Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study

OBJECTIVE To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission. METHODS ACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued. RESULTS Of the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%). CONCLUSIONS Treat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement. TRIAL REGISTRATION NUMBER NCT00810199.

Event-relating to potential dementia. Semantic processing in the course of healthy and pathological aging

While most healthy elderly are able to manage their everyday activities, studies showed that there are both stable and declining abilities during healthy aging. For example, there is evidence that semantic memory processes which involve controlled retrieval mechanism decrease, whereas the automatic functioning of the semantic network remains intact. In contrast, patients with Alzheimer’s disease (AD) suffer from episodic and semantic memory impairments aggravating their daily functioning. In AD, severe episodic as well as semantic memory deficits are observable. While the hallmark symptom of episodic memory decline in AD is well investigated, the underlying mechanisms of semantic memory deterioration remain unclear. By disentangling the semantic memory impairments in AD, the present thesis aimed to improve early diagnosis and to find a biomarker for dementia. To this end, a study on healthy aging and a study with dementia patients were conducted investigating automatic and controlled semantic word retrieval. Besides the inclusion of AD patients, a group of participants diagnosed with semantic dementia (SD) – showing isolated semantic memory loss – was assessed. Automatic and controlled semantic word retrieval was measured with standard neuropsychological tests and by means of event-related potentials (ERP) recorded during the performance of a semantic priming (SP) paradigm. Special focus was directed to the N400 or N400-LPC (late positive component) complex, an ERP that is sensitive to the semantic word retrieval. In both studies, data driven topographical analyses were applied. Furthermore, in the patient study, the combination of the individual baseline cerebral blood flow (CBF) with the N400 topography of each participant was employed in order to relate altered functional electrophysiology to the pathophysiology of dementia. Results of the aging study revealed that the automatic semantic word retrieval remains stable during healthy aging, the N400-LPC complex showed a comparable topography in contrast to the young participants. Both patient groups showed automatic SP to some extent, but strikingly the ERP topographies were altered compared to healthy controls. Most importantly, the N400 was identified as a putative marker for dementia. In particular, the degree of the topographical N400 similarity was demonstrated to separate healthy elderly from demented patients. Furthermore, the marker was significantly related to baseline CBF reduction in brain areas relevant for semantic word retrieval. Summing up, the first major finding of the present thesis was that all groups showed semantic priming, but that the N400 topography differed significantly between healthy and demented elderly. The second major contribution was the identification of the N400 similarity as a putative marker for dementia. To conclude, the present thesis added evidence of preserved automatic processing during healthy aging. Moreover, a possible marker which might contribute to an improved diagnosis and lead consequently to a more effective treatment of dementia was presented and has to be further developed.

A mixed-integer linear programming approach to the optimization of event-bus schedules: a scheduling application in the tourism sector

This paper deals with “The Enchanted Journey,” which is a daily event tour booked by Bollywood-film fans. During the tour, the participants visit original sites of famous Bollywood films at various locations in Switzerland; moreover, the tour includes stops for lunch and shopping. Each day, up to five buses operate the tour. For operational reasons, however, two or more buses cannot stay at the same location simultaneously. Further operative constraints include time windows for all activities and precedence constraints between some activities. The planning problem is how to compute a feasible schedule for each bus. We implement a two-step hierarchical approach. In the first step, we minimize the total waiting time; in the second step, we minimize the total travel time of all buses. We present a basic formulation of this problem as a mixed-integer linear program. We enhance this basic formulation by symmetry-breaking constraints, which reduces the search space without loss of generality. We report on computational results obtained with the Gurobi Solver. Our numerical results show that all relevant problem instances can be solved using the basic formulation within reasonable CPU time, and that the symmetry-breaking constraints reduce that CPU time considerably.

A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke.

AIM To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. METHODS Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. RESULTS Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. CONCLUSION Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Relational and Allegorical Semantics for Constraint Logic Programming

El cálculo de relaciones binarias fue creado por De Morgan en 1860 para ser posteriormente desarrollado en gran medida por Peirce y Schröder. Tarski, Givant, Freyd y Scedrov demostraron que las álgebras relacionales son capaces de formalizar la lógica de primer orden, la lógica de orden superior así como la teoría de conjuntos. A partir de los resultados matemáticos de Tarski y Freyd, esta tesis desarrolla semánticas denotacionales y operacionales para la programación lógica con restricciones usando el álgebra relacional como base. La idea principal es la utilización del concepto de semántica ejecutable, semánticas cuya característica principal es el que la ejecución es posible utilizando el razonamiento estándar del universo semántico, este caso, razonamiento ecuacional. En el caso de este trabajo, se muestra que las álgebras relacionales distributivas con un operador de punto fijo capturan toda la teoría y metateoría estándar de la programación lógica con restricciones incluyendo los árboles utilizados en la búsqueda de demostraciones. La mayor parte de técnicas de optimización de programas, evaluación parcial e interpretación abstracta pueden ser llevadas a cabo utilizando las semánticas aquí presentadas. La demostración de la corrección de la implementación resulta extremadamente sencilla. En la primera parte de la tesis, un programa lógico con restricciones es traducido a un conjunto de términos relacionales. La interpretación estándar en la teoría de conjuntos de dichas relaciones coincide con la semántica estándar para CLP. Las consultas contra el programa traducido son llevadas a cabo mediante la reescritura de relaciones. Para concluir la primera parte, se demuestra la corrección y equivalencia operacional de esta nueva semántica, así como se define un algoritmo de unificación mediante la reescritura de relaciones. La segunda parte de la tesis desarrolla una semántica para la programación lógica con restricciones usando la teoría de alegorías—versión categórica del álgebra de relaciones—de Freyd. Para ello, se definen dos nuevos conceptos de Categoría Regular de Lawvere y _-Alegoría, en las cuales es posible interpretar un programa lógico. La ventaja fundamental que el enfoque categórico aporta es la definición de una máquina categórica que mejora e sistema de reescritura presentado en la primera parte. Gracias al uso de relaciones tabulares, la máquina modela la ejecución eficiente sin salir de un marco estrictamente formal. Utilizando la reescritura de diagramas, se define un algoritmo para el cálculo de pullbacks en Categorías Regulares de Lawvere. Los dominios de las tabulaciones aportan información sobre la utilización de memoria y variable libres, mientras que el estado compartido queda capturado por los diagramas. La especificación de la máquina induce la derivación formal de un juego de instrucciones eficiente. El marco categórico aporta otras importantes ventajas, como la posibilidad de incorporar tipos de datos algebraicos, funciones y otras extensiones a Prolog, a la vez que se conserva el carácter 100% declarativo de nuestra semántica. ABSTRACT The calculus of binary relations was introduced by De Morgan in 1860, to be greatly developed by Peirce and Schröder, as well as many others in the twentieth century. Using different formulations of relational structures, Tarski, Givant, Freyd, and Scedrov have shown how relation algebras can provide a variable-free way of formalizing first order logic, higher order logic and set theory, among other formal systems. Building on those mathematical results, we develop denotational and operational semantics for Constraint Logic Programming using relation algebra. The idea of executable semantics plays a fundamental role in this work, both as a philosophical and technical foundation. We call a semantics executable when program execution can be carried out using the regular theory and tools that define the semantic universe. Throughout this work, the use of pure algebraic reasoning is the basis of denotational and operational results, eliminating all the classical non-equational meta-theory associated to traditional semantics for Logic Programming. All algebraic reasoning, including execution, is performed in an algebraic way, to the point we could state that the denotational semantics of a CLP program is directly executable. Techniques like optimization, partial evaluation and abstract interpretation find a natural place in our algebraic models. Other properties, like correctness of the implementation or program transformation are easy to check, as they are carried out using instances of the general equational theory. In the first part of the work, we translate Constraint Logic Programs to binary relations in a modified version of the distributive relation algebras used by Tarski. Execution is carried out by a rewriting system. We prove adequacy and operational equivalence of the semantics. In the second part of the work, the relation algebraic approach is improved by using allegory theory, a categorical version of the algebra of relations developed by Freyd and Scedrov. The use of allegories lifts the semantics to typed relations, which capture the number of logical variables used by a predicate or program state in a declarative way. A logic program is interpreted in a _-allegory, which is in turn generated from a new notion of Regular Lawvere Category. As in the untyped case, program translation coincides with program interpretation. Thus, we develop a categorical machine directly from the semantics. The machine is based on relation composition, with a pullback calculation algorithm at its core. The algorithm is defined with the help of a notion of diagram rewriting. In this operational interpretation, types represent information about memory allocation and the execution mechanism is more efficient, thanks to the faithful representation of shared state by categorical projections. We finish the work by illustrating how the categorical semantics allows the incorporation into Prolog of constructs typical of Functional Programming, like abstract data types, and strict and lazy functions.

Las presentaciones de trabajo en lengua inglesa: una propuesta de curso on-line.

