1. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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2. |
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3. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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4. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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5. |
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6. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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7. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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8. |
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9. |
- Lind, Lars, et al.
(author)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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In: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Journal article (peer-reviewed)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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10. |
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11. |
- Murari, A., et al.
(author)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Journal article (peer-reviewed)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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14. |
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15. |
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16. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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18. |
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19. |
- Ramdas, S., et al.
(author)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Journal article (peer-reviewed)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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20. |
- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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21. |
- Taddei, C, et al.
(author)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Journal article (peer-reviewed)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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22. |
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23. |
- Abe, H., et al.
(author)
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Gamma-ray observations of MAXI J1820+070 during the 2018 outburst
- 2022
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 517:4, s. 4736-4751
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Journal article (peer-reviewed)abstract
- MAXIJ1820+070 is a low-mass X-ray binary with a black hole (BH) as a compact object. This binary underwent an exceptionally bright X-ray outburst from 2018 March to October, showing evidence of a non-thermal particle population through its radio emission during this whole period. The combined results of 59.5 h of observations of the MAXI J1820+070 outburst with the H.E.S.S., MAGIC and VERITAS experiments at energies above 200 GeV are presented, together with Fermi-LAT data between 0.1 and 500 GeV, and multiwavelength observations from radio to X-rays. Gamma-ray emission is not detected from MAXI J1820+070, but the obtained upper limits and the multiwavelength data allow us to put meaningful constraints on the source properties under reasonable assumptions regarding the non-thermal particle population and the jet synchrotron spectrum. In particular, it is possible to show that, if a high-energy (HE) gamma-ray emitting region is present during the hard state of the source, its predicted flux should be at most a factor of 20 below the obtained Fermi-LAT upper limits, and closer to them for magnetic fields significantly below equipartition. During the state transitions, under the plausible assumption that electrons are accelerated up to similar to 500 GeV, the multiwavelength data and the gamma-ray upper limits lead consistently to the conclusion that a potential HE and very-HE gamma-ray emitting region should be located at a distance from the BH ranging between 10(11) and 10(13) cm. Similar outbursts from low-mass X-ray binaries might be detectable in the near future with upcoming instruments such as CTA.
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24. |
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25. |
- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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26. |
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27. |
- Abdalla, H., et al.
(author)
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Searching for TeV Gamma-Ray Emission from SGR 1935+2154 during Its 2020 X-Ray and Radio Bursting Phase
- 2021
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 919:2
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Journal article (peer-reviewed)abstract
- Magnetar hyperflares are the most plausible explanation for fast radio bursts (FRBs)-enigmatic powerful radio pulses with durations of several milliseconds and high brightness temperatures. The first observational evidence for this scenario was obtained in 2020 April when an FRB was detected from the direction of the Galactic magnetar and soft gamma-ray repeater SGR 1935+2154. The FRB was preceded by two gamma-ray outburst alerts by the BAT instrument aboard the Swift satellite, which triggered follow-up observations by the High Energy Stereoscopic System (H.E.S.S.). H.E.S.S. observed SGR 1935+2154 for 2 hr on 2020 April 28. The observations are coincident with X-ray bursts from the magnetar detected by INTEGRAL and Fermi-GBM, thus providing the first very high energy gamma-ray observations of a magnetar in a flaring state. High-quality data acquired during these follow-up observations allow us to perform a search for short-time transients. No significant signal at energies E > 0.6 TeV is found, and upper limits on the persistent and transient emission are derived. We here present the analysis of these observations and discuss the obtained results and prospects of the H.E.S.S. follow-up program for soft gamma-ray repeaters.
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28. |
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29. |
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30. |
- Abdalla, H., et al.
