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Here, we describe the results of a genome-wide study conducted in 11939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P= 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

ESRETNET Study Group, The ERDC Study Group, The Associated Clinical Study Group., Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations., This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006).

Due to their spatial complexity and dynamic nature, floodplains provide a wide range of ecosystem functions. However, because of flow regulation, many riverine floodplains have lost their characteristic heterogeneity. Restoration of floodplain habitats and the rehabilitation of key ecosystem functions has therefore become a major goal of environmental policy. Many important ecosystem functions are linked to organic carbon (C) dynamics in riparian soils. The fundamental understanding of the factors that drive the processes involved in C cycling in heterogeneous and dynamic systems such as floodplains is however only fragmentary. We quantified soil organic C pools (microbial C and water extractable organic C) and fluxes (soil respiration and net methane production) in functional process zones of adjacent channelized and widened sections of the Thur River, NE Switzerland, on a seasonal basis. The objective was to assess how spatial heterogeneity and temporal variability of these pools and fluxes relate to physicochemical soil properties on one hand, and to soil environmental conditions and flood disturbance on the other hand. Overall, factors related to seasonality and flooding (temperature, water content, organic matter input) affected soil C dynamics more than soil properties did. Coarse-textured soils on gravel bars in the restored section were characterized by low base-levels of organic C pools due to low TOC contents. However, frequent disturbance by flood pulses led to high heterogeneity with temporarily and locally increased pools and soil respiration. By contrast, in stable riparian forests, the finer texture of the soils and corresponding higher TOC contents and water retention capacity led to high base-levels of C pools. Spatial heterogeneity was low, but major floods and seasonal differences in temperature had additional impacts on both pools and fluxes. Soil properties and base levels of C pools in the dam foreland of the channelized section were similar to the gravel bars of the restored section. By contrast, spatial heterogeneity, seasonal effects and flood disturbance were similar to the forests, except for indications of high CH4 production that are explained by long travel times of infiltrating water favouring reducing conditions. Overall, the restored section exhibited both a larger range and a higher heterogeneity of organic C pools and fluxes as well as a higher plant biodiversity than the channelized section. This suggests that restoration has indeed led to an increase in functional diversity.

The prevalence of insulin-dependent diabetes mellitus (IDDM) in cystic fibrosis patients ranges from 2 to 8% and glucose intolerance up to 15%. In recent years, lung transplantation has helped to prolong life expectancy of cystic fibrosis patients and represents 10 to 30% of all indications for lung transplantation. The postoperative need for immunosuppressive therapy using diabetogenic agents has decompensatory effects on glucose regulation and will probably increase the number of insulin-dependent cystic fibrosis patients. We report the case of an insulin-dependent cystic fibrosis patient transplanted with a combined islet-lung allograft. The pre-transplantation C-peptide level was below 0.04 nmol/l and preoperative insulin requirement was some 100 U per day. A sequential bipulmonary lung transplantation was performed and, using the pancreas of the same donor, we isolated and purified the islets of Langerhans by a modified automated method. We obtained 232,200 islets equivalent, which were injected into the liver by portal embolization. The postoperative course was uncomplicated, the insulin requirement decreased to 50% of the preoperative need and the C-peptide value increased to normal values and remained with the normal range during a follow-up period of 15 months. In conclusion, we believe that, besides type I diabetic patients, insulin-dependent cystic fibrosis patients with a negative C-peptide value could also be good candidates for combined islet-lung allotransplantation.

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The Weibull distribution, used to describe the scaling of strength of materials, has been verified on a wide range of materials and geometries; however, the quality of the fitting tended to be less good towards the upper tail. Based on a previously developed probabilistic strength prediction method for adhesively bonded joints composed of pultruded glass fiber-reinforced polymer (GFRP) adherends, where it was verified that a two-parameter Weibull probabilistic distribution was not able to model accurately the upper tail of a material strength distribution, different improved probabilistic distributions were compared to enhance the quality of strength predictions. The following probabilistic distributions were examined: a two-parameter Weibull (as a reference), m-fold Weibull, a Grafted Distribution, a Birnbaum-Saunders Distribution and a Generalized Lambda Distribution. The Generalized Lambda Distribution turned out to be the best analytical approximation for the strength data, providing a good fit to the experimental data, and leading to more accurate joint strength predictions than the original two-parameter Weibull distribution. It was found that a proper modeling of the upper tail leads to a noticeable increase of the quality of the predictions. © 2008 Elsevier Ltd. All rights reserved

Research examining youths' political development mostly focused on young people as a general group; comparatively less attention has been devoted to the examination of gender pathways toward citizenship. Two studies were conducted addressing (a) the role of parents' participation and the moderating role of adolescent gender and age group (n = 1419) and (b) the role of adolescent social and civic participation and the moderating role of adolescent gender and type of school (n = 1871). Results confirmed the gender gap in political interest and in the use of the Internet for political participation, while no differences emerged for political activity and voting intentions. Adolescents' political engagement and participation are influenced by parents' participation (especially among girls) and by adolescents' social and civic participation (especially among boys). The impact of adolescents' social and civic participation on conventional participation (voting intentions) is partially mediated by sense of community and institutional trust.

Finland has typically been considered a country with very durable granitic aggregate that is used in a wide range of construction applications. In general, the chemical reaction between Finnish aggregates and their surrounding environment is usually quite low. In this regard, the risk of Alkali Aggregate Reactions (AAR), where the alkalinity of concrete harmfully reacts with certain aggregates to cause expansion and cracking, has been considered negligible in Finland. However, when investigating reinforced concrete infrastructure in Finland for other types of deterioration attack, such as chloride ingress and frost-salt exposure, AAR has been found. AAR deterioration is limited to certain rock types. The geology of Finnish bedrock and soil is well studied and therefore there is a good general view of the composition of aggregates in different parts of Finland. This helps to estimate the potentiality of AAR. AAR has been investigated at VTT - Technical Research Centre of Finland by use of petrographic thin section microscopy. This paper shares the findings of 25 years of review from in-service structures, with respect to ASR findings. In addition, as new alternative hydraulic binders and aggregate sources (including recycled materials) are used in future concrete production, the mechanisms and risks of AAR need to be addressed in Finnish practice. The hope is that by initiating open discussions within Finland and abroad, the potential risk of future AAR deterioration can be evaluated and a process to handle AAR can be created to ensure concrete durability and service life of our structures.