24 research outputs found

    Fragility Curves for Thin-Walled Cold-Formed Steel Wall Frames Affected by Ground Settlements Due to Land Subsidence

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    Land subsidence phenomenon due to ground water withdrawal is a current problem in many places around the world, particularly in the shallows of Mexico. This causes ground differential settlements that affect structures, mainly dwellings and buildings based on reinforced concrete and masonry. Eventually, these structural materials do not exhibit an adequate performance beyond a certain level of angular distortion. This work presents the results about a study regarding the performance of thin-walled cold-formed steel wall frames with different sheathing systems affected by angular distortions simulating ground differential settlements due to land subsidence. The wall frames are composed by vertical (studs) and horizontal elements (tracks), with different sheathing systems: polystyrene, OSB, gypsum and calcium silicate. By means of experimental testing of wall frames subjected to monotonic lateral loads, the rotational stiffness was obtained for the wall frames with polystyrene. Likewise the rotational stiffness of the other wall frame systems was calculated based on the data provided by other author’s publications. On the other hand, by means of numerical simulation, all the wall frame systems were modeled in structural analysis software, calibrating them based on the rotational stiffness. Also, the moment-rotation curves were calculated for the studs and tracks based on the direct strength method. A non-linear static pull down analysis was performed producing several degrees of angular distortion simulating ground settlements for all the wall frames sheathing systems. With the data acquired fragility curves were calculated according three levels of damage for the wall frames with different sheathing system

    Arquitectura empresarial para la firma de abogados Norton Rose Fulbright, un enfoque BPM-SOA

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    El objetivo de este trabajo de grado se fundamenta en la modelación, optimización y automatización de los procesos de negocio de la firma de abogados Norton Rose Fulbright referentes al årea financiera. Dichos procesos son fundamentales para la actividad contable de la firma y se basan principalmente en el registro de los honorarios de los abogados y la consecuente facturación de estos. Teniendo en cuenta esta información, se realizó el proceso de anålisis, diseño y construcción de un prototipo funcional que soporte el proceso de negocio mencionado anteriormente y solucione los problemas de pérdida, tiempo y productividad en la firma.The objective of this thesis is based in the modeling, optimization and automation of the business processes of the law firm Norton Rose Fulbright. These processes are fundamental for the accounting activity of the firm and are mainly based on the registration of attorneys' fees and the consequent invoicing thereof. Taking into account this information, the process of analysis, design and construction of a functional prototype that supports the business process was performed, previously solved the problems of loss, time and productivity in the firm.Ingeniero (a) de SistemasPregrad

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expertÂŽs group based and informed on evidence

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    La AsociaciĂłn Colombiana de InfectologĂ­a (ACIN) y el Instituto de EvaluaciĂłn de Nuevas TecnologĂ­as de la Salud (IETS) conformĂł un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atenciĂłn, diagnĂłstico y manejo de casos de Covid 19. Estas guĂ­as son dirigidas al personal de salud y buscar dar recomendaciones en los ĂĄmbitos de la atenciĂłn en salud de los casos de Covid-19, en el contexto nacional de Colombia

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

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    From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an <i>Asclepias subulata</i> Extract

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    Asclepias subulata plant extract has previously demonstrated antiproliferative activity and antimutagenicity against heterocyclic aromatic amines (HAAs) commonly found in cooked meat. The objective of this work was to evaluate the in vitro ability of an ethanolic extract from the medicinal plant Asclepias subulata extract (ASE), non-heated and heated (180 °C), to inhibit the activity of CYP1A1 and CYP1A2, which are largely responsible for HAAs bioactivation. Ethoxyresorufin and methoxyresorufin O-dealkylation assays were performed in rat liver microsomes exposed to ASE (0.002–960 ”g/mL). ASE exerted an inhibitory effect in a dose-dependent manner. The half inhibitory concentration (IC50) for unheated ASE was 353.6 ”g/mL and 75.9 ”g/mL for heated ASE in EROD assay. An IC40 value of 288.4 ± 5.8 ”g/mL was calculated for non-heated ASE in MROD assay. However, after heat treatment, the IC50 value was 232.1 ± 7.4 ”g/mL. Molecular docking of corotoxigenin-3-O-glucopyranoside, one of the main components of ASE, with CYP1A1/2 structure, was performed. Results show that the interaction of corotoxigenin-3-O-glucopyranoside with CYP1A1/2s’ α-helices, which are related with the active site and the heme cofactor, may explain the plant extract’s inhibitory properties. Results showed that ASE inhibits CYP1A enzymatic subfamily and may potentially act as a chemopreventive agent by inhibiting bioactivation of promutagenic dietary HAAs

    X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

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    Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

    The immunogenetic diversity of the HLA system in Mexico correlates with underlying population genetic structure

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