An optimization-based rigid block modeling approach to seismic assessment of dry-joint masonry structures subjected to settlements

A rigid block modeling approach is presented for rocking dynamics and nonlinear static analysis of dry-joint masonry structures subjected to settlements and earthquake excitations. For the different types of analysis, a unified optimization-based formulation is adopted, which is equivalent to the system governing the static and dynamic structural response. Sequential solution procedures are used for time integration and for pushover analysis which take into account the effects of large displacements under the combined action of support movements and lateral loads. No-tension elastic contacts with finite shear strength are considered at block in-terfaces for time-history analysis and to obtain the elastic branch of pushover curves in nonlinear static analysis. A unilateral rigid contact behavior is also considered to obtain the descending post-peak branch of pushover curves corresponding to the activation of the rigid-body rocking motion, according to displacement-based assessment methods of failure mechanisms adopted in the standards. Comparisons with numerical models and experimental tests on a rocking block and on a buttressed arch are presented to show the accuracy of the developed approach. Simple tests on dry-joint tuff panels on the tilting table were also carried out to show the effects of imposed movements at support on the response to lateral loads. Finally, an application is presented to a full-scale triumphal arch subjected to the combined action of support movements and earthquake excitation to discuss, on the basis of the developed model, the effects of settlement-induced damage on seismic performance. The numerical analyses showed that the lateral force, the displacement capacity and the rocking response can be significantly affected by support movements, pointing out the relevance of the current building condition in the seismic safety assessment.- The financial support of the research project DPC-ReLUIS 2022-2024: Work Package 5 "Integrated and low-impact strengthening interventions" funded by the Civil Protection Department IT (Grant no. 897-01/04/2022) is acknowledged. The authors are grateful to Prof. Chiara Calderini from the University of Genova for providing data from the experimental tests on the arch-pillars system investigated in the manuscript. The authors are also grateful to Mr. Domenico Imperatrice from the Department of Structures for Engineering and Architecture for his assistance and support throughout the experimental investigation on the wall panels subjected to support movement and lateral loads

Perioperative morbidity and mortality after transmyocardial laser revascularization: incidence and risk factors for adverse events

AbstractOBJECTIVESThe purpose of this study was to describe the incidence and spectrum of perioperative cardiac and noncardiac morbidity and mortality after transmyocardial laser revascularization (TMR) and to identify predictors of these adverse clinical events.BACKGROUNDClinical studies have demonstrated the efficacy of TMR for relieving angina pectoris, although no study to date has specifically addressed the associated perioperative morbidity and mortality.METHODSBetween October 1995 and August 1997, 34 consecutive patients with end-stage coronary artery disease (CAD) underwent isolated TMR. The majority of patients (94%) had class III or IV angina pectoris, and two patients (6%) had unstable symptoms preoperatively. Patient records were reviewed for fatal and nonfatal adverse cardiac and noncardiac events.RESULTSPerioperative death occurred in two patients (5.9%) due to cardiogenic shock complicating acute myocardial infarction. Perioperative cardiac morbidity occurred in 16 patients (47.1%); noncardiac morbidity was seen in 12 patients (35.3%). Preoperative unstable angina was the only variable predictive of perioperative death (p = 0.005). Cardiac (p = 0.005) and noncardiac (p < 0.001) morbidity rates were significantly higher for the initial 15 patients undergoing the procedure. Other predictors of perioperative complications included lack of postoperative treatment with a furosemide infusion (p ≤ 0.04) and preoperative unstable angina (p = 0.05).CONCLUSIONSPerioperative mortality in patients undergoing isolated TMR is low. Transmyocardial laser revascularization patients are at higher risk for adverse perioperative cardiac and noncardiac events, likely reflecting the lack of immediate benefit from the procedure in the setting of severe CAD. These patients merit vigilant surveillance for adverse events and aggressive medical management in the perioperative period

Mechanism of action and therapeutic use of bempedoic acid in atherosclerosis and metabolic syndrome

Bempedoic acid is a new cholesterol-lowering drug, which has recently received US FDA and EMA approval. This drug targets lipid and glucose metabolism as well as inflammation via downregulation of ATP-citrate lyase and upregulation of AMP-activated protein kinase (AMPK). The primary effect is the reduction of cholesterol synthesis in the liver and its administration is generally not associated to unwanted muscle effects. Suppression of hepatic fatty acid synthesis leads to decreased triglycerides and, possibly, improved non-alcoholic fatty liver disease. Bempedoic acid may decrease gluconeogenesis leading to improved insulin sensitivity, glucose metabolism, and metabolic syndrome. The anti-inflammatory action of bempedoic acid is mainly achieved via activation of AMPK pathway in the immune cells, leading to decreased plasma levels of C-reactive protein. Effects of bempedoic acid on atherosclerotic cardiovascular disease, type 2 diabetes and chronic liver disease have been assessed in randomized clinical trials but require further confirmation. Safety clinical trials in phase III indicate that bempedoic acid administration is generally well-tolerated in combination with statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to achieve low-density lipoprotein cholesterol targets. The aim of this narrative review on bempedoic acid is to explore the underlying mechanisms of action and potential clinical targets, present existing evidence from clinical trials, and describe practical management of patients

Mitochondrial diabetes in children: seek and you will find it

Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA). 3243 A.G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A.G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75–98%) and macular dystrophy (54% vs 86%) was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A.G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants