| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 2. |
- Abdalla, H., et al.
(författare)
-
HESS observations of RX J1713.7-3946 with improved angular and spectral resolution : Evidence for gamma-ray emission extending beyond the X-ray emitting shell
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- Supernova remnants exhibit shock fronts (shells) that can accelerate charged particles up to very high energies. In the past decade, measurements of a handful of shell-type supernova remnants in very high-energy gamma rays have provided unique insights into the acceleration process. Among those objects, RX J1713.7-3946 (also known as G347.3-0.5) has the largest surface brightness, allowing us in the past to perform the most comprehensive study of morphology and spatially resolved spectra of any such very high-energy gamma-ray source. Here we present extensive new H.E.S.S. measurements of RX J1713.7-3946, almost doubling the observation time compared to our previous publication. Combined with new improved analysis tools, the previous sensitivity is more than doubled. The H.E.S.S. angular resolution of 0.048 degrees (0.036 degrees above 2 TeV) is unprecedented in gamma-ray astronomy and probes physical scales of 0.8 (0.6) parsec at the remnant's location. The new H. E. S. S. image of RX J1713.7-3946 allows us to reveal clear morphological di ff erences between X-rays and gamma rays. In particular, for the outer edge of the brightest shell region, we find the first ever indication for particles in the process of leaving the acceleration shock region. By studying the broadband energy spectrum, we furthermore extract properties of the parent particle populations, providing new input to the discussion of the leptonic or hadronic nature of the gamma-ray emission mechanism.
|
|
| 3. |
- Abdalla, H., et al.
(författare)
-
The population of TeV pulsar wind nebulae in the HESS Galactic Plane Survey
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- The nine-year H.E.S.S. Galactic Plane Survey (HGPS) has yielded the most uniform observation scan of the inner Milky Way in the TeV gamma-ray band to date. The sky maps and source catalogue of the HGPS allow for a systematic study of the population of TeV pulsar wind nebulae found throughout the last decade. To investigate the nature and evolution of pulsar wind nebulae, for the first time we also present several upper limits for regions around pulsars without a detected TeV wind nebula. Our data exhibit a correlation of TeV surface brightness with pulsar spindown power (E) over dot. This seems to be caused both by an increase of extension with decreasing (E) over dot, and hence with time, compatible with a power law R-PWN((E) over dot) similar to(E) over dot(0.65 +/- 0.20), and by a mild decrease of TeV gamma-ray luminosity with decreasing (E) over dot, compatible with L-1 (10 TeV) similar to (E) over dot(0.59 +/- 0.21). We also find that the off sets of pulsars with respect to the wind nebula centre with ages around 10 kyr are frequently larger than can be plausibly explained by pulsar proper motion and could be due to an asymmetric environment. In the present data, it seems that a large pulsar off set is correlated with a high apparent TeV efficiency L1- 10 TeV / (E) over dot. In addition to 14 HGPS sources considered firmly identified pulsar wind nebulae and 5 additional pulsar wind nebulae taken from literature, we find 10 HGPS sources that are likely TeV pulsar wind nebula candidates. Using a model that subsumes the present common understanding of the very high-energy radiative evolution of pulsar wind nebulae, we find that the trends and variations of the TeV observables and limits can be reproduced to a good level, drawing a consistent picture of present-day TeV data and theory.
|
|
| 4. |
- Abdalla, H., et al.
(författare)
-
The supernova remnant W49B as seen with HESS and Fermi-LAT
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- The supernova remnant (SNR) W49B originated from a core-collapse supernova that occurred between one and four thousand years ago, and subsequently evolved into a mixed-morphology remnant, which is interacting with molecular clouds (MC). Gamma-ray observations of SNR-MC associations are a powerful tool to constrain the origin of Galactic cosmic rays, as they can probe the acceleration of hadrons through their interaction with the surrounding medium and subsequent emission of non-thermal photons. We report the detection of a gamma-ray source coincident with W49B at very high energies (VHE; E > 100 GeV) with the H.E.S.S. Cherenkov telescopes together with a study of the source with five years of Fermi-LAT high-energy gamma-ray (0.06-300 GeV) data. The smoothly connected, combined source spectrum, measured from 60 MeV to multi-TeV energies, shows two significant spectral breaks at 304 +/- 20 MeV and 8.4(-2.5)(+2.5) GeV; the latter is constrained by the joint fit from the two instruments. The detected spectral features are similar to those observed in several other SNR-MC associations and are found to be indicative of gamma-ray emission produced through neutral-pion decay.
