Meta-model assisted continuous vibration-based damage identification of a historical rammed earth tower in the Alhambra complex

This work presents the development of a model-based online damage identification system for a 13th century rammed earth (RE) tower in the Alhambra, the Muhammad Tower. The system is fed with continuous data from an ambient vibration-based monitoring system and a meteorological station. Ambient vibrations are continuously processed through Operational Modal Analysis (OMA), and environmental effects are minimised via statistical pattern recognition. The normalized modal signatures are used to update the stiffness properties of certain parts of the tower through inverse model calibration. To do so, a high-fidelity three-dimensional finite element model (FEM) of the tower is developed. Since its computational burden precludes conducting online calibration, the FEM is bypassed by a light Kriging surrogate model (SM). In this light, the developed SM-assisted system identification constitutes a long-term Structural Health Monitoring (SHM) system outputting quasi-real-time series of modal properties and local stiffness parameters, so providing full damage assessment (detection, localization and quantification). The presented results refer to a time period of three months since January until March 2022. Numerical results and discussion are reported concerning the characterization and removal of environmental effects, and synthetic damage scenarios through non-linear simulations are used to validate the developed damage identification syste

Sensibilización al gato en pacientes con alergia respiratoria, experiencia de una institución universitaria

Antecedentes: La frecuencia de sensibilización al gato en sujetos con alergia respiratoria puede ser hasta de 60% y es un factor de riesgo para desarrollar alergia al gato. Objetivo: Establecer la frecuencia de sensibilización al gato por exposición ambiental y por prueba cutánea al alérgeno de gato Fel d1 en pacientes con alergia respiratoria. Métodos: Estudio transversal prospectivo comparativo realizado de agosto a noviembre del 2009. Se Incluyeron 198 sujetos divididos en dos grupos (un grupo de 98 pacientes con alergia respiratoria y otro con 100 controles sanos). Se les aplicó un cuestionario clínico epidemiológico y prueba cutánea con alérgeno de gato Fel d1 (1:20 p/v) mediante el método de punción epicutánea (Prick-test). Resultados: La frecuencia de sensibilización al gato medida por prueba cutánea en pacientes con alergia respiratoria fue de 25% comparado con 10% en sanos (p = 0.004). En los sujetos con rinitis alérgica y asma la frecuencia de sensibilización al gato fue de 31% y en los sujetos que tenían exclusivamente rinitis alérgica fue de 22% (p = 0.416). La presencia de síntomas a la exposición ambiental con gato en el grupo de pacientes con alergia respiratoria fue de 19%, en los sujetos sanos fue de 2% (p < 0.001). La presencia de gato en casa en pacientes con alergia respiratoria que fueron sensibles a la prueba cutánea de alérgeno de gato fue de 1%. Los pacientes tuvieron una frecuencia de sensibilidad a otros alérgenos como D. pteronyssinus (80%), D. farinae (72%), Cynodon (52%), Amaranthus, Salsola y Fraxinus (40% cada uno). Conclusión: La frecuencia de sensibilización al gato en sujetos con alergia respiratoria fue de 25%, similar a lo informado por otras series

Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKC alpha activation and promotes transforming growth factor alpha (TGF alpha) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.J.P.L.’s lab is sponsored by Grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/ 501100011039; Grant PDC2021-121735-I00 funded by MCIN/AEI/10.13039/501100011039 and by the “European Union Next Generation EU/PRTR”, the Regional Government of Castile and León (CSI144P20). J.P.L. and P.L.S. are supported by the Carlos III Health Institute (PIE14/00066). AGN laboratory and human patients’ studies are supported by an ISCIII project grant (PI18/01242). The Human Genotyping unit is a member of CeGen, PRB3, and is supported by grant PT17/0019 of the PE I + D + i 2013–2016, funded by ISCIII and ERDF. SCLl is supported by MINECO/FEDER research grants (RTI2018-094130-B-100). CH was supported by the Department of Defense (DoD) BCRP, No. BC190820; and the National Cancer Institute (NCI) at the National Institutes of Health (NIH), No. R01CA184476. Lawrence Berkeley National Laboratory (LBNL) is a multi-program national laboratory operated by the University of California for the DOE under contract DE AC02-05CH11231. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D +i, 2017–2020, funded by ISCIII and FEDER. RCC is funded by fellowships from the Spanish Regional Government of Castile and León. NGS is a recipient of an FPU fellowship (MINECO/FEDER). hiPSC-CM studies were funded in part by the “la Caixa” Banking Foundation under the project code HR18-00304 and a Severo Ochoa CNIC Intramural Project (Exp. 12-2016 IGP) to J.J.S

