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1.
  • Algaba, Juan-Carlos, et al. (författare)
  • Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
  • Forskningsöversikt (refereegranskat)abstract
    • In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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3.
  • Abdalla, H., et al. (författare)
  • HESS and MAGIC observations of a sudden cessation of a very-high-energy gamma-ray flare in PKS 1510-089 in May 2016
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 648
  • Tidskriftsartikel (refereegranskat)abstract
    • The flat spectrum radio quasar (FSRQ) PKS 1510-089 is known for its complex multiwavelength behaviour and it is one of only a few FSRQs detected in very-high-energy (VHE, E>100 GeV) gamma rays. The VHE gamma -ray observations with H.E.S.S. and MAGIC in late May and early June 2016 resulted in the detection of an unprecedented flare, which revealed, for the first time, VHE gamma -ray intranight variability for this source. While a common variability timescale of 1.5 h has been found, there is a significant deviation near the end of the flare, with a timescale of similar to 20 min marking the cessation of the event. The peak flux is nearly two orders of magnitude above the low-level emission. For the first time, a curvature was detected in the VHE gamma -ray spectrum of PKS 1510-089, which can be fully explained by the absorption on the part of the extragalactic background light. Optical R-band observations with ATOM revealed a counterpart of the gamma -ray flare, even though the detailed flux evolution differs from the VHE gamma -ray light curve. Interestingly, a steep flux decrease was observed at the same time as the cessation of the VHE gamma -ray flare. In the high-energy (HE, E> 100 MeV) gamma -ray band, only a moderate flux increase was observed with Fermi-LAT, while the HE gamma -ray spectrum significantly hardens up to a photon index of 1.6. A search for broad-line region (BLR) absorption features in the gamma -ray spectrum indicates that the emission region is located outside of the BLR. Radio very-long-baseline interferometry observations reveal a fast-moving knot interacting with a standing jet feature around the time of the flare. As the standing feature is located similar to 50 pc from the black hole, the emission region of the flare may have been located at a significant distance from the black hole. If this is indeed a true correlation, the VHE gamma rays must have been produced far down in the jet, where turbulent plasma crosses a standing shock.
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4.
  • Abdalla, H., et al. (författare)
  • TeV Emission of Galactic Plane Sources with HAWC and HESS
  • 2021
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 917:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The High Altitude Water Cherenkov (HAWC) observatory and the High Energy Stereoscopic System (H.E.S.S.) are two leading instruments in the ground-based very-high-energy gamma-ray domain. HAWC employs the water Cherenkov detection (WCD) technique, while H.E.S.S. is an array of Imaging Atmospheric Cherenkov Telescopes (IACTs). The two facilities therefore differ in multiple aspects, including their observation strategy, the size of their field of view, and their angular resolution, leading to different analysis approaches. Until now, it has been unclear if the results of observations by both types of instruments are consistent: several of the recently discovered HAWC sources have been followed up by IACTs, resulting in a confirmed detection only in a minority of cases. With this paper, we go further and try to resolve the tensions between previous results by performing a new analysis of the H.E.S.S. Galactic plane survey data, applying an analysis technique comparable between H.E.S.S. and HAWC. Events above 1 TeV are selected for both data sets, the point-spread function of H.E.S.S. is broadened to approach that of HAWC, and a similar background estimation method is used. This is the first detailed comparison of the Galactic plane observed by both instruments. H.E.S.S. can confirm the gamma-ray emission of four HAWC sources among seven previously undetected by IACTs, while the three others have measured fluxes below the sensitivity of the H.E.S.S. data set. Remaining differences in the overall gamma-ray flux can be explained by the systematic uncertainties. Therefore, we confirm a consistent view of the gamma-ray sky between WCD and IACT techniques.
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5.
  • Abdalla, H., et al. (författare)
  • Searching for TeV Gamma-Ray Emission from SGR 1935+2154 during Its 2020 X-Ray and Radio Bursting Phase
  • 2021
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 919:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Magnetar hyperflares are the most plausible explanation for fast radio bursts (FRBs)-enigmatic powerful radio pulses with durations of several milliseconds and high brightness temperatures. The first observational evidence for this scenario was obtained in 2020 April when an FRB was detected from the direction of the Galactic magnetar and soft gamma-ray repeater SGR 1935+2154. The FRB was preceded by two gamma-ray outburst alerts by the BAT instrument aboard the Swift satellite, which triggered follow-up observations by the High Energy Stereoscopic System (H.E.S.S.). H.E.S.S. observed SGR 1935+2154 for 2 hr on 2020 April 28. The observations are coincident with X-ray bursts from the magnetar detected by INTEGRAL and Fermi-GBM, thus providing the first very high energy gamma-ray observations of a magnetar in a flaring state. High-quality data acquired during these follow-up observations allow us to perform a search for short-time transients. No significant signal at energies E > 0.6 TeV is found, and upper limits on the persistent and transient emission are derived. We here present the analysis of these observations and discuss the obtained results and prospects of the H.E.S.S. follow-up program for soft gamma-ray repeaters.
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6.
  • Abdalla, H., et al. (författare)
  • Search for Dark Matter Annihilation Signals from Unidentified Fermi-LAT Objects with HESS
  • 2021
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 918:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Cosmological N-body simulations show that Milky Way-sized galaxies harbor a population of unmerged dark matter (DM) subhalos. These subhalos could shine in gamma-rays and eventually be detected in gamma-ray surveys as unidentified sources. We performed a thorough selection among unidentified Fermi-Large Area Telescope Objects (UFOs) to identify them as possible tera-electron-volt-scale DM subhalo candidates. We search for very-high-energy (E greater than or similar to 100 GeV) gamma-ray emissions using H.E.S.S. observations toward four selected UFOs. Since no significant very-high-energy gamma-ray emission is detected in any data set of the four observed UFOs or in the combined UFO data set, strong constraints are derived on the product of the velocity-weighted annihilation cross section sigma v by the J factor for the DM models. The 95% confidence level observed upper limits derived from combined H.E.S.S. observations reach sigma vJ values of 3.7 x 10(-5) and 8.1 x 10(-6) GeV(2 )cm(-2 )s(-1) in the W (+) W (-) and tau (+) tau (-) channels, respectively, for a 1 TeV DM mass. Focusing on thermal weakly interacting massive particles, the H.E.S.S. constraints restrict the J factors to lie in the range 6.1 x 10(19)-2.0 x 10(21) GeV(2 )cm(-5) and the masses to lie between 0.2 and 6 TeV in the W (+) W (-) channel. For the tau (+) tau (-) channel, the J factors lie in the range 7.0 x 10(19)-7.1 x 10(20) GeV(2 )cm(-5) and the masses lie between 0.2 and 0.5 TeV. Assuming model-dependent predictions from cosmological N-body simulations on the J-factor distribution for Milky Way-sized galaxies, the DM models with masses >0.3 TeV for the UFO emissions can be ruled out at high confidence level.
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7.
  • Abdalla, H., et al. (författare)
  • An extreme particle accelerator in the Galactic plane : HESS J1826-130
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The unidentified very-high-energy (VHE; E > 0.1 TeV) gamma -ray source, HESS J1826-130, was discovered with the High Energy Stereoscopic System (HESS) in the Galactic plane. The analysis of 215 h of HESS data has revealed a steady gamma -ray flux from HESS J1826-130, which appears extended with a half-width of 0.21 degrees +/- 0.02 (stat)degrees stat degrees +/- 0.05 (sys)degrees sys degrees . The source spectrum is best fit with either a power-law function with a spectral index Gamma = 1.78 +/- 0.10(stat) +/- 0.20(sys) and an exponential cut-off at 15.2 (+5.5)(-3.2) -3.2+5.5 TeV, or a broken power-law with Gamma (1) = 1.96 +/- 0.06(stat) +/- 0.20(sys), Gamma (2) = 3.59 +/- 0.69(stat) +/- 0.20(sys) for energies below and above E-br = 11.2 +/- 2.7 TeV, respectively. The VHE flux from HESS J1826-130 is contaminated by the extended emission of the bright, nearby pulsar wind nebula, HESS J1825-137, particularly at the low end of the energy spectrum. Leptonic scenarios for the origin of HESS J1826-130 VHE emission related to PSR J1826-1256 are confronted by our spectral and morphological analysis. In a hadronic framework, taking into account the properties of dense gas regions surrounding HESS J1826-130, the source spectrum would imply an astrophysical object capable of accelerating the parent particle population up to greater than or similar to 200 TeV. Our results are also discussed in a multiwavelength context, accounting for both the presence of nearby supernova remnants, molecular clouds, and counterparts detected in radio, X-rays, and TeV energies.
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8.
  • Abdalla, H., et al. (författare)
  • Detection of very-high-energy gamma-ray emission from the colliding wind binary eta Car with HESS
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. Colliding wind binary systems have long been suspected to be high-energy (HE; 100 MeV < E < 100 GeV) gamma-ray emitters. eta Car is the most prominent member of this object class and is confirmed to emit phase-locked HE gamma rays from hundreds of MeV to 100 GeV energies. This work aims to search for and characterise the very-high-energy (VHE; E >100 GeV) gamma-ray emission from eta Car around the last periastron passage in 2014 with the ground-based High Energy Stereoscopic System (H.E.S.S.).Methods. The region around eta Car was observed with H.E.S.S. between orbital phase p = 0.78-1.10, with a closer sampling at p approximate to 0.95 and p approximate to 1.10 (assuming a period of 2023 days). Optimised hardware settings as well as adjustments to the data reduction, reconstruction, and signal selection were needed to suppress and take into account the strong, extended, and inhomogeneous night sky background (NSB) in the eta Car field of view. Tailored run-wise Monte-Carlo simulations (RWS) were required to accurately treat the additional noise from NSB photons in the instrument response functions.Results. H.E.S.S. detected VHE gamma-ray emission from the direction of eta Car shortly before and after the minimum in the X-ray light-curve close to periastron. Using the point spread function provided by RWS, the reconstructed signal is point-like and the spectrum is best described by a power law. The overall flux and spectral index in VHE gamma rays agree within statistical and systematic errors before and after periastron. The gamma-ray spectrum extends up to at least 400 GeV. This implies a maximum magnetic field in a leptonic scenario in the emission region of 0.5 Gauss. No indication for phase-locked flux variations is detected in the H.E.S.S. data.
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9.
  • Abdalla, H., et al. (författare)
  • Evidence of 100 TeV gamma-ray emission from HESS J1702-420 : A new PeVatron candidate
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The identification of PeVatrons, hadronic particle accelerators reaching the knee of the cosmic ray spectrum (few x 10(15) eV), is crucial to understand the origin of cosmic rays in the Galaxy. We provide an update on the unidentified source HESS J1702-420, a promising PeVatron candidate. Methods. We present new observations of HESS J1702-420 made with the High Energy Stereoscopic System (H.E.S.S.), and processed using improved analysis techniques. The analysis configuration was optimized to enhance the collection area at the highest energies. We applied a threedimensional likelihood analysis to model the source region and adjust non thermal radiative spectral models to the gamma-ray data. We also analyzed archival Fermi Large Area Telescope data to constrain the source spectrum at gamma-ray energies >10 GeV. Results. We report the detection of gamma-rays up to 100 TeV from a specific region of HESS J1702-420, which is well described by a new source component called HESS J1702-420A that was separated from the bulk of TeV emission at a 5:4 sigma confidence level. The power law gamma-ray spectrum of HESS J1702-420A extends with an index of Gamma = 1:53 +/- 0:19(stat) +/- 0:20(sys) and without curvature up to the energy band 64 113 TeV, in which it was detected by H.E.S.S. at a 4:0 sigma confidence level. This makes HESS J1702-420A a compelling candidate site for the presence of extremely high energy cosmic rays. With a flux above 2 TeV of (2:08 +/- 0:49(stat) +/- 0:62(sys)) x 10(-13) cm(-2) s(-1) and a radius of (0:06 +/- 0:02(stat) +/- 0:03(sys))degrees, HESS J1702-420A is outshone - below a few tens of TeV - by the companion HESS J1702-420B. The latter has a steep spectral index of = 2:62 +/- 0:10(stat) +/- 0:20(sys) and an elongated shape, and it accounts for most of the low-energy HESS J1702-420 flux. Simple hadronic and leptonic emission models can be well adjusted to the spectra of both components. Remarkably, in a hadronic scenario, the cut-o ff energy of the particle distribution powering HESS J1702-420A is found to be higher than 0:5 PeV at a 95% confidence level. Conclusions. For the first time, H.E.S.S. resolved two components with significantly di fferent morphologies and spectral indices, both detected at >5 sigma confidence level, whose combined emissions result in the source HESS J1702-420. We detected HESS J1702-420A at a 4:0 sigma confidence level in the energy band 64 113 TeV, which brings evidence for the source emission up to 100 TeV. In a hadronic emission scenario, the hard gamma-ray spectrum of HESS J1702-420A implies that the source likely harbors PeV protons, thus becoming one of the most solid PeVatron candidates detected so far in H.E.S.S. data. However, a leptonic origin of the observed TeV emission cannot be ruled out either.
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10.
  • Abdalla, H., et al. (författare)
  • LMC N132D : A mature supernova remnant with a power-law gamma-ray spectrum extending beyond 8 TeV
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Supernova remnants (SNRs) are commonly thought to be the dominant sources of Galactic cosmic rays up to the knee of the cosmic-ray spectrum at a few PeV. Imaging Atmospheric Cherenkov Telescopes have revealed young SNRs as very-high-energy (VHE, >100 GeV) gamma-ray sources, but for only a few SNRs the hadronic cosmic-ray origin of their gamma-ray emission is indisputably established. In all these cases, the gamma-ray spectra exhibit a spectral cutoff at energies much below 100 TeV and thus do not reach the PeVatron regime. Aims. The aim of this work was to achieve a firm detection for the oxygen-rich SNR LMC N132D in the VHE gamma-ray domain with an extended set of data, and to clarify the spectral characteristics and the localization of the gamma-ray emission from this exceptionally powerful gamma-ray-emitting SNR. Methods. We analyzed 252 h of High Energy Stereoscopic System (H.E.S.S.) observations towards SNR N132D that were accumulated between December 2004 and March 2016 during a deep survey of the Large Magellanic Cloud, adding 104 h of observations to the previously published data set to ensure a > 5 sigma detection. To broaden the gamma-ray spectral coverage required for modeling the spectral energy distribution, an analysis of Fermi-LAT Pass 8 data was also included. Results. We unambiguously detect N132D at VHE with a significance of 5.7 sigma. We report the results of a detailed analysis of its spectrum and localization based on the extended H.E.S.S. data set. The joint analysis of the extended H.E.S.S and Fermi-LAT data results in a spectral energy distribution in the energy range from 1.7 GeV to 14.8 TeV, which suggests a high luminosity of N132D at GeV and TeV energies. We set a lower limit on a gamma-ray cutoff energy of 8 TeV with a confidence level of 95%. The new gamma-ray spectrum as well as multiwavelength observations of N132D when compared to physical models suggests a hadronic origin of the VHE gamma-ray emission. Conclusions. SNR N132D is a VHE gamma-ray source that shows a spectrum extending to the VHE domain without a spectral cutoff at a few TeV, unlike the younger oxygen-rich SNR Cassiopeia A. The gamma-ray emission is best explained by a dominant hadronic component formed by diffusive shock acceleration. The gamma-ray properties of N132D may be affected by an interaction with a nearby molecular cloud that partially lies inside the 95% confidence region of the source position.
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11.
  • Abdalla, H., et al. (författare)
  • Revealing x-ray and gamma ray temporal and spectral similarities in the GRB 190829A afterglow
  • 2021
  • Ingår i: Science. - : American Association of Advancement in Science. - 0036-8075 .- 1095-9203. ; 372:6546, s. 1081-1085
  • Tidskriftsartikel (refereegranskat)abstract
    • Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very- high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 +/- 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma- ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.
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12.
  • Abdalla, H., et al. (författare)
  • Simultaneous observations of the blazar PKS 2155-304 from ultra-violet to TeV energies
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 639, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report the results of the first ever contemporaneous multi-wavelength observation campaign on the BL Lac object PKS 2155-304 involving Swift, NuSTAR, Fermi-LAT, and H.E.S.S. The use of these instruments allows us to cover a broad energy range, which is important for disentangling the different radiative mechanisms. The source, observed from June 2013 to October 2013, was found in a low flux state with respect to previous observations but exhibited highly significant flux variability in the X-rays. The high-energy end of the synchrotron spectrum can be traced up to 40 keV without significant contamination by high-energy emission. A one-zone synchrotron self-Compton model was used to reproduce the broadband flux of the source for all the observations presented here but failed for previous observations made in April 2013. A lepto-hadronic solution was then explored to explain these earlier observational results.
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13.
  • Abdallah, H., et al. (författare)
  • Search for dark matter annihilation in the Wolf-Lundmark-Melotte dwarf irregular galaxy with HESS
  • 2021
  • Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 103:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We search for an indirect signal of dark matter through very high-energy gamma rays from the Wolf-Lundmark-Melotte (WLM) dwarf irregular galaxy. The pair annihilation of dark matter particles would produce Standard Model particles in the final state such as gamma rays, which might be detected by ground-based Cherenkov telescopes. Dwarf irregular galaxies represent promising targets as they are dark matter dominated objects with well-measured kinematics and small uncertainties on their dark matter distribution profiles. In 2018, the five-telescopes of the high energy stereoscopic system observed the dwarf irregular galaxy WLM for 18 hours. We present the first analysis based on data obtained from an imaging atmospheric Cherenkov telescope for this subclass of dwarf galaxy. As we do not observe any significant excess in the direction of WLM, we interpret the result in terms of constraints on the velocity-weighted cross section for dark matter pair annihilation as a function of the dark matter particle mass for various continuum channels, as well as the prompt gamma gamma emission. For the tau+tau- channel, the limits reach a value of about 4 x 10-22 cm3 s-1 for a dark matter particle mass of 1 TeV. For the prompt gamma gamma channel, the upper limit reaches a value of about 5 x 10-24 cm3 s-1 for a mass of 370 GeV. These limits represent an improvement of up to a factor 200, with respect to previous results for the dwarf irregular galaxies for TeV dark matter search.
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14.
  • Abdallah, H., et al. (författare)
  • Search for dark matter signals towards a selection of recently detected DES dwarf galaxy satellites of the Milky Way with HESS
  • 2020
  • Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 102:6, s. 1-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Dwarf spheroidal galaxy satellites of the Milky Way are prime targets for indirect detection of dark matter with gamma rays due to their proximity, high dark matter content, and absence of nonthermal emission processes. Recently, the Dark Energy Survey (DES) revealed the existence of new ultrafaint dwarf spheroidal galaxies in the southern-hemisphere sky, therefore ideally located for ground-based observations with the imaging atmospheric Cherenkov telescope array H.E.S.S. We present a search for very-high-energy (E greater than or similar to 100 GeV) gamma-ray emission using H.E.S.S. observations carried out recently towards Reticulum II, Tucana II, Tucana III, Tucana IV, and Grus II satellites. No significant very-high-energy gamma-ray excess is found from the observations on any individual object nor in the combined analysis of all the datasets. Using the most recent modeling of the dark matter distribution in the dwarf galaxy halo, we compute for the first time on DES satellites individual and combined constraints from Cherenkov telescope observations on the annihilation cross section of dark matter particles in the form of Weakly Interacting Massive Particles. The combined 95% C.L. observed upper limits reach similar or equal to 1 x 10(-23) cm(3) s(-1) in the W+W- channel and 4 x 10(-26) cm(3) s(-1) in the gamma gamma channels for a dark matter mass of 1.5 TeV. The H.E.S.S. constraints well complement the results from Fermi-LAT, HAWC, MAGIC, and VERITAS and are currently the most stringent in the gamma gamma channels in the multi-GeV/multi-TeV mass range.
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15.
  • Abdalla, H., et al. (författare)
  • HESS and Fermi-LAT observations of PSR B1259-63/LS 2883 during its 2014 and 2017 periastron passages
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 633, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. PSR B1259-63/LS 2883 is a gamma-ray binary system consisting of a pulsar in an eccentric orbit around a bright Oe stellar-type companion star that features a dense circumstellar disc. The bright broad-band emission observed at phases close to periastron offers a unique opportunity to study particle acceleration and radiation processes in binary systems. Observations at gamma-ray energies constrain these processes through variability and spectral characterisation studies. Aims. The high- and very-high-energy (HE, VHE) gamma-ray emission from PSR B1259-63/LS 2883 around the times of its periastron passage are characterised, in particular, at the time of the HE gamma-ray flares reported to have occurred in 2011, 2014, and 2017. Short-term and average emission characteristics of PSR B1259-63/LS 2883 are determined. Super-orbital variability is searched for in order to investigate possible cycle-to-cycle VHE flux changes due to different properties of the companion star's circumstellar disc and/or the conditions under which the HE gamma-ray flares develop. Methods. Spectra and light curves were derived from observations conducted with the H.E.S.S-II array in 2014 and 2017. Phase-folded light curves are compared with the results obtained in 2004, 2007, and 2011. Fermi-LAT observations from 2010/11, 2014, and 2017 are analysed. Results. A local double-peak profile with asymmetric peaks in the VHE light curve is measured, with a flux minimum at the time of periastron t(p) and two peaks coinciding with the times at which the neutron star crosses the companion's circumstellar disc (similar to t(p) 16 d). A high VHE gamma-ray flux is also observed at the times of the HE gamma-ray flares (similar to t(p) + 30 d) and at phases before the first disc crossing (similar to t(p) - 35 d). The spectral energy range now extends to below 200 GeV and up to similar to 45 TeV. Conclusions. PSR B1259-63/LS 2883 displays periodic flux variability at VHE gamma-rays without clear signatures of super-orbital modulation in the time span covered by the monitoring of the source with the H.E.S.S. telescopes. This flux variability is most probably caused by the changing environmental conditions, particularly at times close to periastron passage at which the neutron star is thought to cross the circumstellar disc of the companion star twice. In contrast, the photon index remains unchanged within uncertainties for about 200 d around periastron. At HE gamma-rays, PSR B1259-63/LS 2883 has now been detected also before and after periastron, close to the disc crossing times. Repetitive flares with distinct variability patterns are detected in this energy range. Such outbursts are not observed at VHEs, although a relatively high emission level is measured. The spectra obtained in both energy regimes displays a similar slope, although a common physical origin either in terms of a related particle population, emission mechanism, or emitter location is ruled out.
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16.
  • Abdalla, H., et al. (författare)
  • HESS detection of very high-energy gamma-ray emission from the quasar PKS 0736+017
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 633, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Flat-spectrum radio-quasars (FSRQs) are rarely detected at very high energies (E& x2004;>=& x2004;100 GeV) due to their low-frequency-peaked spectral energy distributions. At present, only six FSRQs are known to emit very high-energy (VHE) photons, representing only 7% of the VHE extragalactic catalog, which is largely dominated by high-frequency-peaked BL Lacertae objects. Aims. Following the detection of MeV-GeV gamma-ray flaring activity from the FSRQ PKS 0736+017 (z& x2004;=& x2004;0.189) with Fermi-LAT, the H.E.S.S. array of Cherenkov telescopes triggered target-of-opportunity (ToO) observations on February 18, 2015, with the goal of studying the gamma-ray emission in the VHE band. Methods. H.E.S.S. ToO observations were carried out during the nights of February 18, 19, 21, and 24, 2015. Together with Fermi-LAT, the multi-wavelength coverage of the flare includes Swift observations in soft X-ray and optical-UV bands, and optical monitoring (photometry and spectro-polarimetry) by the Steward Observatory, and the ATOM, the KAIT, and the ASAS-SN telescopes. Results. VHE emission from PKS 0736+017 was detected with H.E.S.S. only during the night of February 19, 2015. Fermi-LAT data indicate the presence of a gamma-ray flare, peaking at the time of the H.E.S.S. detection, with a flux doubling timescale of around six hours. The gamma-ray flare was accompanied by at least a 1 mag brightening of the non-thermal optical continuum. No simultaneous observations at longer wavelengths are available for the night of the H.E.S.S. detection. The gamma-ray observations with H.E.S.S. and Fermi-LAT are used to put constraints on the location of the gamma-ray emitting region during the flare: it is constrained to be just outside the radius of the broad-line region r(BLR) with a bulk Lorentz factor Gamma& x2004;similar or equal to& x2004;20, or at the level of the radius of the dusty torus r(torus) with Gamma& x2004;similar or equal to& x2004;60. Conclusions. PKS 0736+017 is the seventh FSRQ known to emit VHE photons, and at z& x2004;=& x2004;0.189 is the nearest so far. The location of the gamma-ray emitting region during the flare can be tightly constrained thanks to opacity, variability, and collimation arguments.
