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Introduction. This study aimed to evaluate whether early vitamin C and thiamine administration was associated with a lower 28-day and in-hospital mortality in surgical critically ill patients with refractory septic shock. Patients and methods. We performed a retrospective before-and-after study on patients with refractory septic shock. According to local protocol, hydrocortisone is initiated in case of refractory septic shock. In January 2017, the protocol was changed and vitamin C and thiamine were included. Patients who were admitted in 2015-2016 and 2017-2018 were included in the control and treatment groups, respectively. The primary end point was 28-day and in-hospital mortality. Secondary end points were ICU mortality, ICU and hospital length of stay, duration of vasopressors and mechanical ventilation, use of renal replacement therapy (RRT), and the modification in serum procalcitonin and SOFA score during the first 72 h. Results. A total of 120 patients were included (58 in the treatment group and 62 in the control group). Log-rank test in Kaplan-Meier curves showed lower 28-day and in-hospital mortality over time in the treatment group (p=0.021 and p=0.035, respectively) but it not reached statistical significance in ICU mortality over time (p=0.100). The need of RRT was less frequent in treatment group (17.2% vs. 37.1%, p=0.024). There were no differences in other secondary outcomes. Conclusions. Intravenous vitamin C and thiamine administration in surgical patients with refractory septic shock may be associated with a lower 28-day and in-hospital mortality. Further prospective studies are needed in refractory septic shock

Resumen La Sociedad Espanola de Medicina Interna ha desarrollado a lo largo de 2018-2019 el proyecto «El hospital del futuro». El hospital del futuro pretende trasladar al contexto del sistema sanitario espanol la reflexion que abordo el Royal College of Physicians en el Reino Unido sobre la organizacion de la asistencia en los hospitales del futuro, desde el conocimiento acumulado sobre el Sistema Nacional de Salud. En el proyecto participaron asimismo numerosas sociedades cientifico-medicas y entidades profesionales del sector salud y asociaciones de pacientes. Este articulo tiene por objeto destacar en 10 puntos las previsiones que consideramos mas relevantes derivadas de este proyecto, dedicando el ultimo a los retos que para la Medicina Interna se deducen de estas propuestas.

Over the course of 2018 and 2019, the Spanish Society of Internal Medicine carried out a project called "The Future Hospital." Based on cumulative knowledge on the Spanish National Health System, this project seeks to transfer the observations on the organization of healthcare in future hospitals made by the Royal College of Physicians in the United Kingdom to the context of the Spanish healthcare system. The project's participants included numerous scientific and medical societies, professional associations in the health sector, and patient associations. This aim of this article is to highlight, in 10 points, predictions that arose from this project that we consider to be the most relevant, reserving the last point for the challenges for the field of internal medicine that can be surmised from these proposals.

Background: Electrical neuromodulation via implanted electrodes is used in treating numerous neurological disorders, yet our knowledge of how different brain regions respond to varying stimulation parameters is sparse. Objective/Hypothesis: We hypothesized that the neural response to electrical stimulation is both region-specific and non-linearly related to amplitude and frequency. Methods: We examined evoked neural responses following 400 ms trains of 10–400 Hz electrical stimulation ranging from 0.1 to 10 mA. We stimulated electrodes implanted in cingulate cortex (dorsal anterior cingulate and rostral anterior cingulate) and subcortical regions (nucleus accumbens, amygdala) of non-human primates (NHP, N = 4) and patients with intractable epilepsy (N = 15) being monitored via intracranial electrodes. Recordings were performed in prefrontal, subcortical, and temporal lobe locations. Results: In subcortical regions as well as dorsal and rostral anterior cingulate cortex, response waveforms depended non-linearly on frequency (Pearson's linear correlation r 0.58). These relationships between location, and input-output characteristics were similar in homologous brain regions with average Pearson's linear correlation values r > 0.75 between species and linear correlation values between participants r > 0.75 across frequency and current values per brain region. Evoked waveforms could be described by three main principal components (PCs) which allowed us to successfully predict response waveforms across individuals and across frequencies using PC strengths as functions of current and frequency using brain region specific regression models. Conclusions: These results provide a framework for creation of an atlas of input-output relationships which could be used in the principled selection of stimulation parameters per brain region.

The Hamilton–Jacobi analysis for gravity without dynamics is performed. We report a detailed analysis where the complete set of Hamilton–Jacobi constraints, the characteristic equations and the gauge transformations of the theory are found. We compare our results with those reported in the literature where alternative approaches are used. In addition, we complete our work by performing the canonical covariant analysis by constructing a gauge invariant symplectic structure, and we find a full consistency between the results obtained from both approaches.

11 páginas La limitación del esfuerzo terapéutico (LET) es toda acción que implique suspender o no iniciar tratamientos o medidas terapéuticas en pacientes que no se beneficiarán clínicamente. En Latinoamérica, las investigaciones realizadas dejan en evidencia la falta de familiarización y discordancia que hay alrededor del tema y sus prácticas. El presente estudio buscó objetivizar el conocimiento en LET del personal de salud de una institución de Medellín, a partir de una encuesta autoaplicada que permitió el desarrollo de un estudio descriptivo de tipo transversal, con muestreo no probabilístico. Dentro de los resultados se encontró que el 56,5 % de los encuestados refirió conocer el concepto, y el 90 % manifestó aplicarlo. Sin embargo, había discordancias dentro de los conceptos clave de la definición y el ejercicio. Limitation of therapeutic effort (LTE) is any action that involves suspending or not initiating medical treatment or therapeutic measures in patients who will not receive any clinical benefit. In Latin America, some research has proven a lack of familiarization and disagreement with the subject and its practices. The present study tried to objectify the knowledge of LTE of healthcare per-sonnel at an institute in Medellín using a self-administered survey that allowed conducting a cross-sectional descriptive study with non-probabilistic sampling. Within the results, 56.5 % of respondents understood the concept of LTE, and 90 % applied it actively. However, there were discrepancies regarding the core concepts of the definition and practice. A limitação de esforço terapêutico (LET) é toda ação que implique suspender ou não iniciar tratamentos ou medidas terapêuticas em pacientes que não se beneficiarão clinicamente. Na América Latina, as pesquisas realizadas evidenciam a falta de familiari-zação e a discordância que há ao redor do tema e suas práticas. O presente estudo procurou objetivar o conhecimento em LET da equipe de saúde de uma instituição de Medellín, utilizando um questionário auto aplicado que permitiu o desenvolvimento de um estudo descritivo de tipo transversal, com amostragem não probabilística. Dentro dos resultados constatou-se que 56,5 % dos pesquisados disseram conhecer o conceito, e 90 % manifestaram aplicá-lo. No entanto, havia discordâncias dentro dos conceitos chave da definição e da prática.

This position paper describes the most relevant and essential aspects of a comprehensive, multidimensional assessment of hospitalized elderly people. The change in demographic patterns and the epidemiological profiles of diseases makes it necessary for internal medicine departments to adapt in order to take into account the vulnerabilities of the elderly in this context. A comprehensive, multidimensional assessment and the multidisciplinary development of a care plan during hospitalization can have an impact in terms of preventing mortality, disability, and institutionalization at discharge. It is necessary for all internists to acquire skills to improve the hospitalization experience in the elderly and obtain better health outcomes in our patients. This document has been developed by the Focus Group on Aging and the Polypathological and Advanced Age Working Group and endorsed by the Spanish Society of Internal Medicine.

In volcanic regions, rockfalls represent a major hazard strongly conditioned by the geomechanical behaviour of volcanic materials, the geomorphological characteristics of the relief and the climatic conditions. Volcanic rocks possess very different properties to those of other lithological groups, presenting highly heterogeneous geomechanical behaviours. Nevertheless, they have received little research attention in the field of geological and geotechnical engineering. To date, the application of geomechanical classifications to characterise and estimate volcanic slope stability has not yielded reliable results, indicating the need to establish specific criteria for these rocks. Consequently, we developed indices to estimate rockfall susceptibility, hazard and risk in volcanic slopes. The index of susceptibility for volcanic slopes (ISVS) is designed to estimate slope susceptibility to instability, which is related to the level of hazard, while the index of risk for volcanic slopes (IRVS) is designed to estimate the level of risk as a function of the potential damage or economic loss caused as a result of rockfalls on slopes. Both indices were developed in order to provide an easily applied procedure that facilitates the adoption of short-term preventive measures against rockfalls. The indices were applied in Tenerife (Canary Islands), which presents exceptional conditions for analysing slope stability in volcanic rocks because of its mountainous orography with very steep slopes and a wide variety of materials. These conditions have frequently precipitated slope instability, causing significant damage to housing, beaches, roads and other infrastructures. After applying these indices to a number of slopes representative of the island’s wide variety of geological, geomorphological and climatic conditions, the results obtained were compared with the actual behaviour of the slopes, determined from extensive rockfall inventory data and in situ geomechanical surveys.

Over the course of 2018 and 2019, the Spanish Society of Internal Medicine carried out a project called "The Future Hospital." Based on cumulative knowledge on the Spanish National Health System, this project seeks to transfer the observations on the organization of healthcare in future hospitals made by the Royal College of Physicians in the United Kingdom to the context of the Spanish healthcare system. The project's participants included numerous scientific and medical societies, professional associations in the health sector, and patient associations. This aim of this article is to highlight, in 10 points, predictions that arose from this project that we consider to be the most relevant, reserving the last point for the challenges for the field of internal medicine that can be surmised from these proposals.

Polypathological patients have specific clinical, functional, psychoaffective, social, family and spiritual characteristics. These patients are generally elderly and frail and have frequent decompensations. They frequently use healthcare resources, have significant functional impairment and have a high index of dependence. This results in a significant social impact, high mortality and a high consumption of resources. The current healthcare models have not answered these needs, which causes problems with accessibility to healthcare services, a lack of coordination among these services, a higher probability of adverse events related to polypharmacy and a high consumption of resources. In the past decade, the healthcare models have changed and are characterized by work in multidisciplinary and interlevel teams, patient self-care, the availability of tools for decision making, information and communication systems and prevention. The goal is to have prepared and proactive health teams and an informed and active patient population. The assessment of health results, processes and the costs for these programs is still based on moderate to low evidence. It is therefore not an easy task to determine the type and intensity of interventions or to determine the patient groups that could gain more benefits.

Polypathological patients have specific clinical, functional, psychoaffective, social, family and spiritual characteristics. These patients are generally elderly and frail and have frequent decompensations. They frequently use healthcare resources, have significant functional impairment and have a high index of dependence. This results in a significant social impact, high mortality and a high consumption of resources. The current healthcare models have not answered these needs, which causes problems with accessibility to healthcare services, a lack of coordination among these services, a higher probability of adverse events related to polypharmacy and a high consumption of resources. In the past decade, the healthcare models have changed and are characterized by work in multidisciplinary and interlevel teams, patient self-care, the availability of tools for decision making, information and communication systems and prevention. The goal is to have prepared and proactive health teams and an informed and active patient population. The assessment of health results, processes and the costs for these programs is still based on moderate to low evidence. It is therefore not an easy task to determine the type and intensity of interventions or to determine the patient groups that could gain more benefits.