Terms of reference for the mediterranean tuna habitat observatory initiative

[EN] We present the Terms of Reference for a case study on a Mediterranean eco-region focusing on the environmental component of the Ecosystem Report Card. The objective of this case study is to describe and monitor the variability of environmental processes in the Mediterranean Sea that affect the ecology of large pelagic fishes, with a particular attention on tunas, and the possible role of climate change on this variability. Here we define the objectives and activities of the initiative, the participant roles, primary indicators and the methodological approach[FR] Ce document présente les termes de référence d’une étude de cas sur une écorégion méditerranéenne consacrée à la composante environnementale de la fiche informative sur les écosystèmes. L'objectif de cette étude de cas est de décrire et de suivre la variabilité des processus environnementaux en mer Méditerranée qui affectent l'écologie des grands poissons pélagiques, en accordant une attention particulière aux thonidés, et de déterminer le rôle possible du changement climatique sur cette variabilité. Nous définissons ici les objectifs et les activités de l'initiative, les rôles des participants, les indicateurs primaires et l'approche méthodologique.[ES] En el documento se presentan los términos de referencia para un estudio de caso sobre una ecorregión mediterránea centrado en el componente medioambiental de la ficha informativa sobre ecosistemas. El objetivo de este estudio de caso es describir y hacer un seguimiento de la variabilidad de los procesos medioambientales en el mar Mediterráneo que afectan a la ecología de los grandes peces pelágicos, con especial atención a los túnidos, y el posible papel del cambio climático en esta variabilidad. A continuación, se definen los objetivos y actividades de la iniciativa, las funciones de los participantes, los indicadores principales y el enfoque metodológico.Peer reviewe

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Passiflora ligularis Juss. (granadilla): estudios químicos y farmacológicos de una planta con potencial terapéutico

ilustracionesEl presente libro es fruto de la investigación interdis- ciplinaria entorno a las hojas de Passiflora ligularis (granadilla) con fines medicinales, entre los grupos de investigación Principios Bioactivos de Plantas Medicinales del Departamento de Farmacia de la Universidad Nacional de Colombia, Estudio y Aprovechamiento de Productos Naturales Marinos y Frutas de Colombia del Departamento de Química de la Universidad Nacional de Colombia y el Grupo de Investigación en Fitoquímica de la Pontificia Universidad Javeriana, con apoyo del Ministerio de Ciencia, Tecnología e Innovación de Colombia. A lo largo de estas páginas, se resumen algunos de los resultados y avances más destacados de estos grupos de investigación en cuanto a la caracterización química de las hojas de esta especie dando énfasis a los flavonoides y saponinas, al estudio in silico, in vitro e in vivo de su actividad farmacológica, principalmente como hipoglicemiante y antinflamatorio, al desarrollo de metodologías analíticas precisas, exactas y reproducibles que permitan la completa caracterización del extracto optimizado obtenido como un ingrediente activo promisorio para el desarrollo de productos fitoterapéuticos, etapa actualmente en progreso. Se pretende que esta publicación permita la divulgación técnica y científica de los resultados de varios años de estudio con el fin de dar valor agregado a los cultivos de Passiflora ligularis, una planta de gran interés comercial debido a sus frutos y cuyas hojas en la actualidad son simplemente un subproducto de su cosecha, desconociendo el potencial terapéutico de las mismas y la posibilidad de convertirse en un materia prima para la obtención de productos fitoterapéuticos estables, seguros y eficaces. (texto tomado de la fuente)Presentación -- Capítulo 1. Estudio in silico y evaluación in vitro de la actividad inhibitoria de flavonoides y saponinas identificados en hojas de Passiflora ligularis Juss. sobre las enzimas α-amilasa y α-glucosidasa -- Capítulo 2. Evaluación de la actividad antiinflamatoria del extracto acuoso, la fracción butanólica y compuestos identificados en las hojas de Passiflora ligularis Juss. -- Capítulo 3. Efecto del extracto acuoso de hojas de Passiflora ligularis Juss. y de sus metabolitos mayoritarios sobre la homeostasis de glucosa -- Capítulo 4. Metodologías analíticas para el estudio y cuantificación de flavonoides en extractos de hojas de Passiflora ligularis Juss. -- Capítulo 5. Estandarización del extracto de hojas de Passiflora ligularis Juss. (granadilla)Primera edició

Multicentre, randomised, single-blind, parallel group trial to compare the effectiveness of a Holter for Parkinson's symptoms against other clinical monitoring methods: study protocol

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson's disease patients (Parkinson's Holter). The effectiveness of these monitoring devices for improving clinical control is not known. Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson?s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months. The primary outcome is the efficiency of the Parkinson?s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor?patient contacts will be analysed. The noninferiority of the Parkinson's Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective. Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson's Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Funding This work is supported by AbbVie S.L.U, the Instituto de Salud Carlos III [DTS17/00195] and the European Fund for Regional Development, 'A way to make Europe'

Vacuna tetravalente de influenza en los programas nacionales de inmunización para los países de América Latina

Since 2012-2013 influenza season, World Health Organization (who) recommends the formulation of tetravalent vaccines. Globally, many countries already use tetravalent vaccines in their national immunization programs, while in Latin America only a small number. Two Influenza b lineages co-circulate, their epidemiological behavior is unpredictable. On average they represent 22.6% of influenza cases and more than 50% in predominant seasons. The lack of concordance between recommended and circulating strains was 25 and 32% in the 2010-2017 and 2000-2013 seasons, respectively. There are no clinical differences between influenza A and B. It occurs more frequently from five to 19 years of age. Influenza b has a higher proportion of attributable deaths than influenza a (1.1 vs. 0.4%), or 2.65 (95% ci 1.18-5.94). A greater number of hospitalizations when the strains mismatch (46.3 vs. 28.5%; p <.0001). Different evaluations have demonstrated its cost effectiveness. The compilation of this information supports the use of quadrivalent vaccines in Latin American countries.Revisión por pare

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality