| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Hjorth, M., et al.
(författare)
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K2-290: A warm Jupiter and a mini-Neptune in a triple-star system
- 2019
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 484:3, s. 3522-3536
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of two transiting planets orbiting K2-290 (EPIC 249624646), a bright (V = 11.11) late F-type star residing in a triple-star system. It was observed during Campaign 15 of the K2 mission, and in order to confirm and characterize the system, follow-up spectroscopy and AO imaging were carried out using the FIES, HARPS, HARPS-N, and IRCS instruments. From AO imaging and Gaia data we identify two M-dwarf companions at a separation of 113 ± 2 and 2467+−177155 au. From radial velocities, K2 photometry, and stellar characterization of the host star, we find the inner planet to be a mini-Neptune with a radius of 3.06 ± 0.16 R and an orbital period of P = 9.2 d. The radius of the mini-Neptune suggests that the planet is located above the radius valley, and with an incident flux of F ∼ 400 F, it lies safely outside the super-Earth desert. The outer warm Jupiter has a mass of 0.774 ± 0.047 MJ and a radius of 1.006 ± 0.050 RJ, and orbits the host star every 48.4 d on an orbit with an eccentricity e < 0.241. Its mild eccentricity and mini-Neptune sibling suggest that the warm Jupiter originates from in situ formation or disc migration.
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| 3. |
- Palle, Enric, et al.
(författare)
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Detection and Doppler monitoring of K2-285 (EPIC 246471491), a system of four transiting planets smaller than Neptune
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Kepler extended mission, also known as K2, has provided the community with a wealth of planetary candidates that orbit stars typically much brighter than the targets of the original mission. These planet candidates are suitable for further spectroscopic follow-up and precise mass determinations, leading ultimately to the construction of empirical mass-radius diagrams. Particularly interesting is to constrain the properties of planets that are between Earth and Neptune in size, the most abundant type of planet orbiting Sun-like stars with periods of less than a few years. Aims. Among many other K2 candidates, we discovered a multi-planetary system around EPIC 246471491, referred to henceforth as K2-285, which contains four planets, ranging in size from twice the size of Earth to nearly the size of Neptune. We aim here at confirming their planetary nature and characterizing the properties of this system. Methods. We measure the mass of the planets of the K2-285 system by means of precise radial-velocity measurements using the CARMENES spectrograph and the HARPS-N spectrograph. Results. With our data we are able to determine the mass of the two inner planets of the system with a precision better than 15%, and place upper limits on the masses of the two outer planets. Conclusions. We find that K2-285b has a mass of M b = 9.68 -1.37+1.21 M · and a radius of R b = 2.59 -0.06+0.06 R · , yielding a mean density of ρ b = 3.07 -0.45+0.45 g cm -3 , while K2-285c has a mass of M c = 15.68 -2.13+2.28 M · , radius of R c = 3.53 -0.08+0.08 R · , and a mean density of ρ c = 1.95 -0.28+0.32 g cm -3 . For K2-285d (R d = 2.48 -0.06+0.06 R · ) and K2-285e (R e = 1.95 -0.05+0.05 R · ), the upper limits for the masses are 6.5 M · and 10.7 M · , respectively. The system is thus composed of an (almost) Neptune-twin planet (in mass and radius), two sub-Neptunes with very different densities and presumably bulk composition, and a fourth planet in the outermost orbit that resides right in the middle of the super-Earth/sub-Neptune radius gap. Future comparative planetology studies of this system would provide useful insights into planetary formation, and also a good test of atmospheric escape and evolution theories.
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| 4. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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| 5. |
- Persson, Carina, 1964, et al.
(författare)
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Greening of the brown-dwarf desert EPIC 212036875b: a 51 M-J object in a 5-day orbit around an F7V star
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 628
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Tidskriftsartikel (refereegranskat)abstract
- Context. Although more than 2000 brown dwarfs have been detected to date, mainly from direct imaging, their characterisation is difficult due to their faintness and model-dependent results. In the case of transiting brown dwarfs, however, it is possible to make direct high-precision observations. Aims. Our aim is to investigate the nature and formation of brown dwarfs by adding a new well-characterised object, in terms of its mass, radius and bulk density, to the currently small sample of less than 20 transiting brown dwarfs. Methods. One brown dwarf candidate was found by the KESPRINT consortium when searching for exoplanets in the K2 space mission Campaign 16 field. We combined the K2 photometric data with a series of multicolour photometric observations, imaging, and radial velocity measurements to rule out false positive scenarios and to determine the fundamental properties of the system. Results. We report the discovery and characterisation of a transiting brown dwarf in a 5.17-day eccentric orbit around the slightly evolved F7V star EPIC 212036875. We find a stellar mass of 1.15 +/- 0.08 M-circle dot, a stellar radius of 1.41 +/- 0.05 R-circle dot, and an age of 5.1 +/- 0.9 Gyr. The mass and radius of the companion brown dwarf are 51 +/- 2 M-J and 0.83 +/- 0.03 R-J, respectively, corresponding to a mean density of 108(-13)(+15) g cm(-3). Conclusions. EPIC 212036875 b is a rare object that resides in the brown-dwarf desert. In the mass-density diagram for planets, brown dwarfs, and stars, we find that all giant planets and brown dwarfs follow the same trend from similar to 0.3 M-J to the turn-over to hydrogen burning stars at similar to 73 M-J. EPIC 212036875 b falls close to the theoretical model for mature H/He dominated objects in this diagram as determined by interior structure models. We argue that EPIC 212036875 b formed via gravitational disc instabilities in the outer part of the disc, followed by a quick migration. Orbital tidal circularisation may have started early in its history for a brief period when the brown dwarf's radius was larger. The lack of spin-orbit synchronisation points to a weak stellar dissipation parameter (Q(star)' greater than or similar to 10(8)), which implies a circularisation timescale of greater than or similar to 23 Gyr, or suggests an interaction between the magnetic and tidal forces of the star and the brown dwarf.
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