Desde la explosión de crecimiento de internet que comenzó en los años 90, se han ido creando y poniendo a disposición de los usuarios diversas herramientas para compartir información y servicios de diversas formas, desde el nacimiento del primer navegador hasta nuestros días, donde hay infinidad de lenguajes aplicables al ámbito web. En esta fase de crecimiento, en primer lugar, de cara a usuarios individuales, saldrían herramientas que permitirían a cada cual hacer su web personal, con sus contenidos expuestos. Más adelante se fue generando el fenómeno “comunidad”, con, por ejemplo, foros, o webs en las que había múltiples usuarios que disfrutaban de contenidos o servicios que la web ofreciese. Este crecimiento del mundo web en lo comunitario ha avanzado en muchas ramas,entre ellas, por supuesto, la educacional, surgiendo plataformas como la que es base del proyecto que a continuación se presenta, y herramienta básica y prácticamente ya imprescindible en la enseñanza universitaria: Moodle. Moodle es una herramienta diseñada para compatir recursos y diseñar actividades para el usuario potencial, complementando su aprendizaje en aula, o incluso siendo una vía autónoma de aprendizaje en sí misma. Se ha realizado un estudio sobre el estado de saludo de los contenidos que se exponen en Moodle, y se ha encontrado que una gran mayoría de los cursos que se pueden visitar tienen un gran número de carencias. Por un lado, hay pocos con material original explotado exclusivamente para el curso, y, si tienen material original, no se ha observado una especial atención por la maquetación. Por otro lado, hay muchos otros sin material original, y, en ambos casos, no se ha encontrado ningún curso que ofrezca material audiovisual exclusivo para el curso, presentando algunos en su lugar material audiovisual encontrado en la red (Youtube, etc). A la vista de estos hechos, se ha realizado un proyecto que intenta aportar soluciones ante estas carencias, y se presenta un curso procedente de diversas referencias bibliográficas, para la parte textual, y material audiovisual original e inédito que también se ha explotado específicamente para este curso. Este material ha sido por un lado vídeo, que se ha visionado, editado y subtitulado con software de libre distribución, y por otro lado, audio, que complementa un completo glosario que se ha añadido como extra al curso y cuyo planteamiento no se ha encontrado en ningún curso online de los revisados. Todo esto se ha envuelto en una maquetación cuidada que ha sido fruto del estudio de los lenguajes web html y CSS, de forma que, por un lado, el curso sea un lugar agradable en el que aprender dentro de internet, y por otro, se pudiesen realizar ciertas operaciones que sin estos conocimientos habrían sido imposibles, como la realización del glosario o la incrustación de imágenes y vídeos. A su vez, se ha tratado de dar un enfoque didáctico a toda la memoria del proyecto, de forma que pueda ser de utilidad a un usuario futuro que quisiese profundizar en los usos de Moodle, introducirse en el lenguaje web, o introducirse en el mundo de la edición de vídeo. ABSTRACT: Since the explosion of Internet growth beginning in the 90s, many tools have been created and made available for users to share information and services in various ways, from the birth of the first browser until today, where there are plenty of web programming languages. This growth stage would give individual users tools that would allow everyone to make an own personal website, with their contents exposed. Later, the "community" phenomenon appeared with, for example, forums, or websites where multiple users enjoyed the content or web services that those websites offered. Also, this growth in the web community world has progressed in many fields, including education, with the emerge of platforms such as the one that this project uses as its basis, and which is the basic and imperative tool in college education: Moodle. Moodle is a tool designed to share resources and design activities for the potential user, completing class learning, or even letting this user learn in an autonomous way. In this project a study on the current situation of the content present in Moodle courses around the net has been carried out, and it has been found that most of them lack of original material exploited exclusively for the courses, and if they have original material, there has been not observed concern on the layout where that material lies. On the other hand, there are many other with non original material, and in both cases, there has not been found any course that offers audio- visual material made specifically for the course, instead of presenting some audiovisual material found on the net (Youtube, etc). In view of these facts, the project presented here seeks to provide solutions to these shortcomings, presenting a course with original material exploited from various references, and unpublished audioevisual material which also has been exploited specifically for this course. This material is, on one hand, video, which has been viewed, edited and subtitled with free software, and on the other, audio, which complements a comprehensive glossary that has been added as an extra feature to the course and whose approach was not found in any of the online courses reviewed. All of this has been packaged in a neat layout that has been the result of the study of web languages HTML and CSS, so that first, the course was a pleasant place to learn on the internet, and second, certain operations could be performed which without this knowledge would have been impossible, as the glossary design or embedding images and videos. Furthermore, a didactic approach has been adopted to the entire project memory, so it can be useful to a future user who wanted to go deeper on the uses of Moodle, containing an intro into the web language, or in the world video editing.

IDRA (IDeal Resource Allocation): Computing ideal speedups in parallel logic programming

We present a technique to estimate accurate speedups for parallel logic programs with relative independence from characteristics of a given implementation or underlying parallel hardware. The proposed technique is based on gathering accurate data describing one execution at run-time, which is fed to a simulator. Alternative schedulings are then simulated and estimates computed for the corresponding speedups. A tool implementing the aforementioned techniques is presented, and its predictions are compared to the performance of real systems, showing good correlation.

Towards a concurrent semantics-based analysis of CC and CLP. principles and practice of constraint programming

Abstract is not available.

O'CIAO an object oriented programming model using CIAO Prolog

There have been several previous proposals for the integration of Object Oriented Programming features into Logic Programming, resulting in much support theory and several language proposals. However, none of these proposals seem to have made it into the mainstream. Perhaps one of the reasons for these is that the resulting languages depart too much from the standard logic programming languages to entice the average Prolog programmer. Another reason may be that most of what can be done with object-oriented programming can already be done in Prolog through the meta- and higher-order programming facilities that the language includes, albeit sometimes in a more cumbersome way. In light of this, in this paper we propose an alternative solution which is driven by two main objectives. The first one is to include only those characteristics of object-oriented programming which are cumbersome to implement in standard Prolog systems. The second one is to do this in such a way that there is minimum impact on the syntax and complexity of the language, i.e., to introduce the minimum number of new constructs, declarations, and concepts to be learned. Finally, we would like the implementation to be as straightforward as possible, ideally based on simple source to source expansions.

A model to develop a platform for personalised health applications

Antecedentes Europa vive una situación insostenible. Desde el 2008 se han reducido los recursos de los gobiernos a raíz de la crisis económica. El continente Europeo envejece con ritmo constante al punto que se prevé que en 2050 habrá sólo dos trabajadores por jubilado [54]. A esta situación se le añade el aumento de la incidencia de las enfermedades crónicas, relacionadas con el envejecimiento, cuyo coste puede alcanzar el 7% del PIB de un país [51]. Es necesario un cambio de paradigma. Una nueva manera de cuidar de la salud de las personas: sustentable, eficaz y preventiva más que curativa. Algunos estudios abogan por el cuidado personalizado de la salud (pHealth). En este modelo las prácticas médicas son adaptadas e individualizadas al paciente, desde la detección de los factores de riesgo hasta la personalización de los tratamientos basada en la respuesta del individuo [81]. El cuidado personalizado de la salud está asociado a menudo al uso de las tecnologías de la información y comunicación (TICs) que, con su desarrollo exponencial, ofrecen oportunidades interesantes para la mejora de la salud. El cambio de paradigma hacia el pHealth está lentamente ocurriendo, tanto en el ámbito de la investigación como en la industria, pero todavía no de manera significativa. Existen todavía muchas barreras relacionadas a la economía, a la política y la cultura. También existen barreras puramente tecnológicas, como la falta de sistemas de información interoperables [199]. A pesar de que los aspectos de interoperabilidad están evolucionando, todavía hace falta un diseño de referencia especialmente direccionado a la implementación y el despliegue en gran escala de sistemas basados en pHealth. La presente Tesis representa un intento de organizar la disciplina de la aplicación de las TICs al cuidado personalizado de la salud en un modelo de referencia, que permita la creación de plataformas de desarrollo de software para simplificar tareas comunes de desarrollo en este dominio. Preguntas de investigación RQ1 >Es posible definir un modelo, basado en técnicas de ingeniería del software, que represente el dominio del cuidado personalizado de la salud de una forma abstracta y representativa? RQ2 >Es posible construir una plataforma de desarrollo basada en este modelo? RQ3 >Esta plataforma ayuda a los desarrolladores a crear sistemas pHealth complejos e integrados? Métodos Para la descripción del modelo se adoptó el estándar ISO/IEC/IEEE 42010por ser lo suficientemente general y abstracto para el amplio enfoque de esta tesis [25]. El modelo está definido en varias partes: un modelo conceptual, expresado a través de mapas conceptuales que representan las partes interesadas (stakeholders), los artefactos y la información compartida; y escenarios y casos de uso para la descripción de sus funcionalidades. El modelo fue desarrollado de acuerdo a la información obtenida del análisis de la literatura, incluyendo 7 informes industriales y científicos, 9 estándares, 10 artículos en conferencias, 37 artículos en revistas, 25 páginas web y 5 libros. Basándose en el modelo se definieron los requisitos para la creación de la plataforma de desarrollo, enriquecidos por otros requisitos recolectados a través de una encuesta realizada a 11 ingenieros con experiencia en la rama. Para el desarrollo de la plataforma, se adoptó la metodología de integración continua [74] que permitió ejecutar tests automáticos en un servidor y también desplegar aplicaciones en una página web. En cuanto a la metodología utilizada para la validación se adoptó un marco para la formulación de teorías en la ingeniería del software [181]. Esto requiere el desarrollo de modelos y proposiciones que han de ser validados dentro de un ámbito de investigación definido, y que sirvan para guiar al investigador en la búsqueda de la evidencia necesaria para justificarla. La validación del modelo fue desarrollada mediante una encuesta online en tres rondas con un número creciente de invitados. El cuestionario fue enviado a 134 contactos y distribuido en algunos canales públicos como listas de correo y redes sociales. El objetivo era evaluar la legibilidad del modelo, su nivel de cobertura del dominio y su potencial utilidad en el diseño de sistemas derivados. El cuestionario incluía preguntas cuantitativas de tipo Likert y campos para recolección de comentarios. La plataforma de desarrollo fue validada en dos etapas. En la primera etapa se utilizó la plataforma en un experimento a pequeña escala, que consistió en una sesión de entrenamiento de 12 horas en la que 4 desarrolladores tuvieron que desarrollar algunos casos de uso y reunirse en un grupo focal para discutir su uso. La segunda etapa se realizó durante los tests de un proyecto en gran escala llamado HeartCycle [160]. En este proyecto un equipo de diseñadores y programadores desarrollaron tres aplicaciones en el campo de las enfermedades cardio-vasculares. Una de estas aplicaciones fue testeada en un ensayo clínico con pacientes reales. Al analizar el proyecto, el equipo de desarrollo se reunió en un grupo focal para identificar las ventajas y desventajas de la plataforma y su utilidad. Resultados Por lo que concierne el modelo que describe el dominio del pHealth, la parte conceptual incluye una descripción de los roles principales y las preocupaciones de los participantes, un modelo de los artefactos TIC que se usan comúnmente y un modelo para representar los datos típicos que son necesarios formalizar e intercambiar entre sistemas basados en pHealth. El modelo funcional incluye un conjunto de 18 escenarios, repartidos en: punto de vista de la persona asistida, punto de vista del cuidador, punto de vista del desarrollador, punto de vista de los proveedores de tecnologías y punto de vista de las autoridades; y un conjunto de 52 casos de uso repartidos en 6 categorías: actividades de la persona asistida, reacciones del sistema, actividades del cuidador, \engagement" del usuario, actividades del desarrollador y actividades de despliegue. Como resultado del cuestionario de validación del modelo, un total de 65 personas revisó el modelo proporcionando su nivel de acuerdo con las dimensiones evaluadas y un total de 248 comentarios sobre cómo mejorar el modelo. Los conocimientos de los participantes variaban desde la ingeniería del software (70%) hasta las especialidades médicas (15%), con declarado interés en eHealth (24%), mHealth (16%), Ambient Assisted Living (21%), medicina personalizada (5%), sistemas basados en pHealth (15%), informática médica (10%) e ingeniería biomédica (8%) con una media de 7.25_4.99 años de experiencia en estas áreas. Los resultados de la encuesta muestran que los expertos contactados consideran el modelo fácil de leer (media de 1.89_0.79 siendo 1 el valor más favorable y 5 el peor), suficientemente abstracto (1.99_0.88) y formal (2.13_0.77), con una cobertura suficiente del dominio (2.26_0.95), útil para describir el dominio (2.02_0.7) y para generar sistemas más específicos (2_0.75). Los expertos también reportan un interés parcial en utilizar el modelo en su trabajo (2.48_0.91). Gracias a sus comentarios, el modelo fue mejorado y enriquecido con conceptos que faltaban, aunque no se pudo demonstrar su mejora en las dimensiones evaluadas, dada la composición diferente de personas en las tres rondas de evaluación. Desde el modelo, se generó una plataforma de desarrollo llamada \pHealth Patient Platform (pHPP)". La plataforma desarrollada incluye librerías, herramientas de programación y desarrollo, un tutorial y una aplicación de ejemplo. Se definieron cuatro módulos principales de la arquitectura: el Data Collection Engine, que permite abstraer las fuentes de datos como sensores o servicios externos, mapeando los datos a bases de datos u ontologías, y permitiendo interacción basada en eventos; el GUI Engine, que abstrae la interfaz de usuario en un modelo de interacción basado en mensajes; y el Rule Engine, que proporciona a los desarrolladores un medio simple para programar la lógica de la aplicación en forma de reglas \if-then". Después de que la plataforma pHPP fue utilizada durante 5 años en el proyecto HeartCycle, 5 desarrolladores fueron reunidos en un grupo de discusión para analizar y evaluar la plataforma. De estas evaluaciones se concluye que la plataforma fue diseñada para encajar las necesidades de los ingenieros que trabajan en la rama, permitiendo la separación de problemas entre las distintas especialidades, y simplificando algunas tareas de desarrollo como el manejo de datos y la interacción asíncrona. A pesar de ello, se encontraron algunos defectos a causa de la inmadurez de algunas tecnologías empleadas, y la ausencia de algunas herramientas específicas para el dominio como el procesado de datos o algunos protocolos de comunicación relacionados con la salud. Dentro del proyecto HeartCycle la plataforma fue utilizada para el desarrollo de la aplicación \Guided Exercise", un sistema TIC para la rehabilitación de pacientes que han sufrido un infarto del miocardio. El sistema fue testeado en un ensayo clínico randomizado en el cual a 55 pacientes se les dio el sistema para su uso por 21 semanas. De los resultados técnicos del ensayo se puede concluir que, a pesar de algunos errores menores prontamente corregidos durante el estudio, la plataforma es estable y fiable. Conclusiones La investigación llevada a cabo en esta Tesis y los resultados obtenidos proporcionan las respuestas a las tres preguntas de investigación que motivaron este trabajo: RQ1 Se ha