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Träfflista för sökning "WFRF:(Carr Michael J.) "

Sökning: WFRF:(Carr Michael J.)

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1.
  • 2017
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
  • Tidskriftsartikel (refereegranskat)
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2.
  • Bombarda, F., et al. (författare)
  • Runaway electron beam control
  • 2019
  • Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
  • Tidskriftsartikel (refereegranskat)
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3.
  • Acharya, B. S., et al. (författare)
  • Introducing the CTA concept
  • 2013
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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4.
  • Murari, A., et al. (författare)
  • A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
  • 2024
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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8.
  • Joffrin, E., et al. (författare)
  • Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
  • Forskningsöversikt (refereegranskat)abstract
    • For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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9.
  • Actis, M., et al. (författare)
  • Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
  • 2011
  • Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
  • Tidskriftsartikel (refereegranskat)abstract
    • Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
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10.
  • Adrian-Martinez, S., et al. (författare)
  • The First Combined Search For Neutrino Point-Sources In The Southern Hemisphere With The Antares And Icecube Neutrino Telescopes
  • 2016
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 823:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of searches for point-like sources of neutrinos based on the first combined analysis of data from both the ANTARES and IceCube neutrino telescopes. The combination of both detectors, which differ in size and location, forms a window in the southern sky where the sensitivity to point sources improves by up to a factor of 2 compared with individual analyses. Using data recorded by ANTARES from 2007 to 2012, and by IceCube from 2008 to 2011, we search for sources of neutrino emission both across the southern sky and from a preselected list of candidate objects. No significant excess over background has been found in these searches, and flux upper limits for the candidate sources are presented for E-2.5 and E-2 power-law spectra with different energy cut-offs.
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11.
  • Meyer, H., et al. (författare)
  • Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
  • 2017
  • Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.
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12.
  • Petroff, E., et al. (författare)
  • A polarized fast radio burst at low Galactic latitude
  • 2017
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford Academic. - 0035-8711 .- 1365-2966. ; 469:4, s. 4465-4482
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 +/- 0.8 pc cm(-3), a pulse duration of 2.8(-0.5)(+1.2) ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7(-0.1)(+0.2) Jy. The FRB originated at a Galactic longitude and latitude of 24.66 degrees, 5.28 degrees and 25 degrees away from the Galactic Center. The burst was found to be 43 +/- 5 per cent linearly polarized with a rotation measure (RM) in the range -9 < RM < 12 rad m(-2) (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X-ray, gamma-ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.
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13.
  • Abdalla, H., et al. (författare)
  • Gamma-ray blazar spectra with HESS II mono analysis : The case of PKS2155-304 and PG1553+113
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 600
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The addition of a 28 m Cherenkov telescope (CT5) to the H.E.S.S. array extended the experiment's sensitivity to lower energies. The lowest energy threshold is obtained using monoscopic analysis of data taken with CT5, providing access to gamma-ray energies below 100 GeV for small zenith angle observations. Such an extension of the instrument's energy range is particularly beneficial for studies of active galactic nuclei with soft spectra, as expected for those at a redshift >= 0.5. The high-frequency peaked BL Lac objects PKS 2155-304 (z = 0.116) and PG 1553 + 113 (0.43 < z < 0.58) are among the brightest objects in the gamma-ray sky, both showing clear signatures of gamma-ray absorption at E > 100 GeV interpreted as being due to interactions with the extragalactic background light (EBL). Aims. The aims of this work are twofold: to demonstrate the monoscopic analysis of CT5 data with a low energy threshold, and to obtain accurate measurements of the spectral energy distributions (SED) of PKS 2155-304 and PG 1553 + 113 near their SED peaks at energies approximate to 100 GeV. Methods. Multiple observational campaigns of PKS 2155 304 and PG 1553 + 113 were conducted during 2013 and 2014 using the full H.E.S.S. II instrument (CT1-5). A monoscopic analysis of the data taken with the new CT5 telescope was developed along with an investigation into the systematic uncertainties on the spectral parameters which are derived from this analysis. Results. Using the data from CT5, the energy spectra of PKS 2155 304 and PG 1553 + 113 were reconstructed down to conservative threshold energies of 80 GeV for PKS 2155 304, which transits near zenith, and 110 GeV for the more northern PG 1553 + 113. The measured spectra, well fitted in both cases by a log-parabola spectral model ( with a 5.0 similar to statistical preference for non-zero curvature for PKS 2155 304 and 4.5 sigma for PG 1553+113), were found consistent with spectra derived from contemporaneous Fermi-LAT data, indicating a sharp break in the observed spectra of both sources at E approximate to 100 GeV. When corrected for EBL absorption, the intrinsic H.E.S.S. II mono and Fermi-LAT spectrum of PKS 2155 304 was found to show significant curvature. For PG 1553+113, however, no significant detection of curvature in the intrinsic spectrum could be found within statistical and systematic uncertainties.
