and theirtiming in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results-Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA(2)DS(2)-VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated > 14 days after acute stroke. Conclusions-In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.
  •  
34.
  • Abdelhameed, A. H., et al. (författare)
  • First results from the CRESST-III low-mass dark matter program
  • 2019
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 100:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The CRESST experiment is a direct dark matter search which aims to measure interactions of potential dark matter particles in an Earth-bound detector. With the current stage, CRESST-III, we focus on a low energy threshold for increased sensitivity towards light dark matter particles. In this paper we describe the analysis of one detector operated in the first run of CRESST-III (05/2016-02/2018) achieving a nuclear recoil threshold of 30.1 eV. This result was obtained with a 23.6 g CaWO4 crystal operated as a cryogenic scintillating calorimeter in the CRESST setup at the Laboratori Nazionali del Gran Sasso (LNGS). Both the primary phonon (heat) signal and the simultaneously emitted scintillation light, which is absorbed in a separate silicon-on-sapphire light absorber, are measured with highly sensitive transition edge sensors operated at similar to 15 mK. The unique combination of these sensors with the light element oxygen present in our target yields sensitivity to dark matter particle masses as low as 160 MeV/c(2).
  •  
35.
  • Abdelhameed, A. H., et al. (författare)
  • Geant4-based electromagnetic background model for the CRESST dark matter experiment
  • 2019
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 79:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The CRESST (Cryogenic Rare Event Search with Superconducting Thermometers) dark matter search experiment aims for the detection of dark matter particles via elastic scattering off nuclei in CaWO4 crystals. To understand the CRESST electromagnetic background due to the bulk contamination in the employed materials, a model based on Monte Carlo simulations was developed using the Geant4 simulation toolkit. The results of the simulation are applied to the TUM40 detector module of CRESST-II phase 2. We are able to explain up to (68 +/- 16)% of the electromagnetic background in the energy range between 1 and 40 keV.
  •  
36.
  • Bertoldo, E., et al. (författare)
  • Lithium-Containing Crystals for Light Dark Matter Search Experiments
  • 2020
  • Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 199:1-2, s. 510-518
  • Tidskriftsartikel (refereegranskat)abstract
    • In the current direct dark matter search landscape, the leading experiments in the sub-GeV mass region mostly rely on cryogenic techniques which employ crystalline targets. One attractive type of crystals for these experiments is those containing lithium, due to the fact that 7Li is an ideal candidate to study spin-dependent dark matter interactions in the low mass region. Furthermore, 6Li can absorb neutrons, a challenging background for dark matter experiments, through a distinctive signature which allows the monitoring of the neutron flux directly on site. In this work, we show the results obtained with three different detectors based on LiAlO 2, a target crystal never used before in cryogenic experiments.
  •  
37.
  • Dalmasso, MC, et al. (författare)
  • Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease
  • 2019
  • Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 55-
  • Tidskriftsartikel (refereegranskat)abstract
    • Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.
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38.
  • Ken-Dror, G., et al. (författare)
  • Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis
  • 2021
  • Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 90:5, s. 777-788
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. Results In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 x 10(-24); odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 x 10(-16)). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 x 10(-16)) increased risk of CVT compared with individuals with blood group O. Interpretation We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021
  •  
39.
  • Kluck, H., et al. (författare)
  • Latest results of CRESST-III's search for sub-GeV/c(2) dark matter
  • 2020
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 1468:1
  • Konferensbidrag (refereegranskat)abstract
    • The CRESST-III experiment searches for direct interactions of dark matter with ordinary matter. The main event signature would be a nuclear recoil inside one of the scintillating CaWO4 crystals. Operating the crystals as cryogenic calorimeters provides a phonon signal as measure of the deposited energy. The simultaneous readout of both signals is used to actively discriminate backgrounds. CRESST-III focuses on the sub-GeV/c(2) mass region where the sensitivity is driven by the threshold. In the first data taking campaign of CRESST-III from 2016-2018 an unprecedented low threshold of 30.1 eV for nuclear recoils was obtained. In this contribution, we will report the status of the experiment and the latest results. [GRAPHICS]
  •  
40.