desarrollado un modelo para representar el dominio de los sistemas personalizados de salud. La evaluación hecha por los expertos de la rama concluye que el modelo representa el dominio con precisión y con un balance apropiado entre abstracción y detalle. RQ2 Se ha desarrollado, con éxito, una plataforma de desarrollo basada en el modelo. RQ3 Se ha demostrado que la plataforma es capaz de ayudar a los desarrolladores en la creación de software pHealth complejos. Las ventajas de la plataforma han sido demostradas en el ámbito de un proyecto de gran escala, aunque el enfoque genérico adoptado indica que la plataforma podría ofrecer beneficios también en otros contextos. Los resultados de estas evaluaciones ofrecen indicios de que, ambos, el modelo y la plataforma serán buenos candidatos para poderse convertir en una referencia para futuros desarrollos de sistemas pHealth. ABSTRACT Background Europe is living in an unsustainable situation. The economic crisis has been reducing governments' economic resources since 2008 and threatening social and health systems, while the proportion of older people in the European population continues to increase so that it is foreseen that in 2050 there will be only two workers per retiree [54]. To this situation it should be added the rise, strongly related to age, of chronic diseases the burden of which has been estimated to be up to the 7% of a country's gross domestic product [51]. There is a need for a paradigm shift, the need for a new way of caring for people's health, shifting the focus from curing conditions that have arisen to a sustainable and effective approach with the emphasis on prevention. Some advocate the adoption of personalised health care (pHealth), a model where medical practices are tailored to the patient's unique life, from the detection of risk factors to the customization of treatments based on each individual's response [81]. Personalised health is often associated to the use of Information and Communications Technology (ICT), that, with its exponential development, offers interesting opportunities for improving healthcare. The shift towards pHealth is slowly taking place, both in research and in industry, but the change is not significant yet. Many barriers still exist related to economy, politics and culture, while others are purely technological, like the lack of interoperable information systems [199]. Though interoperability aspects are evolving, there is still the need of a reference design, especially tackling implementation and large scale deployment of pHealth systems. This thesis contributes to organizing the subject of ICT systems for personalised health into a reference model that allows for the creation of software development platforms to ease common development issues in the domain. Research questions RQ1 Is it possible to define a model, based on software engineering techniques, for representing the personalised health domain in an abstract and representative way? RQ2 Is it possible to build a development platform based on this model? RQ3 Does the development platform help developers create complex integrated pHealth systems? Methods As method for describing the model, the ISO/IEC/IEEE 42010 framework [25] is adopted for its generality and high level of abstraction. The model is specified in different parts: a conceptual model, which makes use of concept maps, for representing stakeholders, artefacts and shared information, and in scenarios and use cases for the representation of the functionalities of pHealth systems. The model was derived from literature analysis, including 7 industrial and scientific reports, 9 electronic standards, 10 conference proceedings papers, 37 journal papers, 25 websites and 5 books. Based on the reference model, requirements were drawn for building the development platform enriched with a set of requirements gathered in a survey run among 11 experienced engineers. For developing the platform, the continuous integration methodology [74] was adopted which allowed to perform automatic tests on a server and also to deploy packaged releases on a web site. As a validation methodology, a theory building framework for SW engineering was adopted from [181]. The framework, chosen as a guide to find evidence for justifying the research questions, imposed the creation of theories based on models and propositions to be validated within a scope. The validation of the model was conducted as an on-line survey in three validation rounds, encompassing a growing number of participants. The survey was submitted to 134 experts of the field and on some public channels like relevant mailing lists and social networks. Its objective was to assess the model's readability, its level of coverage of the domain and its potential usefulness in the design of actual, derived systems. The questionnaires included quantitative Likert scale questions and free text inputs for comments. The development platform was validated in two scopes. As a small-scale experiment, the platform was used in a 12 hours training session where 4 developers had to perform an exercise consisting in developing a set of typical pHealth use cases At the end of the session, a focus group was held to identify benefits and drawbacks of the platform. The second validation was held as a test-case study in a large scale research project called HeartCycle the aim of which was to develop a closed-loop disease management system for heart failure and