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- 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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- Heinonen, M., et al.
(författare)
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New Primary Standards for Establishing SI Traceability for Moisture Measurements in Solid Materials
- 2018
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Ingår i: International journal of thermophysics. - : Springer. - 0195-928X .- 1572-9567. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- A European research project METefnet addresses a fundamental obstacle to improving energy-intensive drying process control: due to ambiguous reference analysis methods and insufficient methods for estimating uncertainty in moisture measurements, the achievable accuracy in the past was limited and measurement uncertainties were largely unknown. This paper reports the developments in METefnet that provide a sound basis for the SI traceability: four new primary standards for realizing the water mass fraction were set up, analyzed and compared to each other. The operation of these standards is based on combining sample weighing with different water vapor detection techniques: cold trap, chilled mirror, electrolytic and coulometric Karl Fischer titration. The results show that an equivalence of 0.2 % has been achieved between the water mass fraction realizations and that the developed methods are applicable to a wide range of materials.
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- Matuozzo, Daniela, 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.
- 2023
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Ingår i: Genome medicine. - 1756-994X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10-4) for 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). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10-8). Finally, the patients with pLOF/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).Rare 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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- Assran, By Mahmoud, et al.
(författare)
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Advances in Asynchronous Parallel and Distributed Optimization
- 2020
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Ingår i: Proceedings of the IEEE. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9219 .- 1558-2256. ; 108:11, s. 2013-2031
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Tidskriftsartikel (refereegranskat)abstract
- Motivated by large-scale optimization problems arising in the context of machine learning, there have been several advances in the study of asynchronous parallel and distributed optimization methods during the past decade. Asynchronous methods do not require all processors to maintain a consistent view of the optimization variables. Consequently, they generally can make more efficient use of computational resources than synchronous methods, and they are not sensitive to issues like stragglers (i.e., slow nodes) and unreliable communication links. Mathematical modeling of asynchronous methods involves proper accounting of information delays, which makes their analysis challenging. This article reviews recent developments in the design and analysis of asynchronous optimization methods, covering both centralized methods, where all processors update a master copy of the optimization variables, and decentralized methods, where each processor maintains a local copy of the variables. The analysis provides insights into how the degree of asynchrony impacts convergence rates, especially in stochastic optimization methods.
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- Bell, S., et al.
(författare)
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METefnet : Developments in metrology for moisture in materials
- 2015
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Ingår i: 17th International Congress of Metrology, CIM 2015. - Les Ulis, France : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- Bien que les mesures de teneur en eau soient largement utilisées dans l'industrie, les considérations métrologiques quant à cette mesure ne sont pas complètement abouties de sorte à fournir des mesures fiables et traçables au SI. Afin de remédier à ceci, le projet de recherche conjoint, Joint Research Project SIB64 “METefnet – Metrology for moisture in materials”, est actuellement en cours, et contribue au programme européen de recherche en métrologie European Metrology Research Programme. Le projet METefnet a pour objectifs de développer et d'améliorer l'approche métrologique de ce sujet. Ceci inclus notamment: le travail sur de nouvelles méthodes de référence pour évaluer la fraction massique en eau, l'amélioration des mesures mettant en œuvre la méthode primaire de type titration Karl Fischer, le développement de nouveaux matériaux de référence certifiés présentant une très bonne stabilité et permettant une traçabilité au SI, le développement de nouveaux étalons de transfert, la réalisation d'études visant à quantifier et réduire les effets liés à la prise d'échantillon, son transport et sa manipulation, le développement d'une nouvelle méthode pour étalonner les instruments mesurant l'humidité de surface, et l'amélioration des méthodes d'estimation d'incertitudes de ces mesures. Ce travail, réalisé dans le domaine de la métrologie de l'humidité au sein des matériaux, couvre à la fois le mesurande décrit comme étant spécifiquement la teneur en eau, seule, dans les matériaux, mais également un mesurande plus large pouvant inclure l'eau ainsi que d'autres liquides ou composés organiques volatiles; ceci afin de bien mettre en exergue la différence qui peut être observée entre ces deux mesurandes. Le projet global a pour objectif de soutenir une action de dissémination et de traçabilité au système SI des mesures de teneur en eau dans les matériaux avec une exactitude optimale et de développer une infrastructure métrologique cohérente pour ce type de mesures. Le travail technique ainsi que les dernières avancées vous sont ainsi présentées.
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