  •  
17.
  • Abdalla, H., et al. (författare)
  • Probing the Magnetic Field in the GW170817 Outflow Using HESS Observations
  • 2020
  • Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 894:2, s. 1-5
  • Tidskriftsartikel (refereegranskat)abstract
    • The detection of the first electromagnetic counterpart to the binary neutron star (BNS) merger remnant GW170817 established the connection between short gamma-ray bursts and BNS mergers. It also confirmed the forging of heavy elements in the ejecta (a so-called kilonova) via the r-process nucleosynthesis. The appearance of nonthermal radio and X-ray emission, as well as the brightening, which lasted more than 100 days, were somewhat unexpected. Current theoretical models attempt to explain this temporal behavior as either originating from a relativistic off-axis jet or a kilonova-like outflow. In either scenario, there is some ambiguity regarding how much energy is transported in the nonthermal electrons versus the magnetic field of the emission region. Combining the Very Large Array (radio) and Chandra (X-ray) measurements with observations in the GeV-TeV domain can help break this ambiguity, almost independently of the assumed origin of the emission. Here we report for the first time on deep H.E.S.S. observations of GW170817/GRB 170817A between 124 and 272 days after the BNS merger with the full H.E.S.S. array of telescopes, as well as on an updated analysis of the prompt (<5 days) observations with the upgraded H.E.S.S. phase-I telescopes. We discuss implications of the H.E.S.S. measurement for the magnetic field in the context of different source scenarios.
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18.
  • Abdalla, H., et al. (författare)
  • Very high energy gamma-ray emission from two blazars of unknown redshift and upper limits on their distance
  • 2020
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 494:4, s. 5590-5602
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the detection of very high energy (VHE; E > 100 GeV) gamma-ray emission from the BL Lac objects KUV 00311-1938 and PKS 1440-389 with the High Energy Stereoscopic System (H.E.S.S.). H.E.S.S. observations were accompanied or preceded by multiwavelength observations with Fermi/LAT, XRT and UVOT onboard the Swift satellite, and ATOM. Based on an extrapolation of the Fermi/LAT spectrum towards the VHE gamma-ray regime, we deduce a 95 per cent confidence level upper limit on the unknown redshift of KUV 00311-1938 of z < 0.98 and of PKS 1440-389 of z < 0.53. When combined with previous spectroscopy results, the redshift of KUV 00311-1938 is constrained to 0.51 <= z < 0.98 and of PKS 1440-389 to 0.14 (sic) z < 0.53.
  •  
19.
  • Abdalla, H., et al. (författare)
  • Resolving acceleration to very high energies along the jet of Centaurus A
  • 2020
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 582:7812, s. 356-359
  • Tidskriftsartikel (refereegranskat)abstract
    • The nearby radio galaxy Centaurus A belongs to a class of active galaxies that are luminous at radio wavelengths. Most show collimated relativistic outflows known as jets, which extend over hundreds of thousands of parsecs for the most powerful sources. Accretion of matter onto the central supermassive black hole is believed to fuel these jets and power their emission(1). Synchrotron radiation from relativistic electrons causes the radio emission, and it has been suggested that the X-ray emission from Centaurus A also originates in electron synchrotron processes(2-4). Another possible explanation is inverse Compton scattering with cosmic microwave background (CMB) soft photons(5-7). Synchrotron radiation needs ultrarelativistic electrons (about 50 teraelectronvolts) and, given their short cooling times, requires some continuous re-acceleration mechanism(8). Inverse Compton scattering, on the other hand, does not require very energetic electrons, but the jets must stay highly relativistic on large scales (exceeding 1 megaparsec). Some recent evidence disfavours inverse Compton-CMB models(9-12), although other work seems to be compatible with them(13,14). In principle, the detection of extended gamma-ray emission, which directly probes the presence of ultrarelativistic electrons, could distinguish between these options. At gigaelectronvolt energies there is also an unusual spectral hardening(15,16)in Centaurus A that has not yet been explained. Here we report observations of Centaurus A at teraelectronvolt energies that resolve its large-scale jet. We interpret the data as evidence for the acceleration of ultrarelativistic electrons in the jet, and favour the synchrotron explanation for the X-rays. Given that this jet is not exceptional in terms of power, length or speed, it is possible that ultrarelativistic electrons are commonplace in the large-scale jets of radio-loud active galaxies. Observations of the radio galaxy Centaurus A at teraelectronvolt energies resolve its large-scale jet and favour electron synchrotron processes as the source of its X-ray emission.
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20.
  • Abdalla, H., et al. (författare)
  • Resolving the Crab pulsar wind nebula at teraelectronvolt energies
  • 2020
  • Ingår i: Nature Astronomy. - : Nature Publishing Group. - 2397-3366. ; 4:2, s. 167-173
  • Tidskriftsartikel (refereegranskat)abstract
    • An angular extension at gamma-ray energies of 52 arcseconds is detected for the Crab nebula, revealing the emission region of the highest-energy gamma rays; simulations of the electromagnetic emission provide a non-trivial test of our understanding of particle acceleration in the Crab nebula. The Crab nebula is one of the most-studied cosmic particle accelerators, shining brightly across the entire electromagnetic spectrum up to very-high-energy gamma rays(1,2). It is known from observations in the radio to gamma-ray part of the spectrum that the nebula is powered by a pulsar, which converts most of its rotational energy losses into a highly relativistic outflow. This outflow powers a pulsar wind nebula, a region of up to ten light-years across, filled with relativistic electrons and positrons. These particles emit synchrotron photons in the ambient magnetic field and produce very-high-energy gamma rays by Compton up-scattering of ambient low-energy photons. Although the synchrotron morphology of the nebula is well established, it has not been known from which region the very-high-energy gamma rays are emitted(3-8). Here we report that the Crab nebula has an angular extension at gamma-ray energies of 52 arcseconds (assuming a Gaussian source width), much larger than at X-ray energies. This result closes a gap in the multi-wavelength coverage of the nebula, revealing the emission region of the highest-energy gamma rays. These gamma rays enable us to probe a previously inaccessible electron and positron energy range. We find that simulations of the electromagnetic emission reproduce our measurement, providing a non-trivial test of our understanding of particle acceleration in the Crab nebula.
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21.
  • Aharonian, F., et al. (författare)
  • Time-resolved hadronic particle acceleration in the recurrent nova RS Ophiuchi
  • 2022
  • Ingår i: Science. - : American Association for Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6588, s. 77-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Recurrent novae are repeating thermonuclear explosions in the outer layers of white dwarfs, due to the accretion of fresh material from a binary companion. The shock generated when ejected material slams into the companion star's wind can accelerate particles. We report very-high-energy [VHE: greater than or similar to 100 giga-electron volts] gamma rays from the recurrent nova RS Ophiuchi, up to 1 month after its 2021 outburst, observed using the High Energy Stereoscopic System (H.E.S.S.). The temporal profile of VHE emission is similar to that of lower-energy giga-electron volt emission, indicating a common origin, with a 2-day delay in peak flux. These observations constrain models of time-dependent particle energization, favoring a hadronic emission scenario over the leptonic alternative. Shocks in dense winds provide favorable environments for efficient acceleration of cosmic rays to very high energies.
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22.
  • Aharonian, F., et al. (författare)
  • Constraining the cosmic-ray pressure in the inner Virgo Cluster using HESS observations of M 87
  • 2023
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 675
  • Tidskriftsartikel (refereegranskat)abstract
    • The origin of the gamma-ray emission from M 87 is currently a matter of debate. This work aims to localize the very high-energy (VHE; 100 GeV - 100 TeV) gamma-ray emission from M 87 and probe a potential extended hadronic emission component in the inner Virgo Cluster. The search for a steady and extended gamma-ray signal around M 87 can constrain the cosmic-ray energy density and the pressure exerted by the cosmic rays onto the intracluster medium and allow us to investigate the role of cosmic rays in the active galactic nucleus feedback as a heating mechanism in the Virgo Cluster. The High Energy Stereoscopic System (H.E.S.S.) telescopes are sensitive to VHE gamma rays and have been used to observe M 87 since 2004. We utilized a Bayesian block analysis to identify M 87 emission states with H.E.S.S. observations from 2004 to 2021, dividing them into low, intermediate, and high states. Because of the causality argument, an extended (≳1 kpc) signal is allowed only in steady emission states. Hence, we fitted the morphology of the 120 h low-state data and find no significant gamma-ray extension. Therefore, we derive for the low state an upper limit of 58″(corresponding to ≈4.6 kpc) in the extension of a single-component morphological model described by a rotationally symmetric 2D Gaussian model at the 99.7% confidence level. Our results exclude the radio lobes (≈30 kpc) as the principal component of the VHE gamma-ray emission from the low state of M 87. The gamma-ray emission is compatible with a single emission region at the radio core of M 87. These results, with the help of two multiple-component models, constrain the maximum cosmic-ray to thermal pressure ratio to XCR, max. ≲ 0.32 and the total energy in cosmic-ray protons to UCR  ≲  5  ×  1058 erg in the inner 20 kpc of the Virgo Cluster for an assumed cosmic-ray proton power-law distribution in momentum with spectral index αp = 2.1
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23.
  • Aharonian, F., et al. (författare)
  • Detection of extended gamma-ray emission around the Geminga pulsar with HESS
  • 2023
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 673
  • Tidskriftsartikel (refereegranskat)abstract
    • Geminga is an enigmatic radio-quiet gamma-ray pulsar located at a mere 250 pc distance from Earth. Extended very-high-energy gamma-ray emission around the pulsar was discovered by Milagro and later confirmed by HAWC, which are both water Cherenkov detector-based experiments. However, evidence for the Geminga pulsar wind nebula in gamma rays has long evaded detection by imaging atmospheric Cherenkov telescopes (IACTs) despite targeted observations. The detection of gamma-ray emission on angular scales greater than or similar to 2 degrees poses a considerable challenge for the background estimation in IACT data analysis. With recent developments in understanding the complementary background estimation techniques of water Cherenkov and atmospheric Cherenkov instruments, the H.E.S.S. IACT array can now confirm the detection of highly extended gamma-ray emission around the Geminga pulsar with a radius of at least 3 degrees in the energy range 0.5-40 TeV. We find no indications for statistically significant asymmetries or energy-dependent morphology. A flux normalisation of (2.8 +/- 0.7) x 10-12 cm-2 s-1 TeV-1 at 1 TeV is obtained within a 1 degrees radius region around the pulsar. To investigate the particle transport within the halo of energetic leptons around the pulsar, we fitted an electron diffusion model to the data. The normalisation of the diffusion coefficient obtained of D-0 = 7.6-1.2+1.5 x 1027 cm2 s-1, at an electron energy of 100 TeV, is compatible with values previously reported for the pulsar halo around Geminga, which is considerably below the Galactic average.
  •  
24.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
  •  
25.
  • 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.
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26.
  • Peters, S., et al. (författare)
  • Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling
  • 2021
  • Ingår i: Neurotherapeutics. - : Springer Nature. - 1933-7213 .- 1878-7479. ; 18:3, s. 1963-1979
  • Tidskriftsartikel (refereegranskat)abstract
    • Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGFβ-RII (Transforming Growth Factor—Receptor Type II) specific LNA-antisense oligonucleotide (“locked nucleotide acid”—“NVP-13”), which reduces TGFβ-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX® cells) in vitro. After we injected cynomolgus non-human primates repeatedly i.th. with NVP-13 in a preclinical regulatory 13-week GLP-toxicity program, we could specifically downregulate TGFβ-RII mRNA and protein in vivo. Subsequently, we observed a dose-dependent upregulation of the neurogenic niche activity within the hippocampus and subventricular zone: human neural progenitor cells showed significantly (up to threefold over control) enhanced differentiation and cell numbers. NVP-13 treatment modulated canonical and non-canonical TGFβ pathways, such as MAPK and PI3K, as well as key transcription factors and epigenetic factors involved in stem cell maintenance, such as MEF2A and pFoxO3. The latter are also dysregulated in clinical neurodegeneration, such as amyotrophic lateral sclerosis. Here, we provide for the first time in vitro and in vivo evidence for a novel translatable approach to treat neurodegenerative disorders by modulating neurogenesis.
