Methodology of a Large Multicenter Observational Study of Patients with COVID-19 in Spanish Intensive Care Units.

Introduction The COVID-19 pandemic created tremendous challenges for health-care systems. Intensive care units (ICU) were hit with a large volume of patients requiring ICU admission, mechanical ventilation, and other organ support with very high mortality. The Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), a network of Spanish researchers to investigate in respiratory disease, commissioned the current proposal in response to the Instituto de Salud Carlos III (ISCIII) call. Methods CIBERESUCICOVID is a multicenter, observational, prospective/retrospective cohort study of patients with COVID-19 admitted to Spanish ICUs. Several work packages were created, including study population and ICU data collection, follow-up, biomarkers and miRNAs, data management and quality. Results This study included 6102 consecutive patients admitted to 55 ICUs homogeneously distributed throughout Spain and the collection of blood samples from more than 1000 patients. We enrolled a large population of COVID-19 ICU-admitted patients including baseline characteristics, ICU and MV data, treatments complications, and outcomes. The in-hospital mortality was 31%, and 76% of patients required invasive mechanical ventilation. A 3-6 month and 1 year follow-up was performed. Few deaths after 1 year discharge were registered. Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. These antibodies contribute to prevent systemic dissemination of SARS-CoV-2. The severity of COVID-19 impacts the circulating miRNA profile. Plasma miRNA profiling emerges as a useful tool for risk-based patient stratification in critically ill COVID-19 patients. Conclusions We present the methodology used in a large multicenter study sponsored by ISCIII to determine the short- and long-term outcomes in patients with COVID-19 admitted to more than 50 Spanish ICUs.post-print1142 K

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study.

Purpose Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. Methods Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. Results Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65–0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58–0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14–1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61–0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. Conclusion Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.post-print910 K

Scale-invariant avalanche dynamics in the temperature-driven martensitic transition of a Cu-Al-Be single crystal

We have combined high sensitivity, extra-low differential temperature scanning rate calorimetry, and acoustic emission (AE) measurements to study avalanches during the cubic ↔ 18R martensitic transition of a Cu-Al-Be single crystalline shape memory alloy. Both AE and calorimetry corroborate a good power-law behavior for cooling with an exponent ε 1.6. For heating, a slope is observed in the maximum likelihood curves, which confirms that our data are affected by an exponential cutoff. An effective energy exponent, ε ∼ 1.85, and a cutoff, λ −1 = 0.115(38)E-3 aJ, were determined by fits of power-laws with exponential damping. The long tail observed in the low-temperature region by calorimetric measurements suggests the existence of significant elastic effects that constrain the progress of the transformation at low temperatures. While thermodynamic features such as transformation enthalpy and entropy are those expected for Cu-based shape-memory alloys undergoing a cubic ↔ 18R transition, the critical behavior deviates from the corresponding behavior expected from this symmetry change. These deviations are a consequence of the elastic hardening induced by the interplay of the transformation with dislocation jamming, which has the effect of effectively reducing the number of pathways connecting the parent and martensitic phaseMinisterio de Ciencia,Innovación y Universidades (MAT2016-75823-R)Engineering and Physical Sciences Research Council (EP/P024904/1

La interacción técnica, social y económica entre las pesquerías de arrastre de Palamós: propuesta de nuevo plan de gestión

Existen diferencias técnicas, sociales y económicas entre los segmentos de flota de arrastre de Palamós, producidas por la competencia histórica entre los armadores pesqueros, que afectan de diferente manera al negocio de los armadores y al estado de los recursos marinos explotados. Estas diferencias socio-tecnológicas y socioeconómicas se han acentuado con la aplicación del Plan de Gestión de la gamba rosada en el año 2013. Para determinar cuáles son los factores que caracterizan las diferencias producidas, se ha estudiado la interacción entre las embarcaciones de las diferentes pesquerías: la pesquería de arrastre costera, la pesquería de cigala y la pesquería de gamba rosada. Se han obtenido los datos referente a capturas e ingresos de venta (Kg y €) y las características constructivas de las embarcaciones (Eslora, volumen y potencia, etc.). Se han realizado reuniones y entrevistas por tal de poder contrastar toda la información. La experiencia del autor como profesional del sector pesquero de Palamós ha sido crucial para el desarrollo del proyecto. El análisis ha permitido conocer el Patrón de Pesca de las embarcaciones, la tendencia del estado de explotación de las principales especies objetivo y la clasificación de las embarcaciones en una pesquería/s determinada/s. Se ha podido conocer que los pescadores de arrastre costero de Palamós sufren una Diferencia Social y una Pérdida de Poder Político, en relación a los otros segmentos de flota. Para solucionar los problemas hallados se ha propuesto un Plan de Gestión que tiene en cuenta la nueva política de Cogestión Pesquera de Cataluña. El modelo propuesto reordena el Patrón de Pesca actual así como la interacción entre los segmentos de flota. Finalmente, el estudio crea un valor añadido a la pesca de arrastre de Palamós

Evaluation of innovative approaches in active distribution network management via time-series simulations

European directives for renewable energies and decreasing costs of these alternative generation technologies are incentivising a transformation of the electricity markets, grid infrastructure and the way the grid is operated. Distribution networks, which were not traditionally designed to host generation, have to deal now with distributed energy resources that feed intermittent power into the grid. Thus, due to the fact that excess energy from these intermittent sources cannot be hosted, not only the need of energy storage in power systems has emerged but also of new control strategies in the eld of grid planning such as demand response or curtailment of generation units. In order to take SmartGrid elements and control strategies into the planning stage, the ETH Zurich spin-o Adaptricity has developed DPG.sim, a time-series simulation software that can overcome traditional grid planning software limitations in representing the behavior of SmartGrid elements for grid planning studies. Within the traditional grid extension planning, this thesis addresses the implementation of an automatic grid upgrade algorithm to be used with DPG.sim to automatically select which elements must be substituted. This work also demonstrates, using temporal simulations in DPG.sim, the scope of active network management strategies to enlarge grid hosting capacity of distributed energy generation. Thus, it will show how these strategies can reduce the technical challenges faced by Distribution System Operators (DSOs) such as overvoltages and line overloadings.Outgoin

Estudio hidrogeológico para el diseño de métodos de recarga de acuíferos en la microcuenca de Unuhuaycco, distrito Oropesa, provincia Quispicanchi - Cusco -2019

El área de estudio se encuentra en el departamento de Cusco, Provincia Quispicanchi, Distrito Oropesa en la microcuenca Unuhuaycco, siendo esta accesible por la pista principal Cusco – Sicuani, sobre esta vía a la altura del distrito de oropesa, se sigue por una vía asfaltada hasta el mismo centro poblado; a partir de allí existe una trocha carrozable que atraviesa por el poblado de Patacalle hasta llegar a la comunidad de Pucara que se ubica en cabecera de cuenca. A nivel regional, morfoestructuralmente la zona de estudio se encuentra en la zona intermedia Altiplano – Cordillera Oriental, donde se identificó las unidades fisiográficas en la microcuenca Unuhuaycco a partir de la identificación de unidades de gran paisaje, unidades de paisaje, y unidades de subpaisaje, partiendo del mapa de pendientes. Posteriormente se integraron estas unidades fisiográficas con la litología, obteniéndose así las unidades geomorfológicas locales correspondientes para la zona de estudio. En el aspecto geológico la microcuenca Unuhuaycco se caracteriza por presentar las Formaciones: Pachatusán, Huambutio, Huancané, Paucarbamba, Quilque, Rumicolca y depósitos cuaternarios (aluviales, glaciares, coluviales y fluviales). El área de estudio presenta fallas normales Pachatuáan y Tambomachay que se encuentra en la parte baja de la microcuenca. En el aspecto hidrológico al realizar el análisis y regionalización de las condiciones meteorológicas de la microcuenca Unuhuaycco se tomó como altitud media de 3657 m.s.n.m obteniendo para el mismo una precipitación anual de 669.97 mm/año y una temperatura media mensual de 9.9 °C. Con respecto a la hidrogeología en la microcuenca Unuhuaycco se han inventariado 16 fuentes de agua, 4 puntos de control y también se han identificado dos unidades hidrogeológicas divididas de la siguiente forma: acuíferos que ocupan un área total de 294.18 hectáreas dentro del cual se encuentran acuíferos porosos non consolidados, fisurados sedimentarios y volcánico sedimentarios y acuitardos ocupando un área total de 534.15 ha dentro de la cual se encuentran acuitardos no consolidados, sedimentarios y volcánicos. Con respecto al balance hídrico la oferta hídrica o cantidad de agua con la que cuenta la microcuenca Unuhuaycco es de 918,203.74 m3/año y con respecto a la demanda de agua esta se ha dividido en tres: una demanda hídrica por consumo humano de 450903.45 m3/año, por consumo pecuario 3650.00 m3/año y demanda para riego de 1020820.41 m3/año, con una demanda total de 1475373.87 m3/año. En los diseños de métodos de recarga de acuíferos se plantearon las zanjas de infiltración, zanjas de infiltración con una forestación intermedia siendo esta una práctica de fácil realización que intercepta el agua de escorrentía facilitando su infiltración al suelo las cuales en laderas muy degradas con pendientes que van entre 50 y 75% permite la recuperación de la vegetación en dichas laderas. El presente estudio servirá de herramienta de consulta para iniciar futuras investigaciones en el manejo y buena gestión del recurso hídrico y un aporte en la toma de decisiones de las autoridades del poblado de Oropesa.Tesi

hCOA3 stabilizes COX1 and promotes cytochrome c oxidase assembly in human mitochondria

Cytochrome c oxidase (COX) or complex IV of the mitochondrial respiratory chain plays a fundamental role in energy production of aerobic cells. In humans, COX deficiency is the most frequent cause of mitochondrial encephalomyopathies. Human COX is composed of 13 subunits of dual genetic origin, whose assembly requires an increasing number of nuclear-encoded accessory proteins known as assembly factors. Here, we have identified and characterized human CCDC56, an 11.7-kDa mitochondrial transmembrane protein, as a new factor essential for COX biogenesis. CCDC56 shares sequence similarity with the yeast COX assembly factor Coa3 and was termed hCOA3. hCOA3-silenced cells display a severe COX functional alteration owing to a decreased stability of newly synthesized COX1 and an impairment in the holoenzyme assembly process. We show that hCOA3 physically interacts with both the mitochondrial translation machinery and COX structural subunits. We conclude that hCOA3 stabilizes COX1 co-translationally and promotes its assembly with COX partner subunits. Finally, our results identify hCOA3 as a new candidate when screening for genes responsible for mitochondrial diseases associated with COX deficiency

Serum Neprilysin and Recurrent Admissions in Patients With Heart Failure

Our aim was to evaluate the association between the soluble form of neprilysin () levels and long-term all-cause, cardiovascular, and acute heart failure () recurrent admissions in an ambulatory cohort of patients with heart failure. has emerged as a new biomarker with promising implications for prognosis and therapy in patients with heart failure. Reducing the recurrent admission rate of heart failure patients has become an important target of public health planning strategies. We measured levels in 1021 consecutive ambulatory heart failure patients. End points were the number of all-cause, cardiovascular, and hospitalizations during follow-up. We used covariate-adjusted incidence rate ratios to identify associations. At a median follow-up of 3.4 years (interquartile range: 1.8-5.7), 391 (38.3%) patients died, 477 (46.7%) patients had 1901 all-cause admissions, 324 (31.7%) patients had 770 cardiovascular admissions, and 218 (21.4%) patients had 488 admissions. The medians for and amino-terminal pro-brain natriuretic peptide were 0.64 ng/mL (interquartile range: 0.39-1.22) and 1248 pg/mL (interquartile range: 538-2825), respectively. In a multivariate setting, the adjusted incidence rate ratios for the top (>1.22 ng/mL) versus the bottom (≤0.39 ng/mL) quartiles of were 1.37 (95% confidence interval: 1.03-1.82), P =0.032; 1.51 (95% confidence interval: 1.10-2.06), P =0.010; and 1.51 (95% confidence interval: 1.05-2.16), P =0.026 for all-cause, cardiovascular, and admissions, respectively. Elevated levels predicted an increased risk of recurrent all-cause, cardiovascular, and admissions in ambulatory patients with heart failure

O IMPACTO DOS SERVIÇOS AO CLIENTE NO MARKETING DE RELACIONAMENTO ENTRE MINIMERCADOS E SEUS FORNECEDORES

Em um ambiente de acirrada competição, a construção de relacionamentos sustentáveis entre os participantes de um canal comercial assume maior importância, tornando o desenvolvimento de parcerias estratégicas e cooperação mútua fundamental para as empresas aumentarem sua competitividade no mercado. Considerando esse contexto, com o estudo desenvolvido objetivou-se examinar as relações existentes entre os serviços ao cliente e o marketing de relacionamento nas transações entre minimercados e seus principais fornecedores. A mensuração do marketing de relacionamento foi feita por meio da escala proposta por Wilson e Vlosky (1997), e o nível de serviços ao cliente foi verificado pelos indicadores de serviços, gerados em uma etapa exploratória com gestores de minimercados. Utilizando-se Regressão Múltipla foi possível identificar que os serviços ao cliente apresentam influência no relacionamento do canal estudado. Os resultados também demonstram que o relacionamento entre minimercados e seus fornecedores é frágil, exceto na dimensão comprometimento. Palavras-chave: Marketing de relacionamento. Serviços ao cliente. Canal de marketing. Minimercados.   The impact of customer service in marketing relationship between minimarkets and its suppliers   Abstract   In a tough competitive environment, building sustainable relationships between the participants of a commercial channel assumes greater importance, making the development of strategic partnerships and mutual cooperation essential for the companies that wish to improve their competitiveness in the market. Given this context, the study developed aimed to examine the existing relationship between customer services and relationship marketing in transactions between minimarkets and its main suppliers. The relationship marketing measurement was evaluated through the scale proposed by Wilson and Vlosky (1997), and the level of customer service was verified through service indicators generated in an exploratory stage with minimarkets owners. Through Multiple Regression it was found that customer services influence in this study channel. The results showed that the relationship between mini-markets’ owners and their suppliers is fragile, except on the commitment dimension. Keywords: Relationship marketing. Customer services. Marketing channel. Minimarket