coronary heart disease patients [160]. During this project three applications were developed by a team of programmers and designers. One of these applications was tested in a clinical trial with actual patients. At the end of the project, the team was interviewed in a focus group to assess the role the platform had within the project. Results For what regards the model that describes the pHealth domain, its conceptual part includes a description of the main roles and concerns of pHealth stakeholders, a model of the ICT artefacts that are commonly adopted and a model representing the typical data that need to be formalized among pHealth systems. The functional model includes a set of 18 scenarios, divided into assisted person's view, caregiver's view, developer's view, technology and services providers' view and authority's view, and a set of 52 Use Cases grouped in 6 categories: assisted person's activities, system reactions, caregiver's activities, user engagement, developer's activities and deployer's activities. For what concerns the validation of the model, a total of 65 people participated in the online survey providing their level of agreement in all the assessed dimensions and a total of 248 comments on how to improve and complete the model. Participants' background spanned from engineering and software development (70%) to medical specialities (15%), with declared interest in the fields of eHealth (24%), mHealth (16%), Ambient Assisted Living (21%), Personalized Medicine (5%), Personal Health Systems (15%), Medical Informatics (10%) and Biomedical Engineering (8%) with an average of 7.25_4.99 years of experience in these fields. From the analysis of the answers it is possible to observe that the contacted experts considered the model easily readable (average of 1.89_0.79 being 1 the most favourable scoring and 5 the worst), sufficiently abstract (1.99_0.88) and formal (2.13_0.77) for its purpose, with a sufficient coverage of the domain (2.26_0.95), useful for describing the domain (2.02_0.7) and for generating more specific systems (2_0.75) and they reported a partial interest in using the model in their job (2.48_0.91). Thanks to their comments, the model was improved and enriched with concepts that were missing at the beginning, nonetheless it was not possible to prove an improvement among the iterations, due to the diversity of the participants in the three rounds. From the model, a development platform for the pHealth domain was generated called pHealth Patient Platform (pHPP). The platform includes a set of libraries, programming and deployment tools, a tutorial and a sample application. The main four modules of the architecture are: the Data Collection Engine, which allows abstracting sources of information like sensors or external services, mapping data to databases and ontologies, and allowing event-based interaction and filtering, the GUI Engine, which abstracts the user interface in a message-like interaction model, the Workow Engine, which allows programming the application's user interaction ows with graphical workows, and the Rule Engine, which gives developers a simple means for programming the application's logic in the form of \if-then" rules. After the 5 years experience of HeartCycle, partially programmed with pHPP, 5 developers were joined in a focus group to discuss the advantages and drawbacks of the platform. The view that emerged from the training course and the focus group was that the platform is well-suited to the needs of the engineers working in the field, it allowed the separation of concerns among the different specialities and it simplified some common development tasks like data management and asynchronous interaction. Nevertheless, some deficiencies were pointed out in terms of a lack of maturity of some technological choices, and for the absence of some domain-specific tools, e.g. for data processing or for health-related communication protocols. Within HeartCycle, the platform was used to develop part of the Guided Exercise system, a composition of ICT tools for the physical rehabilitation of patients who suffered from myocardial infarction. The system developed using the platform was tested in a randomized controlled clinical trial, in which 55 patients used the system for 21 weeks. The technical results of this trial showed that the system was stable and reliable. Some minor bugs were detected, but these were promptly corrected using the platform. This shows that the platform, as well as facilitating the development task, can be successfully used to produce reliable software. Conclusions The research work carried out in developing this thesis provides responses to the three three research questions that were the motivation for the work. RQ1 A model was developed representing the domain of personalised health systems, and the assessment of experts in the field was that it represents the domain accurately, with an appropriate balance between abstraction and detail. RQ2 A development platform based on the model was successfully developed. RQ3 The platform has been shown to assist developers create complex pHealth software. This was demonstrated within the scope of one large-scale project, but the generic approach adopted provides indications that it would offer benefits more widely. The results of these evaluations provide indications that both the model and the platform are good candidates for being a reference for future pHealth developments.

Speech features of the domain of the word in heterosexual twins during the second yeard of life

Speech is the major function, emergence and which development radically changes all course of formation of the identity of the child already in the early childhood. If language and speech development in solitary born children is investigated today quite well, at twin children this process practically is not studied. Our research was carried out for the purpose of studying of an originality of mastering by speech by heterosexual children of pair of twins within communicative and pragmatist approach (T.N. Ushakov,G. V. Chirkina). Application of this approach to the analysis of process of communication at twin children allowed us to allocate those peculiar receptions and means of communication which they functionally develop in a situation of pair of twins, as allows them to show the phenomena of the speech which are not meeting at solitary born contemporaries. In this work results of supervision and research of pair of heterosexual twins of the second year of the life, carried out by a technique developed by us under the scientific guide of G. V. Chirkina

Introducción a la informática para estudiantes de enseñanza secundaria mediante programación de aplicaciones móviles

Este trabajo contiene el diseño y análisis de dos modalidades de docencia de programación de aplicaciones móviles, con el objetivo de aumentar el interés de los estudiantes de enseñanza secundaria por la Ingeniería Informática. Primeramente se analizó la estructura y el contenido de las diferentes materias relacionadas con la informática que existen actualmente en la educación secundaria en España, con el fin de localizar las carencias del currículo. Estas carencias principales son: la falta de reconocimiento de la Ingeniería informática al mismo nivel que el resto de ingenierías y una falta de contenidos relacionados con el desarrollo de software, tanto a nivel de programación como de diseño. A continuación, una vez analizados diferentes posibilidades de entornos con los que desarrollar dichos cursos, se diseñaron los dos modelos de docencia utilizando App Inventor como herramienta conductora, con los que poder cubrir esos conocimientos. El primer modelo consiste en un curso de cuatro semanas a impartir directamente en el centro, mientras que el segundo se trata de un taller de una mañana a impartir en la Escuela Técnica Superior de Ingenieros Informáticos de la Universidad Politécnica de Madrid. De los resultados de esos modelos se han obtenidos resultados muy positivos en cuanto al incremento de los conocimientos de los alumnos sobre informática, además de aumentar su interés por la Ingeniería Informática y obtener una visión más ajustada a la realidad de la misma.---ABSTRACT---This work details the design and realization of a workshop and a course for teaching mobile application programming to Spanish high school students, with the aim of increasing their interest in Computing. In order to locate the shortcomings of the curriculum, the structure and contents of various subjects related to Computing in currently secondary education in Spain were analyzed. The results show a lack of recognition of computer engineering at the same level as the rest of engineering disciplines and a lack of content related to software development, both in terms of programming and design. Then, after analyzing existing programming environments available for covering the basic programming objectives, App Inventor was chosen as mobile programming environment for both teaching activities (the workshop and the course). The first activity consists of a four-week course to teach directly in the high school, while the second one is a 4-hour workshop to be held at the university. The workshop and the course were carried out with students of two secondary schools, obtaining very positive results in terms of increasing students’ knowledge about computers, increasing their interest in Computing, and making them get a more accurate vision of the discipline.

Investigating and Understanding Student Learning Outcomes in an Online and Face-to-Face Graduate Level Legal Administration Course: An Embedded Mixed Methods Design

Online education is a new teaching and learning medium with few current guidelines for faculty, administrators or students. Its rapid growth over the last decade has challenged academic institutions to keep up with the demand, while also providing a quality education. Our understanding of the factors that determine quality and effective online learning experiences that lead to student learning outcomes is still evolving. There is a lack of consensus on the effectiveness of online versus face-to-face education in the current research. The U.S. Department of Education conducted a meta-analysis in 2009 and concluded that student-learning outcomes in online courses were equal to and, often times, better than face-to-face traditional courses. Subsequent research has found contradictory findings, and further inquiry is necessary. The purpose of this embedded mixed methods design research study is to further our understanding of the factors that create quality and successful educational outcomes in an online course. To achieve this, the first phase of this study measured and compared learning outcomes in an online and in class graduate-level legal administration course. The second phase of the study entailed interviews with those students in both the online and face-to-face sections to understand their perspectives on the factors contributing to learning outcomes. Six themes emerged from the qualitative findings: convenience, higher order thinking, discussions, professor engagement, professor and student interaction, and face-to-face interaction. Findings from this study indicate the factors students perceive as contributing to learning outcomes in an online course are consistent among all students and are supported in the existing literature. Higher order thinking, however, emerged as a stronger theme than indicated in the current research, and the face-to-face nature of the traditional classroom may be more an issue of familiarity than a factor contributing to learning outcomes. As education continues to reach new heights and developments in technology advance, the factors found to contribute to student learning outcomes will be refined and enhanced. These developments will continue to transform the ways in which we deliver and receive knowledge in both traditional and online classrooms. While there is a growing body of research on online education, the field’s evolution has unsettled earlier findings and posed new areas to investigate.

Late life second move housing choices of international retiree migrants

Purpose – Many international retirement migrants are amenity movers undertaking the first move in the late life course model of migration. The purpose of this paper is to examine second moves within the retirement destination community to test whether the model of late life course migration accurately portrays the motivations and housing choices local movers make after retiring to another country. Design/methodology/approach – The paper combines secondary data and survey results to examine the composition of the retiree migrant population in the Alicante province of Spain. The socioeconomic characteristics and housing choices of those who have made a second move since retiring to Spain are compared with those who have not moved through a series of t-tests and chi-square tests. Findings – The paper finds that those who have made a second move within Spain are somewhat typical of second movers in the late life course. They are likely to cite mobility or health problems as a reason for moving and appear to recognize the need for a home that provides living area on one floor. Yet, they are choosing to move within an area that does not provide them with access to informal family care givers. Research limitations/implications – The data are restricted to retirees of two nationalities in one province of Spain. Further research is suggested in other locations and with retirees of other nationalities for comparison. Practical implications – Because many international retirees do not plan to return to their countries of origin, they will create demand for formal in-home care services and supportive retiree housing in the near future in their retirement destination countries. Originality/value – This paper provides understanding of a growing consumer housing segment in retirement destinations.

Research in Tourism Course Presentation

Research in Tourism is an optional course that is taught during the second semester of the fourth year of the Undergraduate Degree in Sociology. It is directly linked to Sociology of Tourism. It is held in English.