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| 4. |
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| 5. |
- van Rheenen, W, et al.
(författare)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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| 6. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 7. |
- Feroci, M., et al.
(författare)
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The large observatory for x-ray timing
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
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Konferensbidrag (refereegranskat)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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| 8. |
- van Es, Michael A, et al.
(författare)
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Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
- 2011
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Ingår i: Annals of Neurology. - : Wiley-Blackwell. - 0364-5134 .- 1531-8249. ; 70:6, s. 964-973
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
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| 9. |
- 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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| 10. |
- Psaridi, A., et al.
(författare)
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Discovery of two warm mini-Neptunes with contrasting densities orbiting the young K3V star TOI-815
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery and characterization of two warm mini-Neptunes transiting the K3V star TOI-815 in a K–M binary system. Analysis of its spectra and rotation period reveal the star to be young, with an age of 200+−400200 Myr. TOI-815b has a 11.2-day period and a radius of 2.94 ± 0.05 R+ with transits observed by TESS, CHEOPS, ASTEP, and LCOGT. The outer planet, TOI-815c, has a radius of 2.62 ± 0.10 R+, based on observations of three nonconsecutive transits with TESS; targeted CHEOPS photometry and radial velocity follow-up with ESPRESSO were required to confirm the 35-day period. ESPRESSO confirmed the planetary nature of both planets and measured masses of 7.6 ± 1.5 M+ (ρP = 1.64+−003331 g cm−3) and 23.5 ± 2.4 M+ (ρP = 7.2+−1110 g cm−3), respectively. Thus, the planets have very different masses, which is unusual for compact multi-planet systems. Moreover, our statistical analysis of mini-Neptunes orbiting FGK stars suggests that weakly irradiated planets tend to have higher bulk densities compared to those undergoing strong irradiation. This could be ascribed to their cooler atmospheres, which are more compressed and denser. Internal structure modeling of TOI-815b suggests it likely has a H-He atmosphere that constitutes a few percent of the total planet mass, or higher if the planet is assumed to have no water. In contrast, the measured mass and radius of TOI-815c can be explained without invoking any atmosphere, challenging planetary formation theories. Finally, we infer from our measurements that the star is viewed close to pole-on, which implies a spin-orbit misalignment at the 3σ level. This emphasizes the peculiarity of the system’s orbital architecture, and probably hints at an eventful dynamical history.
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| 11. |
- van Rheenen, Wouter, et al.
(författare)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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| 12. |
- Kenna, Kevin P., et al.
(författare)
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NEK1 variants confer susceptibility to amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1037-1042
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.
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| 13. |
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| 14. |
- Bonfanti, A., et al.
(författare)
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TOI-1055 b: Neptunian planet characterised with HARPS, TESS, and CHEOPS
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Tidskriftsartikel (refereegranskat)abstract
- Context. TOI-1055 is a Sun-like star known to host a transiting Neptune-sized planet on a 17.5-day orbit (TOI-1055 b). Radial velocity (RV) analyses carried out by two independent groups using nearly the same set of HARPS spectra have provided measurements of planetary masses that differ by ∼2σ. Aims. Our aim in this work is to solve the inconsistency in the published planetary masses by significantly extending the set of HARPS RV measurements and employing a new analysis tool that is able to account and correct for stellar activity. Our further aim was to improve the precision on measurements of the planetary radius by observing two transits of the planet with the CHEOPS space telescope. Methods. We fit a skew normal function to each cross correlation function extracted from the HARPS spectra to obtain RV measurements and hyperparameters to be used for the detrending. We evaluated the correlation changes of the hyperparameters along the RV time series using the breakpoint technique. We performed a joint photometric and RV analysis using a Markov chain Monte Carlo scheme to simultaneously detrend the light curves and the RV time series. Results. We firmly detected the Keplerian signal of TOI-1055 b, deriving a planetary mass of Mb = 20.4-2.5+2.6 MO (∼12%). This value is in agreement with one of the two estimates in the literature, but it is significantly more precise. Thanks to the TESS transit light curves combined with exquisite CHEOPS photometry, we also derived a planetary radius of Rb = 3.490-0.064+0.070 RO (∼1.9%). Our mass and radius measurements imply a mean density of ρb = 2.65-0.35+0.37 g cm-3 (∼14%). We further inferred the planetary structure and found that TOI-1055 b is very likely to host a substantial gas envelope with a mass of 0.41-0.20+0.34 MO and a thickness of 1.05-0.29+0.30 RO. Conclusions. Our RV extraction combined with the breakpoint technique has played a key role in the optimal removal of stellar activity from the HARPS time series, enabling us to solve the tension in the planetary mass values published so far for TOI-1055 b.
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| 15. |
- Maxted, P. F. L., et al.
(författare)
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Fundamental effective temperature measurements for eclipsing binary stars - III. SPIRou near-infrared spectroscopy and CHEOPS photometry of the benchmark G0V star EBLM J0113+31
- 2022
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 6042-6057
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Tidskriftsartikel (refereegranskat)abstract
- EBLM J0113+31 is a moderately bright (V = 10.1), metal-poor ([Fe/H] approximate to-0.3) GOV star with a much fainter M dwarf companion on a wide, eccentric orbit (= 14.3 d). We have used near-infrared spectroscopy obtained with the SPIRou spectrograph to measure the semi-amplitude of the M dwarf's spectroscopic orbit, and high-precision photometry of the eclipse and transit from the CHEOPS and TESS space missions to measure the geometry of this binary system. From the combined analysis of these data together with previously published observations, we obtain the following model-independent masses and radii: M-1 = 1.029 +/- 0.025 M-circle dot, M-2 = 0.197 +/- 0.003 M-circle dot, R-1 = 1.417 +/- 0.014 R-circle dot, R-2 = 0.215 +/- 0.002 R-circle dot. Using R-1 and the parallax from Gaia EDR3 we find that this star's angular diameter is theta = 0.0745 +/- 0.0007 mas. The apparent bolometric flux of the GOV star corrected for both extinction and the contribution from the M dwarf (<0.2 per cent) is F-circle plus,F-0 = (2.62 +/- 0.05) x 10(-9) erg cm(-2) S-1. Hence, this G0V star has an effective temperature T-eff(,1) = 6124 K +/- 40 K (rnd.) +/- 10 K (sys.). EBLM J0113+31 is an ideal benchmark star that can be used for 'end-to-end' tests of the stellar parameters measured by large-scale spectroscopic surveys, or stellar parameters derived from asteroseismology with PLATO. The techniques developed here can be applied to many other eclipsing binaries in order to create a network of such benchmark stars.
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| 16. |
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| 17. |
- van Rheenen, Wouter, et al.
(författare)
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H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:5, s. 1517.e5-1517.e7
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Tidskriftsartikel (refereegranskat)abstract
- The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival. (C) 2013 Elsevier Inc. All rights reserved.
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| 18. |
- Alonso, R., et al.
(författare)
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No random transits in CHEOPS observations of HD 139139 *,**
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 680
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Tidskriftsartikel (refereegranskat)abstract
- Context . The star HD 139139 (a.k.a. ‘the Random Transiter’) is a star that exhibited enigmatic transit-like features with no apparent periodicity in K2 data. The shallow depth of the events (-200 ppm - equivalent to transiting objects with radii of -1.5 R⊕ in front of a Sun-like star) and their non-periodicity constitute a challenge for the photometric follow-up of this star. Aims . The goal of this study is to confirm with independent measurements the presence of shallow, non-periodic transit-like features on this object. Methods . We performed observations with CHEOPS for a total accumulated time of 12.75 days, distributed in visits of roughly 20 h in two observing campaigns in years 2021 and 2022. The precision of the data is sufficient to detect 150 ppm features with durations longer than 1.5 h. We used the duration and times of the events seen in the K2 curve to estimate how many events should have been detected in our campaigns, under the assumption that their behaviour during the CHEOPS observations would be the same as in the K2 data of 2017. Results . We do not detect events with depths larger than 150 ppm in our data set. If the frequency, depth, and duration of the events were the same as in the K2 campaign, we estimate the probability of having missed all events due to our limited observing window would be 4.8%. Conclusions . We suggest three different scenarios to explain our results: 1) Our observing window was not long enough, and the events were missed with the estimated 4.8% probability. 2) The events recorded in the K2 observations were time critical, and the mechanism producing them was either not active in the 2021 and 2022 campaigns or created shallower events under our detectability level. 3) The enigmatic events in the K2 data are the result of an unidentified and infrequent instrumental noise in the original data set or its data treatment.
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| 19. |
- Bonfanti, A., et al.
(författare)
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CHEOPS observations of the HD 108236 planetary system: A fifth planet, improved ephemerides, and planetary radii
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 646
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Tidskriftsartikel (refereegranskat)abstract
- Context. The detection of a super-Earth and three mini-Neptunes transiting the bright (V = 9.2 mag) star HD 108236 (also known as TOI-1233) was recently reported on the basis of TESS and ground-based light curves. Aims. We perform a first characterisation of the HD 108236 planetary system through high-precision CHEOPS photometry and improve the transit ephemerides and system parameters. Methods. We characterise the host star through spectroscopic analysis and derive the radius with the infrared flux method. We constrain the stellar mass and age by combining the results obtained from two sets of stellar evolutionary tracks. We analyse the available TESS light curves and one CHEOPS transit light curve for each known planet in the system. Results. We find that HD 108236 is a Sun-like star with R? = 0.877 ± 0.008 R? , M? = 0.869-0.048+0.050 M? , and an age of 6.7-5.1+4.0 Gyr. We report the serendipitous detection of an additional planet, HD 108236 f, in one of the CHEOPS light curves. For this planet, the combined analysis of the TESS and CHEOPS light curves leads to a tentative orbital period of about 29.5 days. From the light curve analysis, we obtain radii of 1.615 ± 0.051, 2.071 ± 0.052, 2.539-0.065+0.062, 3.083 ± 0.052, and 2.017-0.057+0.052 R? for planets HD 108236 b to HD 108236 f, respectively. These values are in agreement with previous TESS-based estimates, but with an improved precision of about a factor of two. We perform a stability analysis of the system, concluding that the planetary orbits most likely have eccentricities smaller than 0.1. We also employ a planetary atmospheric evolution framework to constrain the masses of the five planets, concluding that HD 108236 b and HD 108236 c should have an Earth-like density, while the outer planets should host a low mean molecular weight envelope. Conclusions. The detection of the fifth planet makes HD 108236 the third system brighter than V = 10 mag to host more than four transiting planets. The longer time span enables us to significantly improve the orbital ephemerides such that the uncertainty on the transit times will be of the order of minutes for the years to come. A comparison of the results obtained from the TESS and CHEOPS light curves indicates that for a V - 9 mag solar-like star and a transit signal of -500 ppm, one CHEOPS transit light curve ensures the same level of photometric precision as eight TESS transits combined, although this conclusion depends on the length and position of the gaps in the light curve.
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| 20. |
- Davies, M.B., et al.
(författare)
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Glancing through the debris disk: Photometric analysis of de Boo with CHEOPS
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Tidskriftsartikel (refereegranskat)abstract
- Aims. DE Boo is a unique system, with an edge-on view through the debris disk around the star. The disk, which is analogous to the Kuiper belt in the Solar System, was reported to extend from 74 to 84 AU from the central star. The high photometric precision of the Characterising Exoplanet Satellite (CHEOPS) provided an exceptional opportunity to observe small variations in the light curve due to transiting material in the disk. This is a unique chance to investigate processes in the debris disk. Methods. Photometric observations of DE Boo of a total of four days were carried out with CHEOPS. Photometric variations due to spots on the stellar surface were subtracted from the light curves by applying a two-spot model and a fourth-order polynomial. The photometric observations were accompanied by spectroscopic measurements with the 1m RCC telescope at Piszkésteto and with the SOPHIE spectrograph in order to refine the astrophysical parameters of DE Boo. Results. We present a detailed analysis of the photometric observation of DE Boo. We report the presence of nonperiodic transient features in the residual light curves with a transit duration of 0.3-0.8 days. We calculated the maximum distance of the material responsible for these variations to be 2.47 AU from the central star, much closer than most of the mass of the debris disk. Furthermore, we report the first observation of flaring events in this system. Conclusions. We interpreted the transient features as the result of scattering in an inner debris disk around DE Boo. The processes responsible for these variations were investigated in the context of interactions between planetesimals in the system.
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| 21. |
- Deline, A., et al.
(författare)
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The atmosphere and architecture of WASP-189 b probed by its CHEOPS phase curve
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gas giants orbiting close to hot and massive early-type stars can reach dayside temperatures that are comparable to those of the coldest stars. These 'ultra-hot Jupiters' have atmospheres made of ions and atomic species from molecular dissociation and feature strong day-to-night temperature gradients. Photometric observations at different orbital phases provide insights on the planet's atmospheric properties. Aims. We aim to analyse the photometric observations of WASP-189 acquired with the Characterising Exoplanet Satellite (CHEOPS) to derive constraints on the system architecture and the planetary atmosphere. Methods. We implemented a light-curve model suited for an asymmetric transit shape caused by the gravity-darkened photosphere of the fast-rotating host star. We also modelled the reflective and thermal components of the planetary flux, the effect of stellar oblateness and light-travel time on transit-eclipse timings, the stellar activity, and CHEOPS systematics. Results. From the asymmetric transit, we measure the size of the ultra-hot Jupiter WASP-189 b, R-p = 1.600(-0.016)(+0.017)R(J), with a precision of 1%, and the true orbital obliquity of the planetary system, Psi(P) = 89.6 +/- 1.2 deg (polar orbit). We detect no significant hotspot offset from the phase curve and obtain an eclipse depth of delta ecl = 96.5(-5.9)(+4).(5) ppm, from which we derive an upper limit on the geometric albedo: A(g) < 0.48. We also find that the eclipse depth can only be explained by thermal emission alone in the case of extremely inefficient energy redistribution. Finally, we attribute the photometric variability to the stellar rotation, either through superficial inhomogeneities or resonance couplings between the convective core and the radiative envelope. Conclusions. Based on the derived system architecture, we predict the eclipse depth in the upcoming Transiting Exoplanet Survey Satellite (TESS) observations to be up to similar to 165 ppm. High-precision detection of the eclipse in both CHEOPS and TESS passbands might help disentangle reflective and thermal contributions. We also expect the right ascension of the ascending node of the orbit to precess due to the perturbations induced by the stellar quadrupole moment J(2) (oblateness).
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| 22. |
- Ehrenreich, D., et al.
(författare)
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A full transit of v 2 Lupi d and the search for an exomoon in its Hill sphere with CHEOPS
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Tidskriftsartikel (refereegranskat)abstract
- The planetary system around the naked-eye star v2 Lupi (HD 136352; TOI-2011) is composed of three exoplanets with masses of 4.7, 11.2, and 8.6 Earth masses (M⊕). The TESS and CHEOPS missions revealed that all three planets are transiting and have radii straddling the radius gap separating volatile-rich and volatile-poor super-earths. Only a partial transit of planet d had been covered so we re-observed an inferior conjunction of the long-period 8.6 M⊕ exoplanet v2 Lup d with the CHEOPS space telescope. We confirmed its transiting nature by covering its whole 9.1 h transit for the first time. We refined the planet transit ephemeris to P = 107.13610.0022+0.0019 days and Tc = 2459009.77590.0096+0.0101 BJDTDB, improving by ~40 times on the previously reported transit timing uncertainty. This refined ephemeris will enable further follow-up of this outstanding long-period transiting planet to search for atmospheric signatures or explore the planet s Hill sphere in search for an exomoon. In fact, the CHEOPS observations also cover the transit of a large fraction of the planet s Hill sphere, which is as large as the Earth s, opening the tantalising possibility of catching transiting exomoons. We conducted a search for exomoon signals in this single-epoch light curve but found no conclusive photometric signature of additional transiting bodies larger than Mars. Yet, only a sustained follow-up of v2 Lup d transits will warrant a comprehensive search for a moon around this outstanding exoplanet.
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| 23. |
- Krenn, A., et al.
