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| 2. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 3. |
- Black, Melissa H., et al.
(författare)
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Multi-informant International Perspectives on the Facilitators and Barriers to Employment for Autistic Adults
- 2020
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Ingår i: Autism Research. - : John Wiley & Sons. - 1939-3792 .- 1939-3806. ; 13:7, s. 1195-1214
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Tidskriftsartikel (refereegranskat)abstract
- Employment rates for autistic individuals are poor, even compared to those from other disability groups. Internationally, there remains limited understanding of the factors influencing employment across the stages of preparing for, gaining, and maintaining employment. This is the third in a series of studies conducted as part of an International Society for Autism Research (INSAR) policy brief intended to improve employment outcomes for autistic individuals. A multi-informant international survey with five key stakeholder groups, including autistic individuals, their families, employers, service providers, and researchers, was undertaken in Australia, Sweden, and the United States to understand the facilitators and barriers to employment for autistic adults. A total of 687 individuals participated, including autistic individuals (n = 246), family members (n = 233), employers (n = 35), clinicians/service providers (n = 123), and researchers (n = 50). Perceptions of the facilitators and barriers to employment differed significantly across both key stakeholder groups and countries, however, ensuring a good job match and focusing on strengths were identified by all groups as important for success. Key barriers to employment included stigma, a lack of understanding of autism spectrum disorder (ASD) and communication difficulties. Results suggest that a holistic approach to employment for autistic individuals is required, aimed at facilitating communication between key stakeholders, addressing attitudes and understanding of ASD in the workplace, using strength-based approaches and providing early work experience. LAY SUMMARY: Autistic individuals experience significant difficulty getting and keeping a job. This article presents a survey study involving autistic individuals, their families, employers, service providers and researchers in Australia, Sweden, and the United States to understand their perspectives on the factors that support or act as barriers to employment. While perspectives varied across key stakeholders, strategies such as using a holistic approach, targeting workplace attitudes and understanding, focusing on strengths, and providing early work experience are important for success.
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| 4. |
- Black, Melissa H., et al.
(författare)
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Perspectives of key stakeholders on employment of autistic adults across the United States, Australia and Sweden
- 2019
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Ingår i: Autism Research. - : John Wiley & Sons. - 1939-3792 .- 1939-3806. ; 12:11, s. 1648-1662
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Tidskriftsartikel (refereegranskat)abstract
- Despite efforts to improve employment outcomes for autistic individuals, internationally their employment rates remain low. There is a need to better understand the factors influencing successful employment for autistic adults in the labor market from the perspectives of multiple keystakeholders. This study represents the second in a series of papers conducted as part of an International Society for Autism Research policy brief aimed at improving employment outcomes for autistic individuals. A community consultation methodology using focus groups, forums, and interviews was applied with autistic individuals (n = 19), family members (n = 18), service providers (n = 21), employers (n = 11), researchers (n = 5), and advocacy group representatives (n = 5) in Australia, Sweden, and the United States, aiming to identify the factors perceived to determine gaining and maintaining employment for autistic individuals. Directed content analysis, guided by the International Classification of Functioning, Disability and Health (ICF), was conducted to investigate the key factors influencing employment outcomes for autistic individuals. Meaningful verbal concepts, or units of text with common themes, were also derived from the qualitative data and then linked and compared to the ICF Autism Spectrum Disorder (ASD) Core-sets. Across countries, activity and participation and environmental factor categories of the ICF were the most associated with employment outcomes. Results suggest that removal of environmental barriers and enhancing environmental facilitators may assist to remediate ASD-related difficulties in the workplace.LAY SUMMARY: This study sought to understand the perspectives of autistic individuals and key stakeholders on factors influencing if autistic adults get and keep jobs. Across Australia, Sweden, and the UnitedStates, focus groups and interviews were conducted to understand international perspectives on what helps and hinders getting and keeping a job for autistic individuals. The environment, including supports, relationships, attitudes, and services, were perceived to be the most important for workplace success. Intervention targeting barriers and facilitators in the workplace environment may support autistic adults to be successful in the labor market.
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| 5. |
- Gargiulo, Giuseppe, et al.
(författare)
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Safety and efficacy of double versus triple antithrombotic therapy in patients with atrial fibrillation with or without acute coronary syndrome undergoing percutaneous coronary intervention : a collaborative meta-analysis of NOAC-based randomized clinical trials
- 2020
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 7:FI1, s. f50-f60
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Safety and efficacy of antithrombotic regimens in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) may differ based on clinical presentation. We sought to comparing double vs. triple antithrombotic therapy (DAT vs TAT) in AF patients with or without acute coronary syndrome (ACS) undergoing PCI.METHODS AND RESULTS: A systematic review and meta-analysis was performed using PubMed to search for non-vitamin K antagonist oral anticoagulant (NOAC)-based randomized clinical trials. Data on subgroups of ACS or elective PCI were obtained by published reports or trial investigators. A total of 10,193 patients from 4 NOAC trials were analyzed, of whom 5,675 presenting with ACS (DAT = 3,063 vs. TAT = 2,612) and 4,518 with SCAD (DAT = 2,421 vs. TAT = 2,097). The primary safety endpoint of ISTH major bleeding or CRNMB was reduced with DAT compared with TAT in both ACS (12.2% vs 19.4%; RR 0.63, 95% CI 0.56-0.71; p < 0.0001; I2=0%) and SCAD (14.6% vs 22.0%; RR 0.68, 95% CI 0.55-0.85; p = 0.0008; I2=66%), without interaction (p-int = 0.54). Findings were consistent for secondary bleeding endpoints, including intracranial Haemorrhage. In both subgroups, there was no difference between DAT and TAT for all-cause death, major adverse cardiovascular events, or stroke. Myocardial infarction and stent thrombosis were numerically higher with DAT vs. TAT consistently in ACS and SCAD (p-int = 0.60 and 0.86 respectively). Findings were confirmed by multiple sensitivity analyses, including a separate analysis on dabigatran regimens and a restriction to PCI population.CONCLUSIONS: DAT, compared with TAT, is associated with lower bleeding risks, including intracranial Haemorrhage, and a small non-significant excess of cardiac ischaemic events in both patients with or without ACS.
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| 6. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 7. |
- Šubjak, J., et al.
(författare)
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TOI-1268b: The youngest hot Saturn-mass transiting exoplanet
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 662
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of TOI-1268b, a transiting Saturn-mass planet from the TESS space mission. With an age of less than 1 Gyr, derived from various age indicators, TOI-1268b is the youngest Saturn-mass planet known to date; it contributes to the small sample of well-characterised young planets. It has an orbital period of P = 8.1577080 ± 0.0000044 days, and transits an early K-dwarf star with a mass of M∗ = 0.96 ± 0.04 M+, a radius of R∗ = 0.92 ± 0.06 R+, an effective temperature of Teff = 5300 ± 100 K, and a metallicity of 0.36 ± 0.06 dex. By combining TESS photometry with high-resolution spectra acquired with the Tull spectrograph at the McDonald Observatory, and the high-resolution spectrographs at the Tautenburg and OndR ejov Observatories, we measured a planetary mass of Mp = 96.4 ± 8.3 Mp and a radius of Rp = 9.1 ± 0.6 Rp. TOI-1268 is an ideal system for studying the role of star-planet tidal interactions for non-inflated Saturn-mass planets. We used system parameters derived in this paper to constrain the planeta's tidal quality factor to the range of 104.5-5.3. When compared with the sample of other non-inflated Saturn-mass planets, TOI-1268b is one of the best candidates for transmission spectroscopy studies.
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| 8. |
- Tinetti, Giovanna, et al.
(författare)
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The EChO science case
- 2015
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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