  • Mancuso, M., et al. (författare)
  • Searches for Light Dark Matter with the CRESST-III Experiment
  • 2020
  • Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 199:1-2, s. 547-555
  • Tidskriftsartikel (refereegranskat)abstract
    • Cryogenic Rare Event Search with Superconducting Thermometers (CRESST) is a long-standing direct dark matter detection experiment with cryogenic detectors located at the underground facility Laboratori Nazionali del Gran Sasso in Italy. CRESST-III, the third generation of CRESST, was specifically designed to have a world-leading sensitivity for low-mass dark matter (DM) (less than 2 GeV/c 2) to probe the spin-independent DM-nucleus cross section. At present, a large part of the parameter space for spin-independent scattering off nuclei remains untested for dark matter particles with masses below few GeV/c 2 although many motivated theoretical models having been proposed. The CRESST-III experiment employs scintillating CaWO 4 crystals of ∼ 25 g as target material for dark matter interactions operated as cryogenic scintillating calorimeters at ∼ 10 mK. CRESST-III first data taking was successfully completed in 2018, achieving an unprecedented energy threshold for nuclear recoils. This result extended the present sensitivity to DM particles as light as ∼ 160 MeV/c 2. In this paper, an overview of the CRESST-III detectors and results will be presented.
  •  
41.
  • Ranjan, R., et al. (författare)
  • Age of onset of cerebral venous thrombosis: the BEAST study
  • 2023
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 8:1, s. 344-350
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females. Results: A total of 1309 CVT patients (75.3% females) aged > 18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35-58) years and 37 (28-47) years (p < 0.001), respectively. However, the presence of antibiotic-requiring sepsis (p = 0.03, 95% CI 27-47 years) among males and gender-specific risk factors like pregnancy (p < 0.001, 95% CI 29-34 years), puerperium (p < 0.001, 95% CI 26-34 years) and oral contraceptive use (p < 0.001, 95% CI 33-36 years) were significantly associated with earlier onset of CVT among females. CFA demonstrated a significantly earlier onset of CVT in females, similar to 12 years younger, in those with multiple (> 1) compared to '0' risk factors (p < 0.001, 95% CI 32-35 years). Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (> 1) risk factors suffer CVT similar to 12 years earlier compared to those with no identifiable risk factors.
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42.
  • Wiedorn, Max O., et al. (författare)
  • Megahertz serial crystallography
  • 2018
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.
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43.
  • Angloher, G., et al. (författare)
  • Limits on dark matter effective field theory parameters with CRESST-II
  • 2019
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 79:1
  • Tidskriftsartikel (refereegranskat)abstract
    • CRESST is a direct dark matter search experiment, aiming for an observation of nuclear recoils induced by the interaction of dark matter particles with cryogenic scintillating calcium tungstate crystals. Instead of confining ourselves to standard spin-independent and spin-dependent searches, we re-analyze data from CRESST-II using a more general effective field theory (EFT) framework. On many of the EFT coupling constants, improved exclusion limits in the low-mass region (< 3–4 GeV/c2) are presented.
  •  
44.
  • Reddy, Hemanth K. N., et al. (författare)
  • Coherent soft X-ray diffraction imaging of coliphage PR772 at the Linac coherent light source
  • 2017
  • Ingår i: Scientia Danica. Series H. Humanistica 4. - : Nature Publishing Group. - 1904-5506 .- 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Single-particle diffraction from X-ray Free Electron Lasers offers the potential for molecular structure determination without the need for crystallization. In an effort to further develop the technique, we present a dataset of coherent soft X-ray diffraction images of Coliphage PR772 virus, collected at the Atomic Molecular Optics (AMO) beamline with pnCCD detectors in the LAMP instrument at the Linac Coherent Light Source. The diameter of PR772 ranges from 65-70 nm, which is considerably smaller than the previously reported similar to 600 nm diameter Mimivirus. This reflects continued progress in XFEL-based single-particle imaging towards the single molecular imaging regime. The data set contains significantly more single particle hits than collected in previous experiments, enabling the development of improved statistical analysis, reconstruction algorithms, and quantitative metrics to determine resolution and self-consistency.
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45.
  • Li, Haoyuan, et al. (författare)
  • Diffraction data from aerosolized Coliphage PR772 virus particles imaged with the Linac Coherent Light Source
  • 2020
  • Ingår i: Scientific Data. - : NATURE RESEARCH. - 2052-4463. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Single Particle Imaging (SPI) with intense coherent X-ray pulses from X-ray free-electron lasers (XFELs) has the potential to produce molecular structures without the need for crystallization or freezing. Here we present a dataset of 285,944 diffraction patterns from aerosolized Coliphage PR772 virus particles injected into the femtosecond X-ray pulses of the Linac Coherent Light Source (LCLS). Additional exposures with background information are also deposited. The diffraction data were collected at the Atomic, Molecular and Optical Science Instrument (AMO) of the LCLS in 4 experimental beam times during a period of four years. The photon energy was either 1.2 or 1.7keV and the pulse energy was between 2 and 4 mJ in a focal spot of about 1.3 mu m x 1.7 mu m full width at half maximum (FWHM). The X-ray laser pulses captured the particles in random orientations. The data offer insight into aerosolised virus particles in the gas phase, contain information relevant to improving experimental parameters, and provide a basis for developing algorithms for image analysis and reconstruction.