(författare)
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The geometric albedo of the hot Jupiter HD 189733b measured with CHEOPS
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 672
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Tidskriftsartikel (refereegranskat)abstract
- Context. Measurements of the occultation of an exoplanet at visible wavelengths allow us to determine the reflective properties of a planetary atmosphere. The observed occultation depth can be translated into a geometric albedo. This in turn aids in characterising the structure and composition of an atmosphere by providing additional information on the wavelength-dependent reflective qualities of the aerosols in the atmosphere. Aims. Our aim is to provide a precise measurement of the geometric albedo of the gas giant HD 189733b by measuring the occultation depth in the broad optical bandpass of CHEOPS (350-1100 nm). Methods. We analysed 13 observations of the occultation of HD 189733b performed by CHEOPS utilising the Python package PyCHEOPS. The resulting occultation depth is then used to infer the geometric albedo accounting for the contribution of thermal emission from the planet. We also aid the analysis by refining the transit parameters combining observations made by the TESS and CHEOPS space telescopes. Results. We report the detection of an 24.7 ± 4.5 ppm occultation in the CHEOPS observations. This occultation depth corresponds to a geometric albedo of 0.076 ± 0.016. Our measurement is consistent with models assuming the atmosphere of the planet to be cloud-free at the scattering level and absorption in the CHEOPS band to be dominated by the resonant Na doublet. Taking into account previous optical-light occultation observations obtained with the Hubble Space Telescope, both measurements combined are consistent with a super-stellar Na elemental abundance in the dayside atmosphere of HD 189733b. We further constrain the planetary Bond albedo to between 0.013 and 0.42 at 3σconfidence. Conclusions. We find that the reflective properties of the HD 189733b dayside atmosphere are consistent with a cloud-free atmosphere having a super-stellar metal content. When compared to an analogous CHEOPS measurement for HD 209458b, our data hint at a slightly lower geometric albedo for HD 189733b (0.076 ± 0.016) than for HD 209458b (0.096 ± 0.016), or a higher atmospheric Na content in the same modelling framework. While our constraint on the Bond albedo is consistent with previously published values, we note that the higher-end values of ∼0.4, as derived previously from infrared phase curves, would also require peculiarly high reflectance in the infrared, which again would make it more difficult to disentangle reflected and emitted light in the total observed flux, and therefore to correctly account for reflected light in the interpretation of those phase curves. Lower reported values for the Bond albedos are less affected by this ambiguity.
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| 24. |
- Maxted, P. F. L., et al.
(författare)
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Analysis of Early Science observations with the CHaracterising ExOPlanets Satellite (CHEOPS) using pycheops
- 2022
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 514:1, s. 77-104
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Tidskriftsartikel (refereegranskat)abstract
- CHEOPS (CHaracterising ExOPlanet Satellite) is an ESA S-class mission that observes bright stars at high cadence from low-Earth orbit. The main aim of the mission is to characterize exoplanets that transit nearby stars using ultrahigh precision photometry. Here, we report the analysis of transits observed by CHEOPS during its Early Science observing programme for four well-known exoplanets: GJ 436 b, HD 106315 b, HD 97658 b, and GJ 1132 b. The analysis is done using pycheops, an open-source software package we have developed to easily and efficiently analyse CHEOPS light-curve data using state-of-the-art techniques that are fully described herein. We show that the precision of the transit parameters measured using CHEOPS is comparable to that from larger space telescopes such as Spitzer Space Telescope and Kepler. We use the updated planet parameters from our analysis to derive new constraints on the internal structure of these four exoplanets.
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| 25. |
- Pagano, I., et al.
(författare)
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Constraining the reflective properties of WASP-178 b using CHEOPS photometry
- 2024
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Multiwavelength photometry of the secondary eclipses of extrasolar planets is able to disentangle the reflected and thermally emitted light radiated from the planetary dayside. Based on this, we can measure the planetary geometric albedo Ag, which is an indicator of the presence of clouds in the atmosphere, and the recirculation efficiency ϵ, which quantifies the energy transport within the atmosphere. Aims. We measure Ag and ϵ for the planet WASP-178 b, a highly irradiated giant planet with an estimated equilibrium temperature of 2450 K. Methods. We analyzed archival spectra and the light curves collected by CHEOPS and TESS to characterize the host WASP-178, refine the ephemeris of the system, and measure the eclipse depth in the passbands of the two telescopes. Results. We measured a marginally significant eclipse depth of 70 ± 40 ppm in the TESS passband, and a statistically significant depth of 70 ± 20 ppm in the CHEOPS passband. Conclusions. Combining the eclipse-depth measurement in the CHEOPS (λeff = 6300 Å) and TESS (λeff = 8000 Å) passbands, we constrained the dayside brightness temperature of WASP-178 b in the 2250-2800 K interval. The geometric albedo 0.1< Ag<0.35 generally supports the picture that giant planets are poorly reflective, while the recirculation efficiency ϵ >0.7 makes WASP-178 b an interesting laboratory for testing the current heat-recirculation models.
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| 26. |
- Sulis, S., et al.
(författare)
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Connecting photometric and spectroscopic granulation signals with CHEOPS and ESPRESSO
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 670
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Tidskriftsartikel (refereegranskat)abstract
- Context. Stellar granulation generates fluctuations in photometric and spectroscopic data whose properties depend on the stellar type, composition, and evolutionary state. Characterizing granulation is key for understanding stellar atmospheres and detecting planets. Aims. We aim to detect the signatures of stellar granulation, link spectroscopic and photometric signatures of convection for main-sequence stars, and test predictions from 3D hydrodynamic models. Methods. For the first time, we observed two bright stars (Teff = 5833 and 6205 K) with high-precision observations taken simultaneously with CHEOPS and ESPRESSO. We analyzed the properties of the stellar granulation signal in each individual dataset. We compared them to Kepler observations and 3D hydrodynamic models. While isolating the granulation-induced changes by attenuating and filtering the p-mode oscillation signals, we studied the relationship between photometric and spectroscopic observables. Results. The signature of stellar granulation is detected and precisely characterized for the hotter F star in the CHEOPS and ESPRESSO observations. For the cooler G star, we obtain a clear detection in the CHEOPS dataset only. The TESS observations are blind to this stellar signal. Based on CHEOPS observations, we show that the inferred properties of stellar granulation are in agreement with both Kepler observations and hydrodynamic models. Comparing their periodograms, we observe a strong link between spectroscopic and photometric observables. Correlations of this stellar signal in the time domain (flux versus radial velocities, RV) and with specific spectroscopic observables (shape of the cross-correlation functions) are however difficult to isolate due to S/N dependent variations. Conclusions. In the context of the upcoming PLATO mission and the extreme precision RV surveys, a thorough understanding of the properties of the stellar granulation signal is needed. The CHEOPS and ESPRESSO observations pave the way for detailed analyses of this stellar process.
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| 27. |
- Barros, S. C. C., et al.
