Análisis de un problema de secuenciación en un taller de flujo con dos conjuntos de trabajos

En este presente documento se aborda el análisis de un problema de secuenciación en un taller de flujo con dos máquinas y dos conjuntos de trabajos. Más concretamente, el objetivo es estudiar la resolución en un entorno Flow Shop de un problema multicliente cuando los objetivos son la tardanza total y el tiempo de finalización máximo. Para llevar a cabo la investigación, se han configurado las baterías de problemas mediante un modelo de programación lineal entera mixta capaz de resolverlas de manera eficiente. La creación de dicho modelo se ha realizado mediante la herramienta MATLAB® mientras que la resolución de cada problema se ha efectuado mediante el optimizador de GUROBI®. Finalmente, se detallan los resultados obtenidos mediante tablas y se procede al análisis del tiempo computacional de GUROBI®, así como al de los valores de las funciones objetivo.This document deals with the analysis of a two-agent scheduling problem in a two-machine flowshop. More specifically, the goal is to study the resolution of a flowshop environment of a multi-agent problem when the objectives are the total tardiness and the maximum completion time. To carry out the research, the problem batteries have been configured using a mixed integer linear programming model able to solve them efficiently. The creation of said model have been conducted using the MATLAB® tool, while the resolution of each problem has been carried out using the GUROBI® optimizer. Finally, the results obtained by means of tables are detailed and the computational time of GUROBI® is analyzed, as well as that of the values of the objective functions.Universidad de Sevilla. Grado en Ingeniería de las Tecnologías Industriale

Efecto de las características del biorreactor y de su manejo sobre el desarrollo de cultivos embriogénicos de alcornoque

En el marco del proyecto SEFEAL-2, liderado por TRAGSA, se aplican protocolos de embriogénesis somática (ES) para desarrollar variedades de alcornoque de alta calidad y productividad. Al mismo tiempo se mejora la técnica de ES para abaratar los costes y permitir su aplicación a escala comercial. En el alcornoque, como en otras especies, el desarrollo comercial de la embriogénesis como técnica de multiplicación masiva se basa en el uso de biorreactores y medios líquidos agitados. El diseño del biorreactor, su sistema de cierre y el nivel de agitación determinan el grado de mezclado, el estrés hidrodinámico y el intercambio gaseoso, y por ello afectan tanto al crecimiento como al desarrollo de los cultivos embriogénicos. Mediante un ensayo factorial se testaron 3 tipos de envase y tres niveles de agitación. Los efectos sobre el intercambio gaseoso se estimaron a través de la tasa de transferencia de O2 (OTR) y su coeficiente volumétrico de transferencia de masa (KLa), y los efectos sobre el nivel de mezclado mediante el “shear force index” (SFI), un indicador de estrés hidrodinámico. El tipo de envase afectó básicamente al número total de agregados embriogénicos y a la frecuencia de formación de los agregados de mayor tamaño. El nivel de agitación tuvo mayores efectos que el tipo de envase tanto sobre el número como sobre el tamaño de los agregados. Para las condiciones ensayadas, que dieron lugar a valores de KLa comprendidos entre 0,11 h-1 y 1,47 h-1, la disponibilidad de oxígeno no pareció limitante. En cualquier caso, los efectos del tipo de envase y del nivel de agitación sobre los procesos de crecimiento y desarrollo de los materiales embriogénicos de alcornoque fueron complejos resultando muy significativa la interacción tipo de envase por nivel de agitación

Healthcare risk stratification model for emergency departments based on drugs, income and comorbidities: the DICER-score

Background During the last decade, the progressive increase in age and associated chronic comorbidities and polypharmacy. However, assessments of the risk of emergency department (ED) revisiting published to date often neglect patients' pharmacotherapy plans, thus overseeing the Drug-related problems (DRP) risks associated with the therapy burden. The aim of this study is to develop a predictive model for ED revisit, hospital admission, and mortality based on patient's characteristics and pharmacotherapy.MethodsRetrospective cohort study including adult patients visited in the ED (triage 1, 2, or 3) of multiple hospitals in Catalonia (Spain) during 2019. The primary endpoint was a composite of ED visits, hospital admission, or mortality 30 days after ED discharge. The study population was randomly split into a model development (60%) and validation (40%) datasets. The model included age, sex, income level, comorbidity burden, measured with the Adjusted Morbidity Groups (GMA), and number of medications. Forty-four medication groups, associated with medication-related health problems, were assessed using ATC codes. To assess the performance of the different variables, logistic regression was used to build multivariate models for ED revisits. The models were created using a stepwise-forward approach based on the Bayesian Information Criterion (BIC). Area under the curve of the receiving operating characteristics (AUCROC) curve for the primary endpoint was calculated.Results851.649 patients were included; 134.560 (15.8%) revisited the ED within 30 days from discharge, 15.2% were hospitalized and 9.1% died within 30 days from discharge. Four factors (sex, age, GMA, and income level) and 30 ATC groups were identified as risk factors and combined into a final score. The model showed an AUCROC values of 0.720 (95%CI:0.718-0.721) in the development cohort and 0.719 (95%CI.0.717-0.721) in the validation cohort. Three risk categories were generated, with the following scores and estimated risks: low risk: 18.3%; intermediate risk: 40.0%; and high risk: 62.6%.ConclusionThe DICER score allows identifying patients at high risk for ED revisit within 30 days based on sociodemographic, clinical, and pharmacotherapeutic characteristics, being a valuable tool to prioritize interventions on discharge. Risk scores are often used to predict the clinical outcomes of patients in many healthcare settings.To the date, no prediction model of emergency department (ED) visits based on patients' pharmacotherapy, income level, and comorbidities have been developed.We have designed an ED risk score combined four risk factors (sex, age, comorbidity score and income level) and 30 drug categories to identify those patients at high risk of health-care visit

Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine

Cardiovascular side effects of varenicline and a case report of a hypertensive crisis in a varenicline-prescribed patient with pheochromocytoma have been reported. The goal of the present study was to determine whether such side effects might derive, in part, from increased exocytosis of secretory vesicles and subsequent catecholamine release triggered by varenicline in human chromaffin cells of the adrenal gland. In this study, we performed electrophysiological plasma membrane capacitance and carbon fiber amperometry experiments to evaluate the effect of varenicline on exocytosis and catecholamine release, respectively, at concentrations reached during varenicline therapy (100 nM). Experiments were conducted in the absence or presence of nicotine, at plasma concentrations achieved right after smoking (250 nM) or steady-state concentrations (110 nM), in chromaffin cells of the adrenal gland obtained from human organ donors. Cells were stimulated with short pulses (10 ms) of acetylcholine (ACh; 300 μM) applied at 0.2 Hz, in order to closer mimic the physiological situation at the splanchnic nerve-chromaffin cell synapse. In addition, rat chromaffin cells were used to compare the effects obtained in cells from a more readily available species. Varenicline increased the exocytosis of secretory vesicles in human and rat chromaffin cells in the presence of nicotine, effects that were not due to an increase of plasma membrane capacitance or currents triggered by the nicotinic agonists alone. These results should be considered in nicotine addiction therapies when varenicline is usedThis work was supported by grants from the Spanish Ministry of Science and Innovation [grant number BFU2015-69092 to A.A.] and the U.S. National Institutes of Health [GM136430 and GM103801 to J.M.M

Pharmacological Elevation of Cellular Dihydrosphingomyelin Provides a Novel Antiviral Strategy against West Nile Virus Infection

The flavivirus life cycle is strictly dependent on cellular lipid metabolism. Polyphenols like gallic acid and its derivatives are promising lead compounds for new therapeutic agents as they can exert multiple pharmacological activities, including the alteration of lipid metabolism. The evaluation of our collection of polyphenols against West Nile virus (WNV), a representative medically relevant flavivirus, led to the identification of N,N'-(dodecane-1,12-diyl)bis(3,4,5-trihydroxybenzamide) and its 2,3,4-trihydroxybenzamide regioisomer as selective antivirals with low cytotoxicity and high antiviral activity (half-maximal effective concentrations [EC50s] of 2.2 and 0.24 μM, respectively, in Vero cells; EC50s of 2.2 and 1.9 μM, respectively, in SH-SY5Y cells). These polyphenols also inhibited the multiplication of other flaviviruses, namely, Usutu, dengue, and Zika viruses, exhibiting lower antiviral or negligible antiviral activity against other RNA viruses. The mechanism underlying their antiviral activity against WNV involved the alteration of sphingolipid metabolism. These compounds inhibited ceramide desaturase (Des1), promoting the accumulation of dihydrosphingomyelin (dhSM), a minor component of cellular sphingolipids with important roles in membrane properties. The addition of exogenous dhSM or Des1 blockage by using the reference inhibitor GT-11 {N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide} confirmed the involvement of this pathway in WNV infection. These results unveil the potential of novel antiviral strategies based on the modulation of the cellular levels of dhSM and Des1 activity for the control of flavivirus infection.We thank Theodore C. Pierson (National Institutes of Health, USA) for the subgenomic replicon of WNV. This work was supported by the Spanish Ministry of Science and Innovation AEI/10.13039/501100011033 under grants PID2019-105117RR-C21 (to M.A.M.-A.), PID2019-105117RR-C22 (to M.-J.P.-P.), and PID2020-119195RJ-I00 (to N.J.d.O.) and by the AECSIC under grant PIE-201980E100 (to M.-J.P.-P. and A.S.-F.). This research work was also funded by the European Commission-NextGenerationEU (regulation EU 2020/2094) through CSIC’s Global Health Platform (PTI Salud Global). P.M.-C. was supported by an FPI fellowship (PRE2020-093374) from AEI/10.13039/501100011033. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.Peer reviewe

Identification of West Nile virus RNA-dependent RNA polymerase non-nucleoside inhibitors by real-time high throughput fluorescence screening

West Nile virus (WNV) is a re-emergent mosquito-borne RNA virus that causes major outbreaks of encephalitis around the world. However, there is no therapeutic treatment to struggle against WNV, and the current treatment relies on alleviating symptoms. Therefore, due to the threat virus poses to animal and human health, there is an urgent need to come up with fast strategies to identify and assess effective antiviral compounds. A relevant target when developing drugs against RNA viruses is the viral RNA-dependent RNA polymerase (RdRp), responsible for the replication of the viral genome within a host cell. RdRps are key therapeutic targets based on their specificity for RNA and their essential role in the propagation of the infection. We have developed a fluorescence-based method to measure WNV RdRp activity in a fast and reliable real-time way. Interestingly, rilpivirine has shown in our assay inhibition of the WNV RdRp activity with an IC50 value of 3.3 μM and its antiviral activity was confirmed in cell cultures. Furthermore, this method has been extended to build up a high-throughput screening platform to identify WNV polymerase inhibitors. By screening a small chemical library, novel RdRp inhibitors 1–4 have been identified. When their antiviral activity was tested against WNV in cell culture, 4 exhibited an EC50 value of 2.5 μM and a selective index of 12.3. Thus, rilpivirine shows up as an interesting candidate for repurposing against flavivirus. Moreover, the here reported method allows the rapid identification of new WNV RdRp inhibitors

El practicum como espacio de aprendizaje profesional para docentes en formación del Grado de Maestro en Educación Infantil y Educación Primaria

Memoria ID-0189. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017