|
|
| 5. |
- Abramowski, A., et al.
(författare)
-
Detailed spectral and morphological analysis of the shell type supernova remnant RCW 86
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. We aim for an understanding of the morphological and spectral properties of the supernova remnant RCW 86 and for insights into the production mechanism leading to the RCW 86 very high-energy gamma-ray emission. Methods. We analyzed High Energy Spectroscopic System (H.E.S.S.) data that had increased sensitivity compared to the observations presented in the RCW 86 H.E.S.S. discovery publication. Studies of the morphological correlation between the 0.5-1 keV X-ray band, the 2-5 keV X-ray band, radio, and gamma-ray emissions have been performed as well as broadband modeling of the spectral energy distribution with two different emission models. Results. We present the first conclusive evidence that the TeV gamma-ray emission region is shell-like based on our morphological studies. The comparison with 2-5 keV X-ray data reveals a correlation with the 0.4-50 TeV gamma-ray emission. The spectrum of RCW 86 is best described by a power law with an exponential cutoff at E-cut = (3.5 +/- 1.2(stat)) TeV and a spectral index of Gamma approximate to 1.6 +/- 0.2. A static leptonic one-zone model adequately describes the measured spectral energy distribution of RCW 86, with the resultant total kinetic energy of the electrons above 1 GeV being equivalent to similar to 0.1% of the initial kinetic energy of a Type Ia supernova explosion (10(51) erg). When using a hadronic model, a magnetic field of B approximate to 100 mu G is needed to represent the measured data. Although this is comparable to formerly published estimates, a standard E-2 spectrum for the proton distribution cannot describe the gamma-ray data. Instead, a spectral index of Gamma(p) approximate to 1.7 would be required, which implies that similar to 7 x 10(49)/n(cm-3) erg has been transferred into high-energy protons with the effective density n(cm-3) = n/1 cm(-3). This is about 10% of the kinetic energy of a typical Type Ia supernova under the assumption of a density of 1 cm(-3).
|
|
| 6. |
- Abramowski, A., et al.
(författare)
-
DISCOVERY OF THE HARD SPECTRUM VHE gamma-RAY SOURCE HESS J1641-463
- 2014
-
Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 794:1, s. L1-
-
Tidskriftsartikel (refereegranskat)abstract
- This Letter reports the discovery of a remarkably hard spectrum source, HESS J1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very high energy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis techniques due to confusion with the bright nearby source HESS J1640-465. It emerged at a significance level of 8.5 standard deviations after restricting the analysis to events with energies above 4 TeV. It shows a moderate flux level of phi(E > 1TeV) = (3.64 +/- 0.44(stat)+/- 0.73(sys)) x 10(-13) cm(-2) s(-1), corresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard spectrum with a photon index of Gamma = 2.07 +/- 0.11(stat)+/- 0.20(sys). It is a point-like source, although an extension up to a Gaussian width of sigma = 3 arcmin cannot be discounted due to uncertainties in the H.E.S.S. point-spread function. The VHE gamma-ray flux of HESS J1641-463 is found to be constant over the observed period when checking time binnings from the year-by-year to the 28 minute exposure timescales. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association; however, Chandra and XMM-Newton data reveal some potential weak counterparts. Various VHE gamma-ray production scenarios are discussed. If the emission from HESS J1641-463 is produced by cosmic ray protons colliding with the ambient gas, then their spectrum must extend close to 1 PeV. This object may represent a source population contributing significantly to the galactic cosmic ray flux around the knee.
|
|
| 7. |
- Abdalla, H., et al.
(författare)
-
A search for new supernova remnant shells in the Galactic plane with HESS
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- A search for new supernova remnants (SNRs) has been conducted using TeV gamma-ray data from the H.E.S.S. Galactic plane survey. As an identification criterion, shell morphologies that are characteristic for known resolved TeV SNRs have been used. Three new SNR candidates were identified in the H.E.S.S. data set with this method. Extensive multiwavelength searches for counterparts were conducted. A radio SNR candidate has been identified to be a counterpart to HESS J1534-571. The TeV source is therefore classified as a SNR. For the other two sources, HESS J1614-518 and HESS J1912 + 101, no identifying counterparts have been found, thus they remain SNR candidates for the time being. TeV-emitting SNRs are key objects in the context of identifying the accelerators of Galactic cosmic rays. The TeV emission of the relativistic particles in the new sources is examined in view of possible leptonic and hadronic emission scenarios, taking the current multiwavelength knowledge into account.
|
|
| 8. |
- Abdalla, H., et al.
(författare)
-
Characterising the VHE diffuse emission in the central 200 parsecs of our Galaxy with HESS
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- The diffuse very high-energy (VHE; > 100 GeV) gamma-ray emission observed in the central 200 pc of the Milky Way by H.E.S.S. was found to follow dense matter distribution in the central molecular zone (CMZ) up to a longitudinal distance of about 130 pc to the Galactic centre (GC), where the flux rapidly decreases. This was initially interpreted as the result of a burst-like injection of energetic particles 104 yr ago, but a recent more sensitive H.E.S.S. analysis revealed that the cosmic-ray (CR) density profile drops with the distance to the centre, making data compatible with a steady cosmic PeVatron at the GC. In this paper, we extend this analysis to obtain, for the first time, a detailed characterisation of the correlation with matter and to search for additional features and individual gamma-ray sources in the inner 200 pc. Taking advantage of 250 h of H.E.S.S. data and improved analysis techniques, we perform a detailed morphology study of the diffuse VHE emission observed from the GC ridge and reconstruct its total spectrum. To test the various contributions to the total gamma-ray emission, we used an iterative 2D maximum-likelihood approach that allows us to build a phenomenological model of the emission by summing a number of different spatial components. We show that the emission correlated with dense matter covers the full CMZ and that its flux is about half the total diffuse emission flux. We also detect some emission at higher latitude that is likely produced by hadronic collisions of CRs in less dense regions of the GC interstellar medium. We detect an additional emission component centred on the GC and extending over about 15 pc that is consistent with the existence of a strong CR density gradient and confirms the presence of a CR accelerator at the very centre of our Galaxy. We show that the spectrum of full ridge diffuse emission is compatible with that previously derived from the central regions, suggesting that a single population of particles fills the entire CMZ. Finally, we report the discovery of a VHE gamma-ray source near the GC radio arc and argue that it is produced by the pulsar wind nebula candidate G0.13-0.11.
|
|
| 9. |
- Abdalla, H., et al.
