6 research outputs found

    Numerical modeling in timber engineering – moisture transport and quasi-brittle failure

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    With the rising popularity of timber structures and the increasing complexity of timber engineering projects, the need for numerical simulation tools specific to this building material is gaining rapidly in importance. in particular, moisture transport processes and the quasi-brittle failure behavior, both difficult to describe, present major challenges and are of great relevance in practical construction. For these reasons, this article presents numerical modeling concepts for predicting moisture gradients, estimating effective stiffness and strength, and numerically identifying potential cracking mechanisms in wooden components. These concepts are validated through experimental test programs, and the associated challenges are addressed. selected results ultimately demonstrate the capabilities and relevance of such methods for timber engineering

    Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial

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    Background Baricitinib has shown efcacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifcally on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/ critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modifed intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute diference and 95% CI −0.1% [−8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (−3.2% [−9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a signifcant interac‑ tion between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated partici‑ pants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to con‑ clude on a potential survival beneft of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these fnd‑ ings warrant further investigation in other trials and real-world studies

    Computational mechanics concepts for wood-based products and timber structural elements

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    Conference logo shows incorrect conference date "2020".The mechanical behavior of wood products highly depends on structural features on several length scales. This leads to a high amount of random fluctuation in mechanical properties at the structural level. In practice, homogeneous material behavior within timber elements is assumed and uncertainties in loading and load-bearing capacity are considered by using partial safety factors. Those are not directly linked to the mechanical behavior of the considered elements. Therefore, a stochastic framework opening up the possibility to establish such links by combining structural analysis and probabilistic descriptions of wood could be an important step in timber design. For example, in GLT beams the mechanical behavior mostly depends on the tensile properties of individual boards. To describe their fluctuations, simulations on this level are performed. The reconstruction of knots and the implementation of new fracture mechanical methods allows the prediction of stiffness and strength properties for knot sections. Condensation of those results into stiffness and strength profiles permits the development of probabilistic models and the random generation of such profiles, and their use in wood product simulations. This can be used for sensitivity analyses of timber engineering designs or to obtain probabilistic descriptions of the uncertainties at the level of timber elements.Fonds zur Förderung der wissenschaftlichen Forschung (FWF)BM fĂŒr Land- und Forstwirtschaft, Umwelt und Wasserwirtschaft (bm:lfuw); European Commission17

    A hybrid analysis method for displacement-monitored segmented circular tunnel rings

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    Segmented tunnel rings exhibit load-induced interfacial dislocations. In order to facilitate structural analysis, a hybrid method is developed and applied to a real-scale test of a segmented tunnel ring. Point loads, imposed on the tested ring, and measured interfacial discontinuities serve as input for the analysis. Moreover, the method accounts for the structural behavior of the individual segments by means of newly derived transfer relations. They represent analytical solutions of the first-order theory of slender circular arches, exhibiting constant cross-sectional properties. The tool for the development of this basically well-known theory is the principle of virtual power. Its involvement is motivated by the possibility of a mechanically consistent derivation of relations, some of which have been used for a long time without analyzing their scientific background. The validity and the usefulness of the transfer relations follow from a comparison of newly derived solutions with (i) alternative analytical solutions, (ii) Finite Element solutions, and (iii) experimental data. The computational efficiency and the usefulness of the developed hybrid method are demonstrated by structural analysis of a segmented tunnel ring. It provides valuable insight into the load-carrying behavior of the tested structure without the need to describe the nontrivial behavior of segment-to-segment interfaces.Austrian Science Fund (FWF

    Implementation of a centralized pharmacovigilance system in academic pan-European clinical trials: Experience from EU-Response and conect4children consortia.

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    Setting-up a high quality, compliant and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for companies. To ensure the safety of all participants in academic studies and that the PV system fulfils all regulations, we set up a centralized PV system that allows sponsors to delegate work on PV. This initiative was put in practice by our Inserm-ANRS MIE PV department in two distinct multinational European consortia with 19 participating countries: conect4children (c4c) for paediatrics research and EU-Response for Covid-19 platform trials. The centralized PV system consists of some key procedures to harmonize the complex safety processes, creation of a local safety officer (LSO) network and centralization of all safety activities. The key procedures described the safety management plan for each trial and how tasks were shared and delegated between all stakeholders. Processing of serious adverse events (SAEs) in a unique database guaranteed the full control of the safety data and continuous evaluation of the risk-benefit ratio. The LSO network participated in efficient regulatory compliance across multiple countries. In total, there were 1312 SAEs in EU-Response and 83 SAEs in c4c in the four trials. We present here the lessons learnt from our experience in four clinical trials. We managed heterogeneous European local requirements and implemented efficient communication with all trial teams. Our approach builds capacity for PV that can be used by multiple academic sponsors

    Implementation of a centralized pharmacovigilance system in academic pan‐European clinical trials : experience from EU‐Response and conect4children consortia

    No full text
    Setting-up a high quality, compliant and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for companies. To ensure the safety of all participants in academic studies and that the PV system fulfils all regulations, we set up a centralized PV system that allows sponsors to delegate work on PV. This initiative was put in practice by our Inserm-ANRS MIE PV department in two distinct multinational European consortia with 19 participating countries: conect4children (c4c) for paediatrics research and EU-Response for Covid-19 platform trials. The centralized PV system consists of some key procedures to harmonize the complex safety processes, creation of a local safety officer (LSO) network and centralization of all safety activities. The key procedures described the safety management plan for each trial and how tasks were shared and delegated between all stakeholders. Processing of serious adverse events (SAEs) in a unique database guaranteed the full control of the safety data and continuous evaluation of the risk-benefit ratio. The LSO network participated in efficient regulatory compliance across multiple countries. In total, there were 1312 SAEs in EU-Response and 83 SAEs in c4c in the four trials. We present here the lessons learnt from our experience in four clinical trials. We managed heterogeneous European local requirements and implemented efficient communication with all trial teams. Our approach builds capacity for PV that can be used by multiple academic sponsors
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