Many-objective test suite generation for software product lines

A Software Product Line (SPL) is a set of products built from a number of features, the set of valid products being defined by a feature model. Typically, it does not make sense to test all products defined by an SPL and one instead chooses a set of products to test (test selection) and, ideally, derives a good order in which to test them (test prioritisation). Since one cannot know in advance which products will reveal faults, test selection and prioritisation are normally based on objective functions that are known to relate to likely effectiveness or cost. This paper introduces a new technique, the grid-based evolution strategy (GrES), which considers several objective functions that assess a selection or prioritisation and aims to optimise on all of these. The problem is thus a many-objective optimisation problem. We use a new approach, in which all of the objective functions are considered but one (pairwise coverage) is seen as the most important. We also derive a novel evolution strategy based on domain knowledge. The results of the evaluation, on randomly generated and realistic feature models, were promising, with GrES outperforming previously proposed techniques and a range of many-objective optimisation algorithms

Dioxinas y PCBS en la alimentación de pollos de carne : efecto sobre parámetros productivos y utilización de nutrientes

Este experimento tiene por objetivo evaluar la repercusión de la adición de grasas que presentan dioxinas (D) y bifenilos policlorados (PCBs) en la alimentación de pollos broiler. Se estudió su efecto sobre el rendimiento productivo, coeficiente de digestibilidad y el depósito de grasa de los animales. 64 pollos broiler hembra línea genética Ross 308 fueron alimentados hasta los 47 días de edad con dos piensos experimentales con un nivel de inclusión del 6% de aceite de pescado. Las dos materias grasas utilizadas diferían en el nivel de contaminación: nivel alto HD 9,78 pg TEQD pg/g y 19,02 pg TEQPCBs/g y nivel bajo LD l,95pg TEQD y 7,69 pg TEQPCBs/g. No se observaron diferencias estadísticamente significativas en el consumo medio diario (CMD), ganancia media diaria (GMD) ni en el índice de transformación (IT) entre los tratamientos experimentales. Se realizaron dos balances de digestibilidad desde el día 14 al 16 y del 37 al 39. No se observaron diferencias estadísticamente significativas en la digestibilidad de la materia seca (DMS), y digestibilidad de la materia orgánica (DMO) si bien la digestibilidad del extracto etéreo (DEE) en primeras edades fue superior para los animales del tratamiento HD (LD 80.57% vs. HD 86.39%; P<0.01). Por otro lado, el rendimiento de la canal fue superior para los animales del tratamiento HD (LD 80.51% vs. HD 81.72%; P< 0.01) sin observarse diferencias estadísticamente significativas en el resto de parámetros estudiados (peso vivo PV, peso canal PC, y grasa abdominal GA). En conclusión, los aceites comerciales de pescado con concentraciones de contaminantes de hasta 9,78 pg TEQD/g y19,02 pg TEQPCB/g, no alteran los parámetros productivos ni el rendimiento en los pollos de carne.An experiment was designed to study the effect of the addition of dioxin and polychlorinated biphenyls PCBs contaminated fats in broiler chickens diets, on the productive yield parameters, the fat digestibility and deposit. Sixty four female broilers (genetic line Ross) were lodged in 16 cages distributed in to two treatments consisting of two experimental diets with 6% of fish oil with 9.78 pg TEQD and 19.02 pg TEQPCB/g ofoil for the high level (HD) and 1.95 pg TEQD and 7.69 pg TEQPCB/g of oil for the low level (LD). The experiment lasted until day 47 oflife ofanimals and productive controls were made at days 22 and 47. Studied parameters included, daily mean intake (CMD), daily mean gain (GMD) and the conversion index (IT). No statistical differences were found in this parameters. From day 14 to 16 and from 37 to 39 two digestibility trials were performed. There was no significant statistical difference in dry matter digestibility (DMS), organic matter digestibility (DMO), but ether extract digestibility (EED) was higher during first trial for HD treatment (LD 80,57% vs. HD 86,39%; P < 0.01). Regarding live weight (W), carcase weight (CW), carcase yield (RC) and abdominal fat (AF), only RC showed statistical differences with highervalues for HD treatment (LD 80,51% vs. HD 81,72%; P<0.01)