(författare)
-
Deeper HESS observations of Vela Junior (RX J0852.0-4622) : Morphology studies and resolved spectroscopy
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. We study gamma-ray emission from the shell-type supernova remnant (SNR) RXJ0852.0-4622 to better characterize its spectral properties and its distribution over the SNR. Methods. The analysis of an extended High Energy Spectroscopic System (H.E.S.S.) data set at very high energies (E > 100 GeV) permits detailed studies, as well as spatially resolved spectroscopy, of the morphology and spectrum of the whole RXJ0852.0-4622 region. The H.E.S.S. data are combined with archival data from other wavebands and interpreted in the framework of leptonic and hadronic models. The joint Fermi-LAT-H.E.S.S. spectrum allows the direct determination of the spectral characteristics of the parent particle population in leptonic and hadronic scenarios using only GeV-TeV data. Results. An updated analysis of the H.E.S.S. data shows that the spectrum of the entire SNR connects smoothly to the high-energy spectrum measured by Fermi-LAT. The increased data set makes it possible to demonstrate that the H.E.S.S. spectrum deviates significantly from a power law and is well described by both a curved power law and a power law with an exponential cutoff at an energy of E-cut = (6.7 +/- 1.2(stat) +/- 1.2(syst)) TeV. The joint Fermi-LAT-H.E.S.S. spectrum allows the unambiguous identification of the spectral shape as a power law with an exponential cutoff. No significant evidence is found for a variation of the spectral parameters across the SNR, suggesting similar conditions of particle acceleration across the remnant. A simple modeling using one particle population to model the SNR emission demonstrates that both leptonic and hadronic emission scenarios remain plausible. It is also shown that at least a part of the shell emission is likely due to the presence of a pulsar wind nebula around PSR J0855-4644.
|
|
| 10. |
- Abdalla, H., et al.
(författare)
-
Population study of Galactic supernova remnants at very high gamma-ray energies with HESS
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- Shell-type supernova remnants (SNRs) are considered prime candidates for the acceleration of Galactic cosmic rays (CRs) up to the knee of the CR spectrum at E approximate to 3 x 10(15) eV. Our MilkyWay galaxy hosts more than 350 SNRs discovered at radio wavelengths and at high energies, of which 220 fall into the H.E.S.S. Galactic Plane Survey (HGPS) region. Of those, only 50 SNRs are coincident with a H.E.S.S source and in 8 cases the very high-energy (VHE) emission is firmly identified as an SNR. The H.E.S.S. GPS provides us with a legacy for SNR population study in VHE gamma-rays and we use this rich data set to extract VHE flux upper limits from all undetected SNRs. Overall, the derived flux upper limits are not in contradiction with the canonical CR paradigm. Assuming this paradigm holds true, we can constrain typical ambient density values around shell-type SNRs to n <= 7 cm(-3) and electron-to-proton energy fractions above 10 TeV to epsilon(ep) <= 5 x 10(-3). Furthermore, comparisons of VHE with radio luminosities in non-interacting SNRs reveal a behaviour that is in agreement with the theory of magnetic field amplification at shell-type SNRs.
|
|
| 11. |
- Abdalla, H., et al.
(författare)
-
The HESS Galactic plane survey
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Tidskriftsartikel (refereegranskat)abstract
- We present the results of the most comprehensive survey of the Galactic plane in very high-energy (VHE) gamma-rays, including a public release of Galactic sky maps, a catalog of VHE sources, and the discovery of 16 new sources of VHE gamma-rays. The High Energy Spectroscopic System (H.E.S.S.) Galactic plane survey (HGPS) was a decade-long observation program carried out by the H.E.S.S. I array of Cherenkov telescopes in Namibia from 2004 to 2013. The observations amount to nearly 2700 h of quality-selected data, covering the Galactic plane at longitudes from l = 250 degrees to 65 degrees and latitudes vertical bar b vertical bar <= 3 degrees. In addition to the unprecedented spatial coverage, the HGPS also features a relatively high angular resolution (0.08 degrees approximate to 5 arcmin mean point spread function 68% containment radius), sensitivity (less than or similar to 1.5% Crab flux for point-like sources), and energy range (0.2-100 TeV). We constructed a catalog of VHE gamma-ray sources from the HGPS data set with a systematic procedure for both source detection and characterization of morphology and spectrum. We present this likelihood-based method in detail, including the introduction of a model component to account for unresolved, large-scale emission along the Galactic plane. In total, the resulting HGPS catalog contains 78 VHE sources, of which 14 are not reanalyzed here, for example, due to their complex morphology, namely shell-like sources and the Galactic center region. Where possible, we provide a firm identification of the VHE source or plausible associations with sources in other astronomical catalogs. We also studied the characteristics of the VHE sources with source parameter distributions. 16 new sources were previously unknown or unpublished, and we individually discuss their identifications or possible associations. We firmly identified 31 sources as pulsar wind nebulae (PWNe), supernova remnants (SNRs), composite SNRs, or gamma-ray binaries. Among the 47 sources not yet identified, most of them (36) have possible associations with cataloged objects, notably PWNe and energetic pulsars that could power VHE PWNe.
|
|
| 12. |
- Abdallah, H., et al.