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46.
  • Aleksich, Mariya, et al. (författare)
  • XFEL Microcrystallography of Self-Assembling Silver n-Alkanethiolates
  • 2023
  • Ingår i: Journal of the American Chemical Society. - 0002-7863. ; 145:31, s. 17042-17055
  • Tidskriftsartikel (refereegranskat)abstract
    • New synthetic hybrid materials and their increasing complexity have placed growing demands on crystal growth for single-crystal X-ray diffraction analysis. Unfortunately, not all chemical systems are conducive to the isolation of single crystals for traditional characterization. Here, small-molecule serial femtosecond crystallography (smSFX) at atomic resolution (0.833 Å) is employed to characterize microcrystalline silver n-alkanethiolates with various alkyl chain lengths at X-ray free electron laser facilities, resolving long-standing controversies regarding the atomic connectivity and odd-even effects of layer stacking. smSFX provides high-quality crystal structures directly from the powder of the true unknowns, a capability that is particularly useful for systems having notoriously small or defective crystals. We present crystal structures of silver n-butanethiolate (C4), silver n-hexanethiolate (C6), and silver n-nonanethiolate (C9). We show that an odd-even effect originates from the orientation of the terminal methyl group and its role in packing efficiency. We also propose a secondary odd-even effect involving multiple mosaic blocks in the crystals containing even-numbered chains, identified by selected-area electron diffraction measurements. We conclude with a discussion of the merits of the synthetic preparation for the preparation of microdiffraction specimens and compare the long-range order in these crystals to that of self-assembled monolayers.
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47.
  • Clausen, Niels, et al. (författare)
  • Similar bleeding phenotype in young children with haemophilia A or B : A cohort study
  • 2014
  • Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:6, s. 747-755
  • Tidskriftsartikel (refereegranskat)abstract
    • The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL-1 respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A.
  •  
48.
  • Ekeberg, Tomas, 1983-, et al. (författare)
  • Observation of a single protein by ultrafast X-ray diffraction
  • 2024
  • Ingår i: Light. - : Springer Nature. - 2095-5545 .- 2047-7538. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many. It was one of the arguments for building X-ray free-electron lasers. According to theory, the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier, and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably explodes. This was first demonstrated on biological samples a decade ago on the giant mimivirus. Since then, a large collaboration has been pushing the limit of the smallest sample that can be imaged. The ability to capture snapshots on the timescale of atomic vibrations, while keeping the sample at room temperature, may allow probing the entire conformational phase space of macromolecules. Here we show the first observation of an X-ray diffraction pattern from a single protein, that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays, and demonstrate that the concept of diffraction before destruction extends to single proteins. From the pattern, it is possible to determine the approximate orientation of the protein. Our experiment demonstrates the feasibility of ultrafast imaging of single proteins, opening the way to single-molecule time-resolved studies on the femtosecond timescale.
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49.
  •  
50.
  • Kurta, Ruslan P., et al. (författare)
  • Correlations in Scattered X-Ray Laser Pulses Reveal Nanoscale Structural Features of Viruses
  • 2017
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 119:15
  • Tidskriftsartikel (refereegranskat)abstract
    • We use extremely bright and ultrashort pulses from an x-ray free-electron laser (XFEL) to measure correlations in x rays scattered from individual bioparticles. This allows us to go beyond the traditional crystallography and single-particle imaging approaches for structure investigations. We employ angular correlations to recover the three-dimensional (3D) structure of nanoscale viruses from x-ray diffraction data measured at the Linac Coherent Light Source. Correlations provide us with a comprehensive structural fingerprint of a 3D virus, which we use both for model-based and ab initio structure recovery. The analyses reveal a clear indication that the structure of the viruses deviates from the expected perfect icosahedral symmetry. Our results anticipate exciting opportunities for XFEL studies of the structure and dynamics of nanoscale objects by means of angular correlations.
  •  
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