Un modelo numérico en elementos finitos para la corriente inducida por la marea. Aplicaciones al Estrecho de Gibraltar

Mediante un modelo numérico quasi-3D en elementos finitos que resuelve las ecuaciones de aguas someras a través de una técnica de descomposición armónica, se ha estudiado el comportamiento de la marea en el Estrecho de Gibraltar. En esta región se acoplan dos regímenes de marea sustancialmente diferentes, el correspondiente al océano Atlántico y el de la cuenca mediterránea. Los resultados del modelo confirman la preponderancia de la circulación inducida por la marea en el flujo local de la zona. También se ha comprobado la importancia que en este ámbito tienen los efectos de la difusión turbulenta, de la fricción con el fondo, de la geometría del dominio y de la interacción de las componentes mareales con la circulación residual. El empleo de una interpolación de orden superior para la altura de la superficie libre y de una formulación no lineal para la fricción con el fondo debe permitir mejorar el grado de ajuste entre los resultados numéricos obtenidos y los datos disponibles.Tidal wave propagation patterns in the Gibraltar Strait are analyzed by means of a quasi- 3D finite element model of the shallow water equations whose solver is based on a harmonic descomposition technique. In this region, two substantially different tidal regimes are coupled, the one corresponding to the Atlantic Ocean and that of the Mediterranean basin. The model results confirm that the tidal contribution is prevailing within local circulation patterns. Moreover, our solutions suggest that the turbulent diffusion of momentum, bottom friction effects, the geometry of the Strait and the tide-current interactions have an important influence on the tidal propagations patterns. The use both of a higher order interpolation scheme for the sea surface height and a non-linear formulation for bottom friction is envisaged as a means to obtain better agreement between model results and experimental data.Peer Reviewe

Formation of soy protein-based superabsorbent materials through optimization of a thermal processing

Superabsorbent materials are used in a wide range of products (e.g. personal care, controlled-release of nutrients in agriculture). The present study pretends the development of biodegradable materials from a natural source, a soy protein isolate, which eventually would help to diminish the environmental issues associated to the use of common synthetic materials. Moreover, the present work focuses on the modulation of the water uptake exclusively through the modification of the parameters of the thermal processes carried out during the development of those materials. Firstly, the protein isolate is blended with the plasticizer (glycerol) in a 1/1 ratio. Then, the homogeneous blend is injected using different mould temperatures and, subsequently, the bioplastics obtained are submitted to a dehydrothermal treatment (tdeshid) consisting on the storage of the samples at 50 ºC for a certain time (tdeshid). When the mould temperature is 70 ºC, superabsorbent materials are always obtained at tdeshid, shorter than 12 h. Conversely, viscoelastic properties increase as DHT treatment is longer, reducing the swelling that takes place during water absorption, and resulting more compact matrices. Thus, the present study proves how thermal processing modulation can solely determine the superabsorbent ability of soy protein-based biodegradable materials.Los materiales superabsorbentes son aplicables en campos tan diversos como productos de higiene personal o liberación controlada de nutrientes en agricultura. El presente estudio pretende el desarrollo de materiales biodegradables a partir de una materia prima natural, un aislado de proteína de soja, cuya aplicación supondría una disminución en el uso de materiales sintéticos, repercutiendo beneficiosamente en el medio ambiente; y la modulación de su capacidad de absorción de agua, que se modificará exclusivamente variando las condiciones de los procesos térmicos a los que son sometidas durante su obtención. En primer lugar, el aislado se mezcla con glicerina (plastificante)en una proporción 1/1, para después inyectar la masa homogénea utilizando diferentes temperaturas de moldeo (Tmold). Posteriormente, son sometidas a un tratamiento deshidrotérmico. o almacenamiento a 50ºC, durante cierto periodo de tiempo (tdeshid). Cuando la Tmold utilizada es 70ºC, se obtienen siempre materiales superabsorbentes, cuando el tdeshid seleccionado sea menos de 12h. Por otra parte, las propiedades viscoelásticas aumentan con la duración del tratamiento deshidrotérmico, provocando un menor hinchamiento durante la absorción de agua, resultando matrices menos porosas. Así, el presente estudio permite comprobar cómo modulando exclusivamente las condiciones de procesado pueden conseguirse capacidades superabsorbentes para materiales biodegradables basados en soja.Ministerio de Economía y Competitividad de España-CTQ2015-71164-

