Improving the seismic robustness of Conventional Construction concentrically braced steel frames by mobilizing the gravity load framing system

«RÉSUMÉ: Au Canada, le processus de conception de systèmes de reprise des charges sismiques (SRFSs) en acier de faible ductilité de type Constructions Conventionnelles (Type CC) ne demandent pas de conception par capacité et la majorité de la conception peut être effectuée rapidement avec des résultats d’analyses élastiques. Cette méthode de conception simple et rapide représente un grand incitatif aux ingénieurs de conceptions pour choisir ce système. La ductilité limitée de ce système provient de la ductilité inhérente à l’acier et au glissement des connexions pour accommoder les déformations inélastiques et dissiper l’énergie sismique. Le manque de contrôle sur la réponse inélastique et sur la hiérarchie de plastification peut créer des mécanismes de ruine indésirables comme un étage faible ou des ruptures fragiles dans le SRFS.» et «----------ABSTRACT: In Canada, the design process of steel low-ductility Conventional Construction (Type CC) seismic force resisting systems (SFRSs) does not require capacity design and most of the design can be performed quickly based on elastic analysis results. This quick and simple design procedure represents a strong incentive to design engineers for selecting this type of SFRSs. The limited ductility of this system is provided by the inherent ductility of steel and slip in connections to accommodate inelastic deformations and dissipate the seismic energy. The lack of control on the inelastic response and yielding hierarchy can lead to undesirable failure mechanisms such as a soft story or brittle failures in the SFRS.

Antipsychotic use and myocardial infarction in older patients with treated dementia

Background Antipsychotic agents (APs) are commonly prescribed to older patients with dementia. Antipsychotic use is associated with an increased risk of ischemic stroke in this population. Our study aimed to investigate the association of AP use with the risk of acute myocardial infarction (MI). Methods A retrospective cohort of community-dwelling older patients who initiated cholinesterase inhibitor treatment was identified between January 1, 2000, and December 31, 2009, using the Quebec, Canada, prescription claims database. From this source cohort, all new AP users during the study period were matched with a random sample of AP nonusers. The risk of MI was evaluated using Cox proportional hazards models, adjusting for age, sex, cardiovascular risk factors, psychotropic drug use, and propensity scores. In addition, a self-controlled case series study using conditional Poisson regression modeling was conducted. Results Among the source cohort of 37 138 cholinesterase inhibitor users, 10 969 (29.5%) initiated AP treatment. Within 1 year of initiating AP treatment, 1.3% of them had an incident MI. Hazard ratios for the risk of MI after initiation of AP treatment were 2.19 (95% CI, 1.11-4.32) for the first 30 days, 1.62 (95% CI, 0.99-2.65) for the first 60 days, 1.36 (95% CI, 0.89-2.08) for the first 90 days, and 1.15 (95% CI, 0.89-1.47) for the first 365 days. The self-controlled case series study conducted among 804 incident cases of MI among new AP users yielded incidence rate ratios of 1.78 (95% CI, 1.26-2.52) for the 1- to 30-day period, 1.67 (95% CI, 1.09-2.56) for the 31- to 60-day period, and 1.37 (95% CI, 0.82-2.28) for the 61- to 90-day period. Conclusion Antipsychotic use is associated with a modest and time-limited increase in the risk of MI among community-dwelling older patients treated with cholinesterase inhibitors

16p11.2 haploinsufficiency reduces mitochondrial biogenesis in brain endothelial cells and alters brain metabolism in adult mice

Summary: Neurovascular abnormalities in mouse models of 16p11.2 deletion autism syndrome are reminiscent of alterations reported in murine models of glucose transporter deficiency, including reduced brain angiogenesis and behavioral alterations. Yet, whether cerebrovascular alterations in 16p11.2df/+ mice affect brain metabolism is unknown. Here, we report that anesthetized 16p11.2df/+ mice display elevated brain glucose uptake, a phenomenon recapitulated in mice with endothelial-specific 16p11.2 haplodeficiency. Awake 16p11.2df/+ mice display attenuated relative fluctuations of extracellular brain glucose following systemic glucose administration. Targeted metabolomics on cerebral cortex extracts reveals enhanced metabolic responses to systemic glucose in 16p11.2df/+ mice that also display reduced mitochondria number in brain endothelial cells. This is not associated with changes in mitochondria fusion or fission proteins, but 16p11.2df/+ brain endothelial cells lack the splice variant NT-PGC-1α, suggesting defective mitochondrial biogenesis. We propose that altered brain metabolism in 16p11.2df/+ mice is compensatory to endothelial dysfunction, shedding light on previously unknown adaptative responses