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318 p., El objetivo de esta tesis es comparar la efectividad, seguridad y eficiencia de los nuevos anticoagulantes orales (dabigatran, apixaban y rivaroxaban- NACO) frente a acenocumarol en los pacientes con fibrilación auricular que comienzan tratamiento con alguno de estos fármacos. Se seleccionan 10.843 nuevos usuarios de estos fármacos entre 2013 y 2016 en la CAPV y seguidos hasta diciembre de 2019. Se realizan análisis de efectividad comparada y análisis de supervivencia ajustada mediante técnicas de propensity score, ponderación por el inverso de la probabilidad de tratamiento y gradient boosting machine.Los NACO presentan una efectividad similar a acenocumarol en cuanto al riesgo de aparición de ictus oeventos tromboembólicos; el riesgo de hemorragias severas es menor con el empleo de un NACO, aunque los resultados no sean totalmente concluyentes.El uso de los NACO comparado con acenocumarol es coste-efectivo para una disponibilidad a pagar de 20.000 ¿/Año de Vida Ganado. Esta eficiencia se confirma empleando las distintas técnicas de ajuste mencionadas.El elevado tamaño muestral, una media de seguimiento de los pacientes superior a los 4 años, y la utilización de técnicas adecuadas para el análisis de datos de vida real (RWD) son aspectos novedosos que sobre este tema aporta esta tesis.

The most important advances in our understanding of the viral life cycle, such as genome replication, packaging, transmission, and host interactions, have been made via the development of viral infectious full-length clones. Here, we describe the detailed protocols for the construction of an infectious clone derived from Botrytis virus F (BVF), a mycoflexivirus infecting the plant pathogenic fungus Botrytis cinerea, the determination of the complete sequence of the cloned mycovirus, the preparation of fungal protoplasts, and the transfection of protoplasts using transcripts derived from the BVF infectious clone.

Small RNAS (sRNAs) participate in regulatory RNA interference (RNAi) mechanisms in a wide range of eukaryotic organisms, including fungi. The fungus Fusarium fujikuroi, a model for the study of secondary metabolism, contains a complete set of genes for RNAi pathways. We have analyzed by high-throughput sequencing the content of sRNAs in total RNA samples of F. fujikuroi grown in synthetic medium in the dark or after 1 h of illumination, using libraries below 150 nt, covering sRNAs and their precursors. For comparison, a parallel analysis with Fusarium oxysporum was carried out. The sRNA reads showed a higher proportion of 5′ uracil in the RNA samples of the expected sizes in both species, indicating the occurrence of genuine sRNAs, and putative miRNA-like sRNAs (milRNAS) were identified with prediction software. F. fujikuroi carries at least one transcriptionally expressed Ty1/copia-like retrotransposable element, in which sRNAs were found in both sense and antisense DNA strands, while in F. oxysporum skippy-like elements also show sRNA formation. The finding of sRNA in these mobile elements indicates an active sRNA-based RNAi pathway. Targeted deletion of dcl2, the only F. fujikuroi Dicer gene with significant expression under the conditions tested, did not produce appreciable phenotypic or transcriptomic alterations.

Background: Human Emotion Recognition (HER) has been a popular field of study in the past years. Despite the great progresses made so far, relatively little attention has been paid to the use of HER in autism. People with autism are known to face problems with daily social communication and the prototypical interpretation of emotional responses, which are most frequently exerted via facial expressions. This poses significant practical challenges to the application of regular HER systems, which are normally developed for and by neurotypical people. Objective: This study reviews the literature on the use of HER systems in autism, particularly with respect to sensing technologies and machine learning methods, as to identify existing barriers and possible future directions. Methods: We conducted a systematic review of articles published between January 2011 and June 2023 according to the 2020 PRISMA guidelines. Manuscripts were identified through searching Web of Science and Scopus databases. Manuscripts were included when related to emotion recognition, used sensors and machine learning techniques, and involved children with autism, young, or adults. Results: The search yielded 346 articles. A total of 65 publications met the eligibility criteria and were included in the review. Conclusions: Studies predominantly used facial expression techniques as the emotion recognition method. Consequently, video cameras were the most widely used devices across studies, although a growing trend in the use of physiological sensors was observed lately. Happiness, sadness, anger, fear, disgust, and surprise were most frequently addressed. Classical supervised machine learning techniques were primarily used at the expense of unsupervised approaches or more recent deep learning models. Studies focused on autism in a broad sense but limited efforts have been directed towards more specific disorders of the spectrum. Privacy or security issues were seldom addressed, and if so, at a rather

Light is an important modulating signal in fungi. Fusarium species stand out as research models for their phytopathogenic activity and their complex secondary metabolism. This includes the synthesis of carotenoids, whose induction by light is their best known photoregulated process. In these fungi, light also affects other metabolic pathways and developmental stages, such as the formation of conidia. Photoreceptor proteins are essential elements in signal transduction from light. Fusarium genomes contain genes for at least ten photoreceptors: four flavoproteins, one photolyase, two cryptochromes, two rhodopsins, and one phytochrome. Mutations in five of these genes provide information about their functions in light regulation, in which the flavoprotein WcoA, belonging to the White Collar (WC) family, plays a predominant role. Global transcriptomic techniques have opened new perspectives for the study of photoreceptor functions and have recently been used in Fusarium fujikuroi on a WC protein and a cryptochrome from the DASH family. The data showed that the WC protein participates in the transcriptional control of most of the photoregulated genes, as well as of many genes not regulated by light, while the DASH cryptochrome potentially plays a supporting role in the photoinduction of many genes.

Los objetos del patrimonio industrial a menudo guardan una estrecha relación con el ferrocarril, ya sea para facilitar el transporte de materias primas o de la producción misma. La Azucarera de San Fernando en Los Rosales (Tocina) es uno de esos ejemplos. El propósito de esta investigación es analizar exhaustivamente la evolución de la azucarera en todos sus aspectos: económicos, sociales y culturales, así como su impacto en el desarrollo del núcleo de Los Rosales. Además, se estudiará detenidamente el ferrocarril que atraviesa el municipio debido a su gran influencia en la zona y su estrecha relación con la Azucarera. De esta manera, se podrá comprender las interacciones históricas y actuales entre la fábrica y el ferrocarril. Una vez que se haya adquirido un profundo conocimiento tanto de la Azucarera como del ferrocarril y el núcleo de Los Rosales, se presentará una crítica detallada de su evolución, identificando tanto sus fortalezas como sus debilidades. El objetivo es establecer las claves necesarias para una posible intervención futura en el conjunto azucarero, con el fin de proponer mejoras y preservar su valor patrimonial., Industrial heritage objects are often closely related to the railway, either to facilitate the transport of raw materials or of the production itself. The San Fernando sugar factory in Los Rosales (Tocina) is one such example. The purpose of this research is to thoroughly analyse the evolution of the sugar factory in all its aspects: economic, social and cultural, as well as its impact on the development of Los Rosales. In addition, the railway that crosses the municipality will be studied in detail due to its great influence on the area and its close relationship with the sugar factory. In this way, it will be possible to understand the historical and current interactions between the factory and the railway. Once a thorough knowledge of the sugar factory, the railway and the town of Los Rosales has been acquired, a detailed critique of its evolution will be presented, identifying both its strengths and weaknesses. The aim is to establish the necessary keys for a possible future intervention in the sugar factory complex, in order to propose improvements and preserve its heritage value.

Asumiendo la dificultad de definir los rasgos esenciales de una identidad colectiva, este artículo explora como hipótesis que algunos de esos rasgos son constructos (políticos, ideológicos, culturales, etc.), pero que hay otros que podrían, por un instante, ser causa de reconocimiento de una diferenciación en la globalización. En vez de determinar qué pueda ser una identidad desde métodos antropológicos, este artículo se adentraría en delinear un perfilado, que no pretende ser impositivo, pero sí propositivo, para lo que podría llamarse una forma de vida, desde la literatura y la arquitectura. Para ello, se tomará el concepto “friluftsliv”, una suerte de descriptor para una conciencia colectiva, la noruega, que expresa la preservación del medioambiente y un vivir de manera muy vinculada a la naturaleza. Se encuentra inicialmente ese término en las obras Henrik Ibsen, conocido por establecer una estrecha relación con los sueños, operando en el plano del inconsciente para la creación de sus obras. Haciendo derivar de ese concepto la conocida Deep Ecology, liderada por Arne Naess, se abre una segunda hipótesis sobre el giro nacionalista de una sociedad hasta hace pocos años reconocida en otro de sus rasgos identitarios como abierta y receptiva. Así, se examina el caso de los memoriales de los atentados de 2011, siendo la arquitectura el foco analítico para estudiar el extremismo político conservador en Noruega, concluyendo que es crucial entender las manifestaciones del inconsciente, supuestamente a salvo de injerencias, como la que proveería el “friluftsliv”, que son ya la vía abierta para las manipulaciones identitarias., Assuming the difficulty of defining the essential features of a collective identity, this article explores as a hypothesis that some of these features are constructs (political, ideological, cultural, etc.), but that there are others that could, for a moment, be the cause of recognition of a differentiation in globalisation. Instead of determining what an identity might be from anthropological methods, this article will delve into outlining a profile, which is not intended to be imposing but propositional, for what might be called a form of life, from literature and architecture. To this end, the concept of “friluftsliv” will be taken, a sort of descriptor for a collective consciousness, the Norwegian one, which expresses the preservation of the environment and a way of life closely linked to nature. This term is initially found in the works of Henrik Ibsen, known for establishing a close relationship with dreams, operating on the level of the unconscious for the creation of his plays. Deriving from this concept the well-known Deep Ecology, led by Arne Naess, a second hypothesis opens up about the nationalist turn of a society that until a few years ago was recognised in another of its identity traits as open and receptive. Thus, the case of the memorials to the 2011 attacks is examined, with architecture being the analytical focus for studying conservative political extremism in Norway, concluding that it is crucial to understand the manifestations of the unconscious, supposedly safe from interference, such as that provided by the “friluftsliv”, which are already the open path for identity manipulations., Assumindo a dificuldade de definir as características essenciais de uma identidade coletiva, este artigo explora como hipótese que algumas dessas características são construções (políticas, ideológicas, culturais etc.), mas que há outras que poderiam, por um momento, ser a causa do reconhecimento de uma diferenciação na globalização. Em vez de determinar o que seria uma identidade a partir de métodos antropológicos, este artigo se aprofundará no delineamento de um perfil, que não pretende ser impositivo, mas propositivo, do que poderia ser chamado de forma de vida, a partir da literatura e da arquitetura. Para tanto, será adotado o conceito de “friluftsliv”, uma espécie de descritor de uma consciência coletiva, a norueguesa, que expressa a preservação do meio ambiente e um modo de vida intimamente ligado à natureza. Esse termo é encontrado inicialmente nas obras de Henrik Ibsen, conhecido por estabelecer uma relação próxima com os sonhos, operando no nível do inconsciente para a criação de suas peças. Derivando desse conceito a conhecida Ecologia Profunda, liderada por Arne Naess, abre-se uma segunda hipótese sobre a virada nacionalista de uma sociedade que, até poucos anos atrás, era reconhecida em outro de seus traços de identidade como aberta e receptiva. Assim, o caso dos memoriais dos ataques de 2011 é examinado, sendo a arquitetura o foco analítico para o estudo do extremismo político conservador na Noruega, concluindo que é crucial entender as manifestações do inconsciente, supostamente a salvo de interferências, como as fornecidas pelo “friluftsliv”, que já são o caminho aberto para manipulações de identidade.

