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2.
  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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5.
  • 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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6.
  • 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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9.
  • Abramowski, A., et al. (författare)
  • The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
  • Tidskriftsartikel (refereegranskat)abstract
    • The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
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10.
  • Drake, TM, et al. (författare)
  • Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
  • 2020
  • Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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11.
  • Acciari, V. A., et al. (författare)
  • Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
  • 2009
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
  • Tidskriftsartikel (refereegranskat)abstract
    • The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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13.
  • Patel, Y., et al. (författare)
  • Virtual Ontogeny of Cortical Growth Preceding Mental Illness
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299-313
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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  • Santangelo, James S., et al. (författare)
  • Global urban environmental change drives adaptation in white clover
  • 2022
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
  • Tidskriftsartikel (refereegranskat)abstract
    • Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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16.
  • Ageron, M., et al. (författare)
  • ANTARES : The first undersea neutrino telescope
  • 2011
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 656:1, s. 11-38
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given. (C) 2011 Elsevier B.V. All rights reserved.
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17.
  • Aguilar, J A, et al. (författare)
  • Study of large hemispherical photomultiplier tubes for the ANTARES neutrino telescope
  • 2005
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 555:1-2, s. 132-141
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES neutrino telescope, to be immersed depth in the Mediterranean Sea, will consist of a three-dimensional matrix of 900 large area photomultiplier tubes housed in pressure-resistant glass spheres. The selection of the optimal photomultiplier was a critical step for the project and required an intensive phase of tests and developments carried out in close collaboration with the main manufacturers worldwide. This paper provides an overview of the tests performed by the collaboration and describes in detail the features of the photomultiplier tube chosen for ANTARES. (c) 2005 Elsevier B.V. All rights reserved.
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18.
  • Aguilar, J A, et al. (författare)
  • Transmission of light in deep sea water at the site of the ANTARES neutrino telescope
  • 2005
  • Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 23:1, s. 131-155
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES neutrino telescope is a large photomultiplier array designed to detect neutrino-induced upward-going muons by their Cherenkov radiation. Understanding the absorption and scattering of light in the deep Mediterranean is fundamental to optimising the design and performance of the detector. This paper presents measurements of blue and UV light transmission at the ANTARES site taken between 1997 and 2000. The derived values for the scattering length and the angular distribution of particulate scattering were found to be highly correlated, and results are therefore presented in terms of an absorption length;,ab, and an effective scattering length lambda(sct)(eff). The values for blue (UV) light are found to be lambda(abs) similar or equal to 60(26) m, lambda(sct)(eff similar or equal to) 265(122) m, with significant (similar to15%) time variability. Finally, the results of ANTARES simulations showing the effect of these water properties on the anticipated performance of the detector are presented. (C) 2004 Elsevier B.V. All rights reserved.
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19.
  • Ageron, M., et al. (författare)
  • The ANTARES optical beacon system
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 578:3, s. 498-509
  • Tidskriftsartikel (refereegranskat)abstract
    • ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented. (C) 2007 Elsevier B.V. All rights reserved.
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20.
  • Aguilar, J. A., et al. (författare)
  • First results of the instrumentation line for the deep-sea ANTARES neutrino telescope
  • 2006
  • Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 26:4-5, s. 314-324
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2005, the ANTARES Collaboration deployed and operated at a depth of 2500 m a so-called Mini Instrumentation Line equipped with Optical Modules (MILOM) at the ANTARES site. The various data acquired during the continuous operation from April to December 2005 of the MILOM confirm the satisfactory performance of the Optical Modules, their front-end electronics and readout system. as well as the calibration devices of the detector. The in situ measurement of the Optical Module time response yields a resolution better than 0.5 ns. The performance of the acoustic positioning system, which enables the spatial reconstruction of the ANTARES detector with a precision of about 10 cm, is verified. These results demonstrate that with the full ANTARES neutrino telescope the design angular resolution of better than 0.3 degrees can be realistically achieved.
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21.
  • Aguilar, J. A., et al. (författare)
  • The data acquisition system for the ANTARES neutrino telescope
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 570:1, s. 107-116
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES neutrino telescope is being constructed in the Mediterranean Sea. It consists of a large three-dimensional array of photo-multiplier tubes. The data acquisition system of the detector takes care of the digitisation of the photo-multiplier tube signals, data transport, data filtering, and data storage. The detector is operated using a control program interfaced with all elements. The design and the implementation of the data acquisition system are described. (c) 2006 Elsevier B.V. All rights reserved.
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22.
  • Ahnen, M. L., et al. (författare)
  • Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies
  • 2016
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.
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23.
  • Aleksic, J., et al. (författare)
  • DETECTION OF VERY HIGH ENERGY gamma-RAY EMISSION FROM THE PERSEUS CLUSTER HEAD-TAIL GALAXY IC 310 BY THE MAGIC TELESCOPES
  • 2010
  • Ingår i: The Astrophysical Journal Letters. - 2041-8205. ; 723:2, s. l207-L212
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the detection with the MAGIC telescopes of very high energy (VHE) gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval 2008 November to 2010 February. The Fermi satellite has also detected this galaxy. The source is detected by MAGIC at a high statistical significance of 7.6 sigma in 20.6 hr of stereo data. The observed spectral energy distribution is flat with a differential spectral index of -2.00 +/- 0.14. The mean flux above 300 GeV, between 2009 October and 2010 February, (3.1 +/- 0.5) x 10(-12) cm(-2) s(-1), corresponds to (2.5 +/- 0.4)% of Crab Nebula units. Only an upper limit, of 1.9% of Crab Nebula units above 300 GeV, was obtained with the 2008 data. This, together with strong hints (>3 sigma) of flares in the middle of 2009 October and November, implies that the emission is variable. The MAGIC results favor a scenario with the VHE emission originating from the inner jet close to the central engine. More complicated models than a simple one-zone synchrotron self-Compton (SSC) scenario, e. g., multi-zone SSC, external Compton, or hadronic, may be required to explain the very flat spectrum and its extension over more than three orders of magnitude in energy.
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24.
  • Aleksic, J., et al. (författare)
  • PG 1553+113 : FIVE YEARS OF OBSERVATIONS WITH MAGIC
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 748:1, s. 46-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of five years (2005-2009) of MAGIC observations of the BL Lac object PG 1553+113 at very high energies (VHEs; E > 100 GeV). Power-law fits of the individual years are compatible with a steady mean photon index Gamma = 4.27 +/- 0.14. In the last three years of data, the flux level above 150 GeV shows a clear variability (probability of constant flux < 0.001%). The flux variations are modest, lying in the range from 4% to 11% of the Crab Nebula flux. Simultaneous optical data also show only modest variability that seems to be correlated with VHE gamma-ray variability. We also performed a temporal analysis of (all available) simultaneous Fermi/Large Area Telescope data of PG 1553+113 above 1 GeV, which reveals hints of variability in the 2008-2009 sample. Finally, we present a combination of the mean spectrum measured at VHEs with archival data available for other wavelengths. The mean spectral energy distribution can be modeled with a one-zone synchrotron self-Compton model, which gives the main physical parameters governing the VHE emission in the blazar jet.
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25.
  • Guerreiro, R., et al. (författare)
  • Heritability and genetic variance of dementia with Lewy bodies
  • 2019
  • Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 127, s. 492-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants. © 2019 Elsevier Inc.
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26.
  • Izadi, Z., et al. (författare)
  • Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
  • 2021
  • Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. OBJECTIVE To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age >= 18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. EXPOSURES Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. MAIN OUTCOMES AND MEASURES The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. RESULTS A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. CONCLUSIONS AND RELEVANCE In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.
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27.
  • Lopez-Isac, E, et al. (författare)
  • GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4955-
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.
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28.
  • Sparks, JA, et al. (författare)
  • Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry
  • 2021
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 80:9, s. 1137-1146
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).MethodsWe analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.ResultsOf 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.ConclusionsPeople with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.
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29.
  • Swayne, M.I., et al. (författare)
  • The EBLM Project– XI. Mass, radius, and effective temperature measurements for 23 M-dwarf companions to solar-type stars observed with CHEOPS
  • 2024
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 528:4, s. 5703-5722
  • Tidskriftsartikel (refereegranskat)abstract
    • Observations of low-mass stars have frequently shown a disagreement between observed stellar radii and radii predicted by theoretical stellar structure models. This ‘radius inflation’ problem could have an impact on both stellar and exoplanetary science. We present the final results of our observation programme with the CHaracterising ExOPlanet Satellite (CHEOPS) to obtain high-precision light curves of eclipsing binaries with low-mass stellar companions (EBLMs). Combined with the spectroscopic orbits of the solar-type companions, we can derive the masses, radii, and effective temperatures of 23 M-dwarf stars. We use the PYCHEOPS data analysis software to analyse their primary and secondary occultations. For all but one target, we also perform analyses with Transiting Exoplanet Survey Satellite (TESS) light curves for comparison. We have assessed the impact of starspot-induced variation on our derived parameters and account for this in our radius and effective temperature uncertainties using simulated light curves. We observe trends in inflation with both metallicity and orbital separation. We also observe a strong trend in the difference between theoretical and observational effective temperatures with metallicity. There is no such trend with orbital separation. These results are not consistent with the idea that the observed inflation in stellar radius combines with lower effective temperature to preserve the luminosity predicted by low-mass stellar models. Our EBLM systems provide high-quality and homogeneous measurements that can be used in further studies of radius inflation.
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32.
  • Ageron, M., et al. (författare)
  • Studies of a full-scale mechanical prototype line for the ANTARES neutrino telescope and tests of a prototype instrument for deep-sea acoustic measurements
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 581:3, s. 695-708
  • Tidskriftsartikel (refereegranskat)abstract
    • full-scale mechanical prototype line was deployed to a depth of 2500 m to test the leak tightness of the electronics containers and the pressure-resistant properties of an electromechanical cable under evaluation for use in the ANTARES deep-sea neutrino telescope. During a month-long immersion study, line parameter data were taken using miniature autonomous data loggers and shore-based optical time domain reflectometry. Details of the mechanical prototype line, the electromechanical cable and data acquisition are presented. Data taken during the immersion study revealed deficiencies in the pressure resistance of the electromechanical cable terminations at the entry points to the electronics containers. The improvements to the termination, which have been integrated into subsequent detection lines, are discussed. The line also allowed deep-sea acoustic measurements with a prototype hydrophone system. The technical setup of this system is described, and the first results of the data analysis are presented. (c) 2007 Elsevier B.V. All rights reserved.
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33.
  • Aleksic, J., et al. (författare)
  • Discovery of VHE gamma-rays from the blazar 1ES 1215+303 with the MAGIC telescopes and simultaneous multi-wavelength observations
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 544, s. A142-
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. We present the discovery of very high energy (VHE, E > 100 GeV) gamma-ray emission from the BL Lac object 1ES 1215+303 by the MAGIC telescopes and simultaneous multi-wavelength data in a broad energy range from radio to gamma-rays. Aims. We study the VHE gamma-ray emission from 1ES 1215+303 and its relation to the emissions in other wavelengths. Methods. Triggered by an optical outburst, MAGIC observed the source in 2011 January-February for 20.3 h. The target was monitored in the optical R-band by the KVA telescope that also performed optical polarization measurements. We triggered target of opportunity observations with the Swift satellite and obtained simultaneous and quasi-simultaneous data from the Fermi Large Area Telescope and from the Metsahovi radio telescope. We also present the analysis of older MAGIC data taken in 2010. Results. The MAGIC observations of 1ES 1215+303 carried out in 2011 January-February resulted in the first detection of the source at VHE with a statistical significance of 9.4 sigma. Simultaneously, the source was observed in a high optical and X-ray state. In 2010 the source was observed in a lower state in optical, X-ray, and VHE, while the GeV gamma-ray flux and the radio flux were comparable in 2010 and 2011. The spectral energy distribution obtained with the 2011 data can be modeled with a simple one zone SSC model, but it requires extreme values for the Doppler factor or the electron energy distribution.
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  • Obers, Niels A., et al. (författare)
  • Quantum gravity phenomenology at the dawn of the multi-messenger era—A review
  • 2022
  • Ingår i: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410 .- 1873-2224. ; 125
  • Forskningsöversikt (refereegranskat)abstract
    • The exploration of the universe has recently entered a new era thanks to the multi-messenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 “Quantum gravity phenomenology in the multi-messenger approach”, is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers.
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37.
  • Aleksic, J., et al. (författare)
  • MAGIC reveals a complex morphology within the unidentified gamma-ray source HESS J1857+026
  • 2014
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 571
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. HESS J1857+026 is an extended TeV gamma-ray source that was discovered by H. E. S. S. as part of its Galactic plane survey. Given its broadband spectral energy distribution and its spatial coincidence with the young energetic pulsar PSR J1856+0245, the source has been put forward as a pulsar wind nebula (PWN) candidate. MAGIC has performed follow-up observations aimed at mapping the source down to energies approaching 100 GeV in order to better understand its complex morphology. Methods. HESS J1857+026 was observed by MAGIC in 2010, yielding 29 h of good quality stereoscopic data that allowed us to map the source region in two separate ranges of energy. Results. We detected very-high-energy gamma-ray emission from HESS J1857+026 with a significance of 12 sigma above 150 GeV. The differential energy spectrum between 100 GeV and 13 TeV is described well by a power law function dN/dE = N-0(E/1TeV)(-Gamma) with N-0 = (5.37 +/- 0.44(stat) +/- 1.5(sys)) X 10(-12) (TeV-1 cm(-2) s(-1)) and Gamma = 2.16 +/- 0.07(stat) +/- 0.15(sys), which bridges the gap between the GeV emission measured by Fermi-LAT and the multi-TeV emission measured by H.E.S.S.. In addition, we present a detailed analysis of the energy-dependent morphology of this region. We couple these results with archival multiwavelength data and outline evidence in favor of a two-source scenario, whereby one source is associated with a PWN, while the other could be linked with a molecular cloud complex containing an HII region and a possible gas cavity.
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38.
  • Aleksic, J., et al. (författare)
  • Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes
  • 2015
  • Ingår i: Journal of High Energy Astrophysics. - : Elsevier BV. - 2214-4048 .- 2214-4056. ; 5-6, s. 30-38
  • Tidskriftsartikel (refereegranskat)abstract
    • The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between October 2009 and April 2011. Analysis of this data sample using the latest improvements in the MAGIC stereoscopic software provided an unprecedented precision of spectral and night-by-night light curve determination at gamma rays. We derived a differential spectrum with a single instrument from 50 GeV up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC results, combined with Fermi-LAT data, show a flat and broad Inverse Compton peak. The overall fit to the data between 1 GeV and 30 TeV is not well described by a log-parabola function. We find that a modified log-parabola function with an exponent of 2.5 instead of 2 provides a good description of the data (chi(2)(red) = 35/26). Using systematic uncertainties of the MAGIC and Fermi-LAT measurements we determine the position of the Inverse Compton peak to be at (53 +/- 3(stat)+ 31(syst)-13(syst)) GeV, which is the most precise estimation up to date and is dominated by the systematic effects. There is no hint of the integral flux variability on daily scales at energies above 300 GeV when systematic uncertainties are included in the flux measurement. We consider three state-of-the-art theoretical models to describe the overall spectral energy distribution of the Crab Nebula. The constant B-field model cannot satisfactorily reproduce the VHE spectral measurements presented in this work, having particular difficulty reproducing the broadness of the observed IC peak. Most probably this implies that the assumption of the homogeneity of the magnetic field inside the nebula is incorrect. On the other hand, the time-dependent 1D spectral model provides a good fit of the new VHE results when considering a 80 mu G magnetic field. However, it fails to match the data when including the morphology of the nebula at lower wavelengths.
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  • Aalbers, J., et al. (författare)
  • A next-generation liquid xenon observatory for dark matter and neutrino physics
  • 2023
  • Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 50:1
  • Forskningsöversikt (refereegranskat)abstract
    • The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector.
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  • Yeoh, SA, et al. (författare)
  • FACTORS ASSOCIATED WITH SEVERE COVID-19 OUTCOMES IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY: RESULTS FROM THE COVID-19 GLOBAL RHEUMATOLOGY ALLIANCE PHYSICIAN-REPORTED REGISTRY
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 165-166
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • There is a paucity of data in the literature about the outcome of patients with idiopathic inflammatory myopathy (IIM) who have been infected with SARS-CoV-2.ObjectivesTo investigate factors associated with severe COVID-19 outcomes in patients with IIM.MethodsData on demographics, number of comorbidities, region, COVID-19 time period, physician-reported disease activity, anti-rheumatic medication exposure at the clinical onset of COVID-19, and COVID-19 outcomes of IIM patients were obtained from the voluntary COVID-19 Global Rheumatology Alliance physician-reported registry of adults with rheumatic disease (from 17 March 2020 to 27 August 2021). An ordinal COVID-19 severity scale was used as primary outcome of interest, with each outcome category being mutually exclusive from the other:a) no hospitalization, b) hospitalization (and no death), or c) death. Odds ratios (OR) were estimated using multivariable ordinal logistic regression. In ordinal logistic regression, the effect size of a categorical predictor can be interpreted as the odds of being one level higher on the ordinal COVID-19 severity scale than the reference category.ResultsComplete hospitalization and death outcome data was available in 348 IIM cases. Mean age was 53 years, and 223 (64.1%) were female. Overall, 167/348 (48.0%) people were not hospitalized, 136/348 (39.1%) were hospitalized (and did not die), and 45/348 (12.9%) died. Older age (OR=1.59 per decade of life, 95%CI 1.32-1.93), male sex (OR=1.63, 95%CI 1.004-2.64; versus female), high disease activity (OR=4.05, 95%CI 1.29-12.76; versus remission), presence of two or more comorbidities (OR=2.39, 95%CI 1.22-4.68; versus none), prednisolone-equivalent dose >7.5 mg/day (OR=2.37, 95%CI 1.27-4.44; versus no glucocorticoid intake), and exposure to rituximab (OR=2.60, 95%CI 1.23-5.47; versus csDMARDs only) were associated with worse COVID-19 outcomes (Table 1).Table 1.Multivariable logistic regression analysis of factors associated with the ordinal COVID-19 severity outcomes. AZA, azathioprine; CI, confidence interval; combo, combination; CSA, ciclosporin; CYC, cyclophosphamide; DMARD, disease-modifying anti-rheumatic drug; b/tsDMARD, biologic/targeted synthetic DMARD, csDMARD, conventional synthetic DMARD; HCQ, hydroxychloroquine; IVIg, intravenous immunoglobulin; LEF, leflunomide; MMF, mycophenolate mofetil; mono, monotherapy; MTX, methotrexate; OR, odds ratio; Ref, reference; RTX, rituximab; SSZ, sulfasalazine; TAC, tacrolimus.VariableOR (95%CI)P-valueVariableOR (95%CI)P-valueAge (per decade)1.59 (1.32-1.93)<0.001ComorbiditiesMale sex1.63 (1.004-2.64)0.048NoneRefNAPrednisolone-equivalent doseOne1.46 (0.79-2.72)0.228NoneRefNATwo or more2.39 (1.22-4.68)0.011>0 to 7.5mg/day1.10 (0.57-2.11)0.779Physician-reported disease activity>7.5mg/day2.37 (1.27-4.44)0.007RemissionRefNAIVIg0.41 (0.15-1.16)0.093Low/moderate1.23 (0.67-2.28)0.504DMARDsHigh4.05 (1.29-12.76)0.018csDMARD only (mono or combi - HCQ, MTX, LEF, SSZ)RefNARegionNo DMARD1.84 (0.90-3.75)0.094EuropeRefNAb/tsDMARD mono or combi (except RTX)1.60 (0.49-5.26)0.435North America0.89 (0.49-1.61)0.694CSA/CYC/TAC mono or combi (except RTX or b/tsDMARDs)1.55 (0.52-4.58)0.429Other4.25 (2.21-8.16)<0.001AZA mono1.70 (0.69-4.19)0.249Time periodMMF mono1.22 (0.53-2.82)0.634Before 15 June 2020RefNAAZA/MMF combi (except RTX or b/tsDMARDs)0.71 (0.25-2.00)0.51716 June - 30 September 20200.58 (0.26-1.27)0.171RTX mono or combi2.60 (1.23-5.47)0.012After 1 October 20200.58 (0.35-0.95)0.032ConclusionThese are the first global registry data on the impact of COVID-19 on IIM patients. Older age, male gender, higher comorbidity burden, higher disease activity, higher glucocorticoid intake and rituximab exposure were associated with worse outcomes. These findings will inform risk stratification and management decisions for IIM patients.ReferencesNoneDisclosure of InterestsSu-Ann Yeoh: None declared, Milena Gianfrancesco: None declared, Saskia Lawson-Tovey: None declared, Kimme Hyrich Speakers bureau: AbbVie unrelated to this work, Grant/research support from: Pfizer, BMS, both unrelated to this work, Anja Strangfeld Speakers bureau: AbbVie, Celltrion, MSD, Janssen, Lilly, Roche, BMS, Pfizer, all unrelated to this work, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, all unrelated to this work, Grant/research support from: Amgen, Galapagos, Lilly, Pfizer, Sandoz, all unrelated to this work, Loreto Carmona: None declared, Elsa Mateus Consultant of: Boehringer Ingelheim Portugal, not related to this work, Martin Schaefer: None declared, Christophe Richez Speakers bureau: Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this abstract, Consultant of: Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this abstract, Eric Hachulla Speakers bureau: Johnson & Johnson, GlaxoSmithKline, Roche-Chugai, all unrelated to this work, Consultant of: Bayer, Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, all unrelated to this work, Grant/research support from: CSL Behring, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, all unrelated to this work, Marie Holmqvist: None declared, Carlo Alberto Scirè Grant/research support from: AbbVie, Lilly, both unrelated to this work, Rebecca Hasseli: None declared, Arundathi Jayatilleke: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Victor Pimentel-Quiroz: None declared, Monica Vasquez del Mercado: None declared, Samuel Katsuyuki Shinjo: None declared, Edgard Reis Neto: None declared, Laurindo Rocha Jr: None declared, Ana Carolina de Oliveira e Silva Montandon Speakers bureau: GSK, not related to this work, Paula Jordan: None declared, Emily Sirotich: None declared, Jonathan Hausmann Speakers bureau: Novartis, Biogen, Pfizer, not related to this work, Consultant of: Novartis, Biogen, Pfizer, not related to this work, Jean Liew Grant/research support from: Pfizer research grant, completed in 2021, not related to this work, Lindsay Jacobsohn: None declared, Monique Gore-Massy Speakers bureau: Aurinia Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, not related to this work, Consultant of: Aurinia Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, not related to this work, Paul Sufka: None declared, Rebecca Grainger Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and Cornerstones, all unrelated to this work, Consultant of: AbbVie, Novartis, both unrelated to this work, Suleman Bhana Shareholder of: Pfizer, Inc, Speakers bureau: AbbVie, Horizon, Novartis, and Pfizer, all unrelated to this work, Consultant of: AbbVie, Horizon, Novartis, and Pfizer, all unrelated to this work, Employee of: Pfizer, Inc, Zachary Wallace: None declared, Philip Robinson Speakers bureau: Abbvie, Janssen, Roche, GSK, Novartis, Lilly, UCB, all unrelated to this work, Paid instructor for: Lilly, unrelated to this work, Consultant of: GSK, Kukdong, Atom Biosciences, UCB, all unrelated to this work, Grant/research support from: Janssen, Pfizer, UCB and Novartis, all unrelated to this work, Jinoos Yazdany Consultant of: Aurinia, Astra Zeneca, Pfizer, all unrelated to this work, Grant/research support from: Astra Zeneca, Gilead, BMS Foundation, all unrelated to this work, Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this work., Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this work.
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50.
  • Aranha, M. R., et al. (författare)
  • Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome
  • 2023
  • Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:11, s. 4817-4827
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundBasal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. MethodsWe included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. ResultsIn DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. DiscussionBF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.
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