Comparative study of control algorithms for maneuvers of first generation TECs* and two degrees of freedom

[EN] From the devices for harnessing the energy of ocean currents (In English, they are denoted as TEC “Tidal Energy Converters”. This term does not englobe all the devices for marine current harnessing), those denoted as first-generation devices are used to obtain energy from underwater currents at depths that do not exceed 40 or 50 m, which configures them as structures supported over the seabed. For the energy exploitation of this resource to be competitive, from a technical and economic perspective, it is necessary to overcome various technological challenges, and to reduce operating costs, focusing the effort on lowering maintenance costs too. Thanks to the implementation of a ballast control system, these generators are equipped with the possibility of automatically changing orientation and depth during emersion-immersion maneuvers, which can reduce these costs. This work presents the dynamic modeling of a device with two degrees of freedom and several multivariable control algorithms, all of them based on a non-linear decoupling matrix, together with the compensation of the loss of buoyancy term in the neighborhood of the free surface. The performance of these controllers is evaluated by simulating the emersion maneuver of a full-scale device, and these results are validated with a small-scale prototype in the Model Basin. Finally, the obtained results under simulation are compared, and experimental validation is presented.[ES] Los Dispositivos de Aprovechamiento de la Energía de las Corrientes (DAECs), denominados de primera generación, se emplean para la obtención de la energía de las corrientes submarinas en profundidades que no superan los 40 ó 50 m, lo que los configura como estructuras apoyadas en el fondo marino. Para que la explotación energética de este recurso sea competitiva -desde una perspectiva técnica y económica-, se requiere superar diversos retos tecnológicos y además, reducir los gastos de explotación, focalizando los esfuerzos en un abaratamiento de los costos de mantenimiento. Gracias a la implantación de un sistema de control de lastres, se dotan a estos generadores de la posibilidad de cambiar automáticamente de orientación y profundidad durante las maniobras de emersión-inmersión que pueden reducir dichos costos. En este trabajo se presenta el modelado dinámico de un dispositivo de dos grados de libertad y varios algoritmos de control multivariable, todos ellos basados en una matriz no lineal de desacoplamiento, junto con el término de compensación de la pérdida de empuje en las cercanías de la superficie libre. Se evalúan las prestaciones de estos controladores mediante la simulación de la maniobra de emersión de un dispositivo a escala real, y se validan los resultados con un prototipo a escala en Canal de Ensayos. Finalmente, se comparan los resultados obtenidos en simulación y se presenta su validación experimental.Este trabajo se ha realizado con financiación parcial del Ministerio de Ciencia e Innovación, a través del Proyecto de Investigación Fundamental DPI2014-53499-R CoDMAEC y del Grupo Tecnológico de Investigación en Energías Renovables Marinas de la Universidad Politécnica de Madrid, GIT-ERM. Los autores quieren agradecer al Tribunal que otorgó el premio al mejor trabajo de los presentados a las XL Jornadas de Automática de Ferrol en 2019 por su consideración. También al personal del CEHINAV, en la ETSI Navales de la UPM, por su siempre amable colaboración altruista. Y a los revisores anónimos por sus aportaciones para la mejora de este trabajo.Del Horno, L.; Somolinos, J.; Segura, E.; Morales, R. (2021). Estudio comparativo de algoritmos de control para maniobras de DAECs* de primera generación y dos grados de libertad. Revista Iberoamericana de Automática e Informática industrial. 18(4):407-418. https://doi.org/10.4995/riai.2021.14974407418184Acuerdo de París. 2015. "Acuerdo de París." In Convención Marco de Las Naciones Unidas Sobre El Cambio Climático (CMNUCC).Badcock-Broe, A., Flynn, R., George, S., R. Gruet, R., Medic, N., 2014. Wave and Tidal Energy Market Deployment Strategy for Europe. www.ed.ac.uk.Brown, A., Paasch, R., Tumer, I.Y., Lenee-Bluhm, P., Hovland,J., Von Jouanne, A., Brekken, T., 2010. Towards a Definition and Metric for the Survivability of Ocean Wave Energy Converters. In ASME 2010 4th International Conference on Energy Sustainability, ES 2010, 1:917-27. American Society of Mechanical Engineers Digital Collection. https://doi.org/10.1115/ES2010-90069CEHINAV. Accessed July 10, 2020. http://canal.etsin.upm.es/cehinav/Del Horno, L., Segura, E., Morales, R., Somolinos, J.A., 2020. Exhaustive Closed Loop Behavior of an One Degree of Freedom First-Generation Device for Harnessing Energy from Marine Currents. Applied Energy 276 (October): 115457. https://doi.org/10.1016/j.apenergy.2020.115457Dorf, R. and R. Bishop. 2005. Sistemas de Control Moderno. Pearson Educación S.A.Espín, M. 2015. "Modelado Dinámico y Control de Maniobras de Dispositivos Submarinos." Tesis ETSIN-UPMEuropean Commission. 2018. "A Clean Planet for All A European Strategic Long-Term Vision for a Prosperous, Modern, Competitive and Climate Neutral Economy."Fernández, L., Segura, E., La Portilla, M.P., Morales, R., Somolinos, J.A., 2016. Dynamic Model and Nonlinear Control for a Two Degrees of Freedom First Generation Tidal Energy Converter. In 10th IFAC Conference on Control Applications in Marine Systems CAMS 2016: Trondheim, Norway, 13-16 September 2016, 49:373-79. Elsevier. https://doi.org/10.1016/j.ifacol.2016.10.433García, E., Correcher, A., Quiles, E., Morant, F., 2016. Recursos y Sistemas Energéticos Renovables Del Entorno Marino y Sus Requerimientos de Control. RIAI - Revista Iberoamericana de Automatica e Informatica Industrial 13 (2): 141-61. https://doi.org/10.1016/j.riai.2016.03.002Gulf Stream Turbine. "A Steady Low-Cost Electricity from a Coriolis-Force Current." Accessed January 18, 2021. http://wdstudio.net/gulfstreamturbine/gst.htm.IEC-TC214. 2011. "'Tecnhical Specification: Marine Energy. Wave, Tidal and Other Water Current Converters. Part 1: Terminology.'" In . IEC/TS 62600-1 Ed. International Electrotechnic Commision. Ginebra, Switzerland.La Portilla, M.P., López, A., Somolinos, J.A., Morales, R., 2018. Modelado Dinámico y Control de Un Dispositivo Sumergido Provisto de Actuadores Hidrostáticos. RIAI - Revista Iberoamericana de Automatica e Informatica Industrial 15 (1): 12-23. https://doi.org/10.4995/riai.2017.8824Mathworks. 2016. https://es.mathworks.com/products/matlab/.Morales, R., Fernández, L., Segura, E., Somolinos, J.A., 2016. Maintenance Maneuver Automation for an Adapted Cylindrical Shape TEC. Energies 9 (9): 746. https://doi.org/10.3390/en9090746Ocean Energy Forum. 2016. "Ocean Energy Strategic Roadmap Building Ocean Energy for Europe." https://webgate.ec.europa.eu/maritimeforum/en/frontpage/1036.Ocean Energy Systems. 2018. "Spotlight on Ocean Energy 20 Projects + 5 Policy Initiatives."Orcina. 2016. https://www.orcina.com/SoftwareProducts/OrcaFlex/.Organización Meteorológica Mundial. 2019. Declaración de La OMM Sobre El Estado Del Clima Mundial En 2018. Vol. OMM-No 1233.Perez, R., López, A., Somolinos, J.A., Núñez, L.R., 2018. Detail Design of a Ballast Control Room for an Underwater Tidal Energy Converter. Brodogradnja 69 (1): 39-52. https://doi.org/10.21278/brod69103Perumaal, S., Jawahar, N., 2013. Automated Trajectory Planner of Industrial Robot for Pick-and-Place Task. International Journal of Advanced Robotic Systems 10. DOI: 10.5772/53940.https://doi.org/10.5772/53940Protocolo de Kyoto. 1997. "Protocolo de Kyoto." In Convención Marco de Las Naciones Unidas Sobre El Cambio Climático (CMNUCC). https://doi.org/10.18356/cea22d4e-esProyecto GESMEY. Cátedra Soermar-UPM. Accessed July 12, 2020. https://www.catedra-soermar-upm.com/proyecto-gesmey/.Proyecto MeyGen. SIMEC Atlantis Energy. Accessed July 12, 2020. https://simecatlantis.com/projects/meygen/.Secretaría de Estado de Medio Ambiente. 2019. "Nota Sobre Los Principales Resultados de La Cumbre Del Clima de Madrid." Madrid. https://www.un.org/en/climatechange/index.shtml.Segura, E., Morales, R., Somolinos, J.A., 2017a. Cost Assessment Methodology and Economic Viability of Tidal Energy Projects. Energies 10 (11): 1806. https://doi.org/10.3390/en10111806Segura, E., Morales, R., Somolinos, J.A., López, A., 2017b. Techno-Economic Challenges of Tidal Energy Conversion Systems: Current Status and Trends. Renewable and Sustainable Energy Reviews 77 (September): 536-50. https://doi.org/10.1016/j.rser.2017.04.054Segura, E., Morales, R., Somolinos, J.A., 2018. A Strategic Analysis of Tidal Current Energy Conversion Systems in the European Union. Applied Energy, February 15, 2018. https://doi.org/10.1016/j.apenergy.2017.12.045Segura, E., Morales, R., Somolinos, J.A., 2019a. Increasing the Competitiveness of Tidal Systems by Means of the Improvement of Installation and Maintenance Maneuvers in First Generation Tidal Energy Converters-An Economic Argumentation. Energies 12 (13): 2464. https://doi.org/10.3390/en12132464Segura, E., Morales, R., Somolinos, J.A. 2019b., Influence of Automated Maneuvers on the Economic Feasibility of Tidal Energy Farms. Sustainability 11 (21): 5965. https://doi.org/10.3390/su11215965Segura, E., Morales, R., Somolinos, J.A.. 2019c. Modelo Dinámico y Control No Lineal Para Un Convertidor de Energia de Las Corrientes Marinas de Primera Generación y Dos Grados de Libertad. XL Jornadas de Automática, 42-47. https://doi.org/10.17979/spudc.9788497497169.042Selot, F., Fraile, D., Brindley, G., 2019. Offshore Wind in Europe. Key Trends and Statistics 2018.Somolinos, J. A., López, A., Núñez, L.R., Morales, R., 2017. Dynamic Model and Experimental Validation for the Control of Emersion Manoeuvers of Devices for Marine Currents Harnessing. Renewable Energy 103 (April):333-45. https://doi.org/10.1016/j.renene.2016.10.076U.S. Energy Information Administration. 2019. "International Energy Outlook 2019 with Projections to 2050." www.eia.gov/ieo.University of Southampton. 2008. "Tidal-Current Energy Device Development and Evaluation Protocol URN 08/1317.

Activation of microglia in specific hypothalamic nuclei and the cerebellum of adult rats exposed to neonatal overnutrition

Much attention has been drawn to the possible involvement of hypothalamic inflammation in the pathogenesis of metabolic disorders, especially in response to a high-fat diet. Microglia, the macrophages of the central nervous system, can be activated by proinflammatory signals resulting in the local production of specific interleukins and cytokines, which in turn could exacerbate the pathogenic process. Because obesity itself is considered to be a state of chronic inflammation, we evaluated whether being overweight results in microglial activation in the hypothalamus of rats on a normal diet. Accordingly, we used a model of neonatal overnutrition that entailed adjustment of litter size at birth (small litters: four pups/dam versus normal litters: 12 pups/dam) and resulted in a 15% increase in bodyweight and increased circulating leptin levels at postnatal day 60. Rats that were overnourished during neonatal life had an increased number of activated microglia in specific hypothalamic areas such as the ventromedial hypothalamus, which is an important site for metabolic control. However, this effect was not confined to the hypothalamus because significant microglial activation was also observed in the cerebellar white matter. There was no change in circulating tumour necrosis factor (TNF) α levels or TNFα mRNA levels in either the hypothalamus or cerebellum. Interleukin (IL)6 protein levels were higher in both the hypothalamus and cerebellum, with no change in IL6 mRNA levels. Because circulating IL6 levels were elevated, this rise in central IL6 could be a result of increased uptake. Thus, activation of microglia occurs in adult rats exposed to neonatal overnutrition and a moderate increase in weight gain on a normal diet, possibly representing a secondary response to systemic inflammation. Moreover, this activation could result in local changes in specific hypothalamic nuclei that in turn further deregulate metabolic homeostasi

Separación y Almacenamiento de Hidrógeno Mediante Ciclos Redox en Reactores de Lecho Fijo

El agotamiento de los combustibles f&oacute;siles y los efectos medioambientales generados por su combusti&oacute;n plantean la necesidad de buscar nuevas fuentes de energ&iacute;a que sean limpias y renovables. El hidr&oacute;geno podr&iacute;a ser el vector energ&eacute;tico del futuro en el aprovechamiento de esas fuentes alternativas. Sin embargo, su implantaci&oacute;n en la actualidad no est&aacute; estandarizada, debido a problemas derivados de su obtenci&oacute;n con los niveles de pureza que las pilas de combustible requieren. Este estudio plantea la separaci&oacute;n y almacenamiento de corrientes ricas en hidr&oacute;geno, por ejemplo las provenientes de la pirolisis de biomasa o de gas natural, mediante el proceso llamado Steam Iron. En este proceso c&iacute;clico, una corriente de gas formada principalmente por metano e hidr&oacute;geno es alimentada en un reactor de lecho fijo, donde se encuentra contenido un &oacute;xido met&aacute;lico con alto contenido de hematita (Fe2O3). El s&oacute;lido se reduce por acci&oacute;n del hidr&oacute;geno presente en dicha corriente a temperaturas entre 400 a 600 &ordm;C hasta hierro metal. Como producto se obtiene solamente agua, mientras el metano adicionado se mantiene inalterado. En un proceso de oxidaci&oacute;n posterior, se hace pasar sobre el metal reducido una corriente de vapor de agua que lo oxida gener&aacute;ndose como producto hidr&oacute;geno puro.&nbsp; Fueron probados varios s&oacute;lidos tanto aditivados como naturales a diferentes presiones parciales de reactante y temperaturas. Adem&aacute;s, el efecto del paso de los ciclos tambi&eacute;n fue estudiado, todo ello con el prop&oacute;sito de encontrar las mejores condiciones de regeneraci&oacute;n de hidr&oacute;geno puro a partir del s&oacute;lido

Producción de hidrógeno a partir de biogás mediante óxidos metálicos

La demanda energ&eacute;tica actual se abastece principalmente mediante combustibles f&oacute;siles, perolas reservas mundiales est&aacute;n disminuyendo a gran velocidad y se estima que se agoten en laspr&oacute;ximas d&eacute;cadas. A la inevitable escasez hay que a&ntilde;adir la contribuci&oacute;n de estos combustiblesal conocido como &ldquo;efecto invernadero&rdquo;. La b&uacute;squeda de otras alternativas energ&eacute;ticas es portanto urgente y perentoria, siendo el hidr&oacute;geno utilizado en pilas de combustible una de lasreferencias m&aacute;s eficientes, vers&aacute;tiles y prometedoras. El m&eacute;todo de obtenci&oacute;n de hidr&oacute;genom&aacute;s ampliamente utilizado en la actualidad es el llamado reformado de metano con vapor deagua, que por el momento utiliza como materia prima combustibles f&oacute;siles como el gasnatural. Dadas las actuales circunstancias, la investigaci&oacute;n se est&aacute; centrando en la utilizaci&oacute;nde biog&aacute;s como fuente primaria para la obtenci&oacute;n del hidr&oacute;geno. El biog&aacute;s es el resultado de ladigesti&oacute;n anaerobia de residuos org&aacute;nicos (urbanos, de ganado, de depuradora de aguasresiduales,&hellip;), y tiene como componentes mayoritarios metano y di&oacute;xido de carbono. En elproceso conocido como &ldquo;reformado seco&rdquo;, el metano reacciona catal&iacute;ticamente con el propiodi&oacute;xido de carbono contenido en el biog&aacute;s. La mezcla resultante, que contiene una elevadaproporci&oacute;n de hidr&oacute;geno, debe ser purificada previamente a su utilizaci&oacute;n. La propuesta delCREG consiste en utilizar &oacute;xidos de hierro con aditivos para llevar a cabo, tanto la producci&oacute;ncomo la purificaci&oacute;n y de modo simult&aacute;neo en un mismo recipiente. Este proceso conocidocomo &ldquo;steam‐iron&rdquo; consiste en dos etapas: de reducci&oacute;n del &oacute;xido mediante la corriente degas, y de oxidaci&oacute;n de hierro met&aacute;lico mediante vapor de agua en el que se obtiene hidr&oacute;genopuro.4

Influence of profilin on sensitisation profiles determined by cutaneous tests and IgE to major allergens in polysensitised patients

Background: Profilin sensitisation is considered a diagnostic confounding factor in areas where patients are exposed to multiple pollens. The aim of this study is to assess pollen sensitisation profiles in adults and children and to evaluate, by means of component-resolved diagnosis (CRD) and skin prick testing (SPT), which pollens may be considered as risk factors of profilin sensitisation in order to establish the best diagnostic approach in polysensitised patients. Methods: A total of 231 pollen-allergic patients (adults and children) were included, out of the pollen season, from an area with similar levels of pollen exposure. Allergological diagnosis was performed by SPT and determination of specific IgE (sIgE) to major allergen components (ADVIA-Centaur™). Patients had not received immunotherapy in the last 5 years and had to reside in the area for 5 consecutive years before entering the study. Results: The relation between sensitisation measured by SPT and by sIgE was studied using a model of cases (patients with +sIgE to a specific allergen) and controls (patients with -sIgE to the same allergen). The outcome, in terms of odds-ratios (OR), was statistically significant for Olea (Ole e 1) (p = 0.0005), Salsola (Sal k 1) (p = 0.0118) and Platanus (Pla a 1+ 2) (p = 0.0372). While positivity of SPT to most pollens was statistically associated with a risk of profilin sensitisation, by CRD the association was statistically significant only for Ole e 1 (OR 3.5, CI 95 %, 1.6-7.6, p = 0.0014), and Phl p 5 (OR 11.9, CI 95 %, 4.1-35.2, p < 0.001). When analysing this association using a logistic regression model, Phl p 5 was the only allergen associated with the risk of being sensitised to profilin (p = 0.0023). Conclusions: In patients sensitised to profilin, the concordance between SPT and CRD is much lower than in those not sensitised to profilin. CRD is able to provide refined information about which pollens increase the risk of sensitisation to profilin

Guía de actuación para el farmacéutico comunitario en pacientes con hipertensión arterial y riesgo cardiovascular. Documento de Consenso (versión extendida)

La hipertensión arterial (HTA) es un problema de salud estrechamente relacionado con un aumento del riesgo de padecer una enfermedad cardiovascular. Además, la HTA puede producir o empeorar la lesión de ciertos órganos diana, lo que también puede influir negativamente en el pronóstico cardiovascular del paciente. En España, la HTA es una condición muy frecuente, afectando a unos 10 millones de sujetos adultos. Por su accesibilidad y formación especializada en materia de medicamentos, el farmacéutico comunitario puede jugar un papel clave en la detección y seguimiento del paciente con HTA. Hasta la fecha, se han publicado numerosas guías clínicas sobre la atención a pacientes con HTA, dirigidas principalmente a médicos. Sin embargo, cada vez es más evidente la necesidad de que todos los profesionales de la salud participen en la atención integral a los pacientes con HTA y riesgo cardiovascular (RCV). La cooperación entre farmacéutico, médico, personal de enfermería y otros profesionales sanitarios es imprescindible para conseguir resultados que optimicen la prevención cardiovascular y mejoren la calidad de vida del paciente. Así, a fin de promover la gestión compartida de los pacientes con HTA y RCV se publica este documento, cuyo principal destinatario es el farmacéutico comunitario. El presente documento pretende ser una herramienta de referencia que dé soporte a los programas de Atención Farmacéutica al paciente con HTA y RCV que se están desarrollando actualmente en las oficinas de farmacia. El texto ha sido desarrollado de forma consensuada entre expertos de la Sociedad Española de Hipertensión- Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA), la Sociedad Española de Farmacia Comunitaria (SEFAC) y el Grupo de Investigación en Atención Farmacéutica de la Universidad de Granada (GIAF-UGR).Arterial hypertension (AH) is an important health-related problem, as responsible for an important part of cardiovascular disorders. Moreover, AH is related to the development and progression of organ damage, which has indeed a negative influence in the cardiovascular prognosis of the individual. In Spain, AH is a frequent condition, affecting about 10 millions of the adult population. Due to their accessibility and specific background on drug management, the community pharmacist could play a key role in the detection and follow-up of the hypertensive patient. To date, several guidelines on hypertension management have been released, although almost invariably have been addressed to the medical community. However, it has become more evident the need for a global management of hypertension and cardiovascular risk with the participation of several health-care providers, such as pharmacists and nurses, with the aim of improving cardiovascular prevention and the quality of life of subjects affected. The present document, particularly addressed to the community pharmacist, is intended to provide current knowledge with the aim of a better shared management of patients with hypertension and cardiovascular risk. The present document pretends to serve as a tool for currently developed programs supporting the involvement of the community pharmacy in the care of patients with hypertension and cardiovascular risk. The document has been developed after a consensus between members from the Spanish Society of Hypertension, the Spanish Society of Community Pharmacy and the Research Group on Pharmaceutical Care from the University of Granada

Critical review of technologies for the on-site treatment of hospital wastewater: From conventional to combined advanced processes

This review aims to assess different technologies for the on-site treatment of hospital wastewater (HWW) to remove pharmaceutical compounds (PhCs) as sustances of emerging concern at a bench, pilot, and full scales from 2014 to 2020. Moreover, a rough characterisation of hospital effluents is presented. The main detected PhCs are antibiotics and psychiatric drugs, with concentrations up to 1.1 mg/L. On the one hand, regarding the presented technologies, membrane bioreactors (MBRs) are a good alternative for treating HWW with PhCs removal values higher than 80% in removing analgesics, anti-inflammatories, cardiovascular drugs, and some antibiotics. Moreover, this system has been scaled up to the pilot plant scale. However, some target compounds are still present in the treated effluent, such as psychiatric and contrast media drugs and recalcitrant antibiotics (erythromycin and sulfamethoxazole). On the other hand, ozonation effectively removes antibiotics found in the HWW (>93%), and some studies are carried out at the pilot plant scale. Even though, some families, such as the X-ray contrast media, are recalcitrant to ozone. Other advanced oxidation processes (AOPs), such as Fenton-like or UV treatments, seem very effective for removing pharmaceuticals, Antibiotic Resistance Bacteria (ARBs) and Antibiotic Resistance Genes (ARGs). However, they are not implanted at pilot plant or full scale as they usually consider extra reactants such as ozone, iron, or UV-light, making the scale-up of the processes a challenging task to treat high-loading wastewater. Thus, several examples of biological wastewater treatment methods combined with AOPs have been proposed as the better strategy to treat HWW with high removal of PhCs (generally over 98%) and ARGs/ARBs (below the detection limit) and lower spending on reactants. However, it still requires further development and optimisation of the integrated processes.Comunidad de Madri

Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.

Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here, we analyzed the therapeutic effect of LBH589, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous administration of LBH589 in immunodeficient BALB/c-RAG2(-/-)γc(-/-) mice in which human-derived T and B-ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2(-/-)γc(-/-) mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving vincristine and dexamethasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with vincristine and dexamethasone. Our results show the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL