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3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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4. |
- Acciari, V. A., et al.
(författare)
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Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
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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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5. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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6. |
- Abramowski, A., et al.
(författare)
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The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
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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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7. |
- Abramowski, A., et al.
(författare)
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Simultaneous multi-wavelength campaign on PKS 2005-489 in a high state
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533, s. A110-
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Tidskriftsartikel (refereegranskat)abstract
- The high-frequency peaked BL Lac object PKS 2005-489 was the target of a multi-wavelength campaign with simultaneous observations in the TeV gamma-ray (H.E.S.S.), GeV gamma-ray (Fermi/LAT), X-ray (RXTE, Swift), UV (Swift) and optical (ATOM, Swift) bands. This campaign was carried out during a high flux state in the synchrotron regime. The flux in the optical and X-ray bands reached the level of the historical maxima. The hard GeV spectrum observed with Fermi/LAT connects well to the very high energy (VHE, E > 100 GeV) spectrum measured with H.E.S.S. with a peak energy between similar to 5 and 500 GeV. Compared to observations with contemporaneous coverage in the VHE and X-ray bands in 2004, the X-ray flux was similar to 50 times higher during the 2009 campaign while the TeV gamma-ray flux shows marginal variation over the years. The spectral energy distribution during this multi-wavelength campaign was fit by a one zone synchrotron self-Compton model with a well determined cutoff in X-rays. The parameters of a one zone SSC model are inconsistent with variability time scales. The variability behaviour over years with the large changes in synchrotron emission and small changes in the inverse Compton emission does not warrant an interpretation within a one-zone SSC model despite an apparently satisfying fit to the broadband data in 2009.
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8. |
- Vos, Theo, et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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9. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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10. |
- Kassebaum, Nicholas J., et al.
(författare)
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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
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
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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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11. |
- Lozano, Rafael, et al.
(författare)
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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
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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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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12. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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13. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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14. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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15. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)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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16. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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17. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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18. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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19. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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20. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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21. |
- Abramowski, A., et al.
(författare)
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Discovery of VHE gamma-ray emission and multi-wavelength observations of the BL Lacertae object 1RXSJ101015.9-311909
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 542, s. A94-
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Tidskriftsartikel (refereegranskat)abstract
- 1RXS J101015.9-311909 is a galaxy located at a redshift of z = 0.14 hosting an active nucleus (called AGN) belonging to the class of bright BL Lac objects. Observations at high (HE, E > 100 MeV) and very high (VHE, E > 100 GeV) energies provide insights into the origin of very energetic particles present in such sources and the radiation processes at work. We report on results from VHE observations performed between 2006 and 2010 with the H. E. S. S. instrument, an array of four imaging atmospheric Cherenkov telescopes. H. E. S. S. data have been analysed with enhanced analysis methods, making the detection of faint sources more significant. VHE emission at a position coincident with 1RXS J101015.9-311909 is detected with H. E. S. S. for the first time. In a total good-quality livetime of about 49 h, we measure 263 excess counts, corresponding to a significance of 7.1 standard deviations. The photon spectrum above 0.2 TeV can be described by a power-law with a photon index of Gamma = 3.08 +/- 0.42(stat) +/- 0.20(sys). The integral flux above 0.2 TeV is about 0.8% of the flux of the Crab nebula and shows no significant variability over the time reported. In addition, public Fermi/LAT data are analysed to search for high energy emission from the source. The Fermi/LAT HE emission in the 100 MeV to 200 GeV energy range is significant at 8.3 standard deviations in the chosen 25-month dataset. UV and X-ray contemporaneous observations with the Swift satellite in May 2007 are also reported, together with optical observations performed with the atom telescope located at the H. E. S. S. site. Swift observations reveal an absorbed X-ray flux of F(0.3-7) keV = 1.04(-0.05)(+0.04) x 10(-11) erg cm(-2) s(-1) in the 0.3-7 keV range. Finally, all the available data are used to study the multi-wavelength properties of the source. The spectral energy distribution (SED) can be reproduced using a simple one-zone Synchrotron Self Compton (SSC) model with emission from a region with a Doppler factor of 30 and a magnetic field between 0.025 and 0.16 G. These parameters are similar to those obtained for other sources of this type.
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22. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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23. |
- Abramowski, A., et al.
(författare)
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Revisiting the Westerlund 2 field with the HESS telescope array
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 525, s. A46-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Previous observations with the HESS telescope array revealed the existence of extended very-high-energy (VHE; E > 100 GeV) gamma-ray emission, HESS J1023-575, coincident with the young stellar cluster Westerlund 2. At the time of discovery, the origin of the observed emission was not unambiguously identified, and follow-up observations have been performed to further investigate the nature of this gamma-ray source. Methods. The Carina region towards the open cluster Westerlund 2 has been re-observed, increasing the total exposure to 45.9 h. The combined dataset includes 33 h of new data and now permits a search for energy-dependent morphology and detailed spectroscopy. Results. A new, hard spectrum VHE gamma-ray source, HESS J1026-582, was discovered with a statistical significance of 7 sigma. It is positionally coincident with the Fermi LAT pulsar PSRJ1028-5819. The positional coincidence and radio/gamma-ray characteristics of the LAT pulsar favors a scenario where the TeV emission originates from a pulsar wind nebula. The nature of HESS J1023-575 is discussed in light of the deep HESS observations and recent multi-wavelength discoveries, including the Fermi LAT pulsar PSRJ1022-5746 and giant molecular clouds in the region. Despite the improved VHE dataset, a clear identification of the object responsible for the VHE emission from HESS J1023-575 is not yet possible, and contribution from the nearby high-energy pulsar and/or the open cluster remains a possibility.
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24. |
- Acero, F., et al.
(författare)
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First detection of VHE gamma-rays from SN 1006 by HESS
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 516, s. A62-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Recent theoretical predictions of the lowest very high energy (VHE) luminosity of SN 1006 are only a factor 5 below the previously published HESS upper limit, thus motivating further in-depth observations of this source. Methods. Deep observations at VHE energies (above 100 GeV) were carried out with the high energy stereoscopic system (HESS) of Cherenkov Telescopes from 2003 to 2008. More than 100 h of data have been collected and subjected to an improved analysis procedure. Results. Observations resulted in the detection of VHE gamma-rays from SN 1006. The measured gamma-ray spectrum is compatible with a power-law, the flux is of the order of 1% of that detected from the Crab Nebula, and is thus consistent with the previously established HESS upper limit. The source exhibits a bipolar morphology, which is strongly correlated with non-thermal X-rays. Conclusions. Because the thickness of the VHE-shell is compatible with emission from a thin rim, particle acceleration in shock waves is likely to be the origin of the gamma-ray signal. The measured flux level can be accounted for by inverse Compton emission, but a mixed scenario that includes leptonic and hadronic components and takes into account the ambient matter density inferred from observations also leads to a satisfactory description of the multi-wavelength spectrum.
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25. |
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26. |
- Abramowski, A., et al.
(författare)
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A multiwavelength view of the flaring state of PKS 2155-304 in 2006
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539, s. A149-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Multiwavelength (MWL) observations of the blazar PKS 2155-304 during two weeks in July and August 2006, the period when two exceptional flares at very high energies (VHE, E greater than or similar to 100 GeV) occurred, provide a detailed picture of the evolution of its emission. The complete data set from this campaign is presented, including observations in VHE gamma-rays (H.E.S. S.), X-rays (RXTE, Chandra, Swift XRT), optical (Swift UVOT, Bronberg, Watcher, ROTSE), and in the radio band (NRT, HartRAO, ATCA). Optical and radio light curves from 2004 to 2008 are compared to the available VHE data from this period, to put the 2006 campaign into the context of the long-term evolution of the source. Aims. The data set offers a close view of the evolution of the source on different time scales and yields new insights into the properties of the emission process. The predictions of synchrotron self-Compton (SSC) scenarios are compared to the MWL data, with the aim of describing the dominant features in the data down to the hour time scale. Methods. The spectral variability in the X-ray and VHE bands is explored and correlations between the integral fluxes at different wavelengths are evaluated. SSC modelling is used to interpret the general trends of the varying spectral energy distribution. Results. The X-ray and VHE gamma-ray emission are correlated during the observed high state of the source, but show no direct connection with longer wavelengths. The long-term flux evolution in the optical and radio bands is found to be correlated and shows that the source reaches a high state at long wavelengths after the occurrence of the VHE flares. Spectral hardening is seen in the Swift XRT data. Conclusions. The nightly averaged high-energy spectra of the non-flaring nights can be reproduced by a stationary one-zone SSC model, with only small variations in the parameters. The spectral and flux evolution in the high-energy band during the night of the second VHE flare is modelled with multi-zone SSC models, which can provide relatively simple interpretations for the hour time-scale evolution of the high-energy emission, even for such a complex data set. For the first time in this type of source, a clear indication is found for a relation between high activity at high energies and a long-term increase in the low frequency fluxes.
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27. |
- Abramowski, A., et al.
(författare)
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Constraints on the gamma-ray emission from the cluster-scale AGN outburst in the Hydra A galaxy cluster
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. In some galaxy clusters, powerful active galactic nuclei (AGN) have blown bubbles with cluster scale extent into the ambient medium. The main pressure support of these bubbles is not known to date, but cosmic rays are a viable possibility. For such a scenario copious gamma-ray emission is expected as a tracer of cosmic rays from these systems. Aims. Hydra A, the closest galaxy cluster hosting a cluster scale AGN outburst, located at a redshift of 0.0538, is investigated for being a gamma-ray emitter with the High Energy Stereoscopic System (H.E.S.S.) array and the Fermi Large Area Telescope (Fermi-LAT). Methods. Data obtained in 20.2 h of dedicated H. E. S. S. observations and 38 months of Fermi-LAT data, gathered by its usual all-sky scanning mode, have been analyzed to search for a gamma-ray signal. Results. No signal has been found in either data set. Upper limits on the gamma-ray flux are derived and are compared to models. These are the first limits on gamma-ray emission ever presented for galaxy clusters hosting cluster scale AGN outbursts. Conclusions. The non-detection of Hydra A in gamma-rays has important implications on the particle populations and physical conditions inside the bubbles in this system. For the case of bubbles mainly supported by hadronic cosmic rays, the most favorable scenario, which involves full mixing between cosmic rays and embedding medium, can be excluded. However, hadronic cosmic rays still remain a viable pressure support agent to sustain the bubbles against the thermal pressure of the ambient medium. The largest population of highly-energetic electrons, which are relevant for inverse-Compton gamma-ray production is found in the youngest inner lobes of Hydra A. The limit on the inverse-Compton gamma-ray flux excludes a magnetic field below half of the equipartition value of 16 mu G in the inner lobes.
