Comparative assessment of strut models for the modelling of in-plane seismic response of infill walls

The influence of infills on the seismic response of frame structures has long been recognised. Typically, stiffness and strength of the infill and connections between infill and frame are such that the infill affects the global seismic behaviour of the structure. Hence, the presence of infills should be considered in the analysis and design of new buildings and in the seismic assessment of existing ones. To this aim, simple models for infill walls, such as the equivalent diagonal no-tension strut model, have been developed in the last decades. The objective of the present study is to assess the validity of different strut models. To this aim, 162 experimental tests available in the literature are considered. The data set includes both reinforced concrete and steel frames, as well as confined masonry structures. The mechanical characteristics of masonry and the boundary conditions between frames and infills of the test specimens take into account a large set of situations, reflecting the great variability in the materials and in the construction techniques adopted in different countries. Moreover, the type of tests and the related results are not uniform; in some cases monotonic experiments are performed, whereas in other cases cyclic tests are carried out. As expected, the presence of different types of infill-frame systems results in a large scatter of the data. However, the comparison between experimental results and predictions show that, on the average, the infill strength can be adequately estimated by resorting to the strut model whereas major uncertainties are found for the stiffness prediction

Finite-discrete element modelling of masonry infill walls subjected to out-of-plane loads

In this paper, the out-of-plane response of infill walls is investigated by means of non-linear monotonic (push-over) analyses through a combined finite and discrete modelling approach. The model accounts for material deformability, crack formation, sliding, separa-tion and formation of new contacts. Masonry units are modelled as finite elements, and differ-ent material models are assumed for the masonry. Contact between masonry units, and between masonry and frame elements is modelled by means of interfaces, which permit tan-gential motion with frictional sliding. Frame elements are modelled by means of a linear-elastic material. The results of the numerical analyses are compared with those of experimen-tal tests available in the literature. The advantages and disadvantages of the adopted model-ling strategy are investigated

Effect of ground-motion sequences on a unreinforced masonry wall restrained by an elasto-plastic tie-rod

This work investigates the effect of international ground-motion sequences on the out-of-plane response of an ordinary-building façade. The following assumptions are made on the wall boundary conditions: the wall is resting on a foundation, it is adjacent to transverse walls and restrained by elasto-plastic tie rods with finite elongation capacity. Four walls are considered of different aspect ratio and size; two types of masonry are assumed, and the tie is designed following a force-based procedure according to the Commentary to the Italian Building Code. The walls are modelled as rigid blocks of finite thickness and free to rotate on one side only. The rocking response of the walls, excited in the out-of-plane direction under 56 sequences of records, is evaluated. The effect of sequences is estimated by the comparison of the response experienced during the sequence and under a single record, strongest in terms of either peak ground acceleration or velocity. Finally, in order to reduce the vulnerability originated by a seismic sequence, a proposal of a reduced behaviour factor to be adopted in the design of tie rods is formulated

Patient Experience als Erfolgsfaktor für Spitäler : eine Roadmap zur Optimierung der Patient Journey

Die Transformation zu Value-Based Healthcare (VBHC) steht bei Schweizer Spitälern aktuell ganz oben auf der Prioritätenliste. Dies beinhaltet die Ausrichtung der Leistungserbringung an den Präferenzen, Ergebniserwartungen und Kompetenzen der Patientinnen und Patienten. Damit ist eine optimale Patient Experience ein zentraler Gradmesser für die Umsetzung von VBHC. Ein Team aus Expertinnen und Experten der Unternehmensberatung APP AG, des Winterthurer Instituts für Gesundheitsökonomie und der Schulthess Klinik präsentiert in diesem Whitepaper eine Roadmap zur Optimierung der Patient Experience, die mittels Design Thinking entstanden ist. Die Roadmap zeigt das Vorgehen beispielhaft an einem Fallbeispiel aus der Schulthess Klinik auf. Jeder Schritt auf dem Weg zur Optimierung wird anwendungsorientiert nach einem festen Schema anschaulich erläutert. Es werden das einzelne Vorgehen, sinnvolle Tools, wichtige Herausforderungen sowie die Interdependenzen zwischen den Schritten beschrieben. Das Whitepaper richtet sich an Spitalverantwortliche, die sich ein Grundverständnis der Thematik an-eignen wollen oder ein Projekt zur Verbesserung der Patient Experience planen. Das Studium dieses Whitepapers ermöglicht einen schnellen und effektiven Wissensaufbau und hilft bei der Umsetzung

The circular RNA landscape in multiple sclerosis: Disease-specific associated variants and exon methylation shape circular RNA expression profile

BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs increasingly emerging as crucial actors in the pathogenesis of human diseases, including autoimmune and neurological disorders as multiple sclerosis (MS). Despite several efforts, the mechanisms regulating circRNAs expression are still largely unknown and the circRNA profile and regulation in MS-relevant cell models has not been completely investigated. In this work, we aimed at exploring the global landscape of circRNA expression in MS patients, also evaluating a possible correlation with their genetic and epigenetic background. METHODS: We performed RNA-seq experiments on circRNA-enriched samples, derived from peripheral blood mononuclear cells (PBMCs) of 10 MS patients and 10 matched controls and performed differential circRNA expression. The genetic background was evaluated using array genotyping, and an expression quantitative trait loci (eQTL) analysis was carried out. RESULTS: Expression analysis revealed 166 differentially expressed circRNAs in MS patients, 125 of which are downregulated. One of the top dysregulated circRNAs, hsa_circ_0007990, derives from the PGAP3 gene, encoding a protein relevant for the control of autoimmune responses. The downregulation of this circRNA was confirmed in two independent replication cohorts, suggesting its implementation as a possible RNA-based biomarker. The eQTL analysis evidenced a significant association between 89 MS-associated loci and the expression of at least one circRNA, suggesting that MS-associated variants could impact on disease pathogenesis by altering circRNA profiles. Finally, we found a significant correlation between exon methylation and circRNA expression levels, supporting the hypothesis that epigenetic features may play an important role in the definition of the cell circRNA pool. CONCLUSION: We described the circRNA expression profile of PBMCs in MS patients, suggesting that MS-associated variants may tune the expression levels of circRNAs acting as circ-QTLs , and proposing a role for exon-based DNA methylation in regulating circRNA expression

Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

Background and purpose: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Results: Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI] = 14.3–100.0, p &lt; 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI = 8.3–50.0, p &lt; 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2–4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4–3.8, p = 0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1–2.7, p = 0.012), compared to patients treated with other DMTs. Conclusions: All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (&gt;659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon