| 1. |
- Tinetti, G., et al.
(författare)
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A chemical survey of exoplanets with ARIEL
- 2018
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 2. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 3. |
- Lacour, S., et al.
(författare)
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The mass of β Pictoris c from β Pictoris b orbital motion
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We aim to demonstrate that the presence and mass of an exoplanet can now be effectively derived from the astrometry of another exoplanet.Methods. We combined previous astrometry of β Pictoris b with a new set of observations from the GRAVITY interferometer. The orbital motion of β Pictoris b is fit using Markov chain Monte Carlo simulations in Jacobi coordinates. The inner planet, β Pictoris c, was also reobserved at a separation of 96 mas, confirming the previous orbital estimations.Results. From the astrometry of planet b only, we can (i) detect the presence of β Pictoris c and (ii) constrain its mass to 10.04(-3.10)(+4.53) M-Jup. If one adds the astrometry of β Pictoris c, the mass is narrowed down to 9.15(-1.06)(+1.08) M-Jup. The inclusion of radial velocity measurements does not affect the orbital parameters significantly, but it does slightly decrease the mass estimate to 8.89(-0.75)(+0.75) M-Jup. With a semimajor axis of 2.68 +/- 0.02 au, a period of 1221 +/- 15 days, and an eccentricity of 0.32 +/- 0.02, the orbital parameters of β Pictoris c are now constrained as precisely as those of β Pictoris b. The orbital configuration is compatible with a high-order mean-motion resonance (7:1). The impact of the resonance on the planets' dynamics would then be negligible with respect to the secular perturbations, which might have played an important role in the eccentricity excitation of the outer planet.
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| 4. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 7. |
- Duong, M., et al.
(författare)
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Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV 1 (PURE): an international, community-based cohort study
- 2019
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Ingår i: The Lancet Global Health. - 2214-109X. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: The associations between the extent of forced expiratory volume in 1 s (FEV 1 ) impairment and mortality, incident cardiovascular disease, and respiratory hospitalisations are unclear, and how these associations might vary across populations is unknown. Methods: In this international, community-based cohort study, we prospectively enrolled adults aged 35–70 years who had no intention of moving residences for 4 years from rural and urban communities across 17 countries. A portable spirometer was used to assess FEV 1 . FEV 1 values were standardised within countries for height, age, and sex, and expressed as a percentage of the country-specific predicted FEV 1 value (FEV 1 %). FEV 1 % was categorised as no impairment (FEV 1 % ≥0 SD from country-specific mean), mild impairment (FEV 1 % <0 SD to −1 SD), moderate impairment (FEV 1 % <–1 SD to −2 SDs), and severe impairment (FEV 1 % <–2 SDs [ie, clinically abnormal range]). Follow-up was done every 3 years to collect information on mortality, cardiovascular disease outcomes (including myocardial infarction, stroke, sudden death, or congestive heart failure), and respiratory hospitalisations (from chronic obstructive pulmonary disease, asthma, pneumonia, tuberculosis, or other pulmonary conditions). Fully adjusted hazard ratios (HRs) were calculated by multilevel Cox regression. Findings: Among 126 359 adults with acceptable spirometry data available, during a median 7·8 years (IQR 5·6–9·5) of follow-up, 5488 (4·3%) deaths, 5734 (4·5%) cardiovascular disease events, and 1948 (1·5%) respiratory hospitalisation events occurred. Relative to the no impairment group, mild to severe FEV 1 % impairments were associated with graded increases in mortality (HR 1·27 [95% CI 1·18–1·36] for mild, 1·74 [1·60–1·90] for moderate, and 2·54 [2·26–2·86] for severe impairment), cardiovascular disease (1·18 [1·10–1·26], 1·39 [1·28–1·51], 2·02 [1·75–2·32]), and respiratory hospitalisation (1·39 [1·24–1·56], 2·02 [1·75–2·32], 2·97 [2·45–3·60]), and this pattern persisted in subgroup analyses considering country income level and various baseline risk factors. Population-attributable risk for mortality (adjusted for age, sex, and country income) from mildly to moderately reduced FEV 1 % (24·7% [22·2–27·2]) was larger than that from severely reduced FEV 1 % (3·7% [2·1–5·2]) and from tobacco use (19·7% [17·2–22·3]), previous cardiovascular disease (5·5% [4·5–6·5]), and hypertension (17·1% [14·6–19·6]). Population-attributable risk for cardiovascular disease from mildly to moderately reduced FEV 1 was 17·3% (14·8–19·7), second only to the contribution of hypertension (30·1% [27·6–32·5]). Interpretation: FEV 1 is an independent and generalisable predictor of mortality, cardiovascular disease, and respiratory hospitalisation, even across the clinically normal range (mild to moderate impairment). Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline, Novartis, and King Pharma. Additional funders are listed in the appendix. © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
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| 8. |
- Sathish, T., et al.
(författare)
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Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179000 participants from 63 countries
- 2022
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Ingår i: The Lancet Global Health. - 2214-109X. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. Methods: We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. Findings: In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65–2·12) than in MICs (1·41, 1·34–1·49) and LICs (1·35, 1·25–1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 μM) than in MICs (31·1 μM) and LICs (25·2 μM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 μM) and MICs (11·3 μM) than in HICs (5·0 μM; ANCOVA p=0·0001). Interpretation: The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. Funding: Full funding sources are listed at the end of the paper (see Acknowledgments). © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
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| 9. |
- Sungnak, W., et al.
(författare)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
- 2020
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Ingår i: Nature Medicine. - : Nature Research. - 1078-8956 .- 1546-170X. ; 26:5, s. 681-687
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Tidskriftsartikel (refereegranskat)abstract
- We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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| 10. |
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