LINKING PHYSICAL EDUCATION WITH LOCAL SPORT ORGANIZATIONS: IMPLEMENTATION OF AN “ACTIVE SCHOOL COMMUNITY”

The main purpose of the active school communities project was to act as a starting point for more active school communities throughout seven countries across Europe by strengthening the links between community sport organizations and local schools and provide a low-cost solution to improve physical education and physical activity in schools. Further, opportunities for cooperation were fostered by creating new partnerships between stakeholders that already separately work at the community level to encourage children to move more. Therefore, toolkits were created by the active school communities ERASMUS+ project to promote collaborations between the field of education together with grassroots sport sectors and sport clubs. The aim of this study was a pilot evaluation of these toolkits. A total of 38 members of local sport organizations, 34 members of local schools and 5 national coordinators participated in three parts of the evaluation study. In sum, there are ambivalent results regarding the three toolkits, but the majority of participants supported the aim of the project to create and improve more active school communities. Finally, future recommendations are discussed.  Article visualizations

On the Real-World Instantiability of Admissible Hash Functions and Efficient Verifiable Random Functions

Verifiable random functions (VRFs) are essentially digital signatures with additional properties, namely verifiable uniqueness and pseudorandomness, which make VRFs a useful tool, e.g., to prevent enumeration in DNSSEC Authenticated Denial of Existence and the CONIKS key management system, or in the random committee selection of the Algorand blockchain. Most standard-model VRFs rely on admissible hash functions (AHFs) to achieve security against adaptive attacks in the standard model. Known AHF constructions are based on error-correcting codes, which yield asymptotically efficient constructions. However, previous works do not clarify how the code should be instantiated concretely in the real world. The rate and the minimal distance of the selected code have significant impact on the efficiency of the resulting cryptosystem, therefore it is unclear if and how the aforementioned constructions can be used in practice. First, we explain inherent limitations of code-based AHFs. Concretely, we show that even if we were given codes that achieve the well-known Gilbert-Varshamov or McEliece-Rodemich-Rumsey-Welch bounds, existing AHF-based constructions of VRFs can only be instantiated quite inefficiently. Then we introduce and construct computational AHFs (cAHFs). While classical AHFs are information-theoretic, and therefore work even in presence of computationally unbounded adversaries, cAHFs provide only security against computationally bounded adversaries. However, we show that cAHFs can be instantiated significantly more efficiently. Finally, we present a new VRF scheme using cAHFs and show that it is currently the most efficient verifiable random function with full adaptive security in the standard model

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis

In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients. We defined comprehensive gene co-expression network models of psoriatic lesions and uninvolved skin. Moreover, we curated and exploited a wide range of functional information from multiple public sources in order to systematically annotate the inferred networks. The integrated analysis of transcriptomics data and co-expression networks highlighted genes that are frequently dysregulated and show aberrant patterns of connectivity in the psoriatic lesion compared with the unaffected skin. Our approach allowed us to also identify plausible, previously unknown, actors in the expression of the psoriasis phenotype. Finally, we characterized communities of co-expressed genes associated with relevant molecular functions and expression signatures of specific immune cell types associated with the psoriasis lesion. Overall, integrating experimental driven results with curated functional information from public repositories represents an efficient approach to empower knowledge generation about psoriasis and may be applicable to other complex diseases.Peer reviewe

The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1

PURPOSE: Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients. METHODS: STAT1 was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different STAT1 variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients' peripheral blood cells (PBMC) after stimulation with interferon (IFN)-α, IFN-γ or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients. RESULTS: Heterozygous mutations within STAT1 were identified in 35 of 57 CMC patients (61 %). Out of 39 familial cases from 11 families, 26 patients (67 %) from 9 families and out of 18 sporadic cases, 9 patients (50 %) were shown to have heterozygous mutations within STAT1. Thirteen distinct STAT1 mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five STAT1 variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients. CONCLUSION: STAT1 mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of STAT1 in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

6,6'-(1E,1'E)-((1R,2R)-1,2-Diphenylethane-1,2-diyl)bis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(2-tert-butyl-4-((trimethylsilyl)ethynyl)phenol)

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license.Functionalizable salen derivative, 6,6'-(1E,1'E)-((1R,2R)-1,2-diphenylethane-1,2-diyl)bis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(2-tert-butyl-4-((trimethylsilyl) ethyn-yl)phenol) (3), was synthesized by condensation between (1R,2R)-1,2-diphenylethane-1,2-diamine (2) and 3-tert-butyl-2-hydroxy-5-((trimethylsilyl)ethynyl) benzaldehyde (1) under refluxing conditions. The title compound was characterized by 1H-NMR, 13C-NMR, FT-IR, high-resolution mass spectrometry, optical rotation and melting point determination.We thank CSIC (project PIE 200980I059) and University of Regensburg (Anschubfinanzierung von Wissenschaftlichen Projekten-2011), Ministerio de Ciencia e Innovación – FEDER (CTQ2010-17436) and Gobierno de Aragón-FSE (research group E40) for financial support.Peer reviewe

Additive Fertigung in der Instandhaltungslogistik: Beitrag auf der Internetseite Werkstoffzeitschrift (https://werkstoffzeitschrift.de)

Die Anforderungen an den Produktionssektor werden im Zuge der Digitalisierung immer vielfältiger. Kundenwünsche nach individualisierten Produkten, kurzen Servicezeiten und hohen Verfügbarkeiten nehmen immer weiter zu. Konventionelle Produktionsanlagen stehen damit vielfältigen Herausforderungen gegenüber. Kleiner werdende Losgrößen und verkürzte Lieferzeiten besonders für Ersatzteile zwingen viele Unternehmen zum Umdenken. Vor diesem Hintergrund gewinnt die additive Fertigung (eng.: additive manufacturing) an Relevanz. [Breuniger et al. 2013, S. 5 ff.