(författare)
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Detection of the tidal deformation of WASP-103b at 3σ with CHEOPS
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 657
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Ultra-short period planets undergo strong tidal interactions with their host star which lead to planet deformation and orbital tidal decay.Aims. WASP-103b is the exoplanet with the highest expected deformation signature in its transit light curve and one of the shortest expected spiral-in times. Measuring the tidal deformation of the planet would allow us to estimate the second degree fluid Love number and gain insight into the planet's internal structure. Moreover, measuring the tidal decay timescale would allow us to estimate the stellar tidal quality factor, which is key to constraining stellar physics.Methods. We obtained 12 transit light curves of WASP-103b with the CHaracterising ExOplanet Satellite (CHEOPS) to estimate the tidal deformation and tidal decay of this extreme system. We modelled the high-precision CHEOPS transit light curves together with systematic instrumental noise using multi-dimensional Gaussian process regression informed by a set of instrumental parameters. To model the tidal deformation, we used a parametrisation model which allowed us to determine the second degree fluid Love number of the planet. We combined our light curves with previously observed transits of WASP-103b with the Hubble Space Telescope (HST) and Spitzer to increase the signal-to-noise of the light curve and better distinguish the minute signal expected from the planetary deformation.Results. We estimate the radial Love number of WASP-103b to be h(f) = 1.59(-0.53)(+0.45). This is the first time that the tidal deformation is directly detected (at 3 sigma) from the transit light curve of an exoplanet. Combining the transit times derived from CHEOPS, HST, and Spitzer light curves with the other transit times available in the literature, we find no significant orbital period variation for WASP-103b. However, the data show a hint of an orbital period increase instead of a decrease, as is expected for tidal decay. This could be either due to a visual companion star if this star is bound, the Applegate effect, or a statistical artefact.Conclusions. The estimated Love number of WASP-103b is similar to Jupiter's. This will allow us to constrain the internal structure and composition of WASP-103b, which could provide clues on the inflation of hot Jupiters. Future observations with James Webb Space Telescope can better constrain the radial Love number of WASP-103b due to their high signal-to-noise and the smaller signature of limb darkening in the infrared. A longer time baseline is needed to constrain the tidal decay in this system.
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| 28. |
- Benz, W., et al.
(författare)
-
The CHEOPS mission
- 2021
-
Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51:1, s. 109-151
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Tidskriftsartikel (refereegranskat)abstract
- The CHaracterising ExOPlanet Satellite (CHEOPS) was selected on October 19, 2012, as the first small mission (S-mission) in the ESA Science Programme and successfully launched on December 18, 2019, as a secondary passenger on a Soyuz-Fregat rocket from Kourou, French Guiana. CHEOPS is a partnership between ESA and Switzerland with important contributions by ten additional ESA Member States. CHEOPS is the first mission dedicated to search for transits of exoplanets using ultrahigh precision photometry on bright stars already known to host planets. As a follow-up mission, CHEOPS is mainly dedicated to improving, whenever possible, existing radii measurements or provide first accurate measurements for a subset of those planets for which the mass has already been estimated from ground-based spectroscopic surveys. The expected photometric precision will also allow CHEOPS to go beyond measuring only transits and to follow phase curves or to search for exo-moons, for example. Finally, by unveiling transiting exoplanets with high potential for in-depth characterisation, CHEOPS will also provide prime targets for future instruments suited to the spectroscopic characterisation of exoplanetary atmospheres. To reach its science objectives, requirements on the photometric precision and stability have been derived for stars with magnitudes ranging from 6 to 12 in the V band. In particular, CHEOPS shall be able to detect Earth-size planets transiting G5 dwarf stars (stellar radius of 0.9R⊙) in the magnitude range 6 ≤ V ≤ 9 by achieving a photometric precision of 20 ppm in 6 hours of integration time. In the case of K-type stars (stellar radius of 0.7R⊙) of magnitude in the range 9 ≤ V ≤ 12, CHEOPS shall be able to detect transiting Neptune-size planets achieving a photometric precision of 85 ppm in 3 hours of integration time. This precision has to be maintained over continuous periods of observation for up to 48 hours. This precision and stability will be achieved by using a single, frame-transfer, back-illuminated CCD detector at the focal plane assembly of a 33.5 cm diameter, on-axis Ritchey-Chrétien telescope. The nearly 275 kg spacecraft is nadir-locked, with a pointing accuracy of about 1 arcsec rms, and will allow for at least 1 Gbit/day downlink. The sun-synchronous dusk-dawn orbit at 700 km altitude enables having the Sun permanently on the backside of the spacecraft thus minimising Earth stray light. A mission duration of 3.5 years in orbit is foreseen to enable the execution of the science programme. During this period, 20% of the observing time is available to the wider community through yearly ESA call for proposals, as well as through discretionary time approved by ESA’s Director of Science. At the time of this writing, CHEOPS commissioning has been completed and CHEOPS has been shown to fulfill all its requirements. The mission has now started the execution of its science programme.
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| 29. |
- Brandeker, Alexis, et al.
(författare)
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CHEOPS geometric albedo of the hot Jupiter HD 209458 b
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
-
Tidskriftsartikel (refereegranskat)abstract
- We report the detection of the secondary eclipse of the hot Jupiter HD 209458 b in optical/visible light using the CHEOPS space telescope. Our measurement of 20.4+3.2-3.3 parts per million translates into a geometric albedo of Ag = 0.096 ± 0.016. The previously estimated dayside temperature of about 1500 K implies that our geometric albedo measurement consists predominantly of reflected starlight and is largely uncontaminated by thermal emission. This makes the present result one of the most robust measurements of Ag for any exoplanet. Our calculations of the bandpass-integrated geometric albedo demonstrate that the measured value of Ag is consistent with a cloud-free atmosphere, where starlight is reflected via Rayleigh scattering by hydrogen molecules, and the water and sodium abundances are consistent with stellar metallicity. We predict that the bandpass-integrated TESS geometric albedo is too faint to detect and that a phase curve of HD 209458 b observed by CHEOPS would have a distinct shape associated with Rayleigh scattering if the atmosphere is indeed cloud free.
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| 30. |
- Bruggmann, P., et al.
(författare)
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Historical epidemiology of hepatitis C virus (HCV) in selected countries
- 2014
-
Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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| 31. |
- Kliest, Tessa, et al.
(författare)
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Clinical trials in pediatric ALS: a TRICALS feasibility study
- 2022
-
Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis Group. - 2167-8421 .- 2167-9223. ; 23:7-8, s. 481-488
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
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| 32. |
- Lendl, M., et al.
(författare)
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The hot dayside and asymmetric transit of WASP-189 b seen by CHEOPS
- 2020
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643
-
Tidskriftsartikel (refereegranskat)abstract
- The CHEOPS space mission dedicated to exoplanet follow-up was launched in December 2019, equipped with the capacity to perform photometric measurements at the 20 ppm level. As CHEOPS carries out its observations in a broad optical passband, it can provide insights into the reflected light from exoplanets and constrain the short-wavelength thermal emission for the hottest of planets by observing occultations and phase curves. Here, we report the first CHEOPS observation of an occultation, namely, that of the hot Jupiter WASP-189 b, a MP ≈ 2MJ planet orbiting an A-type star. We detected the occultation of WASP-189 b at high significance in individual measurements and derived an occultation depth of dF = 87.9 ± 4.3 ppm based on four occultations. We compared these measurements to model predictions and we find that they are consistent with an unreflective atmosphere heated to a temperature of 3435 ± 27 K, when assuming inefficient heat redistribution. Furthermore, we present two transits of WASP-189 b observed by CHEOPS. These transits have an asymmetric shape that we attribute to gravity darkening of the host star caused by its high rotation rate. We used these measurements to refine the planetary parameters, finding a ~25% deeper transit compared to the discovery paper and updating the radius of WASP-189 b to 1.619 ± 0.021RJ. We further measured the projected orbital obliquity to be λ = 86.4-4.4+2.9°, a value that is in good agreement with a previous measurement from spectroscopic observations, and derived a true obliquity of ψ = 85.4 ± 4.3°. Finally, we provide reference values for the photometric precision attained by the CHEOPS satellite: for the V = 6.6 mag star, and using a 1-h binning, we obtain a residual RMS between 10 and 17 ppm on the individual light curves, and 5.7 ppm when combining the four visits.
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| 33. |
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| 34. |
- Parviainen, H., et al.
(författare)
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CHEOPS finds KELT-1b darker than expected in visible light: Discrepancy between the CHEOPS and TESS eclipse depths
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 668
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies based on photometry from the Transiting Exoplanet Survey Satellite (TESS) have suggested that the dayside of KELT-1b, a strongly irradiated brown dwarf, is significantly brighter in visible light than what would be expected based on Spitzer observations in the infrared. We observed eight eclipses of KELT-1b with CHaracterising ExOPlanet Satellite (CHEOPS) to measure its dayside brightness temperature in the bluest passband observed so far, and we jointly modelled the CHEOPS photometry with the existing optical and near-infrared photometry from TESS, LBT, CFHT, and Spitzer. Our modelling has led to a self-consistent dayside spectrum for KELT-1b covering the CHEOPS, TESS, H, Ks, and Spitzer IRAC 3.6 and 4.5 μm bands, where our TESS, H, Ks, and Spitzer band estimates largely agree with the previous studies. However, we discovered a strong discrepancy between the CHEOPS and TESS bands. The CHEOPS observations yield a higher photometric precision than the TESS observations, but they do not show a significant eclipse signal, while a deep eclipse is detected in the TESS band. The derived TESS geometric albedo of 0.36-0.13+0.12 is difficult to reconcile with a CHEOPS geometric albedo that is consistent with zero because the two passbands have considerable overlap. Variability in cloud cover caused by the transport of transient nightside clouds to the dayside could provide an explanation for reconciling the TESS and CHEOPS geometric albedos, but this hypothesis needs to be tested by future observations.
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| 35. |
- Razavi, H., et al.
(författare)
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The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
- 2014
-
Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
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Tidskriftsartikel (refereegranskat)abstract
- The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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| 36. |
- Sproviero, William, et al.
(författare)
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ATXN2 trinucleotide repeat length correlates with risk of ALS
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 178.e1-178.e9
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R(2) = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.
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| 37. |
- Szabó, G.M., et al.
(författare)
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The changing face of AU Mic b: Stellar spots, spin-orbit commensurability, and transit timing variations as seen by CHEOPS and TESS
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
-
Tidskriftsartikel (refereegranskat)abstract
- AU Mic is a young planetary system with a resolved debris disc showing signs of planet formation and two transiting warm Neptunes near mean-motion resonances. Here we analyse three transits of AU Mic b observed with the CHaracterising ExOPlanet Satellite (CHEOPS), supplemented with sector 1 and 27 Transiting Exoplanet Survey Satellite (TESS) photometry, and the All-Sky Automated Survey from the ground. The refined orbital period of AU Mic b is 8.462995 ± 0.000003 d, whereas the stellar rotational period is Prot = 4.8367 ± 0.0006 d. The two periods indicate a 7:4 spin-orbit commensurability at a precision of 0.1%. Therefore, all transits are observed in front of one of the four possible stellar central longitudes. This is strongly supported by the observation that the same complex star-spot pattern is seen in the second and third CHEOPS visits that were separated by four orbits (and seven stellar rotations). Using a bootstrap analysis we find that flares and star spots reduce the accuracy of transit parameters by up to 10% in the planet-to-star radius ratio and the accuracy on transit time by 3-4 min. Nevertheless, occulted stellar spot features independently confirm the presence of transit timing variations (TTVs) with an amplitude of at least 4 min. We find that the outer companion, AU Mic c, may cause the observed TTVs.
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| 38. |
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| 39. |
- Wedemeyer, H., et al.
(författare)
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Strategies to manage hepatitis C virus (HCV) disease burden
- 2014
-
Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
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Tidskriftsartikel (refereegranskat)abstract
- The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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| 40. |
- Beeckman, Dimitri, Visiting Professor, 1982-, et al.
(författare)
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Silicone adhesive multilayer foam dressings as adjuvant prophylactic therapy to prevent hospital-acquired pressure ulcers : a pragmatic non-commercial multicentre randomised open label parallel group medical device trial
- 2021
-
Ingår i: British Journal of Dermatology. - : Blackwell Science Ltd.. - 0007-0963 .- 1365-2133. ; 185:1, s. 52-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital-acquired pressure ulcers (PUs).OBJECTIVES: Determine if silicone foam dressings in addition to standard prevention reduce PU incidence category 2 or worse compared to standard prevention alone.METHODS: Multicentre, randomised controlled, medical device trial conducted in eight Belgian hospitals. At risk adult patients were centrally randomised (n=1633) to study groups based on a 1:1:1 allocation: experimental group 1 (n=542) and 2 (n=545) - pooled as the treatment group - and the control group (n=546). Experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on these body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU category 2 or worse at these body sites.RESULTS: In the intention-to-treat population (n=1605); 4.0% of patients developed PUs category 2 or worse in the treatment group and 6.3% in the control group (RR=0.64, 95% CI 0.41 to 0.99, P=0.04). Sacral PUs were observed in 2.8% and 4.8% of the patients in the treatment group and the control group, respectively (RR=0.59, 95% CI 0.35 to 0.98, P=0.04). Heel PUs occurred in 1.4% and 1.9% of patients in the treatment and control group respectively (RR=0.76, 95% CI 0.34 to 1.68, P=0.49).CONCLUSIONS: Silicone foam dressings reduce the incidence of PUs category 2 or worse in hospitalised at-risk patients when used in addition to standard of care. Results show a decrease for sacrum, but no statistical difference for heel/trochanter areas.
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| 41. |
- Böhm, M., et al.
(författare)
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The conservation status of the world’s freshwater molluscs
- 2021
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Ingår i: Hydrobiologia. - : Springer Science and Business Media LLC. - 0018-8158 .- 1573-5117. ; 848, s. 3231-3254
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Tidskriftsartikel (refereegranskat)abstract
- With the biodiversity crisis continuing unchecked, we need to establish levels and drivers of extinction risk, and reassessments over time, to effectively allocate conservation resources and track progress towards global conservation targets. Given that threat appears particularly high in freshwaters, we assessed the extinction risk of 1428 randomly selected freshwater molluscs using the IUCN Red List Categories and Criteria, as part of the Sampled Red List Index project. We show that close to one-third of species in our sample are estimated to be threatened with extinction, with highest levels of threat in the Nearctic, Palearctic and Australasia and among gastropods. Threat levels were higher in lotic than lentic systems. Pollution (chemical and physical) and the modification of natural systems (e.g. through damming and water abstraction) were the most frequently reported threats to freshwater molluscs, with some regional variation. Given that we found little spatial congruence between species richness patterns of freshwater molluscs and other freshwater taxa, apart from crayfish, new additional conservation priority areas emerged from our study. We discuss the implications of our findings for freshwater mollusc conservation, the adequacy of a sampled approach and important next steps to estimate trends in freshwater mollusc extinction risk over time. © 2020, Springer Nature Switzerland AG.
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| 42. |
- Fogh, Isabella, et al.
(författare)
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Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis
- 2016
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 73:7, s. 812-820
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset. OBJECTIVE To identify gene variants influencing survival in ALS. DESIGN, SETTING, AND PARTICIPANTS This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015. MAIN OUTCOMES AND MEASURES Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed bymeta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis. RESULTS Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 x 10(-9)) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 x 10(-8)). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 x 10(-9)), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208 CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 x 10(-8)), corresponding to a 4-month reduction in survival compared with TT carriers. CONCLUSIONS AND RELEVANCE This GWAS robustly identified 2 loci at genome-wide levels of significance that influence survival in patients with ALS. Because ALS is a rare disease and prevention is not feasible, treatment that modifies survival is the most realistic strategy. Therefore, identification of modifier genes that might influence ALS survival could improve the understanding of the biology of the disease and suggest biological targets for pharmaceutical intervention. In addition, genetic risk scores for survival could be used as an adjunct to clinical trials to account for the genetic contribution to survival.
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| 44. |
- Razavi, H., et al.
(författare)
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Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study
- 2017
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 2:5, s. 325-336
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Tidskriftsartikel (refereegranskat)abstract
- Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000-3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0.64% (95% UI 0.41-0.74). We estimated that 1 180 000 (95% UI 1 003 000-1 357 000) people were diagnosed with viraemia (36.4%), 150 000 (12 000-180 000) were treated (4.6% of the total infected population or 12.7% of the diagnosed population), 133 000 (106 000-160 000) were cured (4.1%), and 57 900 (43 900-67 300) were newly infected (1.8%) in 2015. Additionally, 30 400 (26 600-42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary.
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| 45. |
- Claassen, Y. H. M., et al.
(författare)
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Time trends of short-term mortality for octogenarians undergoing a colorectal resection in North Europe
- 2019
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 45:8, s. 1396-1402
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Tidskriftsartikel (refereegranskat)abstract
- Background: Decreased cancer specific survival in older colorectal patients is mainly due to mortality in the first year, emphasizing the importance of the first postoperative year. This study aims to gain an overview and time trends of short-term mortality in octogenarians (>= 80 years) with colorectal cancer across four North European countries. Methods: Patients of 80 years or older, operated for colorectal cancer (stage I-Ill) between 2005 and 2014, were included. Population-based cohorts from Belgium, Denmark, the Netherlands, and Sweden were collected. Separately for colon- and rectal cancer, 30-day, 90-day, one-year, and excess one-year mortality were calculated. Also, short-term mortality over three time periods (2005-2008, 2009-2011, 2012-2014) was analyzed. Results: In total, 35,158 colon cancer patients and 10,144 rectal cancer patients were included. For colon cancer, 90-day mortality rate was highest in Denmark (15%) and lowest in Sweden (8%). For rectal cancer, 90-day mortality rate was highest in Belgium (11%) and lowest in Sweden (7%). One-year excess mortality rate of colon cancer patients decreased from 2005 to 2008 to 2012-2014 for all countries (Belgium: 17%-11%, Denmark: 21%-15%, the Netherlands: 18%-10%, and Sweden: 10%-8%). For rectal cancer, from 2005 to 2008 to 2012-2014 one-year excess mortality rate decreased in the Netherlands from 16% to 7% and Sweden: 8%-2%). Conclusions: Short-term mortality rates were high in octogenarians operated for colorectal cancer. Short-term mortality rates differ across four North European countries, but decreased over time for both colon and rectal cancer patients in all countries.
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| 46. |
- Durno, C., et al.
(författare)
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Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:25
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.
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| 48. |
- Iacoangeli, Alfredo, et al.
(författare)
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SCFD1 expression quantitative trait loci in amyotrophic lateral sclerosis are differentially expressed
- 2021
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Ingår i: Brain Communications. - : Oxford University Press. - 2632-1297. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Evidence indicates that common variants found in genome-wide association studies increase risk of disease through gene regulation via expression Quantitative Trait Loci. Using multiple genome-wide methods, we examined if Single Nucleotide Polymorphisms increase risk of Amyotrophic Lateral Sclerosis through expression Quantitative Trait Loci, and whether expression Quantitative Trait Loci expression is consistent across people who had Amyotrophic Lateral Sclerosis and those who did not. In combining public expression Quantitative Trait Loci data with Amyotrophic Lateral Sclerosis genome-wide association studies, we used Summary-data-based Mendelian Randomization to confirm that SCFD1 was the only gene that was genome-wide significant in mediating Amyotrophic Lateral Sderosis risk via expression Quantitative Trait Loci (Summary-data-based Mendelian Randomization beta = 0.20, standard error = 0.04, P-value = 4.29 x 10(-6)). Using post-mortem motor cortex, we tested whether expression Quantitative Trait Loci showed significant differences in expression between Amyotrophic Lateral Sclerosis (n= 76) and controls (n= 25), genome-wide. Of 20 757 genes analysed, the two most sign ificant expression Quantitative Trait Loci to show differential in expression between Amyotrophic Lateral Sclerosis and controls involve two known Amyotrophic Lateral Sclerosis genes (SCFD1 and VCP). Cis-acting SCFD1 expression Quantitative Trait Loci downstream of the gene showed significant differences in expression between Amyotrophic Lateral Sclerosis and controls (top expression Quantitative Trait Lod beta = 0.34, standard error = 0.063, P-value = 4.54 x 10(-7)). These SCFD1 expression Quantitative Trait Loci also significantly modified Amyotrophic Lateral Sclerosis survival (number of samples = 4265, hazard ratio = 1.11, 95% confidence interval = 1.05-1.17, P-value = 2.06 x 10(-4)) and act as an Amyotrophic Lateral Sclerosis trans-expression Quantitative Trait Loci hotspot for a wider network of genes enriched for SCFD1 function and Amyotrophic Lateral Sderosis pathways. Using gene-set analyses, we found the genes that correlate with this trans-expression Quantitative Trait Loci hotspot significantly increase risk of Amyotrophic La teral Sderosis (beta = 0.247, standard deviation = 0.017, P= 0.001) and schizophrenia (beta = 0.263, standard deviation = 0.008, P-value 1.18 x 10(-5)), a disease that genetically correlates with Amyotrophic Lateral Sclerosis. In summary, SCFD1 expression Quantitative Trait Lod are a major factor in Amyotrophic Lateral Sderosis, not only influencing disease risk but are differentially expressed in post-mortem Amyotrophic Lateral Sclerosis. SCFD1 expression Quantitative Trait Loci show distinct expression profiles in Amyotrophic Lateral Sclerosis that correlate with a wider network of genes that also confer risk of the disease and modify the disease's duration.
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| 50. |
- Adey, Brett N., et al.
(författare)
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Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival
- 2023
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media S.A.. - 1662-5102. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts.Methods: Using large ALS whole-genome sequencing and post-mortem RNA sequencing datasets (5,987 and 365 tissue samples, respectively), and iPSC-derived motor neurons from 55 individuals, we investigated the role of CAV1/2 expression and enhancer variants in the ALS phenotype.Results: We report a differential expression analysis between ALS cases and controls for CAV1 and CAV2 genes across various post-mortem brain tissues and three independent datasets. CAV1 and CAV2 expression was consistently higher in ALS patients compared to controls, with significant results across the primary motor cortex, lateral motor cortex, and cerebellum. We also identify increased survival among carriers of CAV1/2 enhancer mutations compared to non-carriers within Project MinE and slower progression as measured by the ALSFRS. Carriers showed a median increase in survival of 345 days.Discussion: These results add to an increasing body of evidence linking CAV1 and CAV2 genes to ALS. We propose that carriers of CAV1/2 enhancer mutations may be conceptualised as an ALS subtype who present a less severe ALS phenotype with a longer survival duration and slower progression. Upregulation of CAV1/2 genes in ALS cases may indicate a causal pathway or a compensatory mechanism. Given prior research supporting the beneficial role of CAV1/2 expression in ALS patients, we consider a compensatory mechanism to better fit the available evidence, although further investigation into the biological pathways associated with CAV1/2 is needed to support this conclusion.
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