Effective stiffness of unreinforced brick masonry walls

Code design of Unreinforced Masonry (URM) buildings is based on elastic analysis, which requires as input parameter the effective stiffness of URM walls. Current approaches estimate the effective stiffness as fixed ratio of the gross sectional stiffness but comparisons with experimental results have shown that this does not yield satisfactory predictions. In this paper, a recently developed analytical model for the force-displacement response of URM walls is used to investigate the effective stiffness. First, the key features of this model are summarised. In further course, the model is used to predict the effective stiffness of full-scale tests on modern unreinforced clay brick masonry walls and the results are compared to the provisions of Eurocode 8. Concluding, the model is used to investigate the sensitivity of the effec-tive stiffness to the wall geometry and axial loading

Who’s next? Cuts to welfare often target immigrants first but then move to nationals

David Cameron’s deal to cut social benefits for EU citizens may in part be a ploy in the internal politics of the Conservative Party. But it’s also the latest push in a long drive by UK governments to squeeze a once universalist welfare regime into a system of discrimination. Here, analysts from MigrationWork describe how the idea of ‘(un)deservingness’ has been applied since Thatcher and the miner’s strike to subvert the principle of universal entitlement, in parallel on two fronts: class and nationality

Individual variation in field metabolic rates of wild living fish have phenotypic and ontogenetic underpinnings: insights from stable isotope compositions of otoliths

Publication history: Accepted - 17 May 2023; Published -13 June 2023.Introduction: Individual metabolism has been identified as a key variable for predicting responses of individuals and populations to climate change, particularly for aquatic ectotherms such as fishes. Predictions of organism standard metabolic rate (SMR), and the thermal sensitivity of metabolic rate are typically based on allometric scaling rules and respirometry-based measures of respiratory potential under laboratory conditions. The relevance of laboratory-based measurement and theoretical allometric rules to predict performance of free-ranging animals in complex natural settings has been questioned, but determining time averaged metabolic rate in wild aquatic animals is challenging. Methods: Here we draw on stable isotope compositions of aragonite in fish otoliths to estimate time averaged experienced temperature and expressed field metabolic rate (FMR) simultaneously and retrospectively at an individual level. We apply the otolith FMR proxy to a population of European plaice (Pleuronectes platessa) from the North Sea during a period of rapid warming between the 1980s to the mid-2000s, sampling otolith tissue grown in both juvenile and adult stages. Results: Among-individual variations in realized mass-specific FMR were large and independent of temperature and scaled positively with body size in adult life stages, contradicting simplistic assumptions that FMR follows scaling relationships inferred for standard metabolic rates (SMR). In the same individuals, FMR in the first summer of life co-varied positively with temperature. Discussion: We find strong evidence for the presence of consistent metabolic phenotypes within the sampled population, as FMR in the first year of life was the strongest single predictor for among individual variation in FMR at the point of sampling. Nonetheless, best fitting models explained only 20% of the observed variation, pointing to large among-individual variation in FMR that is unexplained by body mass, temperature or metabolic phenotype. Stable isotope-derived estimates of field metabolic rate have great potential to expand our understanding of ecophysiology in general and especially mechanisms underpinning the relationships between animal performance and changing environmental and ecological conditions.This work was funded from NERC Case award NE/P009700/1

Epigenetic therapy in urologic cancers: an update on clinical trials

Epigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clinical trials are already underway to test their clinical potential. In this review we analyze multiple clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers. The most frequently used epigenetic drugs were histone deacetylase inhibitors followed by antisense oligonucleotides, DNA methyltransferase inhibitors and histone demethylase inhibitors, the last of which are only being tested in prostate cancer. In more than 50% of the clinical trials considered, epigenetic drugs were used as part of combination therapy, which achieved the best results. The epigenetic regulation of some cancers is still matter of research but will undoubtedly open a window to new therapeutic approaches in the era of personalized medicine. The future of therapy for urological malignancies is likely to include multidrug regimens in which epigenetic modifying drugs will play an important role

Shake‑table testing of a stone masonry building aggregate: overview of blind prediction study

