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A bstract We show that vector-like fermions can act as the dark matter candidate in the universe whilst also playing a crucial role in electroweak baryogenesis through contributing to the barrier in the one-loop thermal scalar potential. In order for the new fermions to give rise to a strong first order phase transition, we show that one requires rather large Yukawa couplings in the new sector, which are strongly constrained by electroweak precision tests and perturbativity. Strong couplings between the dark matter candidate and the Higgs boson intuitively lead to small values of the relic density and problems with dark matter direct detection bounds. Nevertheless, when considering the most general realisation of the model, we find regions in the parameter space that respect all current constraints and may explain both mysteries simultaneously.

Strain-hardening cement-based composites were named after their ability to resist increased tensile force after crack formation, over a significant tensile deformation range. The increased resistance is achieved through effective crack bridging by fibres, across multiple cracks of widths in the micro-range. Whether these small crack widths are maintained under sustained, cyclic or other load paths, and whether the crack width limitation translates into durability through retardation of moisture, gas and other deleterious matter ingress, are scrutinised in this paper by evaluation of test results from several laboratories internationally. This contribution is a short version of the State-of-the-Art report by RILEM TC 208-HFC, Subcommittee 2: Durability, developed during the committee life 2005–2009.

This paper presents original findings on the heterogeneity of the mechanical properties of concrete of an early age, dependent on the evolution of the hydration reaction. The properties investigated are the compressive strength, the Young’s modulus, and the flexural tensile strength. To achieve this, we employed a testing apparatus in which the samples underwent curing in a chamber that followed the same temperature profile as an adiabatic calorimeter. This method enabled us to monitor the hydration progress across multiple samples. We used a function derived from the literature, with specific adaptations, to model the evolution of normalized properties in relation to hydration. Heterogeneity was quantified through the use of the dispersion coefficient. The key finding of this study is that the dispersion coefficient for the analyzed mechanical properties diminishes with the advancement of hydration, until reaching a specific threshold. Beyond this point, the impact of microcracking on the various properties becomes increasingly pronounced, varying according to the particular property being examined. Moreover, this paper presents initial functions designed to offer formulas that assist in modeling concrete within probabilistic numerical simulations from the early stages of its development.

In this paper, the development of a 3D adaptive probabilistic explicit cracking model for concrete is reported. The contribution offered herein consists in a new adaptive mesh strategy designed to optimize the use of interface elements in probabilistic explicit cracking models. The proposed adaptive mesh procedure is markedly different from other strategies found in the literature, since it takes into account possible influences on the redistribution of stresses after cracking and can also be applied to purely deterministic cracking models. The process of obtaining the most appropriate adaptive mesh procedure involved the development and evaluation of three different adaptivity strategies. Two of these adaptivity strategies were shown to be inappropriate due to issues related to stress redistribution after cracking. The validation results demonstrate that the developed adaptive probabilistic model is capable of predicting the scale effect at a level similar to that experimentally observed, considering the tensile failure of plain concrete specimens. The results also show that different softening levels can be obtained. The proposed adaptive mesh strategy proved to be advantageous, being able to promote significant reductions in the simulation time in comparison with the classical strategy commonly used in probabilistic explicit cracking models.

This study introduces an innovative numerical approach to simulate the construction of large concrete structures incorporating post-cooling systems employing the finite element method (FEM). The proposed methodology integrates critical construction parameters, including temperature control mechanisms, while accounting for concrete hydration and environmental conditions. Compared to traditional discrete models, this approach provides similar accuracy with substantially reduced computational costs, enhancing predictive capabilities in the thermal analysis of mass concrete. The method was applied to simulate the construction of a water intake pillar at the Tocoma hydroelectric plant in Venezuela, where the simulated results closely matched in situ temperature measurements. The findings highlight the method’s efficiency and accuracy in simulating post-cooling systems, offering a practical solution for improving the safety and cost-effectiveness in large-scale concrete construction projects.

BackgroundETN was well tolerated and showed clinical efficacy (ASAS 20: ETN 59%, placebo 28%, p<0.0001) through 24 wks in a phase 3 AS trial;1 efficacy was sustained up to 2 years in pts who completed the study and continued ETN in an OLE.2 No significant difference was found in change in modified Stoke AS Spine Score (mSASSS) from baseline (BL) to yr 2 of the OLE among ETN-treated pts vs a historic cohort not treated with tumour necrosis factor inhibitors (TNFi).3 ObjectivesReport radiographic progression through 4 years in ETN-treated pts with AS.MethodsIn the double-blind, placebo-controlled phase 3 study, pts with active AS were randomised to ETN 25 mg BIW or placebo for 24 wks. Pts who completed the study could enrol in a 168-wk OLE and were treated with ETN 25 mg BIW (amended after 17 months to 50 mg QW). The primary radiographic endpoint was change in mSASSS from BL to yr 2 vs change in mSASSS from yr 2 to yr 4.Results257 pts were treated in the OLE, of whom 126 (49.0%) completed the study and 131 (51.0%) withdrew prior to 168 wks (most common reasons [>5%]: pt refusal [10.1%]; adverse event, infection, or injection-site reaction [8.2%]; lack of efficacy [7.8%]). ETN resulted in sustained improvement in signs and symptoms of active disease for up to 168 wks beyond the 24-wk double-blind study. Of 267 pts who received ≥1 dose of ETN in the phase 3 study or OLE, 124 were included in the 4 year primary radiographic endpoint analysis (8 received a prohibited TNFi and were excluded). BL characteristics were similar between these pts and all pts who received ≥1 dose of ETN in the phase 3 study. Mean change in mSASSS among completers was 1.96 from BL to yr 4 (n=110) while change in mean mSASSS between yr 2 and yr 4 was 0.66 (n=109). The nominal p-value for change in mSASSS from BL to yr 2 vs change from yr 2 to yr 4 was 0.0536. Radiographic data suggest disease progression continued in pts receiving ETN continuously over 4 years; however, mean mSASSS increased from BL to year 2 and not from yr 2 to yr 4 (figure 1) due to a few outlier patients with large mSASSS values at yr 2 but missing 4 year data.Abstract SAT0292 – Table 1Baseline Demographic and Disease CharacteristicsPts Who Received≥1 Dose of ETN in the Phase 3 Study or Its Extension and Had Baseline, 2 year, and 4 year X-rays (n=127) Mean (SD) age, yrs42.43 (9.63)Male, n (%)89 (70.1)HLA-B27 positive, n (%)100 (78.7)Used NSAIDs, n (%)115 (90.6)Used DMARDs, n (%)43 (33.9)Used corticosteroids, n (%)16 (12.6)Mean (SD) mSASSS16.7 (16.3)Mean (SD) disease duration, yrs10.61 (8.67)Abstract SAT0292 – Figure 1Mean mSASSSConclusionsThis is the first report of 4 year radiographic ETN data in AS, and these data suggest that disease progression continued in pts who received ETN continuously throughout, but that disease progression may be slower after longer-term treatment with ETN vs shorter term. This adds to the already-existing data that demonstrate TNFi seem to reduce radiographic progression in pts with AS.References[1] Davis Arthritis Rheum2003.[2] Davis Ann Rheum Dis2005.[3] van der Heijde Arthritis Rheum2008.AcknowledgementsStudy supported by Amgen, Inc. Medical writing assistance provided by BlueMomentum, an Ashfield Company, and funded by Amgen, Inc.Disclosure of InterestN. Haroon Consultant for: Abbvie, Amgen, Janssen, Merck, Novartis, UCB, R. Inman Consultant for: Amgen, Abbvie, Janssen, Merck, Novartis, M. Fairbairn Shareholder of: Amgen, Employee of: Amgen

Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID. We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA. We included adults aged 30–85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented SARS-CoV-2 positive PCR or antigen test within 3 days before enrolment. Participants were randomly assigned via 2 × 3 parallel factorial randomisation (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcomes assessors were masked to study group assignment. The primary outcome was severe COVID-19 by day 14, and those data have been published previously. Because the trial was delivered remotely nationwide, the a priori primary sample was a modified intention-to-treat sample, meaning that participants who did not receive any dose of study treatment were excluded. Long COVID diagnosis by a medical provider was a prespecified, long-term secondary outcome. This trial is complete and is registered with ClinicalTrials.gov, NCT04510194. Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned. Of 1323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least one survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin vs placebo trial were also randomly assigned to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were female and 494 (43·9%) were male; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37–54) and median BMI was 29·8 kg/m2 (IQR 27·0–34·2). Overall, 93 (8·3%) of 1126 participants reported receipt of a long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2–8·2) in participants who received metformin and 10·4% (7·8–12·9) in those who received identical metformin placebo (hazard ratio [HR] 0·59, 95% CI 0·39–0·89; p=0·012). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15–0·95). There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59–1·64) or fluvoxamine (1·36, 0·78–2·34) compared with placebo. Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe. Parsemus Foundation; Rainwater Charitable Foundation; Fast Grants; UnitedHealth Group Foundation; National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; and National Center for Advancing Translational Sciences.

Background Clinical opioid overdose risk prediction models can be useful tools to reduce the risk of overdose in patients prescribed long-term opioid therapy (LTOT). However, evolving overdose risk environments and clinical practices in addition to potential harmful model misapplications require careful assessment prior to widespread implementation into clinical care. Models may need to be tailored to meet local clinical operational needs and intended applications in practice. Objective To update and validate an existing opioid overdose risk model, the Kaiser Permanente Colorado Opioid Overdose (KPCOOR) Model, in patients prescribed LTOT for implementation in clinical care. Design, Setting, and Participants The retrospective cohort study consisted of 33, 625 patients prescribed LTOT between January 2015 and June 2019 at Kaiser Permanente Colorado, with follow-up through June 2021. Main Measures The outcome consisted of fatal opioid overdoses identified from vital records and non-fatal opioid overdoses from emergency department and inpatient settings. Predictors included demographics, medication dispensings, substance use disorder history, mental health history, and medical diagnoses. Cox proportional hazards regressions were used to model 2-year overdose risk. Key Results During follow-up, 65 incident opioid overdoses were observed (111.4 overdoses per 100,000 person-years) in the study cohort, of which 11 were fatal. The optimal risk model needed to risk-stratify patients and to be easily interpreted by clinicians. The original 5-variable model re-validated on the new study cohort had a bootstrap-corrected C -statistic of 0.73 (95% CI, 0.64–0.85) compared to a C -statistic of 0.80 (95% CI, 0.70–0.88) in the updated model and 0.77 (95% CI, 0.66–0.87) in the final adapted 7-variable model, which was also well-calibrated. Conclusions Updating and adapting predictors for opioid overdose in the KPCOOR Model with input from clinical partners resulted in a parsimonious and clinically relevant model that was poised for integration in clinical care.

Cement production gives rise to CO 2 emissions generated by the calcination of CaCO 3 and by the combustion of fossil fuels, being responsible for about 5% of the global CO 2 emissions. These emissions can be substantially reduced if cement replacement materials are used. In this paper two residual ashes that can be used as mineral additions are considered: sugar cane bagasse ash and rice husk ash. A case study of the construction of a dam with a blended material composed by cement and these two ashes is presented, indicating the potentiality of its use for civil engineering applications. The analyses were performed using experimental and numerical tools developed on the basis of a thermo-chemo-mechanical model. This model considers the coupling, within the theory of thermodynamics, of the several phenomena that intervene in the hydration process, namely, exothermicity, thermo-activation, chemo-plasticity, evolution of thermal and mechanical properties with the hydration reaction, which includes creep and relaxation.

We report on a search for ultralow-mass axionlike dark matter by analyzing the ratio of the spin-precession frequencies of stored ultracold neutrons and Hg199 atoms for an axion-induced oscillating electric dipole moment of the neutron and an axion-wind spin-precession effect. No signal consistent with dark matter is observed for the axion mass range 10−24≤ma≤10−17eV . Our null result sets the first laboratory constraints on the coupling of axion dark matter to gluons, which improve on astrophysical limits by up to 3 orders of magnitude, and also improves on previous laboratory constraints on the axion coupling to nucleons by up to a factor of 40.