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Sökning: WFRF:(Mitchell J. T.)

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341.
  • Chauhan, G., et al. (författare)
  • Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
  • 2019
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:5, s. E486-E503
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10(-8); and LINC00539/ZDHHC20, p = 5.82 x 10(-9). Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p([BI]) = 9.38 x 10(-25); p([SSBI]) = 5.23 x 10(-14) for hypertension), smoking (p([BI]) = 4.4 x 10(-10); p([SSBI]) = 1.2 x 10(-4)), diabetes (p([BI]) = 1.7 x 10(-8); p([SSBI]) = 2.8 x 10(-3)), previous cardiovascular disease (p([BI]) = 1.0 x 10(-18); p([SSBI]) = 2.3 x 10(-7)), stroke (p([BI]) = 3.9 x 10(-69); p([SSBI]) = 3.2 x 10(-24)), and MRI-defined white matter hyperintensity burden (p([BI]) = 1.43 x 10(-157); p([SSBI]) = 3.16 x 10(-106)), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
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342.
  • Kassebaum, Nicholas J., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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343.
  • Lozano, Rafael, et al. (författare)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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344.
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345.
  • Abdalla, H., et al. (författare)
  • Characterizing the γ-ray long-term variability of PKS2155 304 with HESS and Fermi-LAT
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : The European Southern Observatory. - 0004-6361 .- 1432-0746. ; 598
  • Tidskriftsartikel (refereegranskat)abstract
    • Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in the high (HE, 100MeV < E < 300 GeV) and very high energy (VHE, E > 200 GeV) gamma-ray domain. Over the course of similar to 9 yr of H. E. S. S. observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index βVHE = 1 .10+ 0.10-0,13) on timescales larger than one day. An analysis of similar to 5.5 yr of HE Fermi-LAT data gives consistent results (βHE = 1 .20+ 0.21-0.23, on timescales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior (beta similar to 2) seen on shorter timescales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.
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346.
  • Abdalla, H., et al. (författare)
  • Detection of variable VHE gamma-ray emission from the extra-galactic gamma-ray binary LMC P3
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 610
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Recently, the high-energy (HE, 0.1-100 GeV) gamma-ray emission from the object LMC P3 in the Large Magellanic Cloud (LMC) has been discovered to be modulated with a 10.3-day period, making it the first extra-galactic gamma-ray binary. Aims. This work aims at the detection of very-high-energy (VHE, >100 GeV) gamma-ray emission and the search for modulation of the VHE signal with the orbital period of the binary system. Methods. LMC P3 has been observed with the High Energy Stereoscopic System (H.E.S.S.); the acceptance-corrected exposure time is 100 h. The data set has been folded with the known orbital period of the system in order to test for variability of the emission. Results. VHE gamma-ray emission is detected with a statistical significance of 6.4 sigma. The data clearly show variability which is phase-locked to the orbital period of the system. Periodicity cannot be deduced from the H.E.S.S. data set alone. The orbit-averaged luminosity in the 1-10 TeV energy range is (1.4 +/- 0.2) x 10(35) erg s(-1). A luminosity of (5 +/- 1) x 10(35) erg s(-1) is reached during 20% of the orbit. HE and VHE gamma-ray emissions are anti-correlated. LMC P3 is the most luminous gamma-ray binary known so far.
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347.
  • Abdalla, H., et al. (författare)
  • Evidence of 100 TeV gamma-ray emission from HESS J1702-420 : A new PeVatron candidate
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The identification of PeVatrons, hadronic particle accelerators reaching the knee of the cosmic ray spectrum (few x 10(15) eV), is crucial to understand the origin of cosmic rays in the Galaxy. We provide an update on the unidentified source HESS J1702-420, a promising PeVatron candidate. Methods. We present new observations of HESS J1702-420 made with the High Energy Stereoscopic System (H.E.S.S.), and processed using improved analysis techniques. The analysis configuration was optimized to enhance the collection area at the highest energies. We applied a threedimensional likelihood analysis to model the source region and adjust non thermal radiative spectral models to the gamma-ray data. We also analyzed archival Fermi Large Area Telescope data to constrain the source spectrum at gamma-ray energies >10 GeV. Results. We report the detection of gamma-rays up to 100 TeV from a specific region of HESS J1702-420, which is well described by a new source component called HESS J1702-420A that was separated from the bulk of TeV emission at a 5:4 sigma confidence level. The power law gamma-ray spectrum of HESS J1702-420A extends with an index of Gamma = 1:53 +/- 0:19(stat) +/- 0:20(sys) and without curvature up to the energy band 64 113 TeV, in which it was detected by H.E.S.S. at a 4:0 sigma confidence level. This makes HESS J1702-420A a compelling candidate site for the presence of extremely high energy cosmic rays. With a flux above 2 TeV of (2:08 +/- 0:49(stat) +/- 0:62(sys)) x 10(-13) cm(-2) s(-1) and a radius of (0:06 +/- 0:02(stat) +/- 0:03(sys))degrees, HESS J1702-420A is outshone - below a few tens of TeV - by the companion HESS J1702-420B. The latter has a steep spectral index of = 2:62 +/- 0:10(stat) +/- 0:20(sys) and an elongated shape, and it accounts for most of the low-energy HESS J1702-420 flux. Simple hadronic and leptonic emission models can be well adjusted to the spectra of both components. Remarkably, in a hadronic scenario, the cut-o ff energy of the particle distribution powering HESS J1702-420A is found to be higher than 0:5 PeV at a 95% confidence level. Conclusions. For the first time, H.E.S.S. resolved two components with significantly di fferent morphologies and spectral indices, both detected at >5 sigma confidence level, whose combined emissions result in the source HESS J1702-420. We detected HESS J1702-420A at a 4:0 sigma confidence level in the energy band 64 113 TeV, which brings evidence for the source emission up to 100 TeV. In a hadronic emission scenario, the hard gamma-ray spectrum of HESS J1702-420A implies that the source likely harbors PeV protons, thus becoming one of the most solid PeVatron candidates detected so far in H.E.S.S. data. However, a leptonic origin of the observed TeV emission cannot be ruled out either.
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348.
  • Abdalla, H., et al. (författare)
  • HESS discovery of very high energy gamma-ray emission from PKS 0625-354
  • 2018
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 476:3, s. 4187-4198
  • Tidskriftsartikel (refereegranskat)abstract
    • PKS 0625-354 (z = 0.055) was observed with the four High Energy Stereoscopic System (H.E.S.S.) telescopes in 2012 during 5.5 h. The source was detected above an energy threshold of 200 GeV at a significance level of 6.1 sigma. No significant variability is found in these observations. The source is well described with a power-law spectrum with photon index Gamma = 2.84 +/- 0.50(stat) +/- 0.10(syst) and normalization (at E-0 = 1.0 TeV) N-0(E-0)=(0.58 +/- 0.22(stat) +/- 0.12(syst)) x 10(-12) TeV-1 cm(-2) s(-1). Multiwavelength data collected with Fermi-LAT, Swift-XRT, Swift-UVOT, ATOM and WISE are also analysed. Significant variability is observed only in the Fermi-LAT gamma-ray and Swift-XRT X-ray energy bands. Having a good multiwavelength coverage from radio to very high energy, we performed a broad-band modelling from two types of emission scenarios. The results from a one zone lepto-hadronic and a multizone leptonic models are compared and discussed. On the grounds of energetics, our analysis favours a leptonic multizone model. Models associated to the X-ray variability constraint support previous results, suggesting a BL Lac nature of PKS 0625-354 with, however, a large-scale jet structure typical of a radio galaxy.
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349.
  • Abdalla, H., et al. (författare)
  • HESS Limits on Linelike Dark Matter Signatures in the 100 GeV to 2 TeV Energy Range Close to the Galactic Center
  • 2016
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 117:15
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l = -1.5 degrees, b = 0 degrees and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. results. No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.
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350.
  • Abdalla, H., et al. (författare)
  • A search for very high-energy flares from the microquasars GRS 1915+105, Circinus X-1, and V4641 Sgr using contemporaneous HESS and RXTE observations
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Microquasars are potential gamma-ray emitters. Indications of transient episodes of gamma-ray emission were recently reported in at least two systems: Cyg X-1 and Cyg X-3. The identification of additional gamma-ray-emitting microquasars is required to better understand how gamma-ray emission can be produced in these systems. Aims. Theoretical models have predicted very high-energy (VHE) gamma-ray emission from microquasars during periods of transient outburst. Observations reported herein were undertaken with the objective of observing a broadband flaring event in the gamma-ray and X-ray bands. Methods. Contemporaneous observations of three microquasars, GRS 1915+105, Circinus X-1, and V4641 Sgr, were obtained using the High Energy Spectroscopic System (H.E.S.S.) telescope array and the Rossi X-ray Timing Explorer (RXTE) satellite. X-ray analyses for each microquasar were performed and VHE gamma-ray upper limits from contemporaneous H.E.S.S. observations were derived. Results. No significant gamma-ray signal has been detected in any of the three systems. The integral gamma-ray photon flux at the observational epochs is constrained to be I(>560 GeV) < 7.3 x 10(-13) cm(-2) S-1, I(>560 GeV) < 1.2 x 10-(12) cm s(-1), and I(>240 GeV) < 4.5 x 10(-12) cm(-2) s(-1) for GRS 1915+105, Circinus X-1, and V4641 Sgr, respectively. Conclusions. The gamma-ray upper limits obtained using H.E.S.S. are examined in the context of previous Cherenkov telescope observations of microquasars. The effect of intrinsic absorption is modelled for each target and found to have negligible impact on the flux of escaping gamma-rays. When combined with the X-ray behaviour observed using RXTE, the derived results indicate that if detectable VHE gamma-ray emission from microquasars is commonplace, then it is likely to be highly transient.
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