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28. |
- Abramowski, A., et al.
(författare)
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Discovery of gamma-ray emission from the extragalactic pulsar wind nebula N 157B with HESS
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. Article ID: L2-
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Tidskriftsartikel (refereegranskat)abstract
- We present the significant detection of the first extragalactic pulsar wind nebula (PWN) detected in gamma rays, N 157B, located in the large Magellanic Cloud (LMC). Pulsars with high spin-down luminosity are found to power energised nebulae that emit gamma rays up to energies of several tens of TeV. N 157B is associated with PSR J0537-6910, which is the pulsar with the highest known spin-down luminosity. The High Energy Stereoscopic System telescope array observed this nebula on a yearly basis from 2004 to 2009 with a dead-time corrected exposure of 46 h. The gamma-ray spectrum between 600 GeV and 12 TeV is well-described by a pure power-law with a photon index of 2.8 +/- 0.2(stat) +/- 0.3(syst) and a normalisation at 1 TeV of (8.2 +/- 0.8(stat) +/- 2.5(syst)) x 10(-13) cm(-2) s(-1) TeV-1. A leptonic multi-wavelength model shows that an energy of about 4 x 10(49) erg is stored in electrons and positrons. The apparent efficiency, which is the ratio of the TeV gamma-ray luminosity to the pulsar's spin-down luminosity, 0.08% +/- 0.01%, is comparable to those of PWNe found in the Milky Way. The detection of a PWN at such a large distance is possible due to the pulsar's favourable spin-down luminosity and a bright infrared photon-field serving as an inverse-Compton-scattering target for accelerated leptons. By applying a calorimetric technique to these observations, the pulsar's birth period is estimated to be shorter than 10 ms.
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29. |
- Abramowski, A., et al.
(författare)
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HESS observations of the Carina nebula and its enigmatic colliding wind binary Eta Carinae
- 2012
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 424:1, s. 128-135
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Tidskriftsartikel (refereegranskat)abstract
- The massive binary system Eta Carinae and the surrounding H ii complex, the Carina nebula, are potential particle acceleration sites from which very high energy (VHE; E= 100 GeV) ?-ray emission could be expected. This paper presents data collected during VHE ?-ray observations with the HESS telescope array from 2004 to 2010, which cover a full orbit of Eta Carinae. In the 33.1-h data set no hint of significant ?-ray emission from Eta Carinae has been found and an upper limit on the ?-ray flux of (99 per cent confidence level) is derived above the energy threshold of 470 GeV. Together with the detection of high energy (HE; 0.1 =E= 100 GeV) ?-ray emission by the Fermi Large Area Telescope up to 100 GeV, and assuming a continuation of the average HE spectral index into the VHE domain, these results imply a cut-off in the ?-ray spectrum between the HE and VHE ?-ray range. This could be caused either by a cut-off in the accelerated particle distribution or by severe ?? absorption losses in the wind collision region. Furthermore, the search for extended ?-ray emission from the Carina nebula resulted in an upper limit on the ?-ray flux of (99 per cent confidence level). The derived upper limit of 23 on the cosmic ray enhancement factor is compared with results found for the old-age mixed-morphology supernova remnant W28.
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30. |
- Abramowski, A., et al.
(författare)
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Identification of HESS J1303-631 as a pulsar wind nebula through gamma-ray, X-ray, and radio observations
- 2012
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 548, s. A46-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The previously unidentified very high-energy (VHE; E > 100 GeV) gamma-ray source HESS J1303-631, discovered in 2004, is re-examined including new data from the H. E. S. S. Cherenkov telescope array in order to identify this object. Archival data from the XMM-Newton X-ray satellite and from the PMN radio survey are also examined. Methods. Detailed morphological and spectral studies of VHE gamma-ray emission as well as of the XMM-Newton X-ray data are performed. Radio data from the PMN survey are used as well to construct a leptonic model of the source. The gamma-ray and X-ray spectra and radio upper limit are used to construct a one zone leptonic model of the spectral energy distribution (SED). Results. Significant energy-dependent morphology of the gamma-ray source is detected with high-energy emission (E > 10 TeV) positionally coincident with the pulsar PSR J1301-6305 and lower energy emission (E < 2 TeV) extending similar to 0.4 degrees to the southeast of the pulsar. The spectrum of the VHE source can be described with a power-law with an exponential cut-off N-0 = (5.6 +/- 0.5) x 10(-12) TeV-1 cm(-2) s(-1), Gamma = 1.5 +/- 0.2) and E-cut = (7.7 +/- 2.2) TeV. The pulsar wind nebula (PWN) is also detected in X-rays, extending similar to 2-3' from the pulsar position towards the center of the gamma-ray emission region. A potential radio counterpart from the PMN survey is also discussed, showing a hint for a counterpart at the edge of the X-ray PWN trail and is taken as an upper limit in the SED. The extended X-ray PWN has an unabsorbed flux of F2-10 (keV) similar to 1.6(-0.4)(+0.2) x 10(-13) erg cm(-2)s(-1) and is detected at a significance of 6.5 sigma. The SED is well described by a one zone leptonic scenario which, with its associated caveats, predicts a very low average magnetic field for this source. Conclusions. Significant energy-dependent morphology of this source, as well as the identification of an associated X-ray PWN from XMM-Newton observations enable identification of the VHE source as an evolved PWN associated to the pulsar PSR J1301-6305. This identification is supported by the one zone leptonic model, which suggests that the energetics of the gamma-ray and X-ray radiation are such that they may have a similar origin in the pulsar nebula. However, the large discrepancy in emission region sizes and the low level of synchrotron radiation suggest a multi-population leptonic nature. The low implied magnetic field suggests that the PWN has undergone significant expansion. This would explain the low level of synchrotron radiation and the difficulty in detecting counterparts at lower energies, the reason this source was originally classified as a "dark" VHE gamma-ray source.
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31. |
- Abramowski, A., et al.
(författare)
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Multi-wavelength observations of H 2356-309
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 516, s. A56-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The properties of the broad-band emission from the high-frequency peaked BL Lac H 2356-309 (z = 0.165) are investigated. Methods. Very high energy (VHE; E > 100 GeV) observations of H 2356-309 were performed with the High Energy Stereoscopic System (HESS) from 2004 through 2007. Simultaneous optical/UV and X-ray observations were made with the XMM-Newton satellite on June 12/13 and June 14/15, 2005. NRT radio observations were also contemporaneously performed in 2005. ATOM optical monitoring observations were also made in 2007. Results. A strong VHE signal, similar to 13 sigma total, was detected by HESS after the four years HESS observations (116.8 h live time). The integral flux above 240 GeV is I(> 240 GeV) = (3.06 +/- 0.26(stat) +/- 0.61(syst)) x 10(-12) cm(-2) s(-1), corresponding to similar to 1.6% of the flux observed from the Crab Nebula. A time-averaged energy spectrum is measured from 200 GeV to 2 TeV and is characterized by a power law (photon index of Gamma = 3.06 +/- 0.15(stat) +/- 0.10(syst)). Significant small-amplitude variations in the VHE flux from H 2356-309 are seen on time scales of months and years, but not on shorter time scales. No evidence for any variations in the VHE spectral slope are found within these data. The XMM-Newton X-ray measurements show a historically low X-ray state, characterized by a hard, broken-power-law spectrum on both nights. Conclusions. The broad-band spectral energy distribution (SED) of the blazar can be adequately fit using a simple one-zone synchrotron self-Compton (SSC) model. In the SSC scenario, higher VHE fluxes could be expected in the future since the observed X-ray flux is at a historically low level.
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32. |
- Abramowski, A., et al.
(författare)
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Spectral Analysis and Interpretation of the γ-ray Emission from the Starburst Galaxy NGC 253
- 2012
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 757:2, s. 158-
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Tidskriftsartikel (refereegranskat)abstract
- Very high energy (VHE; E >= 100 GeV) and high-energy (HE; 100 MeV <= E <= 100 GeV) data from gamma-ray observations performed with the H. E. S. S. telescope array and the Fermi-LAT instrument, respectively, are analyzed in order to investigate the non-thermal processes in the starburst galaxy NGC 253. The VHE gamma-ray data can be described by a power law in energy with differential photon index Gamma = 2.14 +/- 0.18(stat) +/- 0.30(sys) and differential flux normalization at 1 TeV of F-0 = (9.6 +/- 1.5(stat)(+5.7, -2.9)(sys)) x 10(-14) TeV-1 cm(-2) s(-1). A power-law fit to the differential HE gamma-ray spectrum reveals a photon index of Gamma = 2.24 +/- 0.14(stat) +/- 0.03(sys) and an integral flux between 200 MeV and 200 GeV of F(0.2-200 GeV) = (4.9 +/- 1.0(stat) +/- 0.3(sys)) x 10(-9) cm(-2) s(-1). No evidence for a spectral break or turnover is found over the dynamic range of both the LAT instrument and the H.E.S.S. experiment: a combined fit of a power law to the HE and VHE gamma-ray data results in a differential photon index Gamma = 2.34 +/- 0.03 with a p-value of 30%. The gamma-ray observations indicate that at least about 20% of the energy of the cosmic rays (CRs) capable of producing hadronic interactions is channeled into pion production. The smooth alignment between the spectra in the HE and VHE gamma-ray domain suggests that the same transport processes dominate in the entire energy range. Advection is most likely responsible for charged particle removal from the starburst nucleus from GeV to multiple TeV energies. In a hadronic scenario for the gamma-ray production, the single overall power-law spectrum observed would therefore correspond to the mean energy spectrum produced by the ensemble of CR sources in the starburst region.
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33. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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34. |
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35. |
- Abramowski, A., et al.
(författare)
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Detection of very-high-energy gamma-ray emission from the vicinity of PSR B1706-44 and G 343.1-2.3 with HESS
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 528, s. A143-
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Tidskriftsartikel (refereegranskat)abstract
- The gamma-ray pulsar PSR B1706-44 and the adjacent supernova remnant (SNR) candidate G 343.1-2.3 were observed by H. E. S. S. during a dedicated observation campaign in 2007. As a result of this observation campaign, a new source of very-high-energy (VHE; E > 100 GeV) gamma-ray emission, H.E.S.S. J1708-443, was detected with a statistical significance of 7 sigma, although no significant point-like emission was detected at the position of the energetic pulsar itself. In this paper, the morphological and spectral analyses of the newly-discovered TeV source are presented. The centroid of H. E. S. S. J1708-443 is considerably offset from the pulsar and located near the apparent center of the SNR, at alpha(J2000) = 17(h)08(m)11(s) +/- 17(s) and delta(J2000) = -44 degrees 20' +/- 4'. The source is found to be significantly more extended than the H. E. S. S. point spread function (similar to 0.1 degrees), with an intrinsic Gaussian width of 0.29 degrees +/- 0.04 degrees. Its integral flux between 1 and 10 TeV is similar to 3.8 x 10(-1)2 ph cm(-2) s(-1), equivalent to 17% of the Crab Nebula flux in the same energy range. The measured energy spectrum is well-fit by a power law with a relatively hard photon index Gamma = 2.0 +/- 0.1(stat) +/-0.2(sys). Additional multi-wavelength data, including 330 MHz VLA observations, were used to investigate the VHE gamma-ray source's possible associations with the pulsar wind nebula of PSR B1706-44 and/or with the complex radio structure of the partial shell-type SNR G 343.1-2.3.
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36. |
- Abramowski, A., et al.
(författare)
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Discovery of VHE emission towards the Carina arm region with the HESS telescope array : HESSJ1018-589
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541, s. A5-
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Tidskriftsartikel (refereegranskat)abstract
- The Carina arm region, containing the supernova remnant SNRG284.3-1.8, the high-energy (HE; E > 100 MeV) binary 1FGL J1018.6-5856 and the energetic pulsar PSRJ1016-5857 and its nebula, has been observed with the H. E. S. S. telescope array. The observational coverage of the region in very-high-energy (VHE; E > 0.1TeV) gamma-rays benefits from deep exposure (40 h) of the neighboring open cluster Westerlund 2. The observations have revealed a new extended region of VHE gamma-ray emission. The new VHE source HESS J1018-589 shows a bright, point-like emission region positionally coincident with SNRG284.3-1.8 and 1FGL J1018.6-5856 and a diffuse extension towards the direction of PSRJ1016-5857. A soft (Gamma = 2.7 +/- 0.5(stat)) photon index, with a differential flux at 1 TeV of N-0 = (4.2 +/- 1.1) x 10(-13) TeV-1 cm(-2) s(-1) is found for the point-like source, whereas the total emission region including the diffuse emission region is well fit by a power-law function with spectral index Gamma = 2.9 +/- 0.4(stat) and differential flux at 1 TeV of N-0 = (6.8 +/- 1.6) x 10(-1)3 TeV-1 cm(-2) s(-1). This H. E. S. S. detection motivated follow-up X-ray observations with the XMM-Newton satellite to investigate the origin of the VHE emission. The analysis of the XMM-Newton data resulted in the discovery of a bright, non-thermal point-like source (XMMU J101855.4-58564) with a photon index of Gamma = 1.65 +/- 0.08 in the center of SNRG284.3-1.8, and a thermal, extended emission region coincident with its bright northern filament. The characteristics of this thermal emission are used to estimate the plasma density in the region as n approximate to 0.5 cm(-3) (2.9 kpc/d)(2). The position of XMMUJ101855.4-58564 is compatible with the position reported by the Fermi-LAT collaboration for the binary system 1FGL J1018.6-5856 and the variable Swift XRT source identified with it. The new X-ray data are used alongside archival multi-wavelength data to investigate the relationship between the VHE gamma-ray emission from HESS J1018-589 and the various potential counterparts in the Carina arm region.
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37. |
- Abramowski, A., et al.
(författare)
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Search for Lorentz Invariance breaking with a likelihood fit of the PKS 2155-304 flare data taken on MJD 53944
- 2011
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:9, s. 738-747
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Tidskriftsartikel (refereegranskat)abstract
- Several models of Quantum Gravity predict Lorentz Symmetry breaking at energy scales approaching the Planck scale (similar to 10(19) GeV). With present photon data from the observations of distant astrophysical sources, it is possible to constrain the Lorentz Symmetry breaking linear term in the standard photon dispersion relations. Gamma Ray Bursts (GRB) and flaring Active Galactic Nuclei (AGN) are complementary to each other for this purpose, since they are observed at different distances in different energy ranges and with different levels of variability. Following a previous publication of the High Energy Stereoscopic System (H.E.S.S.) collaboration [1], a more sensitive event-by-event method consisting of a likelihood fit is applied to PKS 2155-304 flare data of MJD 53944 (July 28, 2006) as used in the previous publication. The previous limit on the linear term is improved by a factor of similar to 3 up to M(QG)(1), > 2.1 X 10(1B) GeV and is currently the best result obtained with blazars. The sensitivity to the quadratic term is lower and provides a limit of M(QG)(q) > 6.4 x 10(10) GeV, which is the best value obtained so far with an AGN and similar to the best limits obtained with GRB. (C) 2011 Elsevier B.V. All rights reserved.
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38. |
- Acero, F., et al.
(författare)
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Detection of Gamma Rays from a Starburst Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5956, s. 1080-1082
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Tidskriftsartikel (refereegranskat)abstract
- Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of similar to 10(15) electron volts. We report the detection of gamma rays-tracers of such cosmic rays-from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H. E. S. S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 +/- 1.0(stat) +/- 2.8(sys)) x 10(-13) cm(-2) s(-1), implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy.
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39. |
- Acero, F., et al.
(författare)
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Discovery and follow-up studies of the extended, off-plane, VHE gamma-ray source HESS J1507-622
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 525, s. A45-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The detection of gamma-rays in the very-high-energy (VHE) range (100 GeV-100 TeV) offers the possibility of studying the parent population of ultrarelativistic particles found in astrophysical sources, so it is useful for understanding the underlying astrophysical processes in nonthermal sources. Aims. The discovery of the VHE gamma-ray source HESS J1507-622 is reported and possibilities regarding its nature are investigated. Methods. The H. E. S. S. array of imaging atmospheric Cherenkov telescopes (IACTs) has a high sensitivity compared with previous instruments (similar to 1% of the Crab flux in 25 h observation time for a 5 sigma point-source detection) and has a large field of view (similar to 5 degrees in diameter). HESS J1507-622 was discovered within the ongoing H. E. S. S. survey of the inner Galaxy, and the source was also studied by means of dedicated multiwavelength observations. Results. A Galactic gamma-ray source, HESS J1507-622, located similar to 3.5 degrees. from the Galactic plane was detected with a statistical significance >9 sigma. Its energy spectrum is well fitted by a power law with spectral index Gamma = 2.24 +/- 0.16(stat) +/- 0.20(sys) and a flux above 1 TeV of (1.5 +/- 0.4(stat) +/- 0.3(sys)) x 10(-12) cm(-2) s(-1). Possible interpretations (considering both hadronic and leptonic models) of the VHE gamma-ray emission are discussed in the absence of an obvious counterpart.
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40. |
- Acero, F., et al.
(författare)
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PKS2005-489 at VHE : four years of monitoring with HESS and simultaneous multi-wavelength observations
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 511, s. A52-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Our aim is to study the very high energy (VHE; E > 100 GeV) gamma-ray emission from BL Lac objects and the evolution in time of their broad-band spectral energy distribution (SED). Methods. VHE observations of the high-frequency peaked BL Lac object PKS 2005-489 were made with the High Energy Stereoscopic System (HESS) from 2004 through 2007. Three simultaneous multi-wavelength campaigns at lower energies were performed during the HESS data taking, consisting of several individual pointings with the XMM-Newton and RXTE satellites. Results. A strong VHE signal, similar to 17 sigma total, from PKS 2005-489 was detected during the four years of HESS observations (90.3 h live time). The integral flux above the average analysis threshold of 400 GeV is similar to 3% of the flux observed from the Crab Nebula and varies weakly on time scales from days to years. The average VHE spectrum measured from similar to 300 GeV to similar to 5 TeV is characterized by a power law with a photon index, Gamma = 3.20 +/- 0.16(stat) +/- 0.10(syst). At X-ray energies the flux is observed to vary by more than an order of magnitude between 2004 and 2005. Strong changes in the X-ray spectrum (Delta Gamma(X) approximate to 0.7) are also observed, which appear to be mirrored in the VHE band. Conclusions. The SED of PKS 2005-489, constructed for the first time with contemporaneous data on both humps, shows significant evolution. The large flux variations in the X-ray band, coupled with weak or no variations in the VHE band and a similar spectral behavior, suggest the emergence of a new, separate, harder emission component in September 2005.
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41. |
- Aharonian, F., et al.
(författare)
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Discovery of VHE gamma-rays from the BL Lacertae object PKS 0548-322
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. A69-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. PKS 0548-322 (z = 0.069) is a "high-frequency-peaked" BL Lac object and a candidate very high energy (VHE, E > 100 GeV) gamma-ray emitter, due to its high X-ray and radio flux. Observations at the VHE band provide insights into the origin of very energetic particles present in this source and the radiation processes at work. Methods. We report observations made between October 2004 and January 2008 with the HESS array, a four imaging atmospheric-Cherenkov telescopes. Contemporaneous UV and X-ray observations with the Swift satellite in November 2006 are also reported. Results. PKS 0548-322 is detected for the first time in the VHE band with HESS We measure an excess of 216 gamma-rays corresponding to a significance of 5.6 standard deviations. The photon spectrum of the source is described by a power-law, with a photon index of Gamma = 2.86 +/- 0.34(stat) +/- 0.10(sys). The integral flux above 200 GeV is similar to 1.3% of the flux of the Crab Nebula, and is consistent with being constant in time. Contemporaneous Swift/XRT observations reveal an X-ray flux between 2 and 10 keV of F2-10 keV = (2.3 +/- 0.2) x 10(-11) erg cm(-2) s(-1), an intermediate intensity state with respect to previous observations. The spectral energy distribution can be reproduced using a simple one-zone synchrotron self Compton model, with parameters similar those observed for other sources of this type.
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42. |
- Aharonian, F., et al.
(författare)
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Probing the ATIC peak in the cosmic-ray electron spectrum with HESS
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 508:2, s. 561-564
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Tidskriftsartikel (refereegranskat)abstract
- The measurement of an excess in the cosmic-ray electron spectrum between 300 and 800 GeV by the ATIC experiment has - together with the PAMELA detection of a rise in the positron fraction up to approximate to 100 GeV - motivated many interpretations in terms of dark matter scenarios; alternative explanations assume a nearby electron source like a pulsar or supernova remnant. Here we present a measurement of the cosmic-ray electron spectrum with H. E. S. S. starting at 340 GeV. While the overall electron flux measured by H. E. S. S. is consistent with the ATIC data within statistical and systematic errors, the H. E. S. S. data exclude a pronounced peak in the electron spectrum as suggested for interpretation by ATIC. The H. E. S. S. data follow a power-law spectrum with spectral index of 3.0 +/- 0.1(stat.) +/- 0.3(syst.), which steepens at about 1 TeV.
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43. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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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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44. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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45. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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46. |
- Abramowski, A., et al.
(författare)
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Discovery of extended VHE gamma-ray emission from the vicinity of the young massive stellar cluster Westerlund 1
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537, s. A114-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Results obtained in very-high-energy (VHE; E >= 100 GeV) gamma-ray observations performed with the H.E.S.S. telescope array are used to investigate particle acceleration processes in the vicinity of the young massive stellar cluster Westerlund 1 (Wd 1). Methods. Imaging of Cherenkov light from gamma-ray induced particle cascades in the Earth's atmosphere is used to search for VHE gamma rays from the region around Wd 1. Possible catalogued counterparts are searched for and discussed in terms of morphology and energetics of the H.E.S.S. source. Results. The detection of the degree-scale extended VHE gamma-ray source HESS J1646-458 is reported based on 45 h of H.E.S.S. observations performed between 2004 and 2008. The VHE gamma-ray source is centred on the nominal position of Wd 1 and detected with a total statistical significance of similar to 20 sigma. The emission region clearly extends beyond the H.E.S.S. point-spread function (PSF). The differential energy spectrum follows a power law in energy with an index of Gamma = 2.19 +/- 0.08(stat) +/- 0.20(sys) and a flux normalisation at 1 TeV of Phi(0) = (9.0 +/- 1.4(stat) +/- 1.8(sys)) x 10(-12) TeV-1 cm(-2) s(-1). The integral flux above 0.2 TeV amounts to (5.2 +/- 0.9) x 10(-11) cm(-2) s(-1). Conclusions. Four objects coincident with HESS J1646-458 are discussed in the search of a counterpart, namely the magnetar CXOU J164710.2-455216, the X-ray binary 4U 1642-45, the pulsar PSR J1648-4611 and the massive stellar cluster Wd 1. In a single-source scenario, Wd 1 is favoured as site of VHE particle acceleration. Here, a hadronic parent population would be accelerated within the stellar cluster. Beside this, there is evidence for a multi-source origin, where a scenario involving PSR J1648-4611 could be viable to explain parts of the VHE gamma-ray emission of HESS J1646-458.
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47. |
- Abramowski, A., et al.
(författare)
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Discovery of hard-spectrum gamma- ray emission from the BL Lacertae object 1ES 0414+009
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 538, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. 1ES 0414+009 (z = 0.287) is a distant high-frequency- peaked BL Lac object, and has long been considered a likely emitter of very-highenergy (VHE, E > 100 GeV) gamma-rays due to its high X-ray and radio flux. Aims. Observations in the VHE gamma-ray band and across the electromagnetic spectrum can provide insights into the origin of highly energetic particles present in the source and the radiation processes at work. Because of the distance of the source, the gamma-ray spectrum might provide further limits on the level of the extragalactic background light (EBL). Methods. We report observations made between October 2005 and December 2009 with H. E. S. S., an array of four imaging atmospheric Cherenkov telescopes. Observations at high energies (HE, 100 MeV-100 GeV) with the Fermi-LAT instrument in the first 20 months of its operation are also reported. To complete the multi-wavelength picture, archival UV and X-ray observations with the Swift satellite and optical observations with the ATOM telescope are also used. Results. Based on the observations with H.E.S.S., 1ES 0414+009 is detected for the first time in the VHE band. An excess of 224 events is measured, corresponding to a significance of 7.8 sigma. The photon spectrum of the source is well described by a power law, with photon index of Gamma(VHE) = 3.45 +/- 0.25(stat) +/- 0.20(syst). The integral flux above 200 GeV is (1.88 +/- 0.20(stat) +/- 0.38(syst)) x10(-12) cm(-2) s(-1). Observations with the Fermi-LAT in the first 20 months of operation show a flux between 200 MeV and 100 GeV of (2.3 +/- 0.2(stat)) x 10(-9) erg cm(-2) s(-1), and a spectrum well described by a power-law function with a photon index Gamma(HE) = 1.85 +/- 0.18. Swift/XRT observations show an X-ray flux between 2 and 10 keV of (0.8-1) x 10(-11) erg cm(-2) s(-1), and a steep spectrum Gamma(X) = (2.2-2.3). Combining X-ray with optical-UV data, a fit with a log-parabolic function locates the synchrotron peak around 0.1 keV. Conclusions. Although the GeV-TeV observations do not provide better constraints on the EBL than previously obtained, they confirm a low density of the EBL, close to the lower limits from galaxy counts. The absorption-corrected HE and VHE gamma-ray spectra are both hard and have similar spectral indices (approximate to 1.86), indicating no significant change of slope between the HE and VHE gamma-ray bands, and locating the gamma-ray peak in the SED above 1-2 TeV. As for other TeV BL Lac objects with the gamma-ray peak at such high energies and a large separation between the two SED humps, this average broad-band SED represents a challenge for simple one-zone synchrotron self-Compton models, requiring a high Doppler factor and very low B-field.
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48. |
- Abramowski, A., et al.
(författare)
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HESS constraints on dark matter annihilations towards the sculptor and carina dwarf galaxies
- 2011
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:8, s. 608-616
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Tidskriftsartikel (refereegranskat)abstract
- The Sculptor and Carina dwarf spheroidal galaxies were observed with the H.E.S.S. Cherenkov telescope array between January 2008 and December 2009. The data sets consist of a total of 11.8 h and 14.811 of high quality data, respectively. No gamma-ray signal was detected at the nominal positions of these galaxies above 220 GeV and 320 GeV, respectively. Upper limits on the gamma-ray fluxes at 95% CL assuming two forms for the spectral energy distribution (a power law shape and one derived from dark matter annihilation) are obtained at the level of 10(-13)-10(-12) cm(-2) s(-1) in the TeV range. Constraints on the velocity weighted dark matter particle annihilation cross section for both Sculptor and Carina dwarf galaxies range from 10(-21) cm(3) s(-1) down to similar to 10(-2)2 cm(3) s(-1) on the dark matter halo model used. Possible enhancements of the gamma-ray flux are studied: the Sommerfeld effect, which is found to exclude some dark matter particle masses, the internal Bremsstrahlung and clumps in the dark-matter halo distributions. (C) 2010 Elsevier B.V. All rights reserved.
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49. |
- Abramowski, A., et al.
(författare)
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HESS J1943+213 : a candidate extreme BL Lacertae object
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 529, s. A49-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The H. E. S. S. Cherenkov telescope array has been surveying the Galactic plane for new VHE (>100 GeV) gamma-ray sources. Aims. We report on a newly detected point-like source, HESS J1943+213. This source coincides with an unidentified hard X-ray source IGR J19443+2117, which was proposed to have radio and infrared counterparts. Methods. We combine new H. E. S. S., Fermi/LAT and Nancay Radio Telescope observations with pre-existing non-simultaneous multi-wavelength observations of IGR J19443+2117 and discuss the likely source associations as well as the interpretation as an active galactic nucleus, a gamma-ray binary or a pulsar wind nebula. Results. HESS J1943+213 is detected at the significance level of 7.9 sigma (post-trials) at RA(J2000) = 19(h)43(m)55(s) +/- 1(stat)(s) +/- 1(sys)(s), Dec(J2000) = +21 degrees 18'8 '' +/- 17(stat)'' +/- 20(sys)''. The source has a soft spectrum with photon index Gamma = 3.1 +/- 0.3(stat) +/- 0.2(sys) and a flux above 470 GeV of (1.3 +/- 0.2(stat) +/- 0.3(sys)) x 10(-12) cm(-2) s(-1). There is no Fermi/LAT counterpart down to a flux limit of 6 x 10(-9) cm(-2) s(-1) in the 0.1-100 GeV energy range (95% confidence upper limit calculated for an assumed power-law model with a photon index Gamma = 2.0). The data from radio to VHE gamma-rays do not show any significant variability. Conclusions. The lack of a massive stellar counterpart disfavors the binary hypothesis, while the soft VHE spectrum would be very unusual in case of a pulsar wind nebula. In addition, the distance estimates for Galactic counterparts places them outside of the Milky Way. All available observations favor an interpretation as an extreme, high-frequency peaked BL Lac object with a redshift z > 0.14. This would be the first time a blazar is detected serendipitously from ground-based VHE observations, and the first VHE AGN detected in the Galactic Plane.
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50. |
- Abramowski, A., et al.
(författare)
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HESS OBSERVATIONS OF THE GLOBULAR CLUSTERS NGC 6388 AND M15 AND SEARCH FOR A DARK MATTER SIGNAL
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 735:1
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Tidskriftsartikel (refereegranskat)abstract
- Observations of the globular clusters (GCs) NGC 6388 and M15 were carried out by the High Energy Stereoscopic System array of Cherenkov telescopes for a live time of 27.2 and 15.2 hr, respectively. No gamma-ray signal is found at the nominal target position of NGC 6388 and M15. In the primordial formation scenario, GCs are formed in a dark matter (DM) halo and DM could still be present in the baryon-dominated environment of GCs. This opens the possibility of observing a DM self-annihilation signal. The DM content of the GCs NGC 6388 and M15 is modeled taking into account the astrophysical processes that can be expected to influence the DM distribution during the evolution of the GC: the adiabatic contraction of DM by baryons, the adiabatic growth of a black hole in the DM halo, and the kinetic heating of DM by stars. Ninety-five percent confidence level exclusion limits on the DM particle velocity-weighted annihilation cross section are derived for these DM halos. In the TeV range, the limits on the velocity-weighted annihilation cross section are derived at the 10(-25) cm(3) s(-1) level and a few 10(-24) cm(3) s(-1) for NGC 6388 and M15, respectively.
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