(författare)
-
Search for gamma-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with HESS
- 2018
-
Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 120:20
-
Tidskriftsartikel (refereegranskat)abstract
- Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy gamma rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant gamma-ray excess above the background is found. We derive upper limits on the annihilation cross section (sigma v) for monoenergetic DM lines at the level of 4 x 10(-28) cm(3) s(-1) at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based gamma-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two gamma-ray photons at the level expected from the thermal relic density for TeV DM particles.
|
|
| 13. |
|
|
| 14. |
- Naghavi, Mohsen, et al.
(författare)
-
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
-
Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
-
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.
|
|
| 15. |
- Smith, Jennifer A, et al.
(författare)
-
Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
-
Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
-
Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
|
|
| 16. |
- Jelenkovic, Aline, et al.
(författare)
-
Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
-
Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
-
Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
|
|
| 17. |
- Silventoinen, Karri, et al.
(författare)
-
The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- 2015
-
Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
-
Tidskriftsartikel (refereegranskat)abstract
- For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
|
|
| 18. |
- Jelenkovic, Aline, et al.
(författare)
-
Associations between birth size and later height from infancy through adulthood : An individual based pooled analysis of 28 twin cohorts participating in the CODATwins project
- 2018
-
Ingår i: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 120, s. 53-60
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14–4.25 cm and 0.18–0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight.
|
|
| 19. |
- Silventoinen, Karri, et al.
(författare)
-
Education in twins and their parents across birth cohorts over 100 years : an individual-level pooled analysis of 42 twin cohorts
- 2017
-
Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
-
Tidskriftsartikel (refereegranskat)abstract
- Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
|
|
| 20. |
- Silventoinen, Karri, et al.
(författare)
-
Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts
- 2020
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
|
|
| 21. |
- Yokoyama, Yoshie, et al.
(författare)
-
Genetic and environmental factors affecting birth size variation : A pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts
- 2018
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 47:4, s. 1195-1206
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. Conclusions: The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.
|
|
| 22. |
- Frazier-Wood, Alexis C., et al.
(författare)
-
Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
-
Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
-
Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
|
|
| 23. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 24. |
- Bolton, Kelly L., et al.
(författare)
-
Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
- 2012
-
Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
-
Tidskriftsartikel (refereegranskat)abstract
- Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
|
|
| 25. |
- Finkel, Deborah, et al.
(författare)
-
Financial strain moderates genetic influences on self-rated health : support for diathesis–stress model of gene–environment interplay
- 2022
-
Ingår i: Biodemography and Social Biology. - : Taylor & Francis. - 1948-5565 .- 1948-5573. ; 67:1, s. 58-70
-
Tidskriftsartikel (refereegranskat)abstract
- Data from the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium were used to examine predictions of different models of gene-by-environment interaction to understand how genetic variance in self-rated health (SRH) varies at different levels of financial strain. A total of 11,359 individuals from 10 twin studies in Australia, Sweden, and the United States contributed relevant data, including 2,074 monozygotic and 2,623 dizygotic twin pairs. Age ranged from 22 to 98 years, with a mean age of 61.05 (SD = 13.24). A factor model was used to create a harmonized measure of financial strain across studies and items. Twin analyses of genetic and environmental variance for SRH incorporating age, age2, sex, and financial strain moderators indicated significant financial strain moderation of genetic influences on self-rated health. Moderation results did not differ across sex or country. Genetic variance for SRH increased as financial strain increased, matching the predictions of the diathesis–stress and social comparison models for components of variance. Under these models, environmental improvements would be expected to reduce genetically based health disparities.
|
|
