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2. |
- 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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3. |
- Leleu, A., et al.
(författare)
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Six transiting planets and a chain of Laplace resonances in TOI-178
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
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Tidskriftsartikel (refereegranskat)abstract
- Determining the architecture of multi-planetary systems is one of the cornerstones of understanding planet formation and evolution. Resonant systems are especially important as the fragility of their orbital configuration ensures that no significant scattering or collisional event has taken place since the earliest formation phase when the parent protoplanetary disc was still present. In this context, TOI-178 has been the subject of particular attention since the first TESS observations hinted at the possible presence of a near 2:3:3 resonant chain. Here we report the results of observations from CHEOPS, ESPRESSO, NGTS, and SPECULOOS with the aim of deciphering the peculiar orbital architecture of the system. We show that TOI-178 harbours at least six planets in the super-Earth to mini-Neptune regimes, with radii ranging from 1.152 to 2.87 Earth radii and periods of 1.91, 3.24, 6.56, 9.96, 15.23, and 20.71 days. All planets but the innermost one form a 2:4:6:9:12 chain of Laplace resonances, and the planetary densities show important variations from planet to planet, jumping from 1.02 to 0.177 times the Earth's density between planets c and d. Using Bayesian interior structure retrieval models, we show that the amount of gas in the planets does not vary in a monotonous way, contrary to what one would expect from simple formation and evolution models and unlike other known systems in a chain of Laplace resonances. The brightness of TOI-178 (H = 8.76 mag, J = 9.37 mag, V = 11.95 mag) allows for a precise characterisation of its orbital architecture as well as of the physical nature of the six presently known transiting planets it harbours. The peculiar orbital configuration and the diversity in average density among the planets in the system will enable the study of interior planetary structures and atmospheric evolution, providing important clues on the formation of super-Earths and mini-Neptunes. -0.070 -0.13 -0.23 -0.061 +0.073 +0.14 +0.28 +0.055
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4. |
- Cabrera, J., et al.
(författare)
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The planetary system around HD 190622 (TOI-1054): Measuring the gas content of low-mass planets orbiting F-stars
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675
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Tidskriftsartikel (refereegranskat)abstract
- Context. Giant planets are known to dominate the long-term stability of planetary systems due to their prevailing gravitational interactions, but they are also thought to play an important role in planet formation. Observational constraints improve our understanding of planetary formation processes such as the delivery of volatile-rich planetesimals from beyond the ice line into the inner planetary system. Additional constraints may come from studies of the atmosphere, but almost all such studies of the atmosphere investigate the detection of certain species, and abundances are not routinely quantitatively measured. Aims. Accurate measurements of planetary bulk parameters-that is, mass and density-provide constraints on the inner structure and chemical composition of transiting planets. This information provides insight into properties such as the amounts of volatile species, which in turn can be related to formation and evolution processes. Methods. The Transiting Exoplanet Survey Satellite (TESS) reported a planetary candidate around HD 190622 (TOI-1054), which was subsequently validated and found to merit further characterization with photometric and spectroscopic facilities. The KESPRINT collaboration used data from the High Accuracy Radial Velocity Planet Searcher (HARPS) to independently confirm the planetary candidate, securing its mass, and revealing the presence of an outer giant planet in the system. The CHEOPS consortium invested telescope time in the transiting target in order to reduce the uncertainty on the radius, improving the characterization of the planet. Results. We present the discovery and characterization of the planetary system around HD 190622 (TOI-1054). This system hosts one transiting planet, which is smaller than Neptune (3.087-0.053+0.058REarth, 7.7 ± 1.0 MEarth) but has a similar bulk density (1.43 ± 0.21 g cm-3) and an orbital period of 16 days; and a giant planet, not known to be transiting, with a minimum mass of 227.0 ± 6.7 MEarth in an orbit with a period of 315 days. Conclusions. Our measurements constrain the structure and composition of the transiting planet. HD 190622b has singular properties among the known population of transiting planets, which we discuss in detail. Among the sub-Neptune-sized planets known today, this planet stands out because of its large gas content.
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5. |
- Alqasim, A., et al.
(författare)
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TOI−757 b: an eccentric transiting mini−Neptune on a 17.5−d orbit
- 2024
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 533:1, s. 1-26
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Tidskriftsartikel (refereegranskat)abstract
- We report the spectroscopic confirmation and fundamental properties of TOI−757 b, a mini−Neptune on a 17.5−d orbit transiting a bright star (V = 9.7 mag) discovered by the TESS mission. We acquired high−precision radial velocity measurements with the HARPS, ESPRESSO, and PFS spectrographs to confirm the planet detection and determine its mass. We also acquired space−borne transit photometry with the CHEOPS space telescope to place stronger constraints on the planet radius, supported with ground−based LCOGT photometry. WASP and KELT photometry were used to help constrain the stellar rotation period. We also determined the fundamental parameters of the host star. We find that TOI−757 b has a radius of Rp = 2.5 ± 0.1R. and a mass of Mp = 10.5+−2212M, implying a bulk density of ρp = 3.6 ± 0.8 g cm−3. Our internal composition modelling was unable to constrain the composition of TOI−757 b, highlighting the importance of atmospheric observations for the system. We also find the planet to be highly eccentric with e = 0.39+−000708, making it one of the very few highly eccentric planets among precisely characterized mini−Neptunes. Based on comparisons to other similar eccentric systems, we find a likely scenario for TOI−757 b’s formation to be high eccentricity migration due to a distant outer companion. We additionally propose the possibility of a more intrinsic explanation for the high eccentricity due to star−star interactions during the earlier epoch of the Galactic disc formation, given the low metallicity and older age of TOI−757.
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6. |
- Luque, R., et al.
(författare)
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A planetary system with two transiting mini-Neptunes near the radius valley transition around the bright M dwarf TOI-776
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery and characterization of two transiting planets around the bright M1 V star LP 961-53 (TOI-776, J = 8.5 mag, M = 0.54 ± 0.03 M⊙) detected during Sector 10 observations of the Transiting Exoplanet Survey Satellite (TESS). Combining the TESS photometry with HARPS radial velocities, as well as ground-based follow-up transit observations from the MEarth and LCOGT telescopes, for the inner planet, TOI-776 b, we measured a period of Pb = 8.25 d, a radius of Rb = 1.85 ± 0.13 R⊙, and a mass of Mb = 4.0 ± 0.9 M⊙; and for the outer planet, TOI-776 c, a period of Pc = 15.66 d, a radius of Rc = 2.02 ± 0.14 R⊙, and a mass of Mc = 5.3 ± 1.8 M⊙. The Doppler data shows one additional signal, with a period of ~34 d, associated with the rotational period of the star. The analysis of fifteen years of ground-based photometric monitoring data and the inspection of different spectral line indicators confirm this assumption. The bulk densities of TOI-776 b and c allow for a wide range of possible interior and atmospheric compositions. However, both planets have retained a significant atmosphere, with slightly different envelope mass fractions. Thanks to their location near the radius gap for M dwarfs, we can start to explore the mechanism(s) responsible for the radius valley emergence around low-mass stars as compared to solar-like stars. While a larger sample of well-characterized planets in this parameter space is still needed to draw firm conclusions, we tentatively estimate that the stellar mass below which thermally-driven mass loss is no longer the main formation pathway for sculpting the radius valley is between 0.63 and 0.54 M⊙. Due to the brightness of the star, the TOI-776 system is also an excellent target for the James Webb Space Telescope, providing a remarkable laboratory in which to break the degeneracy in planetary interior models and to test formation and evolution theories of small planets around low-mass stars.
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- Serrano, L. M., et al.
(författare)
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A low-eccentricity migration pathway for a 13-h-period Earth analogue in a four-planet system
- 2022
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 6:6, s. 736-750
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Tidskriftsartikel (refereegranskat)abstract
- It is commonly accepted that exoplanets with orbital periods shorter than one day, also known as ultra-short-period (USP) planets, formed further out within their natal protoplanetary disks before migrating to their current-day orbits via dynamical interactions. One of the most accepted theories suggests a violent scenario involving high-eccentricity migration followed by tidal circularization. Here we present the discovery of a four-planet system orbiting the bright (V = 10.5) K6 dwarf star TOI-500. The innermost planet is a transiting, Earth-sized USP planet with an orbital period of ~13 hours, a mass of 1.42 ± 0.18 M⊕, a radius of 1.166−0.058+0.061R⊕ and a mean density of 4.89−0.88+1.03gcm−3. Via Doppler spectroscopy, we discovered that the system hosts 3 outer planets on nearly circular orbits with periods of 6.6, 26.2 and 61.3 days and minimum masses of 5.03 ± 0.41 M⊕, 33.12 ± 0.88 M⊕ and 15.05−1.11+1.12M⊕, respectively. The presence of both a USP planet and a low-mass object on a 6.6-day orbit indicates that the architecture of this system can be explained via a scenario in which the planets started on low-eccentricity orbits then moved inwards through a quasi-static secular migration. Our numerical simulations show that this migration channel can bring TOI-500 b to its current location in 2 Gyr, starting from an initial orbit of 0.02 au. TOI-500 is the first four-planet system known to host a USP Earth analogue whose current architecture can be explained via a non-violent migration scenario.
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8. |
- Grundberg, Elin, et al.
(författare)
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Global Analysis of the Impact of Environmental Perturbation on cis-Regulation of Gene Expression
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:1, s. e1001279-
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent by which controlled, environmental perturbation influences cis-eQTLs is unclear. We carried out large-scale induction experiments using primary human bone cells derived from unrelated donors of Swedish origin treated with 18 different stimuli (7 treatments and 2 controls, each assessed at 2 time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t = 2h), dexamethasone (DEX) (t = 24h), and PGE(2) (t = 24h). Using these treatments and control, we performed expression profiling for 18,144 RefSeq transcripts on biological replicates of the complete study cohort of 113 individuals (n(total) = 782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs (defined as SNPs located within the gene +/- 250 kb). We found that 93% of cis-eQTLs at 1% FDR were observed in at least one additional treatment, and in fact, on average, only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment. Treatment-specific cis-regulatory effects were, however, 2- to 6-fold more abundant among differently expressed genes upon treatment. We further followed-up and validated the DEX-specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 kb and 250 kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interactions between cellular environment and cis-variants are relatively rare (similar to 1.5%), but that detection of such specific interactions can be achieved by a combination of functional genomic approaches as described here.
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9. |
- Grundberg, Elin, et al.
(författare)
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Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells
- 2008
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 33:3, s. 301-11
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Tidskriftsartikel (refereegranskat)abstract
- Osteoblasts are key players in bone remodeling. The accessibility of human primary osteoblast-like cells (HObs) from bone explants makes them a lucrative model for studying molecular physiology of bone turnover, for discovering novel anabolic therapeutics, and for mesenchymal cell biology in general. Relatively little is known about resting and dynamic expression profiles of HObs, and to date no studies have been conducted to systematically assess the osteoblast transcriptome. The aim of this study was to characterize HObs and investigate signaling cascades and gene networks with genomewide expression profiling in resting and bone morphogenic protein (BMP)-2- and dexamethasone-induced cells. In addition, we compared HOb gene expression with publicly available samples from the Gene Expression Omnibus. Our data show a vast number of genes and networks expressed predominantly in HObs compared with closely related cells such as fibroblasts or chondrocytes. For instance, genes in the insulin-like growth factor (IGF) signaling pathway were enriched in HObs (P = 0.003) and included the binding proteins (IGFBP-1, -2, -5) and IGF-II and its receptor. Another HOb-specific expression pattern included leptin and its receptor (P < 10(-8)). Furthermore, after stimulation of HObs with BMP-2 or dexamethasone, the expression of several interesting genes and pathways was observed. For instance, our data support the role of peripheral leptin signaling in bone cell function. In conclusion, we provide the landscape of tissue-specific and dynamic gene expression in HObs. This resource will allow utilization of osteoblasts as a model to study specific gene networks and gene families related to human bone physiology and diseases.
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10. |
- Kwan, Tony, et al.
(författare)
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Tissue effect on genetic control of transcript isoform variation.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- Current genome-wide association studies (GWAS) are moving towards the use of large cohorts of primary cell lines to study a disease of interest and to assign biological relevance to the genetic signals identified. Here, we use a panel of human osteoblasts (HObs) to carry out a transcriptomic survey, similar to recent studies in lymphoblastoid cell lines (LCLs). The distinct nature of HObs and LCLs is reflected by the preferential grouping of cell type-specific genes within biologically and functionally relevant pathways unique to each tissue type. We performed cis-association analysis with SNP genotypes to identify genetic variations of transcript isoforms, and our analysis indicates that differential expression of transcript isoforms in HObs is also partly controlled by cis-regulatory genetic variants. These isoforms are regulated by genetic variants in both a tissue-specific and tissue-independent fashion, and these associations have been confirmed by RT-PCR validation. Our study suggests that multiple transcript isoforms are often present in both tissues and that genetic control may affect the relative expression of one isoform to another, rather than having an all-or-none effect. Examination of the top SNPs from a GWAS of bone mineral density show overlap with probeset associations observed in this study. The top hit corresponding to the FAM118A gene was tested for association studies in two additional clinical studies, revealing a novel transcript isoform variant. Our approach to examining transcriptome variation in multiple tissue types is useful for detecting the proportion of genetic variation common to different cell types and for the identification of cell-specific isoform variants that may be functionally relevant, an important follow-up step for GWAS.
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