(author)
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Search for Dark Matter Annihilation Signals from Unidentified Fermi-LAT Objects with HESS
- 2021
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 918:1
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Journal article (peer-reviewed)abstract
- Cosmological N-body simulations show that Milky Way-sized galaxies harbor a population of unmerged dark matter (DM) subhalos. These subhalos could shine in gamma-rays and eventually be detected in gamma-ray surveys as unidentified sources. We performed a thorough selection among unidentified Fermi-Large Area Telescope Objects (UFOs) to identify them as possible tera-electron-volt-scale DM subhalo candidates. We search for very-high-energy (E greater than or similar to 100 GeV) gamma-ray emissions using H.E.S.S. observations toward four selected UFOs. Since no significant very-high-energy gamma-ray emission is detected in any data set of the four observed UFOs or in the combined UFO data set, strong constraints are derived on the product of the velocity-weighted annihilation cross section sigma v by the J factor for the DM models. The 95% confidence level observed upper limits derived from combined H.E.S.S. observations reach sigma vJ values of 3.7 x 10(-5) and 8.1 x 10(-6) GeV(2 )cm(-2 )s(-1) in the W (+) W (-) and tau (+) tau (-) channels, respectively, for a 1 TeV DM mass. Focusing on thermal weakly interacting massive particles, the H.E.S.S. constraints restrict the J factors to lie in the range 6.1 x 10(19)-2.0 x 10(21) GeV(2 )cm(-5) and the masses to lie between 0.2 and 6 TeV in the W (+) W (-) channel. For the tau (+) tau (-) channel, the J factors lie in the range 7.0 x 10(19)-7.1 x 10(20) GeV(2 )cm(-5) and the masses lie between 0.2 and 0.5 TeV. Assuming model-dependent predictions from cosmological N-body simulations on the J-factor distribution for Milky Way-sized galaxies, the DM models with masses >0.3 TeV for the UFO emissions can be ruled out at high confidence level.
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31. |
- Abdalla, H., et al.
(author)
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LMC N132D : A mature supernova remnant with a power-law gamma-ray spectrum extending beyond 8 TeV
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
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Journal article (peer-reviewed)abstract
- Context. Supernova remnants (SNRs) are commonly thought to be the dominant sources of Galactic cosmic rays up to the knee of the cosmic-ray spectrum at a few PeV. Imaging Atmospheric Cherenkov Telescopes have revealed young SNRs as very-high-energy (VHE, >100 GeV) gamma-ray sources, but for only a few SNRs the hadronic cosmic-ray origin of their gamma-ray emission is indisputably established. In all these cases, the gamma-ray spectra exhibit a spectral cutoff at energies much below 100 TeV and thus do not reach the PeVatron regime. Aims. The aim of this work was to achieve a firm detection for the oxygen-rich SNR LMC N132D in the VHE gamma-ray domain with an extended set of data, and to clarify the spectral characteristics and the localization of the gamma-ray emission from this exceptionally powerful gamma-ray-emitting SNR. Methods. We analyzed 252 h of High Energy Stereoscopic System (H.E.S.S.) observations towards SNR N132D that were accumulated between December 2004 and March 2016 during a deep survey of the Large Magellanic Cloud, adding 104 h of observations to the previously published data set to ensure a > 5 sigma detection. To broaden the gamma-ray spectral coverage required for modeling the spectral energy distribution, an analysis of Fermi-LAT Pass 8 data was also included. Results. We unambiguously detect N132D at VHE with a significance of 5.7 sigma. We report the results of a detailed analysis of its spectrum and localization based on the extended H.E.S.S. data set. The joint analysis of the extended H.E.S.S and Fermi-LAT data results in a spectral energy distribution in the energy range from 1.7 GeV to 14.8 TeV, which suggests a high luminosity of N132D at GeV and TeV energies. We set a lower limit on a gamma-ray cutoff energy of 8 TeV with a confidence level of 95%. The new gamma-ray spectrum as well as multiwavelength observations of N132D when compared to physical models suggests a hadronic origin of the VHE gamma-ray emission. Conclusions. SNR N132D is a VHE gamma-ray source that shows a spectrum extending to the VHE domain without a spectral cutoff at a few TeV, unlike the younger oxygen-rich SNR Cassiopeia A. The gamma-ray emission is best explained by a dominant hadronic component formed by diffusive shock acceleration. The gamma-ray properties of N132D may be affected by an interaction with a nearby molecular cloud that partially lies inside the 95% confidence region of the source position.
