| 1. |
- 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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| 2. |
- Fang, Li Tai, et al.
(författare)
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Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1151-1160
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-normal paired DNA samples from a breast cancer cell line and a matched lymphoblastoid cell line enable calibration of clinical sequencing pipelines and benchmarking 'tumor-only' or 'matched tumor-normal' analyses. The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
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| 3. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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| 4. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. III. Imaging of the Galactic Center Supermassive Black Hole
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first event-horizon-scale images and spatiotemporal analysis of Sgr A* taken with the Event Horizon Telescope in 2017 April at a wavelength of 1.3 mm. Imaging of Sgr A* has been conducted through surveys over a wide range of imaging assumptions using the classical CLEAN algorithm, regularized maximum likelihood methods, and a Bayesian posterior sampling method. Different prescriptions have been used to account for scattering effects by the interstellar medium toward the Galactic center. Mitigation of the rapid intraday variability that characterizes Sgr A* has been carried out through the addition of a "variability noise budget" in the observed visibilities, facilitating the reconstruction of static full-track images. Our static reconstructions of Sgr A* can be clustered into four representative morphologies that correspond to ring images with three different azimuthal brightness distributions and a small cluster that contains diverse nonring morphologies. Based on our extensive analysis of the effects of sparse (u, v)-coverage, source variability, and interstellar scattering, as well as studies of simulated visibility data, we conclude that the Event Horizon Telescope Sgr A* data show compelling evidence for an image that is dominated by a bright ring of emission with a ring diameter of similar to 50 mu as, consistent with the expected "shadow" of a 4 x 10(6) M (circle dot) black hole in the Galactic center located at a distance of 8 kpc.
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| 5. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. IV. Variability, Morphology, and Black Hole Mass
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we quantify the temporal variability and image morphology of the horizon-scale emission from Sgr A*, as observed by the EHT in 2017 April at a wavelength of 1.3 mm. We find that the Sgr A* data exhibit variability that exceeds what can be explained by the uncertainties in the data or by the effects of interstellar scattering. The magnitude of this variability can be a substantial fraction of the correlated flux density, reaching similar to 100% on some baselines. Through an exploration of simple geometric source models, we demonstrate that ring-like morphologies provide better fits to the Sgr A* data than do other morphologies with comparable complexity. We develop two strategies for fitting static geometric ring models to the time-variable Sgr A* data; one strategy fits models to short segments of data over which the source is static and averages these independent fits, while the other fits models to the full data set using a parametric model for the structural variability power spectrum around the average source structure. Both geometric modeling and image-domain feature extraction techniques determine the ring diameter to be 51.8 +/- 2.3 mu as (68% credible intervals), with the ring thickness constrained to have an FWHM between similar to 30% and 50% of the ring diameter. To bring the diameter measurements to a common physical scale, we calibrate them using synthetic data generated from GRMHD simulations. This calibration constrains the angular size of the gravitational radius to be 4.8(-0.7)(+1.4) mu as, which we combine with an independent distance measurement from maser parallaxes to determine the mass of Sgr A* to be 4.0(-0.6)(+1.1) x 10(6) M-circle dot.
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| 6. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. V. Testing Astrophysical Models of the Galactic Center Black Hole
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we provide a first physical interpretation for the Event Horizon Telescope's (EHT) 2017 observations of Sgr A*. Our main approach is to compare resolved EHT data at 230 GHz and unresolved non-EHT observations from radio to X-ray wavelengths to predictions from a library of models based on time-dependent general relativistic magnetohydrodynamics simulations, including aligned, tilted, and stellar-wind-fed simulations; radiative transfer is performed assuming both thermal and nonthermal electron distribution functions. We test the models against 11 constraints drawn from EHT 230 GHz data and observations at 86 GHz, 2.2 mu m, and in the X-ray. All models fail at least one constraint. Light-curve variability provides a particularly severe constraint, failing nearly all strongly magnetized (magnetically arrested disk (MAD)) models and a large fraction of weakly magnetized models. A number of models fail only the variability constraints. We identify a promising cluster of these models, which are MAD and have inclination i <= 30 degrees. They have accretion rate (5.2-9.5) x 10(-9) M (circle dot) yr(-1), bolometric luminosity (6.8-9.2) x 10(35) erg s(-1), and outflow power (1.3-4.8) x 10(38) erg s(-1). We also find that all models with i >= 70 degrees fail at least two constraints, as do all models with equal ion and electron temperature; exploratory, nonthermal model sets tend to have higher 2.2 mu m flux density; and the population of cold electrons is limited by X-ray constraints due to the risk of bremsstrahlung overproduction. Finally, we discuss physical and numerical limitations of the models, highlighting the possible importance of kinetic effects and duration of the simulations.
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| 7. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. VI. Testing the Black Hole Metric
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- Astrophysical black holes are expected to be described by the Kerr metric. This is the only stationary, vacuum, axisymmetric metric, without electromagnetic charge, that satisfies Einstein's equations and does not have pathologies outside of the event horizon. We present new constraints on potential deviations from the Kerr prediction based on 2017 EHT observations of Sagittarius A* (Sgr A*). We calibrate the relationship between the geometrically defined black hole shadow and the observed size of the ring-like images using a library that includes both Kerr and non-Kerr simulations. We use the exquisite prior constraints on the mass-to-distance ratio for Sgr A* to show that the observed image size is within similar to 10% of the Kerr predictions. We use these bounds to constrain metrics that are parametrically different from Kerr, as well as the charges of several known spacetimes. To consider alternatives to the presence of an event horizon, we explore the possibility that Sgr A* is a compact object with a surface that either absorbs and thermally reemits incident radiation or partially reflects it. Using the observed image size and the broadband spectrum of Sgr A*, we conclude that a thermal surface can be ruled out and a fully reflective one is unlikely. We compare our results to the broader landscape of gravitational tests. Together with the bounds found for stellar-mass black holes and the M87 black hole, our observations provide further support that the external spacetimes of all black holes are described by the Kerr metric, independent of their mass.
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| 8. |
- Amano, Tatsuya, et al.
(författare)
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Transforming Practice : Checklists for Delivering Change
- 2022
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Ingår i: Transforming Conservation : A Practical Guide to Evidence and Decision Making - A Practical Guide to Evidence and Decision Making. - 9781800648562 - 9781800648586 ; , s. 367-386
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Bokkapitel (refereegranskat)abstract
- Delivering a revolution in evidence use requires a cultural change across society. For a wide range of groups (practitioners, knowledge brokers, organisations, organisational leaders, policy makers, funders, researchers, journal publishers, the wider conservation community, educators, writers, and journalists), options are described to facilitate a change in practice, and a series of downloadable checklists is provided.
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| 9. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 10. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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