Treball de fi de grau en Llengües aplicades. Tutora: Verònica López-Garcia. Aquest treball presenta una proposta de guia per a l’adaptació a audiollibre de referències intratextuals i interpel·lacions al lector presents en llibres de no-ficció. És una proposta per a Grupo Planeta, tot i que és aplicable a qualsevol editorial dedicada que publiqui els seus títols en format audiollibre. Per realitzar aquesta proposta, s’han analitzat exemples reals d’adaptacions proporcionats per l’estudi de gravació Sounds & Words a partir dels quals es va elaborar una classificació general dels tipus d’adaptacions. A part de ser útil pels estudis de gravació i per a les editorials, és una novetat, ja que no tenim coneixement de què existeixi res semblant. Una de les possibles aplicacions d’aquesta guia és la seva distribució entre els diferents estudis de gravació amb els que treballa una editorial amb l’objectiu d’unificar l’adaptació d’aquestes referències en els audiollibres que comercialitza. Així com la de facilitar la comprensió del text una vegada passat a format àudio. In this project it is presented an original proposal of a guide aimed to the adaptation of the context of the audiobook of intratextual references and insertions to the reader present in non-fiction books. It is a proposal for Grupo Planeta, although applicable to any publishing house that publishes its titles in audiobook format. In order to carry out this proposal, real adaptations examples, provided by the Sounds & words recording studio, have been analyzed to define a general classification of these types of adaptations. Apart from being useful for recording studios and publishers, it is a unprecedent resource, as we are not aware of anything similar. One of the possible applications of this guide is its distribution among the different recording studios with which a publishing house works in order to unify the adaptation of these references in the audiobooks it sells. As well as facilitating the understanding of the text once it has been converted into audio format. One of the most current linguistic problems in Terres de l’Ebre is the underestimate and ignorance of the Catalan standard linguistic uses of the area’s dialectal variant, named Tortosí. As a consequence, the genuine and normative linguistic features of Tortosí are replaced by those of the central Catalan standard and a situation of endo-diglossia is created. The educational system, as part of the linguistic implementation process, should provide the required tools and the needed knowledge to students to be able to create a Catalan standard model consistent with the features of their dialect. Having said that, how do the characteristics of the linguistic model that is taught in the classrooms of Terres de l’Ebre influence the spreading of social prestige or the growing of linguistic prejudices towards the uses of Tortosí? This paper covers two main objectives: on the one hand, it analyses which Catalan standard model is used by teachers of the Catalan language subject from a sample of eight high schools among Terres de l’Ebre and, on the other hand, it discovers the influence of the educational system on the creation of a specific Catalan standard model. The results of this research show that there is a clear concern about the presence of Tortosí both in the Catalan classes taught by the teachers who have participated in this analysis, and in the language projects of the educational centres that the Catalan Department of Education helps to develop. However, other factors that play against the diffusion of a standard based on the linguistic features of Tortosí have been discovered, such as the model that the teaching materials disseminate or some teachers’ preference for the spread of the standard model of central Catalan.

Background Antimicrobial resistance has become a global challenge in healthcare and is usually associated with poor antibiotic-prescribing patterns. Purpose We sought to determine the rate and characteristics of antibiotic prescription in order to design future targeted antimicrobial stewardship interventions. Material and methods A point prevalence survey was carried out in the framework of the multi-centre study of international prevalence Global PPS 2017 (www.globalpps.com) in November 2017. The study was conducted from the analysis of all prescriptions of active antibiotics at 8 am at the hospital in a single day. A descriptive study (frequency and percentage) of the variables explored was carried out. Results Of 174 patients eligible for the study, quality indicators for antimicrobial prescriptions were: compliance with institutional guidelines: 100%, 62.3% and 57.8% (p There were therapeutic indications in 129 of the prescriptions, of which 22.5% were for skin and soft-tissue infections, followed by 15.5% complicated urinary tract infections and 9.3% pneumonia. Amoxicillin-clavulanate was the most prescribed antibiotic for treatment and prophylaxis purposes (48.1% and 29.8% respectively). According to syndrome, worst guideline compliance was observed in complicated urinary tract infections 57.9% and skin and soft-tissue infections (65.5%). Conclusion In our setting, adequate acquisition definition, compliance with local guidelines, obtaining of microbiological samples and certain clinical syndromes (skin and soft tissue and urinary) were the main variables identified to prioritise ASP-targeted intervention. References and/or acknowledgements No conflict of interest.

Objective Deep brain stimulation (DBS) is a valuable tool for ameliorating drug resistant pathologies such as movement disorders and epilepsy. DBS is also being considered for complex neuro-psychiatric disorders, which are characterized by high variability in symptoms and slow responses that hinder DBS setting optimization. The objective of this work was to develop an in silico platform to examine the effects of electrical stimulation in regions neighboring a stimulated brain region. Approach We used the Jansen-Rit neural mass model of single and coupled nodes to simulate the response to a train of electrical current pulses at different frequencies (10-160 Hz) of the local field potential recorded in the amygdala and cortical structures in human subjects and a non-human primate. Results We found that using a single node model, the evoked responses could be accurately modeled following a narrow range of stimulation frequencies. Including a second coupled node increased the range of stimulation frequencies whose evoked responses could be efficiently modeled. Furthermore, in a chronic recording from a non-human primate, features of the in vivo evoked response remained consistent for several weeks, suggesting that model re-parameterization for chronic stimulation protocols would be infrequent. Significance Using a model of neural population activity, we reproduced the evoked response to cortical and subcortical stimulation in human and non-human primate. This modeling framework provides an environment to explore, safely and rapidly, a wide range of stimulation settings not possible in human brain stimulation studies. The model can be trained on a limited dataset of stimulation responses to develop an optimal stimulation strategy for an individual patient.

Polypathological patients have specific clinical, functional, psychoaffective, social, family and spiritual characteristics. These patients are generally elderly and frail and have frequent decompensations. They frequently use healthcare resources, have significant functional impairment and have a high index of dependence. This results in a significant social impact, high mortality and a high consumption of resources. The current healthcare models have not answered these needs, which causes problems with accessibility to healthcare services, a lack of coordination among these services, a higher probability of adverse events related to polypharmacy and a high consumption of resources. In the past decade, the healthcare models have changed and are characterized by work in multidisciplinary and interlevel teams, patient self-care, the availability of tools for decision making, information and communication systems and prevention. The goal is to have prepared and proactive health teams and an informed and active patient population. The assessment of health results, processes and the costs for these programs is still based on moderate to low evidence. It is therefore not an easy task to determine the type and intensity of interventions or to determine the patient groups that could gain more benefits.

Deficits in emotion processing, a known clinical feature of major depressive disorder (MDD), have been widely investigated using emotional face paradigms and neuroimaging. However, most studies have not accounted for the high inter-subject variability of symptom severity. Similarly, only sparse research has focused on MDD in adolescence, early in the course of the illness. Here we sought to investigate neural responses to emotional faces using both categorical and dimensional analyses with a focus on anhedonia, a core symptom of MDD associated with poor outcomes. Nineteen medication-free depressed adolescents and 18 healthy controls (HC) were scanned during presentation of happy, sad, fearful, and neutral faces. ANCOVAs and regressions assessed group differences and relationships with illness and anhedonia severity, respectively. Findings included a group by valence interaction with depressed adolescents exhibiting decreased activity in the superior temporal gyrus (STG), putamen and premotor cortex. Post-hoc analyses confirmed decreased STG activity in MDD adolescents. Dimensional analyses revealed associations between illness severity and altered responses to negative faces in prefrontal, cingulate, striatal, and limbic regions. However, anhedonia severity was uniquely correlated with responses to happy faces in the prefrontal, cingulate, and insular regions. Our work highlights the need for studying specific symptoms dimensionally in psychiatric research.

Global change is impacting forests worldwide, threatening biodiversity and ecosystem services including climate regulation. Understanding how forests respond is critical to forest conservation and climate protection. This review describes an international network of 59 long-term forest dynamics research sites (CTFS-ForestGEO) useful for characterizing forest responses to global change. Within very large plots (median size 25ha), all stems 1cm diameter are identified to species, mapped, and regularly recensused according to standardized protocols. CTFS-ForestGEO spans 25 degrees S-61 degrees N latitude, is generally representative of the range of bioclimatic, edaphic, and topographic conditions experienced by forests worldwide, and is the only forest monitoring network that applies a standardized protocol to each of the world's major forest biomes. Supplementary standardized measurements at subsets of the sites provide additional information on plants, animals, and ecosystem and environmental variables. CTFS-ForestGEO sites are experiencing multifaceted anthropogenic global change pressures including warming (average 0.61 degrees C), changes in precipitation (up to +/- 30% change), atmospheric deposition of nitrogen and sulfur compounds (up to 3.8g Nm(-2)yr(-1) and 3.1g Sm(-2)yr(-1)), and forest fragmentation in the surrounding landscape (up to 88% reduced tree cover within 5km). The broad suite of measurements made at CTFS-ForestGEO sites makes it possible to investigate the complex ways in which global change is impacting forest dynamics. Ongoing research across the CTFS-ForestGEO network is yielding insights into how and why the forests are changing, and continued monitoring will provide vital contributions to understanding worldwide forest diversity and dynamics in an era of global change.

Existing methods for sorting, labeling, registering, and across-subject localization of electrodes in intracranial encephalography (iEEG) may involve laborious work requiring manual inspection of radiological images. We describe a new open-source software package, the interactive electrode localization utility which presents a full pipeline for the registration, localization, and labeling of iEEG electrodes from CT and MR images. In addition, we describe a method to automatically sort and label electrodes from subdural grids of known geometry. We validated our software against manual inspection methods in twelve subjects undergoing iEEG for medically intractable epilepsy. Our algorithm for sorting and labeling performed correct identification on 96% of the electrodes. The sorting and labeling methods we describe offer nearly perfect performance and the software package we have distributed may simplify the process of registering, sorting, labeling, and localizing subdural iEEG grid electrodes by manual inspection.

The behavior of advanced cladding materials under challenging conditions needs to be fully characterized, understood and modeled. This paper assesses the current predictability of fuel performance codes under loadings expected from pellet–clad mechanical interactions. A set of scenarios experimentally characterized within the SCIP project, were chosen so that a variety of materials and ramp power sequences could be examined. Four codes have been used in this study: ALCYONE V1.1, FALCON-PSI, FRAPCON-3 v3.3 and STAV7.3. Their predictions have been compared to data in terms of cladding oxidation, diameters and elongation. Predictability of clad oxidation was certainly scattered and while some codes showed reasonable accuracy, other results were notably deviated. As for diameters, most of the codes were capable of qualitatively capturing the axial profile, and showed consistency between diameters and hoop stress and strain predictions. Elongation estimates were generally poor, and were rather far from measurements in most cases (even the trends observed just vaguely followed by the codes). The results reported have been discussed in the light of the set of individual hypotheses and approximations made by modelers and codes regarding both boundary conditions (i.e., power histories, inlet coolant temperature, refabrication, etc.) and fuel and clad characterization (i.e., densification, rim porosity, materials properties, etc.). Additionally, code-to-code comparisons of some key variables (i.e., fuel temperature, contact pressure, hoop and axial stresses, etc.) highlighted systematic tendencies of the codes and supported the observations made.

Adequate radioprotection of the environment requires the identification of biomonitors sensitive to the variation of its radionuclide content. Due to the chemical similarities between calcium and strontium, calcified tissues of mammals are considered to be good 90Sr biomonitors. This work considered Cervus elaphus antlers which, being shed annually, can give information about the importance of radiostrontium contamination in an ecosystem in the time period required for the growth of the antler. The samples were collected at various points of W and SW Spain. The mean value of their 90Sr content was (70 ± 43 (S.D.)) Bq/kg d.w., range (16–218) Bq/kg d.w., and the radionuclide was evenly distributed in the different parts of the antler. There was a good correlation between the antlers’ 90Sr content and the 90Sr deposited in the soil. The antlers’ content of 226Ra (from the natural uranium series) and the contents of some stable elements (Ca, Mg, Sr, and K) were also determined. The values for these stable elements were practically constant in the analyzed samples, and the concentrations measured decreased in the following order: Ca » Mg > K > Sr » 90Sr > 226Ra

— La señalética es una disciplina del diseño gráfico relacionada con la comunicación; es la información que estudia y desarrolla un sistema de comunicación visual, que es reducido a un conjunto de señales o símbolos gráficos de fácil compresión, los cuales cumplen la función de guiar a una persona o conjunto de personas en aquellos puntos o lugares donde se prestan servicios o se planteen dudas acerca del comportamiento. El objetivo de esta investigación fue identificar los lugares más afectados por la escasez de señalización dentro de la Universidad Técnica de Manabí (UTM) y los tipos de señaléticas adecuadas para estos. Para ello, se utilizó las principales técnicas de recolección de información, en las cuales se aplicaron los métodos cualitativos y cuantitativos. La población de esta investigación, como antes mencionada, es la UTM, de la cual se tomó como muestra un 20% que es perteneciente a las facultades de Medicina, Electricidad, Idiomas y el Instituto de Ciencias Básicas (ICB) Con los resultados obtenidos se demostró que el tema de la investigación realizada es de interés entre los involucrados, reconociendo la falta de señaléticas en diferentes puntos, lo cual está provocando el irrespeto de los conductores hacia los peatones o ciclistas, corroborando con ello la necesidad de cubrir diferentes áreas con señales que disminuyan el riesgo en el interior de la universidadn. Index Terms— señales, riesgo, disciplina

Specific binding for progesterone has been determined in rat hepatocytes and mouse liver purified plasma membranes. The binding is saturable, reversible and temperature dependent. Two types of binding sites have been characterized in hepatocytes. The first is of high affinity and low binding capacity and the other one is of low affinity and high capacity of binding. In plasma membranes one type of specific binding site only exists. These high affinity sites are different from nuclear progesterone receptor, nuclear glucocorticoid receptor, digitalis receptor of Na+, K(+)-ATPase, transcortine and from corticoid binding sites determined previously in plasma membrane. We also have observed that specific progesterone binding to hepatocytes and plasma membrane is independent from the alpha and beta adrenergic receptors and from P-site adenosine receptor.

The patients being treated in our health care system are becoming increasingly older and have a greater prevalence of chronic diseases. Due to these factors, these patients require greater and easier accessibility to the system as well as continuity of medical care. Collaboration between the different levels of health care has been instrumental in the success of the system and has produced changes in the hospital medical care protocol. Our hospital has developed a care model oriented towards the patient's needs, resulting in a higher grade of satisfaction among the medical professionals. In this paper, we have given a detailed description of part of our medical model, illustrating its different components and indicating several parameters of its evaluation. We have also reviewed the current state of the various models published on this topic. In summary, we believe that this medical care model presents a different approach to management that benefits patients, medical professionals and the health system alike.

Suspension bridge typology among other types of bridges is the most optimal for spans higher than 1100 m.In recent years, suspension bridges have had a breakthrough in technology, materials and methods of design and construction, which has led them to be bigger and longer. Furthermore, with the emergence of the new typology as multi-span bridges, such as Taizhou Bridge in China and will be the Chacao Bridge in Chile with two asymmetric spans of 1055 and 1155 m each.

Calculation methods of spur and helical gear drives with a transverse contact ratio higher than 2, accurate enough for preliminary designs or standardization purposes, are not available in technical literature. If the load is assumed to be uniformly distributed along the line of contact, simple equations given by the linear theory of elasticity and the Hertzian contact model are not in good agreement with experimental results. However, these simple equations may work quite accurately with a more realistic model of load distribution accounting the changing rigidity of the pair of teeth along the path of contact. In this paper a nonuniform model of load distribution along the line of contact, obtained from the minimum elastic potential criterion, has been considered for stress calculation of spur and helical gear drives with transverse contact ratio between 2 and 2.5. The determinant load conditions have been calculated and the nominal contact stress and the nominal tooth-root stress have been computed.

Approximately 50% of hypertensive patients are salt sensitive (they increase their Blood Pressure in response to sodium intake or volume expansion). Mechanisms underlying salt sensitivity are not completely elucidated although there is evidence that they may be genetically determined. The aim of this study is to establish the relation among some genetic polymorphisms of the renin-angiotensin system (RAAS) and the beta-3 subunit of the protein G and salt sensitivity. We studied 102 essential hypertensive patients, stage 1-2 and without target organ damage. Salt sensitivity was assessed by the rapid protocol of Weinberger. We determined by polymerase Chain reaction techniques the following polymorphisms: insertion/deletion (I/D) of the angiotensin-converting enzyme (ACE), A1166C of the angiotensin II type 1 receptor (AT1R), -344C/T and intron 2 conversion (IC) of the aldosterone synthase (CYP11B2), and C825T of the beta-3 subunit of the protein G (GNB3). 41 patients (40.19%) were salt sensitive. The distribution of the different polymorphisms was similar in both groups of patients, but subjects carriers of the W allele of the CYP11B2 IC polymorphism had a greater risk for salt sensitivity as compared with no carriers (37 of 41, 90.2% vs 4 of 41, 9.8%, OR 3.02, P

La hipertension arterial (HTA) resulta de la interaccion entre factores geneticos y ambientales. Aunque las bases geneticas de la enfermedad estan firmemente establecidas y el desarrollo en el campo de la biologia molecular y genetica ha sido muy importante en los ultimos anos, el avance en el conocimiento de las alteraciones geneticas causantes de la HTA no ha sido muy satisfactorio. Se han identificado las mutaciones geneticas responsables de algunas formas raras de hipertension de origen mendeliano, pero el estudio de los genes posiblemente implicados en la herencia de la HTA (genes candidatos) ha dado en general resultados contradictorios. En esta revision resumimos los estudios mas recientes y significativos realizados sobre los genes candidatos en la HTA.

International audience; One of the most important challenges facing nanotechnology is to identify methods that relate the synthesis of nanomaterials with their final applications. This work proposes a thermodynamic method to understand the stimuli–response of functionalized polymeric particles with NaOH using the partial volumes of interaction, partial compressibilities of interaction, partial enthalpies of interaction and the average hydrodynamic diameter. These properties have been calculated from experimental measurements made by mechanical oscillation densimetry, the sound speed technique, isothermal titration calorimetry, dynamic light scattering and zeta potential. The thermodynamic method allows determination of how and where the interactions take place on the polymeric particles. From the methodological point of view, the thermodynamic fundamentals of the method were tested by simulating the partial properties calculated from volumetric data of a ternary liquid mixture taken from the literature.

Background The switch from the intravenous (IV) formulation to the subcutaneous (SC) formulation of abatacept (ABA) had been analysed in clinical trials but there are few data regarding the effectiveness and safety of the SC formulation in clinical practice. Purpose To evaluate the impact of switching from IV to SC abatacept (SC ABA) in patients who were controlled on the IV formulation in a real world setting. Material and methods Observational retrospective study of patients switched from IV to SC ABA, 125 mg once weekly, between September 2013 and April 2015. Data were collected by reviewing patient clinical records and the database of the local advisory committee for rheumatoid arthritis (RA). Measured parameters were: disease activity score at 28 joints (DAS28), treatment duration, reasons for withdrawal and new biologic agent introduced. Results 19 patients were included in our study, 17 women (89.5%) and 2 men (10.5%), mean age 59.6 years. All the patients had low RA activity at the beginning of SC ABA treatment (mean DAS28=3.1). 6 patients (31.6%) discontinued; all experienced an arthritic flare (mean DAS28=4.21; p = 0.02 vs baseline) but no adverse effects were described. 5 (83.3%) returned to IV administration after a mean of 7.1 months (range 2.7–10.8). The other patient (16.7%) switched to etanercept. 13 patients (68.4%) have continued SC administration to date with good disease control and no adverse reactions. All five patients that returned to IV ABA also have good disease control to date. Conclusion In our small case series, SC ABA showed a risk of relapse in 31.6% of cases but reinsertion of IV administration seemed to reinstate disease control. It could be possible that an eventual failure of the SC formulation does not compromise the effectiveness of the ABA therapy itself. Further research with a greater number of patients is needed. References and/or Acknowledgements 1. Reggia R, et al . J Rheumato. 2015;42:193–5 References and/or Acknowledgements No conflict of interest.

In the case of large burnup, a control rod (CR) guide tube in the pressurized water reactor of a commercial nuclear power plant might bend. As a consequence, a CR drop experiment may indicate an event of a CR partially inserted and whether the CR should be deemed inoperable. Early prevention of such an event can be achieved by measuring two friction coefficients: the hydraulic coefficient and the sliding coefficient. The hydraulic coefficient hardly changes, so that the curvature of the guide tube can only be detected thanks to a variation of the sliding coefficient. A simple model for the CR drop is established and validated with CR drop experiments. If tmx denotes the instant of CR maximum velocity, a linear relationship between (tmx)_2 and the sliding coefficient is found.

Adequate radioprotection of the environment requires the identification of biomonitors sensitive to the variation of its radionuclide content. Due to the chemical similarities between calcium and strontium, calcified tissues of mammals are considered to be good ⁹⁰Sr biomonitors. This work considered Cervus elaphus antlers which, being shed annually, can give information about the importance of radiostrontium contamination in an ecosystem in the time period required for the growth of the antler. The samples were collected at various points of W and SW Spain. The mean value of their ⁹⁰Sr content was (70 ± 43 (S.D.)) Bq/kg d.w., range (16-218) Bq/kg d.w., and the radionuclide was evenly distributed in the different parts of the antler. There was a good correlation between the antlers' ⁹⁰Sr content and the ⁹⁰Sr deposited in the soil. The antlers' content of ²²⁶Ra (from the natural uranium series) and the contents of some stable elements (Ca, Mg, Sr, and K) were also determined. The values for these stable elements were practically constant in the analyzed samples, and the concentrations measured decreased in the following order: Ca » MgKSr » ⁹⁰Sr²²⁶Ra.

The patients being treated in our health care system are becoming increasingly older and have a greater prevalence of chronic diseases. Due to these factors, these patients require greater and easier accessibility to the system as well as continuity of medical care. Collaboration between the different levels of health care has been instrumental in the success of the system and has produced changes in the hospital medical care protocol. Our hospital has developed a care model oriented towards the patient's needs, resulting in a higher grade of satisfaction among the medical professionals. In this paper, we have given a detailed description of part of our medical model, illustrating its different components and indicating several parameters of its evaluation. We have also reviewed the current state of the various models published on this topic. In summary, we believe that this medical care model presents a different approach to management that benefits patients, medical professionals and the health system alike.

A Regulatory Commission Requisition compels the NPPs to a periodic inspection in order to know the pressure sensors response time. During the recharge period, a pressure signal is applied to the sensor, and the response time to this signal is observed. This method is certainly accurate, of course, but it is also very cumbersome, little versatile and expensive. So alternatives have arised, in the recent years, based in the Noise Analysis Technique. These alternatives provide satisfactory results, not only from the safety point of view but also from the economics, with a really smaller effort. In this work Neural Networks are going to be used to obtain the pressure sensors response time. The purpose is to connect the noise correlation function to this time via a Neural Network. It will be plausible that an easy architecture is able to “learn” this problem, offering satisfactory results.

The aim of this review is to present and discuss the effect of different levels of alcohol consumption on the immune system. Not only the amount consumed but also the type of alcoholic beverage have to be taken into account in order to determine the consequences on activity, number, distribution, balance, interaction and response of immunocompetent cells. The association between alcohol exposure and the risk of developing an alcohol-related disease is multifactorial. In fact, age, gender, smoking habits, dietary intake and exercise are involved among other factors. The evaluation of the host cellular and humoral immune responses has shown that alcohol may induce some benefits when consumption is moderate. Moreover, those alcoholic beverages that contain antioxidants, such as red wine, could be protectors against immune cell damage. According to the literature consulted, the daily consumption of 10-12 g and 20-24 g of alcohol for women and men, respectively, is considered to be a moderate intake; the type of beverage has been established not to be important when defining moderation. Particular attention is often focused on the U- or J-shaped curve which also suggests that light to moderate drinking produces a protective effect. Such an inverse relationship indicates a reduction of risk for both light and moderate consumers and a higher risk not only for hard drinkers, but also for non-consumers.

Background As the result of Resolution SC 0403/10 of December 22, 2010 in the region of Andalucia (Spain) some medicines for outpatient treatment are no longer dispensed in community pharmacies but in hospital pharmacies, given that they require special surveillance, supervision and control. Purpose To determine the savings made by dispensing oral cytostatic drugs in a third-level hospital. Materials and methods Descriptive observational study of the oral cytostatics dispensed between December 2010 and March 2013. Data were collected from APD software. We determined: The total expenditure on dispensing cytostatics for out-patients, The percentage of this expenditure relative to the total expenditure on all oral medicines for outpatients, The cost savings, The most expensive active ingredients. Results The value of oral cytostatics totalled 6,731,547.87 € during the period of study. This meant 6.37% of the total amount of out-patient prescriptions for oral medicines for the same period. These prescriptions would have cost € 7,141,037.52 if they had been made at community pharmacies. Therefore, these results equate to a saving of € 409,489.64. The active ingredients that affected the cost most were imatinib and sunitinib. Conclusions Hospital dispensing of oral cytostatics led to a cost saving of 5.73% when compared to community pharmacy dispensing. Two factors explain this cost saving: The Avoidance of Any Commercial Expenditure Undertaken by Community Pharmacies The Optimisation of Resources Driven by Patients Taking the Exact Amount Needed of the Drug as They Are Required to Return Any Untaken Medicine When Completing or Changing Their Treatment No conflict of interest.

Analysis of colorectal anastomosis stricture incidence after anterior resection of the rectum performed with the EEA-Stapler. To find out if differences existed in stricture incidence considering factors such, as age, neoplasia, postoperative radiotherapy, tumor stage and anastomic level.Longitudinal descriptive study.67 patients who underwent rectal anterior resection using the EEA-Stapler were evaluated. Data from sex, age, indication for operation, postoperative radiotherapy, tumor staging and anastomic level were recorded and compared with presence of stricture anastomosis. Stenosis was evaluated and graded as follows: grade O, no stenosis; grade I, no symptoms, X-ray or endoscopic finding; grade II, symptoms, the patients require ballon catheter dilation; and grade III, invalidant symptoms, the patients require surgery.Twelve patients (20%) were recorded as grade II and 3 patients (5%) as grade III. There were no statistically significant differences between prevalence of stricture and sex, age, neoplasic or non-neoplasic conditions, previous radiotherapy, level of anastomosis, and tumor stage.Stenosis after colorectal anastomosis with stapler devices must not be considered as an uncommon complication. In 20% of patients it may be a serious state that may require repeated catheter balloon dilations or surgery. Such condition is not dependent on diverse factors studied.

Background Adverse drug reactions (ADRs) are especially important with antineoplastic drugs because of their implications on patients’ health and quality of life. Purpose To study the epidemiology, clinical features, diagnosis and pharmacology of ADRs detected in hospitalised patients treated with antineoplastic drugs. Materials and Methods Analytical observational study (2011). We included all patients receiving cancer treatment. Study variables were: sociodemographic characteristics (age, sex), clinical (diagnostic, stage) and ADRs. The analysis was epidemiological: ADRs conducted (cumulative incidence, CI), clinical: (physiological system affected, type, duration, production mechanism, frequency, severity), pharmacological: (drug, administration, cycle) and diagnostic: (causality, chronological sequence). Results 125 patients (mean age 51 years), 68% male, 32% female, 90% comorbidities. The most common diagnoses were lymphoma (28%), specifically non-Hodgkin’s Lymphoma (11%), acute lymphoblastic leukaemia (9%), acute myeloid leukaemia (6%) mainly in advanced stages (68%). We detected a total of 170 ADRs with antineoplastic agents (28% CI). Physiological systems primarily affected were: blood (89%), digestive system (23%). The most common ADR was cytopenia (49%) specifically febrile neutropenia (37%). The duration was 7 days (25%). ADRs were mostly produced in a dose-dependent way (85%), were very common (94%) and according to severity were: lethal (2%), severe (5%), moderate (73%), mild (19%). The drugs involved were: cytarabine, methotrexate, idarubicin, carmustine, cisplatin by intravenous administration (97%) and during first treatment cycles: cycle 1 (53%), cycle 2 (23%). 92% of the ADRs are tested and produced after drug administration (99%). In 60% and 19% of cases the measure was the continuation and discontinuation of antineoplastic therapy, respectively. In cases of re-exposure, the emergence of drug ADRs was positive in 45% of patients and in the disappearance of ADRs discontinuation was positive in 92%. Conclusions The incidence of ADRs was high, the majority of ADRs were well known, moderate and positive outcome according to the measurements. It would be better to understand the ADRs as it can help develop other strategies to reduce their impact on the safety of cancer treatments in the first cycles. No conflict of interest.

Background Cetuximab label indication includes treatment of epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer in several possible ways: combination with irinotecan-based chemotherapy, first-line in combination with FOLFOX and as a single agent after oxaliplatin- and irinotecan-based treatment failure in irinotecan-intolerant patients. In our hospital, a multidisciplinary team drawn from the Oncology and Pharmacy services has established a consensus for the rational use of cetuximab as first or second-line agent in association with other chemotherapeutic agents and as monotherapy in third-line treatment after the failure of oxaliplatin and irinotecan-based treatment. Purpose To verify the relevance of cetuximab prescription to the local protocol and cheque the label indications for cetuximab in our hospital. Materials and Methods A retrospective study of patients diagnosed with metastatic colorectal cancer between 2006–2012 with available KRAS status. Patients were followed up for a minimum of three months after diagnosis. Results Twenty-six patients were collected (mean age: 62.2 ± 12.6 years; 53.8% male). KRAS mutation was negative in 42.3% (11/26) patients and therefore they were eligible for treatment with cetuximab. Five out of those 11 patients underwent cetuximab treatment (5/11; 45.5%): three associated with oxaliplatin in first-line treatment, one associated with irinotecan in second-line treatment and one as monotherapy in second-line treatment. Four out of these 5 prescriptions of cetuximab were in accordance to our local protocol and label (4/5; 80.0%). One prescription was not in accordance with either the local protocol or the cetuximab label; due to this the patient was treated with oral capecitabine as first-line and cetuximab monotherapy as second-line treatment. Three KRAS-negative patients (3/11; 27.3%) are currently in treatment with irinotecan as second-line therapy. Three KRAS-negative patients were lost to follow-up after undergoing second-line treatment not known to contain a cetuximab prescription (3/11; 27.3%). Fifteen patients positive for KRAS mutation (15/26; 57.7%) were not treated with cetuximab. Conclusions Ninety-five percent of cetuximab prescriptions in our hospital are in accordance with the established local protocol and the cetuximab label (19/20). No conflict of interest.

Background Chemoembolization of hepatic melanoma metastases refractory to treatment using irinotecan-loaded DC beads [embolic Drug-Eluting Beads]: a novel palliative treatment with which there is as yet little experience. Purpose To show the progress of a clinical case of metastatic choroidal melanoma treated with irinotecan-loaded DC Beads. Materials and Methods The pharmacy department loaded the particles with irinotecan ourselves and monitored the patient through the clinical history. The patient was a 38-year-old man with stage IV choroidal melanoma in the left eye (2007). Results In October 2011, 4 hepatic nodules were detected: 3 in segment VII (23, 25, 11 mm) and 1 in segment II (16 mm). 2 cycles of dacarbazine treatment (1649 mg × 1day) stabilised the disease. The patient experienced emesis and diarrhoea. Given this intolerance and negative BRAFV600E mutation, ipilimumab reinforcement treatment was administered (225 mg × 1day q21days). After 4 cycles of ipilimumab, the disease stabilised for 5 months. In May 2012, an increase in size of the nodules was described and 6 new nodules in both hepatic lobes: segment II (42 × 34 mm), IVb (15 mm), VII (25, 26 and 61.4 × 43 mm) and VIII (14 mm) were observed. Surgery was rejected due to the presence of multinodular lesions and transarterial chemoembolization with irinotecan-loaded DC beads was attempted. Hypervascular lesions were observed in the distal branches of the hepatic artery by bilobar hepatic arteriography using selective catheterization of both hepatic arteries. Subsequently, hepatic chemoembolization was performed by administering 100 mg irinotecan-loaded beads (75–100 microns). After 2 cycles in each hepatic lobe, treatment response was assessed by the RECIST criteria. One month after the last chemoembolization, stable disease (no new nodules and arterial necrosis Conclusions Hepatic chemoembolization using irinotecan-loaded beads is a viable alternative with good prognosis for hepatic metastases of choroidal melanoma. A higher concentration of chemotherapeutical drug is achieved within the hepatic lesions using lower doses of irinotecan, which therefore has less systemic impact. No conflict of interest.

This autoradiographic study of sections of the rabbit stomach fundus labelled with [ 35 S]dATPαS, a radioligand for P2Y purinoceptors, has demonstrated a discrete pattern of distribution of the binding sites, i.e., the specific binding was only over the mucosa, but not over the muscular layer. Radioligand binding assays carried out on gastric gland plasma membranes showed that the binding process was saturable and a high density of a homogeneous population of binding sites was observed. These binding sites presented high affinity with a value of K d = 4.1 ± 0.8 nM and the maximum density of the binding sites was 16.8 ± 1.6 pmol/mg protein. The displacement by purinoceptor ligands showed the following order of potency: ATP = 2-methylthio ATP ⪢ α,β-methylene ATP ⪢ adenosine. Neither UTP nor pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) were able to displace the binding. The data support the presence of P2Y purinceptors in rabbit gastric glands.