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32. |
- Winkler, TW, et al.
(author)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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33. |
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34. |
- Aharonian, F., et al.
(author)
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Detection of extended gamma-ray emission around the Geminga pulsar with HESS
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 673
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Journal article (peer-reviewed)abstract
- Geminga is an enigmatic radio-quiet gamma-ray pulsar located at a mere 250 pc distance from Earth. Extended very-high-energy gamma-ray emission around the pulsar was discovered by Milagro and later confirmed by HAWC, which are both water Cherenkov detector-based experiments. However, evidence for the Geminga pulsar wind nebula in gamma rays has long evaded detection by imaging atmospheric Cherenkov telescopes (IACTs) despite targeted observations. The detection of gamma-ray emission on angular scales greater than or similar to 2 degrees poses a considerable challenge for the background estimation in IACT data analysis. With recent developments in understanding the complementary background estimation techniques of water Cherenkov and atmospheric Cherenkov instruments, the H.E.S.S. IACT array can now confirm the detection of highly extended gamma-ray emission around the Geminga pulsar with a radius of at least 3 degrees in the energy range 0.5-40 TeV. We find no indications for statistically significant asymmetries or energy-dependent morphology. A flux normalisation of (2.8 +/- 0.7) x 10-12 cm-2 s-1 TeV-1 at 1 TeV is obtained within a 1 degrees radius region around the pulsar. To investigate the particle transport within the halo of energetic leptons around the pulsar, we fitted an electron diffusion model to the data. The normalisation of the diffusion coefficient obtained of D-0 = 7.6-1.2+1.5 x 1027 cm2 s-1, at an electron energy of 100 TeV, is compatible with values previously reported for the pulsar halo around Geminga, which is considerably below the Galactic average.
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35. |
- Aharonian, F., et al.
(author)
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Discovery of a radiation component from the Vela pulsar reaching 20 teraelectronvolts
- 2023
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In: Nature Astronomy. - : Nature Publishing Group. - 2397-3366. ; 7:11, s. 1341-1350
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Journal article (peer-reviewed)abstract
- Gamma-ray observations have established energetic isolated pulsars as outstanding particle accelerators and antimatter factories. However, many questions are still open regarding the acceleration and radiation processes involved, as well as the locations where they occur. The radiation spectra of all gamma-ray pulsars observed to date show strong cutoffs or a break above energies of a few gigaelectronvolts. Using the High Energy Stereoscopic System's Cherenkov telescopes, we discovered a radiation component from the Vela pulsar which emerges beyond this generic cutoff and extends up to energies of at least 20 teraelectronvolts. This is an order of magnitude larger than in the case of the Crab pulsar, the only other pulsar detected in the teraelectronvolt energy range. Our results challenge the state-of-the-art models for the high-energy emission of pulsars. Furthermore, they pave the way for investigating other pulsars through their multiteraelectronvolt emission, thereby imposing additional constraints on the acceleration and emission processes in their extreme energy limit. The H.E.S.S. gamma-ray observatory has observed gamma rays with energies of at least 20 TeV from a pulsar, an energy regime that is hard to reconcile with the existing theories of gamma-ray production for such objects.
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36. |
- Aharonian, F., et al.