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27.
  • Schönhense, G., et al. (författare)
  • Suppression of the vacuum space-charge effect in fs-photoemission by a retarding electrostatic front lens
  • 2021
  • Ingår i: Review of Scientific Instruments. - : American Institute of Physics (AIP). - 0034-6748 .- 1089-7623. ; 92:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The performance of time-resolved photoemission experiments at fs-pulsed photon sources is ultimately limited by the e-e Coulomb interaction, downgrading energy and momentum resolution. Here, we present an approach to effectively suppress space-charge artifacts in momentum microscopes and photoemission microscopes. A retarding electrostatic field generated by a special objective lens repels slow electrons, retaining the k-image of the fast photoelectrons. The suppression of space-charge effects scales with the ratio of the photoelectron velocities of fast and slow electrons. Fields in the range from -20 to -1100 V/mm for E-kin = 100 eV to 4 keV direct secondaries and pump-induced slow electrons back to the sample surface. Ray tracing simulations reveal that this happens within the first 40 to 3 mu m above the sample surface for E-kin = 100 eV to 4 keV. An optimized front-lens design allows switching between the conventional accelerating and the new retarding mode. Time-resolved experiments at E-kin = 107 eV using fs extreme ultraviolet probe pulses from the free-electron laser FLASH reveal that the width of the Fermi edge increases by just 30 meV at an incident pump fluence of 22 mJ/cm(2) (retarding field -21 V/mm). For an accelerating field of +2 kV/mm and a pump fluence of only 5 mJ/cm(2), it increases by 0.5 eV (pump wavelength 1030 nm). At the given conditions, the suppression mode permits increasing the slow-electron yield by three to four orders of magnitude. The feasibility of the method at high energies is demonstrated without a pump beam at E-kin = 3830 eV using hard x rays from the storage ring PETRA III. The approach opens up a previously inaccessible regime of pump fluences for photoemission experiments.
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28.
  • 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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29.
  • Archambault, Alexi N., et al. (författare)
  • Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
  • 2020
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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30.
  • Dixon-Suen, Suzanne C, et al. (författare)
  • Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
  • 2022
  • Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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31.
  • Ji, Xuemei, et al. (författare)
  • Protein-altering germline mutations implicate novel genes related to lung cancer development
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
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32.
  • Ahearn, Thomas U., et al. (författare)
  • Common variants in breast cancer risk loci predispose to distinct tumor subtypes
  • 2022
  • Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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33.
  • Anderzen, J., et al. (författare)
  • International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study
  • 2020
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 21:4, s. 621-627
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. Subjects 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. Methods Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. Results Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. Conclusions In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.
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34.
  • Chen, Zhishan, et al. (författare)
  • Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
  • 2024
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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35.
  • Gaziano, Liam, et al. (författare)
  • Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
  • 2022
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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36.
  • Grånäs, Oscar, 1979-, et al. (författare)
  • Ultrafast modification of the electronic structure of a correlated insulator
  • 2022
  • Ingår i: Physical Review Research. - : American Physical Society. - 2643-1564. ; 4:3
  • Tidskriftsartikel (refereegranskat)abstract
    • A nontrivial balance between Coulomb repulsion and kinematic effects determines the electronic structure of correlated electron materials. The use of electromagnetic fields strong enough to rival these native microscopic interactions allows us to study the electronic response as well as the time scales and energies involved in using quantum effects for possible applications. We use element-specific transient x-ray absorption spectroscopy and high-harmonic generation to measure the response to ultrashort off-resonant optical fields in the prototypical correlated electron insulator NiO. Surprisingly, fields of up to 0.22 V/angstrom lead to no detectable changes in the correlated Ni 3d orbitals contrary to previous predictions. A transient directional charge transfer is uncovered, a behavior that is captured by first-principles theory. Our results highlight the importance of retardation effects in electronic screening and pinpoints a key challenge in functionalizing correlated materials for ultrafast device operation.
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37.
  • Huyghe, Jeroen R, et al. (författare)
  • Genetic architectures of proximal and distal colorectal cancer are partly distinct
  • 2021
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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38.
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39.
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40.
  • Middha, Pooja K., et al. (författare)
  • A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
  • 2023
  • Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
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41.
  • Saddiki, H., et al. (författare)
  • Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study
  • 2020
  • Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The epsilon 4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association betweenAPOEgenotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of beta-amyloid peptide (A, beta-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated withAPOEgenotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least oneAPOE epsilon 4 allele. Compared with non-epsilon 4 carriers, heterozygous epsilon 4 carriers had a 4.6 (95% confidence interval 4.1-5.2;p< 0.001) and epsilon 4/epsilon 4 homozygotes a 25.4 (20.4-31.2;p< 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (pfor interaction < 0.001). The PAF associated with carrying at least one epsilon 4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect ofAPOE epsilon 2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE epsilon 4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect ofAPOE epsilon 4 at the population level. Author summaryWhy was this study done? The epsilon 4 allele of apolipoprotein E () gene () and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The recent development of diagnostic criteria based on biomarkers that reflect brain beta-amyloid and tau lesions (beta-amyloid deposition, pathologic tau, neurodegeneration [A/T/N] classification]) increases homogeneity in diagnosed cases. The strength of association of AD with risk factors can be better determined using biomarker-based AD compared with AD diagnosis based only on clinical criteria because the latter are known to lack specificity as a result of difficulties in ruling out other causes of dementia. What did the researchers do and find? We compared the overall and age-specific association between and AD using a case-control study that included 1,593 AD cases from memory clinics with positive cerebrospinal fluid biomarkers and 11,723 dementia-free controls drawn from two longitudinal cohort studies. The use of a large number of cases and controls allows assessment of whether the association between and AD is dependent on age. Compared with controls, patients with AD were more likely to carry one (odds ratio [OR] = 4.6) or two (OR = 25.3). This association was significantly modified by age, with the strongest association seen between 65 and 70 years of age and weaker associations at the two tails of the age distribution. What do these findings mean? Incorporating biomarkers for diagnosis of AD identified an association with that is apparently greater than has been previously reported using clinical diagnosis of the disease. The impact of on the risk of AD was strongest between the 65 and 70 years of age, earlier than the mean age at diagnosis in this study, which was 72.8 years.
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42.
  • Zanti, Maria, et al. (författare)
  • A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2
  • 2023
  • Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 2023
  • Tidskriftsartikel (refereegranskat)abstract
    • A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
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43.
  • Brandão, Andreia, et al. (författare)
  • The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor
  • 2020
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
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44.
  • Bruno, D., et al. (författare)
  • A comparison of diagnostic performance of word-list and story recall tests for biomarker-determined Alzheimer's disease
  • 2023
  • Ingår i: Journal of Clinical and Experimental Neuropsychology. - 1380-3395. ; 45:8, s. 763-769
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWordlist and story recall tests are routinely employed in clinical practice for dementia diagnosis. In this study, our aim was to establish how well-standard clinical metrics compared to process scores derived from wordlist and story recall tests in predicting biomarker determined Alzheimer's disease, as defined by CSF ptau/A & beta;42 ratio.MethodsData from 295 participants (mean age = 65 & PLUSMN; 9.) were drawn from the University of Wisconsin - Madison Alzheimer's Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer's Prevention (WRAP). Rey's Auditory Verbal Learning Test (AVLT; wordlist) and Logical Memory Test (LMT; story) data were used. Bayesian linear regression analyses were carried out with CSF ptau/A & beta;42 ratio as outcome. Sensitivity analyses were carried out with logistic regressions to assess diagnosticity.ResultsLMT generally outperformed AVLT. Notably, the best predictors were primacy ratio, a process score indexing loss of information learned early during test administration, and recency ratio, which tracks loss of recently learned information. Sensitivity analyses confirmed this conclusion.ConclusionsOur study shows that story recall tests may be better than wordlist tests for detection of dementia, especially when employing process scores alongside conventional clinical scores.
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45.
  • Bruno, D., et al. (författare)
  • The recency ratio assessed by story recall is associated with cerebrospinal fluid levels of neurodegeneration biomarkers
  • 2023
  • Ingår i: Cortex. - : Elsevier BV. - 0010-9452. ; 159, s. 167-174
  • Tidskriftsartikel (refereegranskat)abstract
    • Recency refers to the information learned at the end of a study list or task. Recency forgetting, as tracked by the ratio between recency recall in immediate and delayed con-ditions, i.e., the recency ratio (Rr), has been applied to list-learning tasks, demonstrating its efficacy in predicting cognitive decline, conversion to mild cognitive impairment (MCI), and cerebrospinal fluid (CSF) biomarkers of neurodegeneration. However, little is known as to whether Rr can be effectively applied to story recall tasks. To address this question, data were extracted from the database of the Alzheimer's Disease Research Center at the Uni-versity of Wisconsin -Madison. A total of 212 participants were included in the study. CSF biomarkers were amyloid-beta (Ab) 40 and 42, phosphorylated (p) and total (t) tau, neu-rofilament light (NFL), neurogranin (Ng), and a-synuclein (a-syn). Story Recall was measured with the Logical Memory Test (LMT). We carried out Bayesian regression ana-lyses with Rr, and other LMT scores as predictors; and CSF biomarkers (including the Ab42/ 40 and p-tau/Ab42 ratios) as outcomes. Results showed that models including Rr consis-tently provided best fits with the data, with few exceptions. These findings demonstrate the applicability of Rr to story recall and its sensitivity to CSF biomarkers of neuro-degeneration, and encourage its inclusion when evaluating risk of neurodegeneration with story recall. (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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46.
  • Buschur, Kristina L., et al. (författare)
  • Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease
  • 2024
  • Ingår i: Annals of the American Thoracic Society. - : American Thoracic Society. - 2329-6933 .- 2325-6621. ; 21:6, s. 884-894
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.
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47.
  • Byun, Jinyoung, et al. (författare)
  • Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
  • 2022
  • Ingår i: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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48.
  • Cuni-Sanchez, Aida, et al. (författare)
  • High aboveground carbon stock of African tropical montane forests
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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49.
  • Engel, Robin Y., et al. (författare)
  • Parallel Broadband Femtosecond Reflection Spectroscopy at a Soft X-Ray Free-Electron Laser
  • 2020
  • Ingår i: Applied Sciences. - : MDPI. - 2076-3417. ; 10:19
  • Tidskriftsartikel (refereegranskat)abstract
    • Featured Application Exploiting the full flux and temporal resolution of SASE-FELs for highly sensitive X-ray absorption measurements. X-ray absorption spectroscopy (XAS) and the directly linked X-ray reflectivity near absorption edges yield a wealth of specific information on the electronic structure around the resonantly addressed element. Observing the dynamic response of complex materials to optical excitations in pump-probe experiments requires high sensitivity to small changes in the spectra which in turn necessitates the brilliance of free electron laser (FEL) pulses. However, due to the fluctuating spectral content of pulses generated by self-amplified spontaneous emission (SASE), FEL experiments often struggle to reach the full sensitivity and time-resolution that FELs can in principle enable. Here, we implement a setup which solves two common challenges in this type of spectroscopy using FELs: First, we achieve a high spectral resolution by using a spectrometer downstream of the sample instead of a monochromator upstream of the sample. Thus, the full FEL bandwidth contributes to the measurement at the same time, and the FEL pulse duration is not elongated by a monochromator. Second, the FEL beam is divided into identical copies by a transmission grating beam splitter so that two spectra from separate spots on the sample (or from the sample and known reference) can be recorded in-parallel with the same spectrometer, enabling a spectrally resolved intensity normalization of pulse fluctuations in pump-probe scenarios. We analyze the capabilities of this setup around the oxygen K- and nickel L-edges recorded with third harmonic radiation of the free electron laser in Hamburg (FLASH), demonstrating the capability for pump-probe measurements with sensitivity to reflectivity changes on the per mill level.
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50.
  • Feigin, Valery L., et al. (författare)
  • Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
  • 2021
  • Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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