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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 4. |
- Matuozzo, D, et al.
(författare)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- 2022
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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| 5. |
- Lustig, S, et al.
(författare)
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The impact of school-based screening on service use in adolescents at risk for mental health problems and risk-behaviour
- 2023
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Ingår i: European child & adolescent psychiatry. - : Springer Science and Business Media LLC. - 1435-165X .- 1018-8827. ; 32:9, s. 1745-1754
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Tidskriftsartikel (refereegranskat)abstract
- Early detection and intervention can counteract mental disorders and risk behaviours among adolescents. However, help-seeking rates are low. School-based screenings are a promising tool to detect adolescents at risk for mental problems and to improve help-seeking behaviour. We assessed associations between the intervention “Screening by Professionals” (ProfScreen) and the use of mental health services and at-risk state at 12 month follow-up compared to a control group. School students (aged 15 ± 0.9 years) from 11 European countries participating in the “Saving and Empowering Young Lives in Europe” (SEYLE) study completed a self-report questionnaire on mental health problems and risk behaviours. ProfScreen students considered “at-risk” for mental illness or risk behaviour based on the screening were invited for a clinical interview with a mental health professional and, if necessary, referred for subsequent treatment. At follow-up, students completed another self-report, additionally reporting on service use. Of the total sample (N = 4,172), 61.9% were considered at-risk. 40.7% of the ProfScreen at-risk participants invited for the clinical interview attended the interview, and 10.1% of subsequently referred ProfScreen participants engaged in professional treatment. There were no differences between the ProfScreen and control group regarding follow-up service use and at-risk state. Attending the ProfScreen interview was positively associated with follow-up service use (OR = 1.783, 95% CI = 1.038–3.064), but had no effect on follow-up at-risk state. Service use rates of professional care as well as of the ProfScreen intervention itself were low. Future school-based interventions targeting help-seeking need to address barriers to intervention adherence.Clinical Trials Registration: The trial is registered at the US National Institute of Health (NIH) clinical trial registry (NCT00906620, registered on 21 May, 2009), and the German Clinical Trials Register (DRKS00000214, registered on 27 October, 2009).
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| 6. |
- Jones, Geraint H., et al.
(författare)
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The Comet Interceptor Mission
- 2024
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Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 9. |
- Stephan, K., et al.
(författare)
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Regions of interest on Ganymede's and Callisto's surfaces as potential targets for ESA's JUICE mission
- 2021
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Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- The JUpiter Icy moons Explorer (JUICE) will investigate Ganymede's and Callisto's surfaces and subsurfaces from orbit to explore the geologic processes that have shaped and altered their surfaces by impact, tectonics, possible cryovolcanism, space weathering due to micrometeorites, radiation and charged particles as well as explore the structure and properties of the icy crust and liquid shell (Grasset et al., 2013). The best possible synergy of the JUICE instruments is required to answer the major science objective of this mission and to fully exploit the po-tential of the JUICE mission. Therefore, the JUICE team is aiming to define high priority targets on both Gany-mede's and Callisto's surfaces to support the coordination of the planning activities by the individual instrument teams. Based on the science objectives of the JUICE mission and the most recent knowledge of Ganymede's and Callisto's geologic evolution we propose a collection of Regions of Interest (RoIs), which characterize surface features and terrain types representing important traces of geologic processes, from past and/or present cryovolcanic and tectonic activity to space weathering processes, which are crucial to understand the geologic evolution of Ganymede and Callisto. The proposed evaluation of RoIs is based on their scientific importance as well as on the opportunities and conditions to observe them during the currently discussed mission profile.
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