Summary
Reinforced concrete waffle‐flat plate (WFP) structures present 2 important drawbacks for use as a main seismic resisting system: low lateral stiffness and limited ductility. Yet the former ...can serve a positive purpose when, in parallel, the flexible WFP structure is combined with a stiff system lending high‐energy dissipation capacity, to form a “flexible‐stiff mixed structure.” This paper experimentally investigates the seismic performance of WFP structures (flexible system) equipped with hysteretic dampers (stiff system) through shake‐table tests conducted on a 2/5‐scale test specimen. The WFP structure was designed only for gravitational loads. The lateral strength and stiffness provided by the dampers at each story were, respectively, about 3 and 7 times greater than those of the bare WFP structure. The mixed system was subjected to a sequence of seismic simulations representing frequent to very rare ground motions. Under the seismic simulations associated with earthquakes having return periods ranging from 93 to 1894 years, the WFP structure performed in the level of “immediate occupancy,” with maximum interstory drifts up to about 1%. The dampers dissipated most (75%) of the energy input by the earthquake.
Although genome‐wide association studies have identified a number of common variants associated with multiple sclerosis (MS) susceptibility, little is known about the relevance of rare variants. ...Here, we aimed to explore the role of rare variants in 14 MS risk genes (FCRL1, RGS1, TIMMDC1, HHEX, CXCR5, LTBR, TSFM, GALC, TRAF3, STAT3, TNFSF14, IFI30, CD40, and CYP24A1) by targeted resequencing in an Iberian population of 524 MS cases and 546 healthy controls. Four rare variants‐enriched regions within CYP24A1, FCRL1, RGS1, and TRAF3 were identified as significantly associated with MS. Functional studies revealed significantly decreased regulator of G protein signaling 1 (RGS1) gene expression levels in peripheral blood mononuclear cells from MS patients with RGS1 rare variants compared to noncarriers, whereas no significant differences in gene expression were observed for CYP24A1, FCRL1, and TRAF3 between rare variants carriers and noncarriers. Immunophenotyping showed significant decrease in RGS1 expression in peripheral blood B lymphocytes from MS patients with RGS1 rare variants relative to noncarriers. Lastly, peripheral blood mononuclear cell from MS patients carrying RGS1 rare variants showed significantly lower induction of RGS1 gene expression by interferon‐β compared to MS patients lacking RGS1 variants. The presence of rare variants in RGS1 reinforce the ideas of high genetic heterogeneity and a role of rare variants in MS pathogenesis.
We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple ...sclerosis (MS) treated with natalizumab.
HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration.
A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (p M-H = 3 × 10(-7); odds ratio ORM-H = 8.96, 95% confidence interval CI = 3.40-23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (p M-H = 6 × 10(-4); ORM-H = 0.2, 95% CI = 0.08-0.50), with a PPV of 81%.
HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration.
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