Efecto del procesado sobre las propiedades y morfología de bioplásticos de proteína de soja

La industria de los plásticos ha crecido notablemente en los últimos años. Este crecimiento, ligado a la baja biodegradabilidad de estos materiales, ha causado un grave problema medioambiental. La presente investigación pretende la obtención de materiales con alta capacidad de absorción de agua, que sean biodegradables y obtenidos a partir de fuentes renovables. Deberían además poseer propiedades mecánicas adecuadas para constituir una alternativa real a los plásticos sintéticos. Estos bioplásticos son obtenidos mediante un proceso con diferentes etapas: una de mezclado de los componentes para conformar una masa homogénea; y una segunda de inyección en la que, aplicando presión, la masa es introducida en un molde de forma deseada. La capacidad de absorción de agua es afectada por la composición y las condiciones de procesado. El presente documento estudia cómo la temperatura y duración de la etapa de moldeo, además del tratamiento dehidrotérmico, modifican la capacidad de absorción del bioplástico. Los resultados concluyen que la capacidad de absorción de agua aumenta con menores temperaturas y tiempos de moldeo, a la vez que aumenta cuando el tratamiento dehidrotérmico es más corto. Asimismo, los módulos viscoelásticos poseen una tendencia a disminuir cuando la capacidad de absorción de agua en las muestras aumenta.The remarkable growth experienced by the production and demand of the plastic industry during the last few years has resulted in a serious environmental issue associated specially to their low biodegradability. This work is focused on the manufacture of bioplastics with high water absorption capacity, obtained from renewable sources. Bioplastics produced should have adequate mechanical properties to be able to replace eventually synthetic plastics in specific markets. In order to obtain these bioplastics, two steps were carried out: the first one consists of a mixing stage to achieve a homogenous blend that is injection-molded during the second step. The water uptake capacity of these samples is influenced by both the formulation and the processing conditions of the blends. The present study is focused on the evolution of water uptake values when either the molding conditions (temperature and duration) or the length of a post-dehydrothermal treatment are modified. Results indicated an improvement in the water uptake when lower mold temperatures and shorter compaction stages were used. An analogous improvement was observed when the dehydrotermal process was shorter. Mechanical properties usually decreased as the water uptake of samples was improved.Plan Propio de la Universidad de Sevilla Proyecto: 2017/00000962MINECO (España)/FEDER (UE) proyecto CTQ2015-71164-

Prospective multicenter study of carbapenemase-producing Enterobacteriaceae from 83 hospitals in Spain reveals high in vitro susceptibility to colistin and meropenem

The aim of this study was to determine the impact of carbapenemase-producing Enterobacteriaceae (CPE) in Spain in 2013 by describing the prevalence, dissemination, and geographic distribution of CPE clones, and their population structure and antibi- otic susceptibility. From February 2013 to May 2013, 83 hospitals (about 40,000 hospital beds) prospectively collected nondupli- cate Enterobacteriaceae using the screening cutoff recommended by EUCAST. Carbapenemase characterization was performed by phenotypic methods and confirmed by PCR and sequencing. Multilocus sequencing types (MLST) were determined for Kleb- siella pneumoniae and Escherichia coli. A total of 702 Enterobacteriaceae isolates met the inclusion criteria; 379 (54%) were CPE. OXA-48 (71.5%) and VIM-1 (25.3%) were the most frequent carbapenemases, and K. pneumoniae (74.4%), Enterobacter cloacae (10.3%), and E. coli (8.4%) were the species most affected. Susceptibility to colistin, amikacin, and meropenem was 95.5%, 81.3%, and 74.7%, respectively. The most prevalent sequence types (STs) were ST11 and ST405 for K. pneumoniae and ST131 for E. coli. Forty-five (54.1%) of the hospitals had at least one CPE case. For K. pneumoniae, ST11/OXA-48, ST15/OXA-48, ST405/ OXA-48, and ST11/VIM-1 were detected in two or more Spanish provinces. ST11 isolates carried four carbapenemases (VIM-1, OXA-48, KPC-2, and OXA-245), but ST405 isolates carried OXA-48 only. A wide interregional spread of CPE in Spain was ob- served, mainly due to a few successful clones of OXA-48-producing K. pneumoniae (e.g., ST11 and ST405). The dissemination of OXA-48-producing E. coli is a new finding of public health concern. According to the susceptibilities determined in vitro, most of the CPE (94.5%) had three or more options for antibiotic treatment

Prospective multicenter study of carbapenemase-producing Enterobacteriaceae from 83 hospitals in Spain reveals high in vitro susceptibility to colistin and meropenem

The aim of this study was to determine the impact of carbapenemase-producing Enterobacteriaceae (CPE) in Spain in 2013 by describing the prevalence, dissemination, and geographic distribution of CPE clones, and their population structure and antibiotic susceptibility. From February 2013 to May 2013, 83 hospitals (about 40,000 hospital beds) prospectively collected nonduplicate Enterobacteriaceae using the screening cutoff recommended by EUCAST. Carbapenemase characterization was performed by phenotypic methods and confirmed by PCR and sequencing. Multilocus sequencing types (MLST) were determined for Klebsiella pneumoniae and Escherichia coli. A total of 702 Enterobacteriaceae isolates met the inclusion criteria; 379 (54%) were CPE. OXA-48 (71.5%) and VIM-1 (25.3%) were the most frequent carbapenemases, and K. pneumoniae (74.4%), Enterobacter cloacae (10.3%), and E. coli (8.4%) were the species most affected. Susceptibility to colistin, amikacin, and meropenem was 95.5%, 81.3%, and 74.7%, respectively. The most prevalent sequence types (STs) were ST11 and ST405 for K. pneumoniae and ST131 for E. coli. Forty-five (54.1%) of the hospitals had at least one CPE case. For K. pneumoniae, ST11/OXA-48, ST15/OXA-48, ST405/OXA-48, and ST11/VIM-1 were detected in two or more Spanish provinces. ST11 isolates carried four carbapenemases (VIM-1, OXA-48, KPC-2, and OXA-245), but ST405 isolates carried OXA-48 only. A wide interregional spread of CPE in Spain was observed, mainly due to a few successful clones of OXA-48-producing K. pneumoniae (e.g., ST11 and ST405). The dissemination of OXA-48-producing E. coli is a new finding of public health concern. According to the susceptibilities determined in vitro, most of the CPE (94.5%) had three or more options for antibiotic treatment.This work was supported by a grant from the Fondo de Investigación Sanitaria (grant PI12/01242); the Antibiotic Resistance Surveillance Programme of the Spanish Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad; the Plan Nacional de I+D+I 2008–2011; and the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), cofinanced by the European Development Regional Fund (ERDF) “A way to achieve Europe.”S

Effectiveness of a gamified digital intervention based on lifestyle modification (iGAME) in secondary prevention: a protocol for a randomised controlled trial

Introduction Combating physical inactivity and reducing sitting time are one of the principal challenges proposed by public health systems. Gamification has been seen as an innovative, functional and motivating strategy to encourage patients to increase their physical activity (PA) and reduce sedentary lifestyles through behaviour change techniques (BCT). However, the effectiveness of these interventions is not usually studied before their use. The main objective of this study will be to analyse the effectiveness of a gamified mobile application (iGAME) developed in the context of promoting PA and reducing sitting time with the BCT approach, as an intervention of secondary prevention in sedentary patients.Methods and analysis A randomised clinical trial will be conducted among sedentary patients with one of these conditions: non-specific low back pain, cancer survivors and mild depression. The experimental group will receive a 12-week intervention based on a gamified mobile health application using BCT to promote PA and reduce sedentarism. Participants in the control group will be educated about the benefits of PA. The International Physical Activity Questionnaire will be considered the primary outcome. International Sedentary Assessment Tool, EuroQoL-5D, MEDRISK Instruments and consumption of Health System resources will be evaluated as secondary outcomes. Specific questionnaires will be administered depending on the clinical population. Outcomes will be assessed at baseline, at 6 weeks, at the end of the intervention (12 weeks), at 26 weeks and at 52 weeks.Ethics and dissemination The study has been approved by the Portal de Ética de la Investigación Biomédica de Andalucía Ethics Committee (RCT-iGAME 24092020). All participants will be informed about the purpose and content of the study and written informed consent will be completed. The results of this study will be published in a peer-reviewed journal and disseminated electronically and in print.Trial registration number NCT0401911

Insights into the Complex Formed by Matrix Metalloproteinase-2 and Alloxan Inhibitors: Molecular Dynamics Simulations and Free Energy Calculations

Matrix metalloproteinases (MMP) are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. Hence, the development of potent and selective inhibitors targeting these enzymes continues to be eagerly sought. In this paper, a number of alloxan-based compounds, initially conceived to bias other therapeutically relevant enzymes, were rationally modified and successfully repurposed to inhibit MMP-2 (also named gelatinase A) in the nanomolar range. Importantly, the alloxan core makes its debut as zinc binding group since it ensures a stable tetrahedral coordination of the catalytic zinc ion in concert with the three histidines of the HExxHxxGxxH metzincin signature motif, further stabilized by a hydrogen bond with the glutamate residue belonging to the same motif. The molecular decoration of the alloxan core with a biphenyl privileged structure allowed to sample the deep S1′ specificity pocket of MMP-2 and to relate the high affinity towards this enzyme with the chance of forming a hydrogen bond network with the backbone of Leu116 and Asn147 and the side chains of Tyr144, Thr145 and Arg149 at the bottom of the pocket. The effect of even slight structural changes in determining the interaction at the S1′ subsite of MMP-2 as well as the nature and strength of the binding is elucidated via molecular dynamics simulations and free energy calculations. Among the herein presented compounds, the highest affinity (pIC50 = 7.06) is found for BAM, a compound exhibiting also selectivity (>20) towards MMP-2, as compared to MMP-9, the other member of the gelatinases

Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization

Background and Objectives Genetic white matter disorders (GWMD) are of heterogeneous origin, with >100 causal genes identified to date. Classic targeted approaches achieve a molecular diagnosis in only half of all patients. We aimed to determine the clinical utility of singleton whole-exome sequencing and whole-genome sequencing (sWES-WGS) interpreted with a phenotype- and interactome-driven prioritization algorithm to diagnose GWMD while identifying novel phenotypes and candidate genes. Methods A case series of patients of all ages with undiagnosed GWMD despite extensive standard-of-care paraclinical studies were recruited between April 2017 and December 2019 in a collaborative study at the Bellvitge Biomedical Research Institute (IDIBELL) and neurology units of tertiary Spanish hospitals. We ran sWES and WGS and applied our interactome-prioritization algorithm based on the network expansion of a seed group of GWMD-related genes derived from the Human Phenotype Ontology terms of each patient. Results We evaluated 126 patients (101 children and 25 adults) with ages ranging from 1 month to 74 years. We obtained a first molecular diagnosis by singleton WES in 59% of cases, which increased to 68% after annual reanalysis, and reached 72% after WGS was performed in 16 of the remaining negative cases. We identified variants in 57 different genes among 91 diagnosed cases, with the most frequent being RNASEH2B, EIF2B5, POLR3A, and PLP1, and a dual diagnosis underlying complex phenotypes in 6 families, underscoring the importance of genomic analysis to solve these cases. We discovered 9 candidate genes causing novel diseases and propose additional putative novel candidate genes for yet-to-be discovered GWMD. Discussion Our strategy enables a high diagnostic yield and is a good alternative to trio WES/WGS for GWMD. It shortens the time to diagnosis compared to the classical targeted approach, thus optimizing appropriate management. Furthermore, the interactome-driven prioritization pipeline enables the discovery of novel disease-causing genes and phenotypes, and predicts novel putative candidate genes, shedding light on etiopathogenic mechanisms that are pivotal for myelin generation and maintenance

Large-scale unit commitment under uncertainty: an updated literature survey

The Unit Commitment problem in energy management aims at finding the optimal production schedule of a set of generation units, while meeting various system-wide constraints. It has always been a large-scale, non-convex, difficult problem, especially in view of the fact that, due to operational requirements, it has to be solved in an unreasonably small time for its size. Recently, growing renewable energy shares have strongly increased the level of uncertainty in the system, making the (ideal) Unit Commitment model a large-scale, non-convex and uncertain (stochastic, robust, chance-constrained) program. We provide a survey of the literature on methods for the Uncertain Unit Commitment problem, in all its variants. We start with a review of the main contributions on solution methods for the deterministic versions of the problem, focussing on those based on mathematical programming techniques that are more relevant for the uncertain versions of the problem. We then present and categorize the approaches to the latter, while providing entry points to the relevant literature on optimization under uncertainty. This is an updated version of the paper "Large-scale Unit Commitment under uncertainty: a literature survey" that appeared in 4OR 13(2), 115--171 (2015); this version has over 170 more citations, most of which appeared in the last three years, proving how fast the literature on uncertain Unit Commitment evolves, and therefore the interest in this subject

Preventing the onset of major depression based on the level and profile of risk of primary care attendees: protocol of a cluster randomised trial (the predictD-CCRT study)

BACKGROUND: The 'predictD algorithm' provides an estimate of the level and profile of risk of the onset of major depression in primary care attendees. This gives us the opportunity to develop interventions to prevent depression in a personalized way. We aim to evaluate the effectiveness, cost-effectiveness and cost-utility of a new intervention, personalized and implemented by family physicians (FPs), to prevent the onset of episodes of major depression. METHODS: This is a multicenter randomized controlled trial (RCT), with cluster assignment by health center and two parallel arms. Two interventions will be applied by FPs, usual care versus the new intervention predictD-CCRT. The latter has four components: a training workshop for FPs; communicating the level and profile of risk of depression; building up a tailored bio-psycho-family-social intervention by FPs to prevent depression; offering a booklet to prevent depression; and activating and empowering patients. We will recruit a systematic random sample of 3286 non-depressed adult patients (1643 in each trial arm), nested in 140 FPs and 70 health centers from 7 Spanish cities. All patients will be evaluated at baseline, 6, 12 and 18 months. The level and profile of risk of depression will be communicated to patients by the FPs in the intervention practices at baseline, 6 and 12 months. Our primary outcome will be the cumulative incidence of major depression (measured by CIDI each 6 months) over 18 months of follow-up. Secondary outcomes will be health-related quality of life (SF-12 and EuroQol), and measurements of cost-effectiveness and cost-utility. The inferences will be made at patient level. We shall undertake an intention-to-treat effectiveness analysis and will handle missing data using multiple imputations. We will perform multi-level logistic regressions and will adjust for the probability of the onset of major depression at 12 months measured at baseline as well as for unbalanced variables if appropriate. The economic evaluation will be approached from two perspectives, societal and health system. DISCUSSION: To our knowledge, this will be the first RCT of universal primary prevention for depression in adults and the first to test a personalized intervention implemented by FPs. We discuss possible biases as well as other limitations.Trial registration: ClinicalTrials.gov identifier: NCT01151982