(author)
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A deep spectromorphological study of the ϒ-ray emission surrounding the young massive stellar cluster Westerlund 1
- 2022
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In: Astronomy and Astrophysics. - : EPD Sciences. - 0004-6361 .- 1432-0746. ; 666
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Journal article (peer-reviewed)abstract
- Context. Young massive stellar clusters are extreme environments and potentially provide the means for efficient particle acceleration. Indeed, they are increasingly considered as being responsible for a significant fraction of cosmic rays (CRs) that are accelerated within the Milky Way. Westerlund 1, the most massive known young stellar cluster in our Galaxy, is a prime candidate for studying this hypothesis. While the very-high-energy gamma-ray source HESS J1646-458 has been detected in the vicinity of Westerlund 1 in the past, its association could not be firmly identified. Aims. We aim to identify the physical processes responsible for the gamma-ray emission around Westerlund 1 and thus to understand the role of massive stellar clusters in the acceleration of Galactic CRs better. Methods. Using 164 h of data recorded with the High Energy Stereoscopic System (H.E.S.S.), we carried out a deep spectromorphological study of the gamma-ray emission of HESS J1646-458. We furthermore employed H I and CO observations of the region to infer the presence of gas that could serve as target material for interactions of accelerated CRs. Results. We detected large-scale (similar to 2 degrees diameter) gamma-ray emission with a complex morphology, exhibiting a shell-like structure and showing no significant variation with gamma-ray energy. The combined energy spectrum of the emission extends to several tens of TeV, and it is uniform across the entire source region. We did not find a clear correlation of the gamma-ray emission with gas clouds as identified through H I and CO observations. Conclusions. We conclude that, of the known objects within the region, only Westerlund 1 can explain the majority of the gamma-ray emission. Several CR acceleration sites and mechanisms are conceivable and discussed in detail. While it seems clear that Westerlund 1 acts as a powerful particle accelerator, no firm conclusions on the contribution of massive stellar clusters to the flux of Galactic CRs in general can be drawn at this point.
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37. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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38. |
- Aharonian, F., et al.
(author)
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HESS J1809-193 : A halo of escaped electrons around a pulsar wind nebula?
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 672
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Journal article (peer-reviewed)abstract
- Context. HESS J1809-193 is an unassociated very-high-energy gamma-ray source located on the Galactic plane. While it has been connected to the nebula of the energetic pulsar PSR J1809-1917, supernova remnants and molecular clouds present in the vicinity also constitute possible associations. Recently, the detection of gamma-ray emission up to energies of similar to 100 TeV with the HAWC observatory has led to renewed interest in HESS J1809-193.Aims. We aim to understand the origin of the gamma-ray emission of HESS J1809-193.Methods. We analysed 93.2 h of data taken on HESS J1809-193 above 0.27 TeV with the High Energy Stereoscopic System (H.E.S.S.), using a multi-component, three-dimensional likelihood analysis. In addition, we provide a new analysis of 12.5 yr of Fermi-LAT data above 1 GeV within the region of HESS J1809-193. The obtained results are interpreted in a time-dependent modelling framework.Results. For the first time, we were able to resolve the emission detected with H.E.S.S. into two components: an extended component (modelled as an elongated Gaussian with a 1-sigma semi-major and semi-minor axis of similar to 0.62 degrees and similar to 0.35 degrees, respectively) that exhibits a spectral cutoff at similar to 13 TeV, and a compact component (modelled as a symmetric Gaussian with a 1-sigma radius of similar to 0.1 degrees) that is located close to PSR J1809-1917 and shows no clear spectral cutoff. The Fermi-LAT analysis also revealed extended gamma-ray emission, on scales similar to that of the extended H.E.S.S. component.Conclusions. Our modelling indicates that based on its spectrum and spatial extent, the extended H.E.S.S. component is likely caused by inverse Compton emission from old electrons that form a halo around the pulsar wind nebula. The compact component could be connected to either the pulsar wind nebula or the supernova remnant and molecular clouds. Due to its comparatively steep spectrum, modelling the Fermi-LAT emission together with the H.E.S.S. components is not straightforward.
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39. |
- Aharonian, F., et al.
(author)
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Time-resolved hadronic particle acceleration in the recurrent nova RS Ophiuchi
- 2022
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In: Science. - : American Association for Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6588, s. 77-80
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Journal article (peer-reviewed)abstract
- Recurrent novae are repeating thermonuclear explosions in the outer layers of white dwarfs, due to the accretion of fresh material from a binary companion. The shock generated when ejected material slams into the companion star's wind can accelerate particles. We report very-high-energy [VHE: greater than or similar to 100 giga-electron volts] gamma rays from the recurrent nova RS Ophiuchi, up to 1 month after its 2021 outburst, observed using the High Energy Stereoscopic System (H.E.S.S.). The temporal profile of VHE emission is similar to that of lower-energy giga-electron volt emission, indicating a common origin, with a 2-day delay in peak flux. These observations constrain models of time-dependent particle energization, favoring a hadronic emission scenario over the leptonic alternative. Shocks in dense winds provide favorable environments for efficient acceleration of cosmic rays to very high energies.
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40. |
- Chibueze, J. O., et al.
(author)
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A MeerKAT, e-MERLIN, HESS, and Swift search for persistent and transient emission associated with three localized FRBs
- 2022
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 515:1, s. 1365-1379
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Journal article (peer-reviewed)abstract
- We report on a search for persistent radio emission from the one-off fast radio burst (11(B) 20190714A, as well as from two repeating FRBs, 20190711A and 20171019A, using the MeerKAT radio telescope. For FRB 20171019A, we also conducted simultaneous observations with the High-Energy Stereoscopic System (H.E.S.S.) in very high-energy gamma rays and searched for signals in the ultraviolet, optical, and X-ray bands. For this FRB, we obtain a UV flux upper limit of 1.39 x 10(-16) erg cm(-2) s(-1) angstrom(-1), X-ray limit of similar to 6.6 x 10(-14) erg cm(-2) s(-1) and a limit on the very high energy gamma-ray flux Phi(E > 120 GeV) < 1.7 x 10(-12) erg cm(-2) S-1. We obtain a radio upper limit of similar to 15 mu Jy beam(-1) for persistent emission at the locations of both FRBs 20190711A and 20171019A with MeerKAT. However, we detected an almost unresolved (ratio of integrated flux to peak flux is similar to 1.7 beam) radio emission, where the synthesized beam size was similar to 8 arcsec size with a peak brightness of similar to 53 mu Jy beam(-1) at MeerKAT and similar to 86 mu Jy beam(-1) at e-MERLIN, possibly associated with FRB 20190714A at z = 0.2365. This represents the first detection of persistent continuum radio emission potentially associated with a (as-yet) non- repeating FRB. If the association is confirmed, one of the strongest remaining distinction between repeaters and non-repeaters would no longer be applicable. A parallel search for repeat bursts from these FRBs revealed no new detections down to a fluence of 0.08 Jy ms for a 1 ms duration burst.
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41. |
- Abdalla, H., et al.
(author)
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H.E.S.S. Follow-up Observations of Binary Black Hole Coalescence Events during the Second and Third Gravitational-wave Observing Runs of Advanced LIGO and Advanced Virgo
- 2021
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 923:1
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Journal article (peer-reviewed)abstract
- We report on the observations of four well-localized binary black hole (BBH) mergers by the High Energy Stereoscopic System (H.E.S.S.) during the second and third observing runs of Advanced LIGO and Advanced Virgo, O2 and O3. H.E.S.S. can observe 20 deg(2) of the sky at a time and follows up gravitational-wave (GW) events by "tiling" localization regions to maximize the covered localization probability. During O2 and O3, H.E.S.S. observed large portions of the localization regions, between 35% and 75%, for four BBH mergers (GW170814, GW190512_180714, GW190728_064510, and S200224ca). For these four GW events, we find no significant signal from a pointlike source in any of the observations, and we set upper limits on the very high energy (>100 GeV) gamma-ray emission. The 1-10 TeV isotropic luminosity of these GW events is below 10(45) erg s(-1) at the times of the H.E.S.S. observations, around the level of the low-luminosity GRB 190829A. Assuming no changes are made to how follow-up observations are conducted, H.E.S.S. can expect to observe over 60 GW events per year in the fourth GW observing run, O4, of which eight would be observable with minimal latency.
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42. |
- Aharonian, F., et al.
(author)
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Constraints on the Intergalactic Magnetic Field Using Fermi-LAT and HESS Blazar Observations
- 2023
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In: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 950:2
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Journal article (peer-reviewed)abstract
- Magnetic fields in galaxies and galaxy clusters are believed to be the result of the amplification of intergalactic seed fields during the formation of large-scale structures in the universe. However, the origin, strength, and morphology of this intergalactic magnetic field (IGMF) remain unknown. Lower limits on (or indirect detection of) the IGMF can be obtained from observations of high-energy gamma rays from distant blazars. Gamma rays interact with the extragalactic background light to produce electron-positron pairs, which can subsequently initiate electromagnetic cascades. The gamma-ray signature of the cascade depends on the IGMF since it deflects the pairs. Here we report on a new search for this cascade emission using a combined data set from the Fermi Large Area Telescope and the High Energy Stereoscopic System. Using state-of-the-art Monte Carlo predictions for the cascade signal, our results place a lower limit on the IGMF of B > 7.1 x 10(-16) G for a coherence length of 1 Mpc even when blazar duty cycles as short as 10 yr are assumed. This improves on previous lower limits by a factor of 2. For longer duty cycles of 10(4) (10(7)) yr, IGMF strengths below 1.8 x 10(-14) G (3.9 x 10(-14) G) are excluded, which rules out specific models for IGMF generation in the early universe.
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43. |
- Aharonian, F., et al.
(author)
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Search for the evaporation of primordial black holes with HESS
- 2023
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In: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :4
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Journal article (peer-reviewed)abstract
- Primordial Black Holes (PBHs) are hypothetical black holes predicted to have been formed from density fluctuations in the early Universe. PBHs with an initial mass around 1014-1015 g are expected to end their evaporation at present times in a burst of particles and very-high-energy (VHE) gamma rays. Those gamma rays may be detectable by the High Energy Stereoscopic System (H.E.S.S.), an array of imaging atmospheric Cherenkov telescopes. This paper reports on the search for evaporation bursts of VHE gamma rays with H.E.S.S., ranging from 10 to 120 seconds, as expected from the final stage of PBH evaporation and using a total of 4816 hours of observations. The most constraining upper limit on the burst rate of local PBHs is 2000 pc-3 yr-1 for a burst interval of 120 seconds, at the 95% confidence level. The implication of these measurements for PBH dark matter are also discussed.
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44. |
- Abdalla, H., et al.
(author)
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Search for Dark Matter Annihilation Signals in the HESS Inner Galaxy Survey
- 2022
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In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 129:11
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Journal article (peer-reviewed)abstract
- The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new observations from an unprecedented gamma-ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies (& GSIM;100 GeV) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant gamma-ray excess is found in the search region of the 2014-2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section (sigma v). Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach (sigma v) values of 3.7 x 10-26 cm3 s-1 for 1.5 TeV DM mass in the W+W- annihilation channel, and 1.2 x 10-26 cm3 s-1 for 0.7 TeV DM mass in the tau+tau- annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based gamma-ray observations thus probe (sigma v) values expected from thermal-relic annihilating TeV DM particles.
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45. |
- Aharonian, F., et al.
(author)
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HESS observations of the 2021 periastron passage of PSR B1259-63/LS 2883
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 687
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Journal article (peer-reviewed)abstract
- PSR B1259-63/LS 2883 is a gamma-ray binary system that hosts a pulsar in an eccentric orbit, with a 3.4 yr period, around an O9.5Ve star (LS 2883). At orbital phases close to periastron passages, the system radiates bright and variable non-thermal emission, for which the temporal and spectral properties of this emission are, for now, poorly understood. In this regard, very high-energy (VHE) emission is especially useful to study and constrain radiation processes and particle acceleration in the system. We report on an extensive VHE observation campaign conducted with the High Energy Stereoscopic System, comprised of approximately 100 h of data taken over five months, from t(p) - 24 days to t(p) + 127 days around the system's 2021 periastron passage (where t(p) is the time of periastron). We also present the timing and spectral analyses of the source. The VHE light curve in 2021 is consistent overall with the stacked light curve of all previous observations. Within the light curve, we report a VHE maximum at times coincident with the third X-ray peak first detected in the 2021 X-ray light curve. In the light curve - although sparsely sampled in this time period - we see no VHE enhancement during the second disc crossing. In addition, we see no correspondence to the 2021 GeV flare in the VHE light curve. The VHE spectrum obtained from the analysis of the 2021 dataset is best described by a power law of spectral index Gamma = 2.65 +/- 0.04(stat) +/- 0.04(sys), a value consistent with the spectral index obtained from the analysis of data collected with H.E.S.S. during the previous observations of the source. We report spectral variability with a difference of Delta Gamma = 0.56 +/- 0.18(stat) +/- 0.10(sys) at 95% confidence intervals, between sub-periods of the 2021 dataset. We also detail our investigation into X-ray/TeV and GeV/TeV flux correlations in the 2021 periastron passage. We find a linear correlation between contemporaneous flux values of X-ray and TeV datasets, detected mainly after t(p) + 25 days, suggesting a change in the available energy for non-thermal radiation processes. We detect no significant correlation between GeV and TeV flux points, within the uncertainties of the measurements, from similar to t(p) - 23 days to similar to t(p) + 126 days. This suggests that the GeV and TeV emission originate from different electron populations.
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46. |
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47. |
- Kang, E. Y., et al.
(author)
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MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma
- 2022
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In: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 480, s. 855-871
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Journal article (peer-reviewed)abstract
- Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naive HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naive tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naive HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
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48. |
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49. |
- Dankiewicz, Josef, et al.
(author)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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In: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Journal article (peer-reviewed)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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50. |
- Ehrenreich, D., et al.
(author)
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A full transit of v 2 Lupi d and the search for an exomoon in its Hill sphere with CHEOPS
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Journal article (peer-reviewed)abstract
- The planetary system around the naked-eye star v2 Lupi (HD 136352; TOI-2011) is composed of three exoplanets with masses of 4.7, 11.2, and 8.6 Earth masses (M⊕). The TESS and CHEOPS missions revealed that all three planets are transiting and have radii straddling the radius gap separating volatile-rich and volatile-poor super-earths. Only a partial transit of planet d had been covered so we re-observed an inferior conjunction of the long-period 8.6 M⊕ exoplanet v2 Lup d with the CHEOPS space telescope. We confirmed its transiting nature by covering its whole 9.1 h transit for the first time. We refined the planet transit ephemeris to P = 107.13610.0022+0.0019 days and Tc = 2459009.77590.0096+0.0101 BJDTDB, improving by ~40 times on the previously reported transit timing uncertainty. This refined ephemeris will enable further follow-up of this outstanding long-period transiting planet to search for atmospheric signatures or explore the planet s Hill sphere in search for an exomoon. In fact, the CHEOPS observations also cover the transit of a large fraction of the planet s Hill sphere, which is as large as the Earth s, opening the tantalising possibility of catching transiting exomoons. We conducted a search for exomoon signals in this single-epoch light curve but found no conclusive photometric signature of additional transiting bodies larger than Mars. Yet, only a sustained follow-up of v2 Lup d transits will warrant a comprehensive search for a moon around this outstanding exoplanet.
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