Energy damage index based on capacity and response spectra

To assess the expected seismic damage of a structure, non-linear dynamic analysis and the damage index of Park-Ang have been often used. Depending on the size of the structure and on the duration of the record, the computational effort in dynamic analyses is usually high. In this research a new damage index is proposed based on nonlinear static analysis. The damage index is a linear combination of two energy functions: 1) the strain energy associated to the stiffness variation and the ductility of the structure and 2) the energy dissipated associated to hysteretic cycles. These two energy functions are obtained from the capacity curve of the structure and from the energy balance with the spectral acceleration. To show the ability of the index to represent damage, low-rise steel buildings subjected to seismic actions expected in Mexico City are studied. The results obtained with the new method show a good agreement with those calculated by means of dynamic analyses using the Park-Ang damage index. In average, the Park-Ang damage index is well fitted by the combination of 62% of the strain energy and 38% of the energy dissipated by hysteresis. Moreover, this new damage index allows linking damage to certain characteristics of the seismic actions as, for instance, intensity and duration of the applied seismic action. Therefore, the new approach results in a practice and powerful tool for estimating the seismic damage in buildings, especially when considering probabilistic approaches, where massive computations are needed

Un examen actualizado de la percepción de las barreras para la implementación de la farmacogenómica y la utilidad de los pares fármaco/gen en América Latina y el Caribe

La farmacogenómica (PGx) se considera un campo emergente en los países en desarrollo. La investigación sobre PGx en la región de América Latina y el Caribe (ALC) sigue siendo escasa, con información limitada en algunas poblaciones. Por lo tanto, las extrapolaciones son complicadas, especialmente en poblaciones mixtas. En este trabajo, revisamos y analizamos el conocimiento farmacogenómico entre la comunidad científica y clínica de ALC y examinamos las barreras para la aplicación clínica. Realizamos una búsqueda de publicaciones y ensayos clínicos en este campo en todo el mundo y evaluamos la contribución de ALC. A continuación, realizamos una encuesta regional estructurada que evaluó una lista de 14 barreras potenciales para la aplicación clínica de biomarcadores en función de su importancia. Además, se analizó una lista emparejada de 54 genes/fármacos para determinar una asociación entre los biomarcadores y la respuesta a la medicina genómica. Esta encuesta se comparó con una encuesta anterior realizada en 2014 para evaluar el progreso en la región. Los resultados de la búsqueda indicaron que los países de América Latina y el Caribe han contribuido con el 3,44% del total de publicaciones y el 2,45% de los ensayos clínicos relacionados con PGx en todo el mundo hasta el momento. Un total de 106 profesionales de 17 países respondieron a la encuesta. Se identificaron seis grandes grupos de obstáculos. A pesar de los continuos esfuerzos de la región en la última década, la principal barrera para la implementación de PGx en ALC sigue siendo la misma, la "necesidad de directrices, procesos y protocolos para la aplicación clínica de la farmacogenética/farmacogenómica". Las cuestiones de coste-eficacia se consideran factores críticos en la región. Los puntos relacionados con la reticencia de los clínicos son actualmente menos relevantes. Según los resultados de la encuesta, los pares gen/fármaco mejor clasificados (96%-99%) y percibidos como importantes fueron CYP2D6/tamoxifeno, CYP3A5/tacrolimus, CYP2D6/opioides, DPYD/fluoropirimidinas, TMPT/tiopurinas, CYP2D6/antidepresivos tricíclicos, CYP2C19/antidepresivos tricíclicos, NUDT15/tiopurinas, CYP2B6/efavirenz y CYP2C19/clopidogrel. En conclusión, aunque la contribución global de los países de ALC sigue siendo baja en el campo del PGx, se ha observado una mejora relevante en la región. La percepción de la utilidad de las pruebas PGx en la comunidad biomédica ha cambiado drásticamente, aumentando la concienciación entre los médicos, lo que sugiere un futuro prometedor en las aplicaciones clínicas de PGx en ALC.Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Capacity, damage and fragility models for steel buildings: a probabilistic approach

Recently proposed capacity-based damage indices and parametric models for capacity curves are applied to frame steel buildings located in soft soils of the Mexico City. To do that, the seismic performance of 2D models of low-, mid- and high-rise buildings is assessed. Deterministic and probabilistic nonlinear static and incremental dynamic analyses are implemented. Monte Carlo simulations and the Latin Hypercube sampling technique are used. Seismic actions are selected among accelerograms recorded in the study area. Spectral matching techniques are applied, so that the acceleration time histories have a predefined mean response spectrum and controlled error. The design spectrum of the Mexican seismic code for the zone is used as target spectrum. The well-known Park and Ang damage index allows calibrating the capacity-based damage index. Both damage indices take into account the contribution to damage of the stiffness degradation and of the energy dissipation. Damage states and fragility curves are also obtained and discussed in detail. The results reveal the versatility, robustness and reliability of the parametric model for capacity curves, which allow modelling the nonlinear part of the capacity curves by the cumulative integral of a cumulative lognormal function. However, these new capacity-based damage index and capacity models have been tested for and applied to 2D frame buildings only; they have not been applied to 3D building models yet. The Park and Ang and the capacity-based damage indices show that for the analysed buildings, the contribution to damage of the stiffness degradation is in the range 66–77% and that of energy loss is in the range 29–34%. The lowest contribution of energy dissipation (29%) is found for the low-rise, more rigid, building. The energy contribution would raise with the ductility of the building and with the duration of the strong ground motion. High-rise frame buildings in soft soils of Mexico City show the worst performance so that the use of adequate braced frames to control the displacements could be recommended.Ministry of Economy and Competitiveness (MINECO)/[CGL2011-23621and CGL2015-65913-P]/MINECO/EspañaUniversidad Autónoma de Tabasco/[]/UJAT/MéxicoPrograma de Mejoramiento del Profesorado/[]/PROMEP/MéxicoUniversidad de Costa Rica/[]/UCR/Costa RicaConsejo Nacional para Investigaciones Científicas y Tecnológicas/[]/CONICIT/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ingeniería::Instituto Investigaciones en Ingeniería (INII