A comprehensive review of C-S-H empirical and computational models, their applications, and practical aspects

[EN] The C-S-H gel is an elusive material. Its variable composition and disordered nature complicate a complete characterization of its atomic structure, and the elaboration of models is key to understanding it. This work aims to review those proposed models, dividing them into empirical and computational models. After a brief description of related crystalline calcium silicate hydrates, empirical C-S-H models based on interpretation of experimental data are presented. Then, we focus on the historic development of atomistic models to study the C-S-H, until the current state of the art. We describe current computational C-S-H models built from the empirical models and computer simulations. We review common applications of these computational models: the aluminum incorporation, the elastic and mechanical properties, the diffusion of water and ions in nanopores, and C-S-H/organic composites. Finally, we discuss some practical aspects of the computational models and their interpretation, as well as possible future directions.The authors would like to acknowledge funding from “Departamento de Educación, Política Lingüística y Cultura del Gobierno Vasco” (Grant No. IT912-16 and IT1639-22) and the technical and human support provided by the Scientific Computing Service of SGIker (UPV/EHU/ ERDF, EU). E.D.-R. also acknowledges the postdoctoral fellowship from “Programa Posdoctoral de Perfeccionamiento de Personal Investigador Doctor” of the Basque Government

Hysteresis from Multiscale Porosity: Modeling Water Sorption and Shrinkage in Cement Paste

Cement paste has a complex distribution of pores and molecular-scale spaces. This distribution controls the hysteresis of water sorption isotherms and associated bulk dimensional changes (shrinkage). We focus on two locations of evaporable water within the fine structure of pastes, each having unique properties, and we present applied physics models that capture the hysteresis by dividing drying and rewetting into two related regimes based on relative humidity (RH). We show that a continuum model, incorporating a pore-blocking mechanism for desorption and equilibrium thermodynamics for adsorption, explains well the sorption hysteresis for a paste that remains above approximately 20% RH. In addition, we show with molecular models and experiments that water in spaces of ≲1  nm width evaporates below approximately 20% RH but reenters throughout the entire RH range. This water is responsible for a drying shrinkage hysteresis similar to that of clays but opposite in direction to typical mesoporous glass. Combining the models of these two regimes allows the entire drying and rewetting hysteresis to be reproduced accurately and provides parameters to predict the corresponding dimensional changes. The resulting model can improve the engineering predictions of long-term drying shrinkage accounting also for the history dependence of strain induced by hysteresis. Alternative strategies for quantitative analyses of the microstructure of cement paste based on this mesoscale physical model of water content within porous spaces are discussed.Portland Cement AssociationNational Ready Mixed Concrete Association (Research and Education Foundation)Schlumberger Foundatio

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

Future directions in conservation research on petrels and shearwaters

Shearwaters and petrels (hereafter petrels) are highly adapted seabirds that occur across all the world's oceans. Petrels are a threatened seabird group comprising 124 species. They have bet-hedging life histories typified by extended chick rearing periods, low fecundity, high adult survival, strong philopatry, monogamy and long-term mate fidelity and are thus vulnerable to change. Anthropogenic alterations on land and at sea have led to a poor conservation status of many petrels with 52 (42%) threatened species based on IUCN criteria and 65 (52%) suffering population declines. Some species are well-studied, even being used as bioindicators of ocean health, yet for others there are major knowledge gaps regarding their breeding grounds, migratory areas or other key aspects of their biology and ecology. We assembled 38 petrel conservation researchers to summarize information regarding the most important threats according to the IUCN Red List of threatened species to identify knowledge gaps that must be filled to improve conservation and management of petrels. We highlight research advances on the main threats for petrels (invasive species at breeding grounds, bycatch, overfishing, light pollution, climate change, and pollution). We propose an ambitious goal to reverse at least some of these six main threats, through active efforts such as restoring island habitats (e.g., invasive species removal, control and prevention), improving policies and regulations at global and regional levels, and engaging local communities in conservation efforts

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Higher than expected growth rate of the Endangered West African giraffe \textitGiraffa camelopardalis peralta : a successful human\textendashwildlife cohabitation

International audienc

Attosecond control of collective electron motion in plasmas

International audienceToday, light fields of controlled and measured waveform can be used to guide electron motion in atoms and molecules with attosecond precision. Here, we demonstrate attosecond control of collective electron motion in plasmas driven by extreme intensity ($\approx$10$^{18}$ W cm$^{−2}$) light fields. Controlled few-cycle near-infrared waves are tightly focused at the interface between vacuum and a solid-density plasma, where they launch and guide subcycle motion of electrons from the plasma with characteristic energies in the multi-kiloelectronvolt range--two orders of magnitude more than has been achieved so far in atoms and molecules. The basic spectroscopy of the coherent extreme ultraviolet radiation emerging from the light-plasma interaction allows us to probe this collective motion of charge with sub-200 as resolution. This is an important step towards attosecond control of charge dynamics in laser-driven plasma experiments