City centres of Europe are often composed of unreinforced masonry structural aggregates, whose seismic response is challenging to predict. To advance the state of the art on the seismic response of these aggregates, the Adjacent Interacting Masonry Structures (AIMS) subproject from Horizon 2020 project Seismology and Earthquake Engineering Research Infrastructure Alliance for Europe (SERA) provides shake-table test data of a two-unit, double-leaf stone masonry aggregate subjected to two horizontal components of dynamic excitation. A blind prediction was organized with participants from academia and industry to test modelling approaches and assumptions and to learn about the extent of uncertainty in modelling for such masonry aggregates. The participants were provided with the full set of material and geometrical data, construction details and original seismic input and asked to predict prior to the test the expected seismic response in terms of damage mechanisms, base-shear forces, and roof displacements. The modelling approaches used differ significantly in the level of detail and the modelling assumptions. This paper provides an overview of the adopted modelling approaches and their subsequent predictions. It further discusses the range of assumptions made when modelling masonry walls, floors and connections, and aims at discovering how the common solutions regarding modelling masonry in general, and masonry aggregates in particular, affect the results. The results are evaluated both in terms of damage mechanisms, base shear forces, displacements and interface openings in both directions, and then compared with the experimental results. The modelling approaches featuring Discrete Element Method (DEM) led to the best predictions in terms of displacements, while a submission using rigid block limit analysis led to the best prediction in terms of damage mechanisms. Large coefficients of variation of predicted displacements and general underestimation of displacements in comparison with experimental results, except for DEM models, highlight the need for further consensus building on suitable modelling assumptions for such masonry aggregates

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Stiffness, force and drift capacity of in-plane loaded modern unreinforced brick masonry walls

In countries of low to moderate seismicity, such as Switzerland, unreinforced masonry (URM) is mainly used in residential buildings due to its good insulation capacity and fire resistance along with a fair compressive strength. URM walls however show a limited horizontal in-plane deformation capacity, which can lead to an unfavorable seismic response. To predict this response, at least the walls' effective stiffness, shear force and drift capacity are required. While mechanics-based models for the force capacity are well established, such approaches are largely lacking for the effective stiffness and the drift capacity. The mostly empirical code equations for the two latter parameters lead to unsatisfactory and, in the case of drift capacities, often unconservative predictions when compared to tests. To address the issue, this thesis introduces an analytical model describing the monotonic force-displacement response of in-plane loaded URM walls. Based on a Timoshenko beam, the influence of diagonal shear and horizontal flexural cracking is captured by mechanical models, leading to an analytical description of the pre-peak force-displacement response. The shear force capacity is determined using local stress criteria and the ultimate drift capacity is estimated with a plastic zone approach evaluating a crushed region of high curvatures at the wall toe at ultimate failure. A comparison with experiments indicates that the model yields reliable predictions of stiffness, strength and drift capacity. Moreover, the monotonic model is extended to capture the full cyclic response including stiffness degradation and residual displacements. Furthermore, an existing numerical mesoscale approach is used to conduct parametric studies. The wall is modelled with solid elements, capturing brick crushing, and interface elements, simulating sliding and flexural uplift in the bed-joints. A study of the load history influence shows that for walls failing in shear, the drift capacity can reduce to half from monotonic to reversed-cyclic loading. The second study simulates different test setups used in the literature to impose double-fixed support conditions. While there appears to be hardly any difference between the force and the mixed-controlled mode, simulating the double-fixed wall as a cantilever with half its original height leads in many cases to a strong overestimation of force and drift capacities. The final investigation concerns a change in axial force during horizontal loading. The force and drift capacities of walls under changing normal force appear to be very similar to those of walls under a constant normal force that corresponds to the changing axial load towards ultimate failure. In addition, a database of shear-compression tests is extended and analysed for trends in stiffness and drift capacity. Both, the initial and the effective stiffness increase with increasing axial load, while the ratio of effective-to-initial stiffness is rather constant and lies around 0.75. As for the drift capacity, an upward trend with increasing shear span ratio and a downward trend with increasing axial load are observed. Concluding, simple mechanics-based formulations for the effective stiffness, the force and the drift capacity to be used in design are proposed. A validation with the database shows that the new formulations are more accurate in predicting effective stiffness and drift capacity than currently used code equations

Force–displacement response of in-plane loaded unreinforced brick masonry walls: the Critical Diagonal Crack model

This article introduces an analytical model to compute the monotonic force–displacement response of in-plane loaded unreinforced brick masonry walls accounting for walls failing in shear or flexure. The masonry wall is modelled as elastic in compression with zero tensile strength using a Timoshenko beam element. Its cross-section properties (moment of inertia and area) are continuously updated to capture the non-linearity that results from flexural and shear cracking. For this purpose, diagonal cracking of shear critical walls is represented by one Critical Diagonal Crack. The ultimate drift capacity of the wall is determined based on an approach evaluating a plastic zone at the wall toe. Validation against results of cyclic full-scale tests of unreinforced masonry walls made with vertically perforated clay units shows that the presented formulation is capable of accurately predicting the effective stiffness, the maximum strength and the ultimate drift capacity of the wall. It outperforms current empirical code equations with regard to stiffness and ultimate drift capacity estimates and yields similar results concerning strength prediction