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14.
  • Abdalla, H., et al. (författare)
  • The supernova remnant W49B as seen with HESS and Fermi-LAT
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • The supernova remnant (SNR) W49B originated from a core-collapse supernova that occurred between one and four thousand years ago, and subsequently evolved into a mixed-morphology remnant, which is interacting with molecular clouds (MC). Gamma-ray observations of SNR-MC associations are a powerful tool to constrain the origin of Galactic cosmic rays, as they can probe the acceleration of hadrons through their interaction with the surrounding medium and subsequent emission of non-thermal photons. We report the detection of a gamma-ray source coincident with W49B at very high energies (VHE; E > 100 GeV) with the H.E.S.S. Cherenkov telescopes together with a study of the source with five years of Fermi-LAT high-energy gamma-ray (0.06-300 GeV) data. The smoothly connected, combined source spectrum, measured from 60 MeV to multi-TeV energies, shows two significant spectral breaks at 304 +/- 20 MeV and 8.4(-2.5)(+2.5) GeV; the latter is constrained by the joint fit from the two instruments. The detected spectral features are similar to those observed in several other SNR-MC associations and are found to be indicative of gamma-ray emission produced through neutral-pion decay.
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15.
  • Abdallah, H., et al. (författare)
  • Search for gamma-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with HESS
  • 2018
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 120:20
  • Tidskriftsartikel (refereegranskat)abstract
    • Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy gamma rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant gamma-ray excess above the background is found. We derive upper limits on the annihilation cross section (sigma v) for monoenergetic DM lines at the level of 4 x 10(-28) cm(3) s(-1) at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based gamma-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two gamma-ray photons at the level expected from the thermal relic density for TeV DM particles.
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16.
  • Abdalla, H., et al. (författare)
  • A search for new supernova remnant shells in the Galactic plane with HESS
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for new supernova remnants (SNRs) has been conducted using TeV gamma-ray data from the H.E.S.S. Galactic plane survey. As an identification criterion, shell morphologies that are characteristic for known resolved TeV SNRs have been used. Three new SNR candidates were identified in the H.E.S.S. data set with this method. Extensive multiwavelength searches for counterparts were conducted. A radio SNR candidate has been identified to be a counterpart to HESS J1534-571. The TeV source is therefore classified as a SNR. For the other two sources, HESS J1614-518 and HESS J1912 + 101, no identifying counterparts have been found, thus they remain SNR candidates for the time being. TeV-emitting SNRs are key objects in the context of identifying the accelerators of Galactic cosmic rays. The TeV emission of the relativistic particles in the new sources is examined in view of possible leptonic and hadronic emission scenarios, taking the current multiwavelength knowledge into account.
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17.
  • Abdalla, H., et al. (författare)
  • Characterising the VHE diffuse emission in the central 200 parsecs of our Galaxy with HESS
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • The diffuse very high-energy (VHE; > 100 GeV) gamma-ray emission observed in the central 200 pc of the Milky Way by H.E.S.S. was found to follow dense matter distribution in the central molecular zone (CMZ) up to a longitudinal distance of about 130 pc to the Galactic centre (GC), where the flux rapidly decreases. This was initially interpreted as the result of a burst-like injection of energetic particles 104 yr ago, but a recent more sensitive H.E.S.S. analysis revealed that the cosmic-ray (CR) density profile drops with the distance to the centre, making data compatible with a steady cosmic PeVatron at the GC. In this paper, we extend this analysis to obtain, for the first time, a detailed characterisation of the correlation with matter and to search for additional features and individual gamma-ray sources in the inner 200 pc. Taking advantage of 250 h of H.E.S.S. data and improved analysis techniques, we perform a detailed morphology study of the diffuse VHE emission observed from the GC ridge and reconstruct its total spectrum. To test the various contributions to the total gamma-ray emission, we used an iterative 2D maximum-likelihood approach that allows us to build a phenomenological model of the emission by summing a number of different spatial components. We show that the emission correlated with dense matter covers the full CMZ and that its flux is about half the total diffuse emission flux. We also detect some emission at higher latitude that is likely produced by hadronic collisions of CRs in less dense regions of the GC interstellar medium. We detect an additional emission component centred on the GC and extending over about 15 pc that is consistent with the existence of a strong CR density gradient and confirms the presence of a CR accelerator at the very centre of our Galaxy. We show that the spectrum of full ridge diffuse emission is compatible with that previously derived from the central regions, suggesting that a single population of particles fills the entire CMZ. Finally, we report the discovery of a VHE gamma-ray source near the GC radio arc and argue that it is produced by the pulsar wind nebula candidate G0.13-0.11.
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18.
  • Abdalla, H., et al. (författare)
  • Characterizing the γ-ray long-term variability of PKS2155 304 with HESS and Fermi-LAT
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : The European Southern Observatory. - 0004-6361 .- 1432-0746. ; 598
  • Tidskriftsartikel (refereegranskat)abstract
    • Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in the high (HE, 100MeV < E < 300 GeV) and very high energy (VHE, E > 200 GeV) gamma-ray domain. Over the course of similar to 9 yr of H. E. S. S. observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index βVHE = 1 .10+ 0.10-0,13) on timescales larger than one day. An analysis of similar to 5.5 yr of HE Fermi-LAT data gives consistent results (βHE = 1 .20+ 0.21-0.23, on timescales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior (beta similar to 2) seen on shorter timescales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.
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19.
  • Abdalla, H., et al. (författare)
  • Deeper HESS observations of Vela Junior (RX J0852.0-4622) : Morphology studies and resolved spectroscopy
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. We study gamma-ray emission from the shell-type supernova remnant (SNR) RXJ0852.0-4622 to better characterize its spectral properties and its distribution over the SNR. Methods. The analysis of an extended High Energy Spectroscopic System (H.E.S.S.) data set at very high energies (E > 100 GeV) permits detailed studies, as well as spatially resolved spectroscopy, of the morphology and spectrum of the whole RXJ0852.0-4622 region. The H.E.S.S. data are combined with archival data from other wavebands and interpreted in the framework of leptonic and hadronic models. The joint Fermi-LAT-H.E.S.S. spectrum allows the direct determination of the spectral characteristics of the parent particle population in leptonic and hadronic scenarios using only GeV-TeV data. Results. An updated analysis of the H.E.S.S. data shows that the spectrum of the entire SNR connects smoothly to the high-energy spectrum measured by Fermi-LAT. The increased data set makes it possible to demonstrate that the H.E.S.S. spectrum deviates significantly from a power law and is well described by both a curved power law and a power law with an exponential cutoff at an energy of E-cut = (6.7 +/- 1.2(stat) +/- 1.2(syst)) TeV. The joint Fermi-LAT-H.E.S.S. spectrum allows the unambiguous identification of the spectral shape as a power law with an exponential cutoff. No significant evidence is found for a variation of the spectral parameters across the SNR, suggesting similar conditions of particle acceleration across the remnant. A simple modeling using one particle population to model the SNR emission demonstrates that both leptonic and hadronic emission scenarios remain plausible. It is also shown that at least a part of the shell emission is likely due to the presence of a pulsar wind nebula around PSR J0855-4644.
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20.
  • Abdalla, H., et al. (författare)
  • First limits on the very-high energy gamma-ray afterglow emission of a fast radio burst HESS observations of FRB 150418
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : The European Southern Observatory (ESO). - 0004-6361 .- 1432-0746. ; 597
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. Following the detection of the fast radio burst FRB150418 by the SUPERB project at the Parkes radio telescope, we aim to search for very-high energy gamma-ray afterglow emission. Methods. Follow-up observations in the very-high energy gamma-ray domain were obtained with the H.E.S.S. imaging atmospheric Cherenkov telescope system within 14.5 h of the radio burst. Results. The obtained 1.4 h of gamma-ray observations are presented and discussed. At the 99% C.L. we obtained an integral upper limit on the gamma-ray flux of Phi(gamma)(E > 350 GeV) < 1.33 x 10(-8) m(-2) s(-1). Differential flux upper limits as function of the photon energy were derived and used to constrain the intrinsic high-energy afterglow emission of FRB 150418. Conclusions. No hints for high-energy afterglow emission of FRB 150418 were found. Taking absorption on the extragalactic background light into account and assuming a distance of z = 0 : 492 based on radio and optical counterpart studies and consistent with the FRB dispersion, we constrain the gamma-ray luminosity at 1 TeV to L < 5 : 1 x 10(47) erg/s at 99% C.L.
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21.
  • Abdalla, H., et al. (författare)
  • HESS discovery of very high energy gamma-ray emission from PKS 0625-354
  • 2018
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 476:3, s. 4187-4198
  • Tidskriftsartikel (refereegranskat)abstract
    • PKS 0625-354 (z = 0.055) was observed with the four High Energy Stereoscopic System (H.E.S.S.) telescopes in 2012 during 5.5 h. The source was detected above an energy threshold of 200 GeV at a significance level of 6.1 sigma. No significant variability is found in these observations. The source is well described with a power-law spectrum with photon index Gamma = 2.84 +/- 0.50(stat) +/- 0.10(syst) and normalization (at E-0 = 1.0 TeV) N-0(E-0)=(0.58 +/- 0.22(stat) +/- 0.12(syst)) x 10(-12) TeV-1 cm(-2) s(-1). Multiwavelength data collected with Fermi-LAT, Swift-XRT, Swift-UVOT, ATOM and WISE are also analysed. Significant variability is observed only in the Fermi-LAT gamma-ray and Swift-XRT X-ray energy bands. Having a good multiwavelength coverage from radio to very high energy, we performed a broad-band modelling from two types of emission scenarios. The results from a one zone lepto-hadronic and a multizone leptonic models are compared and discussed. On the grounds of energetics, our analysis favours a leptonic multizone model. Models associated to the X-ray variability constraint support previous results, suggesting a BL Lac nature of PKS 0625-354 with, however, a large-scale jet structure typical of a radio galaxy.
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22.
  • Abdalla, H., et al. (författare)
  • HESS observations of RX J1713.7-3946 with improved angular and spectral resolution : Evidence for gamma-ray emission extending beyond the X-ray emitting shell
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • Supernova remnants exhibit shock fronts (shells) that can accelerate charged particles up to very high energies. In the past decade, measurements of a handful of shell-type supernova remnants in very high-energy gamma rays have provided unique insights into the acceleration process. Among those objects, RX J1713.7-3946 (also known as G347.3-0.5) has the largest surface brightness, allowing us in the past to perform the most comprehensive study of morphology and spatially resolved spectra of any such very high-energy gamma-ray source. Here we present extensive new H.E.S.S. measurements of RX J1713.7-3946, almost doubling the observation time compared to our previous publication. Combined with new improved analysis tools, the previous sensitivity is more than doubled. The H.E.S.S. angular resolution of 0.048 degrees (0.036 degrees above 2 TeV) is unprecedented in gamma-ray astronomy and probes physical scales of 0.8 (0.6) parsec at the remnant's location. The new H. E. S. S. image of RX J1713.7-3946 allows us to reveal clear morphological di ff erences between X-rays and gamma rays. In particular, for the outer edge of the brightest shell region, we find the first ever indication for particles in the process of leaving the acceleration shock region. By studying the broadband energy spectrum, we furthermore extract properties of the parent particle populations, providing new input to the discussion of the leptonic or hadronic nature of the gamma-ray emission mechanism.
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23.
  • Abdalla, H., et al. (författare)
  • Measurement of the EBL spectral energy distribution using the VHE gamma-ray spectra of HESS blazars
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : The European Southern Observatory (ESO). - 0004-6361 .- 1432-0746. ; 606
  • Tidskriftsartikel (refereegranskat)abstract
    • Very high-energy gamma rays (VHE, E greater than or similar to 100 GeV) propagating over cosmological distances can interact with the low-energy photons of the extragalactic background light (EBL) and produce electron-positron pairs. The transparency of the Universe to VHE gamma rays is then directly related to the spectral energy distribution (SED) of the EBL. The observation of features in the VHE energy spectra of extragalactic sources allows the EBL to be measured, which otherwise is very difficult. An EBL model-independent measurement of the EBL SED with the H.E.S.S. array of Cherenkov telescopes is presented. It was obtained by extracting the EBL absorption signal from the reanalysis of high-quality spectra of blazars. From H.E.S.S. data alone the EBL signature is detected at a significance of 9.5 sigma, and the intensity of the EBL obtained in different spectral bands is presented together with the associated gamma-ray horizon.
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24.
  • Abdalla, H., et al. (författare)
  • Systematic search for very-high-energy gamma-ray emission from bow shocks of runaway stars
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Runaway stars form bow shocks by ploughing through the interstellar medium at supersonic speeds and are promising sources of non-thermal emission of photons. One of these objects has been found to emit non-thermal radiation in the radio band. This triggered the development of theoretical models predicting non-thermal photons from radio up to very-high-energy (VHE, E >= 0.1 TeV) gamma rays. Subsequently, one bow shock was also detected in X-ray observations. However, the data did not allow discrimination between a hot thermal and a non-thermal origin. Further observations of different candidates at X-ray energies showed no evidence for emission at the position of the bow shocks either. A systematic search in the Fermi-LAT energy regime resulted in flux upper limits for 27 candidates listed in the E-BOSS catalogue. Aims. Here we perform the first systematic search for VHE gamma-ray emission from bow shocks of runaway stars. Methods. Using all available archival H.E.S.S. data we search for very-high-energy gamma-ray emission at the positions of bow shock candidates listed in the second E-BOSS catalogue release. Out of the 73 bow shock candidates in this catalogue, 32 have been observed with H.E.S.S. Results. None of the observed 32 bow shock candidates in this population study show significant emission in the H.E.S.S. energy range. Therefore, flux upper limits are calculated in five energy bins and the fraction of the kinetic wind power that is converted into VHE gamma rays is constrained. Conclusions. Emission from stellar bow shocks is not detected in the energy range between 0.14 and 18 TeV. The resulting upper limits constrain the level of VHE gamma-ray emission from these objects down to 0.1-1% of the kinetic wind energy.
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25.
  • Abdalla, H., et al. (författare)
  • A search for very high-energy flares from the microquasars GRS 1915+105, Circinus X-1, and V4641 Sgr using contemporaneous HESS and RXTE observations
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Microquasars are potential gamma-ray emitters. Indications of transient episodes of gamma-ray emission were recently reported in at least two systems: Cyg X-1 and Cyg X-3. The identification of additional gamma-ray-emitting microquasars is required to better understand how gamma-ray emission can be produced in these systems. Aims. Theoretical models have predicted very high-energy (VHE) gamma-ray emission from microquasars during periods of transient outburst. Observations reported herein were undertaken with the objective of observing a broadband flaring event in the gamma-ray and X-ray bands. Methods. Contemporaneous observations of three microquasars, GRS 1915+105, Circinus X-1, and V4641 Sgr, were obtained using the High Energy Spectroscopic System (H.E.S.S.) telescope array and the Rossi X-ray Timing Explorer (RXTE) satellite. X-ray analyses for each microquasar were performed and VHE gamma-ray upper limits from contemporaneous H.E.S.S. observations were derived. Results. No significant gamma-ray signal has been detected in any of the three systems. The integral gamma-ray photon flux at the observational epochs is constrained to be I(>560 GeV) < 7.3 x 10(-13) cm(-2) S-1, I(>560 GeV) < 1.2 x 10-(12) cm s(-1), and I(>240 GeV) < 4.5 x 10(-12) cm(-2) s(-1) for GRS 1915+105, Circinus X-1, and V4641 Sgr, respectively. Conclusions. The gamma-ray upper limits obtained using H.E.S.S. are examined in the context of previous Cherenkov telescope observations of microquasars. The effect of intrinsic absorption is modelled for each target and found to have negligible impact on the flux of escaping gamma-rays. When combined with the X-ray behaviour observed using RXTE, the derived results indicate that if detectable VHE gamma-ray emission from microquasars is commonplace, then it is likely to be highly transient.
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26.
  • Abdalla, H., et al. (författare)
  • Extended VHE gamma-ray emission towards SGR1806-20, LBV 1806-20, and stellar cluster Cl*1806-20
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the High Energy Spectroscopic System (H.E.S.S.) telescopes we have discovered a steady and extended very high-energy (VHE) gamma-ray source towards the luminous blue variable candidate LBV 1806-20, massive stellar cluster Cl* 1806-20, and magnetar SGR 1806-20. The new VHE source, HESS J1808-204, was detected at a statistical significance of >6 sigma (post-trial) with a photon flux normalisation (2.9 +/- 0.4(stat) +/- 0.5(sys)) x 10(-13) ph cm(-2) s(-1) TeV-1 at 1 TeV and a power-law photon index of 2.3 +/- 0.2(stat) +/- 0.3(sys). The luminosity of this source (0.2 to 10 TeV; scaled to distance d = 8 : 7 kpc) is L-VHE similar to 1.6 x 10(34)(d = 8.7 kpc)(2) erg s(-1). The VHE gamma-ray emission is extended and is well fit by a single Gaussian with statistical standard deviation of 0.095 degrees +/- 0.015 degrees. This extension is similar to that of the synchrotron radio nebula G10.0-0.3, which is thought to be powered by LBV 1806-20. The VHE gamma-ray luminosity could be provided by the stellar wind luminosity of LBV 1806-20 by itself and/or the massive star members of Cl* 1806-20. Alternatively, magnetic dissipation (e.g. via reconnection) from SGR 1806-20 can potentially account for the VHE luminosity. The origin and hadronic and/or leptonic nature of the accelerated particles responsible for HESS J1808-204 is not yet clear. If associated with SGR 1806 20, the potentially young age of the magnetar (650 yr) can be used to infer the transport limits of these particles to match the VHE source size. This discovery provides new interest in the potential for high-energy particle acceleration from magnetars, massive stars, and/or stellar clusters.
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27.
  • Abdalla, H., et al. (författare)
  • HESS Limits on Linelike Dark Matter Signatures in the 100 GeV to 2 TeV Energy Range Close to the Galactic Center
  • 2016
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 117:15
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l = -1.5 degrees, b = 0 degrees and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. results. No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.
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28.
  • Abdalla, H., et al. (författare)
  • The population of TeV pulsar wind nebulae in the HESS Galactic Plane Survey
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • The nine-year H.E.S.S. Galactic Plane Survey (HGPS) has yielded the most uniform observation scan of the inner Milky Way in the TeV gamma-ray band to date. The sky maps and source catalogue of the HGPS allow for a systematic study of the population of TeV pulsar wind nebulae found throughout the last decade. To investigate the nature and evolution of pulsar wind nebulae, for the first time we also present several upper limits for regions around pulsars without a detected TeV wind nebula. Our data exhibit a correlation of TeV surface brightness with pulsar spindown power (E) over dot. This seems to be caused both by an increase of extension with decreasing (E) over dot, and hence with time, compatible with a power law R-PWN((E) over dot) similar to(E) over dot(0.65 +/- 0.20), and by a mild decrease of TeV gamma-ray luminosity with decreasing (E) over dot, compatible with L-1 (10 TeV) similar to (E) over dot(0.59 +/- 0.21). We also find that the off sets of pulsars with respect to the wind nebula centre with ages around 10 kyr are frequently larger than can be plausibly explained by pulsar proper motion and could be due to an asymmetric environment. In the present data, it seems that a large pulsar off set is correlated with a high apparent TeV efficiency L1- 10 TeV / (E) over dot. In addition to 14 HGPS sources considered firmly identified pulsar wind nebulae and 5 additional pulsar wind nebulae taken from literature, we find 10 HGPS sources that are likely TeV pulsar wind nebula candidates. Using a model that subsumes the present common understanding of the very high-energy radiative evolution of pulsar wind nebulae, we find that the trends and variations of the TeV observables and limits can be reproduced to a good level, drawing a consistent picture of present-day TeV data and theory.
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29.
  • Abdallah, H., et al. (författare)
  • Search for Dark Matter Annihilations towards the Inner Galactic Halo from 10 Years of Observations with HESS
  • 2016
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 117:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section . These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe values expected from the thermal relic density for TeV DM particles.
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30.
  • Meyer, H.F., et al. (författare)
  • Overview of physics studies on ASDEX Upgrade
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
  • Forskningsöversikt (refereegranskat)abstract
    • The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
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31.
  • Abramowski, A., et al. (författare)
  • Detailed spectral and morphological analysis of the shell type supernova remnant RCW 86
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. We aim for an understanding of the morphological and spectral properties of the supernova remnant RCW 86 and for insights into the production mechanism leading to the RCW 86 very high-energy gamma-ray emission. Methods. We analyzed High Energy Spectroscopic System (H.E.S.S.) data that had increased sensitivity compared to the observations presented in the RCW 86 H.E.S.S. discovery publication. Studies of the morphological correlation between the 0.5-1 keV X-ray band, the 2-5 keV X-ray band, radio, and gamma-ray emissions have been performed as well as broadband modeling of the spectral energy distribution with two different emission models. Results. We present the first conclusive evidence that the TeV gamma-ray emission region is shell-like based on our morphological studies. The comparison with 2-5 keV X-ray data reveals a correlation with the 0.4-50 TeV gamma-ray emission. The spectrum of RCW 86 is best described by a power law with an exponential cutoff at E-cut = (3.5 +/- 1.2(stat)) TeV and a spectral index of Gamma approximate to 1.6 +/- 0.2. A static leptonic one-zone model adequately describes the measured spectral energy distribution of RCW 86, with the resultant total kinetic energy of the electrons above 1 GeV being equivalent to similar to 0.1% of the initial kinetic energy of a Type Ia supernova explosion (10(51) erg). When using a hadronic model, a magnetic field of B approximate to 100 mu G is needed to represent the measured data. Although this is comparable to formerly published estimates, a standard E-2 spectrum for the proton distribution cannot describe the gamma-ray data. Instead, a spectral index of Gamma(p) approximate to 1.7 would be required, which implies that similar to 7 x 10(49)/n(cm-3) erg has been transferred into high-energy protons with the effective density n(cm-3) = n/1 cm(-3). This is about 10% of the kinetic energy of a typical Type Ia supernova under the assumption of a density of 1 cm(-3).
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32.
  • Abramowski, A., et al. (författare)
  • Acceleration of petaelectronvolt protons in the Galactic Centre
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 531:7595, s. 476-479
  • Tidskriftsartikel (refereegranskat)abstract
    • Galactic cosmic rays reach energies of at least a few petaelectronvolts(1) (of the order of 1015 electronvolts). This implies that our Galaxy contains petaelectronvolt accelerators ('PeVatrons'), but all proposed models of Galactic cosmic-ray accelerators encounter difficulties at exactly these energies(2). Dozens of Galactic accelerators capable of accelerating particles to energies of tens of teraelectronvolts (of the order of 10(13) electronvolts) were inferred from recent gamma-ray observations(3). However, none of the currently known accelerators-not even the handful of shell-type supernova remnants commonly believed to supply most Galactic cosmic rays-has shown the characteristic tracers of petaelectronvolt particles, namely, power-law spectra of.-rays extending without a cut-off or a spectral break to tens of teraelectronvolts(4). Here we report deep.-ray observations with arcminute angular resolution of the region surrounding the Galactic Centre, which show the expected tracer of the presence of petaelectronvolt protons within the central 10 parsecs of the Galaxy. We propose that the supermassive black hole Sagittarius A* is linked to this PeVatron. Sagittarius A* went through active phases in the past, as demonstrated by X-ray outbursts(5) and an outflow from the Galactic Centre(6). Although its current rate of particle acceleration is not sufficient to provide a substantial contribution to Galactic cosmic rays, Sagittarius A* could have plausibly been more active over the last 10(6)-10(7) years, and therefore should be considered as a viable alternative to supernova remnants as a source of petaelectronvolt Galactic cosmic rays.
  •  
33.
  • Abramowski, A., et al. (författare)
  • Discovery of variable VHE gamma-ray emission from the binary system 1FGL J1018.6-5856
  • 2015
  • Ingår i: Astronomy and Astrophysics Supplement Series. - : EDP Sciences. - 0365-0138 .- 1286-4846. ; 577
  • Tidskriftsartikel (refereegranskat)abstract
    • Re-observations with the HESS telescope array of the very high-energy (VHE) source HESS J1018-589 A that is coincident with the Fermi-LAT γ-ray binary 1FGL J1018.6-5856 have resulted in a source detection significance of more than 9σ and the detection of variability (χ$^2$/ν of 238.3/155) in the emitted γ-ray flux. This variability confirms the association of HESS J1018-589 A with the high-energy γ-ray binary detected by Fermi-LAT and also confirms the point-like source as a new VHE binary system. The spectrum of HESS J1018-589 A is best fit with a power-law function with photon index Γ = 2.20 \plusmn 0.14$_stat$ \plusmn 0.2$_sys$. Emission is detected up to ~20 TeV. The mean differential flux level is (2.9 \plusmn 0.4) \times 10$^-13$ TeV$^-1$ cm$^-2$ s$^-1$ at 1 TeV, equivalent to ~1% of the flux from the Crab Nebula at the same energy. Variability is clearly detected in the night-by-night light curve. When folded on the orbital period of 16.58 days, the rebinned light curve peaks in phase with the observed X-ray and high-energy phaseograms. The fit of the HESS phaseogram to a constant flux provides evidence of periodicity at the level of N$_sigma$\gt 3σ. The shape of the VHE phaseogram and measured spectrum suggest a low-inclination, low-eccentricity system with amodest impact from VHE γ-ray absorption due to pair production (τ \lsim 1 at 300 GeV).
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34.
  • Kirk, A., et al. (författare)
  • Overview of recent physics results from MAST
  • 2017
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 57:10
  • Tidskriftsartikel (refereegranskat)abstract
    • New results from MAST are presented that focus on validating models in order to extrapolate to future devices. Measurements during start-up experiments have shown how the bulk ion temperature rise scales with the square of the reconnecting field. During the current ramp-up, models are not able to correctly predict the current diffusion. Experiments have been performed looking at edge and core turbulence. At the edge, detailed studies have revealed how filament characteristics are responsible for determining the near and far scrape off layer density profiles. In the core the intrinsic rotation and electron scale turbulence have been measured. The role that the fast ion gradient has on redistributing fast ions through fishbone modes has led to a redesign of the neutral beam injector on MAST Upgrade. In H-mode the turbulence at the pedestal top has been shown to be consistent with being due to electron temperature gradient modes. A reconnection process appears to occur during edge localized modes (ELMs) and the number of filaments released determines the power profile at the divertor. Resonant magnetic perturbations can mitigate ELMs provided the edge peeling response is maximised and the core kink response minimised. The mitigation of intrinsic error fields with toroidal mode number n > 1 has been shown to be important for plasma performance.
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35.
  • Chapman, I. T., et al. (författare)
  • Overview of MAST results
  • 2015
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The Mega Ampere Spherical Tokamak (MAST) programme is strongly focused on addressing key physics issues in preparation for operation of ITER as well as providing solutions for DEMO design choices. In this regard, MAST has provided key results in understanding and optimizing H-mode confinement, operating with smaller edge localized modes (ELMs), predicting and handling plasma exhaust and tailoring auxiliary current drive. In all cases, the high-resolution diagnostic capability on MAST is complemented by sophisticated numerical modelling to facilitate a deeper understanding. Mitigation of ELMs with resonant magnetic perturbations (RMPs) with toroidal mode number n(RMP) = 2, 3, 4, 6 has been demonstrated: at high and low collisionality; for the first ELM following the transition to high confinement operation; during the current ramp-up; and with rotating n(RMP) = 3 RMPs. n(RMP) = 4, 6 fields cause less rotation braking whilst the power to access H-mode is less with n(RMP) = 4 than n(RMP) = 3, 6. Refuelling with gas or pellets gives plasmas with mitigated ELMs and reduced peak heat flux at the same time as achieving good confinement. A synergy exists between pellet fuelling and RMPs, since mitigated ELMs remove fewer particles. Inter-ELM instabilities observed with Doppler backscattering are consistent with gyrokinetic simulations of micro-tearing modes in the pedestal. Meanwhile, ELM precursors have been strikingly observed with beam emission spectroscopy (BES) measurements. A scan in beta at the L-H transition shows that pedestal height scales strongly with core pressure. Gyro-Bohm normalized turbulent ion heat flux (as estimated from the BES data) is observed to decrease with increasing tilt of the turbulent eddies. Fast ion redistribution by energetic particle modes depends on density, and access to a quiescent domain with 'classical' fast ion transport is found above a critical density. Highly efficient electron Bernstein wave current drive (1 A W-1) has been achieved in solenoid-free start-up. A new proton detector has characterized escaping fusion products. Langmuir probes and a high-speed camera suggest filaments play a role in particle transport in the private flux region whilst coherence imaging has measured scrape-off layer (SOL) flows. BOUT++ simulations show that fluxes due to filaments are strongly dependent on resistivity and magnetic geometry of the SOL, with higher radial fluxes at higher resistivity. Finally, MAST Upgrade is due to begin operation in 2016 to support ITER preparation and importantly to operate with a Super-X divertor to test extended leg concepts for particle and power exhaust.
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36.
  • 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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37.
  • Postmus, Iris, et al. (författare)
  • Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
  • 2014
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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38.
  • Soranno, Patricia A., et al. (författare)
  • LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
  • 2017
  • Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
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39.
  • Bousquet, Jean, et al. (författare)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Forskningsöversikt (refereegranskat)abstract
    • Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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40.
  • Evangelou, Evangelos, et al. (författare)
  • A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
  • 2014
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
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41.
  • Schijven, Dick, et al. (författare)
  • Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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42.
  • Blösch, Günter, et al. (författare)
  • Twenty-three unsolved problems in hydrology (UPH) - a community perspective
  • 2019
  • Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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43.
  • Bousquet, J. Jean, et al. (författare)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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44.
  • Evangelou, Evangelos, et al. (författare)
  • Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
  • 2011
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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45.
  • Roy, Sushmita, et al. (författare)
  • Identification of functional elements and regulatory circuits by Drosophila modENCODE.
  • 2010
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
  • Tidskriftsartikel (refereegranskat)abstract
    • To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
  •  
46.
  • Speliotes, Elizabeth K, et al. (författare)
  • Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.
  • 2011
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n=880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.
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47.
  • Heckman, Michael G., et al. (författare)
  • Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
  • 2013
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:12, s. 1740-1744
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society
  •  
48.
  • Holmberg, Carl Jacob, et al. (författare)
  • The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
  • 2022
  • Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
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49.
  • Moncrieff, Marc D, et al. (författare)
  • Clinical Outcomes and Risk Stratification of Early-Stage Melanoma Micrometastases From an International Multicenter Study: Implications for the Management of American Joint Committee on Cancer IIIA Disease.
  • 2022
  • Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 40:34, s. 3940-3951
  • Tidskriftsartikel (refereegranskat)abstract
    • Indications for offering adjuvant systemic therapy for patients with early-stage melanomas with low disease burden sentinel node (SN) micrometastases, namely, American Joint Committee on Cancer (AJCC; eighth edition) stage IIIA disease, are presently controversial. The current study sought to identify high-risk SN-positive AJCC stage IIIA patients who are more likely to derive benefit from adjuvant systemic therapy.Patients were recruited from an intercontinental (Australia/Europe/North America) consortium of nine high-volume cancer centers. All were adult patients with pathologic stage pT1b/pT2a primary cutaneous melanomas who underwent SN biopsy between 2005 and 2020. Patient data, primary tumor and SN characteristics, and survival outcomes were analyzed.Three thousand six hundred seven patients were included. The median follow-up was 34 months. Pairwise disease comparison demonstrated no significant survival difference between N1a and N2a subgroups. Survival analysis identified a SN tumor deposit maximum dimension of 0.3 mm as the optimal cut point for stratifying survival. Five-year disease-specific survival rates were 80.3% and 94.1% for patients with SN metastatic tumor deposits ≥ 0.3 mm and < 0.3 mm, respectively (hazard ratio, 1.26 [1.11 to 1.44]; P < .0001). Similar findings were seen for overall disease-free and distant metastasis-free survival. There were no survival differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients. The newly identified high-risk (≥ 0.3 mm) subgroup comprised 271 (66.4%) of the AJCC IIIA cohort, whereas only 142 (34.8%) patients had SN tumor deposits > 1 mm in maximum dimension.Patients with AJCC IIIA melanoma with SN tumor deposits ≥ 0.3 mm in maximum dimension are at higher risk of disease progression and may benefit from adjuvant systemic therapy or enrollment into a clinical trial. Patients with SN deposits < 0.3 mm in maximum dimension can be managed similar to their SN-negative, AJCC IB counterparts, thereby avoiding regular radiological surveillance and more intensive follow-up.
  •  
50.
  • Ross, Owen A., et al. (författare)
  • Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
  • 2011
  • Ingår i: Lancet Neurology. - 1474-4465. ; 10:10, s. 898-908
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health.
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