Se ofrece una presentación del Monográfico titulado: los derechos fundamentales en el s.XXI por el Decano de la facultad de Derecho de la Universidad de Valladolid y presidente de la AFDL, D. Javier García Medina; y, el prof. Catedrático de Derecho Civil y vicepresidente de la AFDL, D. Andrés Domínguez Luelmo.

El artículo presenta el Enfoque basado en derechos humanos como una metodología que coloca a los derechos humanos como principio, norma y fin de cualquier agente público o privado de cuya acción puedan derivarse consecuencias que de maneras diferentes pueden vulnerar o limitar la protección o garantía de los derechos humanos. Las empresas han sido llamadas recientemente por Naciones Unidas como sujetos especialmente relevantes para convertirse en protagonistas en la protección de derechos humanos, habida cuenta de la impunidad con la que en muchas ocasiones habían actuado en el pasado, siendo sometidas a los deberes de diligencia debida en términos similares a los que se piden a los Estados, a la hora de rendir cuentas a través de los procedimientos establecidos en el derecho internacional de los derechos humanos.

El presente trabajo de investigación se basa en analizar los factores que contribuyen y limitan la implementación del componente sociocultural del proyecto de tramo Vilcashuamán – Sangalla ubicado en el departamento de Ayacucho, provincia de Vilcashuamán. Implementado y supervisado por el proyecto Qhapaq Ñan, el cual se encuentra adscrito al Ministerio de Cultura. El proyecto Qhapaq Ñan tiene como finalidad según la ley N°28260: “Identificar, investigar, registrar, conservar y poner en valor la red de caminos inca que aún subsisten en el territorio nacional”. Es menester de esta investigación conocer aquellos factores que contribuyen y limitan la implementación y la realización de las actividades propuestas por el componente sociocultural del proyecto en la provincia de Vilcashuamán, durante el periodo 2018 – 2019, analizando factores como: las acciones de apropiación social incentivadas por el proyecto, los espacios de participación y concertación, el fortalecimiento de capacidades y el empoderamiento de las mujeres de la comunidad, el reconocimiento de los actores clave y el nivel de articulación y cooperación de los mismos para con el proyecto. La presente investigación se enmarca en el enfoque de la gerencia social, la cual comprende la cogestión intersectorial, mediante la cooperación mutua entro todos los actores de un proyecto con la finalidad de generar beneficios para todos, así mismo mediante el uso de las herramientas metodológicas de la gerencia social se espera conocer más de cerca las dinámicas sociales y culturales que se dan entre el componente sociocultural del proyecto y la comunidad., This research work is based on analyzing the factors that contribute and limit the implementation of the sociocultural component of the Vilcashuamán - Sangalla section project located in the department of Ayacucho, province of Vilcashuamán. Implemented and supervised by the Qhapaq Ñan project, which is attached to the Ministry of Culture. The Qhapaq Ñan project has as its purpose, according to Law No. 28260: "Identify, investigate, register, preserve and value the network of Inca trails that still exist in the national territory." It is necessary for this research to know those factors that contribute and limit the implementation and carrying out of the activities proposed by the sociocultural component of the project in the province of Vilcashuamán, during the period 2018 - 2019, analyzing factors such as: actions of social appropriation encouraged by the project, the spaces for participation and agreement, the strengthening of capacities and the empowerment of the women of the community, the recognition of the key actors and the level of articulation and cooperation of the same towards the project. The present investigation is part of the approach of social management, which includes intersectoral co-management, through mutual cooperation between all the actors of a project in order to generate benefits for all, likewise through the use of methodological tools of Social management is expected to learn more about the social and cultural dynamics that occur between the sociocultural component of the project and the community.

Purpose The objective of this study was to estimate the incidence and age of onset of mental disorders diagnosed by gender and socioeconomic status (SES) in children, adolescents, and young adults up to 30 years of age in the whole population of the Basque Country (Spain). Methods All mental health diagnoses documented in Basque Health Service records from 1 January 2003 to 31 December 2018, were classified into eight clusters: anxiety, attention deficit hyperactivity disorder (ADHD), conduct disorders, depression, psychosis/personality disorders, substance use, eating disorders, and self-harm. We calculated incidence and cumulative incidence for each cluster, disaggregated by gender, and socioeconomic status (SES). Poisson regression analyses were performed. Results Overall, 9,486,853 person-years of observation were available for the 609,281 individuals included. ADHD and conduct disorders were diagnosed in the first decade, anxiety and depression disorders in the second and third decades, and psychosis/personality and substance use in the third. The cumulative incidence at 18 years of age for any type of disorder was 15.5%. The group with low SES had a statistically significantly higher incidence of all eight clusters. The incidence of ADHD, conduct disorders, depression, psychosis/personality disorders, and substance use was higher in males and that of anxiety, eating disorders and self-harm was higher in females. Conclusions The incidence of mental disorders is high among children, adolescents, and young adults in the Basque Country underlining the need for preventive interventions. Marked differences by gender and SES highlight mental health inequalities, especially for depression and psychosis in low SES males.

Background As mental health in adulthood is related to mental status during adolescence, school-based interventions have been proposed to improve resilience. The objective of this study was to build a simulation model representing the natural history of mental disorders in childhood, adolescence and youth to estimate the cost-effectiveness of the UPRIGHT school-based intervention in promoting resilience and mental health in adolescence. Methods We built a discrete event simulation model fed with real-world data (cumulative incidence disaggregated into eight clusters) from the Basque Health Service database (609,381 individuals) to calculate utilities (quality-adjusted life years [QALYs]) and costs for the general population in two scenarios (base case and intervention). The model translated changes in the wellbeing of adolescents into different risks of mental illnesses for a time horizon of 30 years. Results The number of cases of anxiety was estimated to fall by 5,125 or 9,592 and those of depression by 1,269 and 2,165 if the effect of the intervention lasted 2 or 5 years respectively. From a healthcare system perspective, the intervention was cost-effective for all cases considered with incremental cost-utility ratios always lower than €10,000/QALY and dominant for some subgroups. The intervention was always dominant when including indirect and non-medical costs (societal perspective). Conclusions Although the primary analysis of the trial did not did not detect significant differences, the UPRIGHT intervention promoting positive mental health was dominant in the economic evaluation from the societal perspective. Promoting resilience was more cost-effective in the most deprived group. Despite a lack of information about the spillover effect in some sectors, the economic evaluation framework developed principally for pharmacoeconomics can be applied to interventions to promote resilience in adolescents. As prevention of mental health disorders is even more necessa

Light is an important modulating signal in fungi. Fusarium species stand out as research models for their phytopathogenic activity and their complex secondary metabolism. This includes the synthesis of carotenoids, whose induction by light is their best known photoregulated process. In these fungi, light also affects other metabolic pathways and developmental stages, such as the formation of conidia. Photoreceptor proteins are essential elements in signal transduction from light. Fusarium genomes contain genes for at least ten photoreceptors: four flavoproteins, one photolyase, two cryptochromes, two rhodopsins, and one phytochrome. Mutations in five of these genes provide information about their functions in light regulation, in which the flavoprotein WcoA, belonging to the White Collar (WC) family, plays a predominant role. Global transcriptomic techniques have opened new perspectives for the study of photoreceptor functions and have recently been used in Fusarium fujikuroi on a WC protein and a cryptochrome from the DASH family. The data showed that the WC protein participates in the transcriptional control of most of the photoregulated genes, as well as of many genes not regulated by light, while the DASH cryptochrome potentially plays a supporting role in the photoinduction of many genes.