A Bayesian approach to estimating the regression coefficients of a multinomial logit model

A Bayesian approach to estimation of the regression coefficients of a multinominal logit model with ordinal scale response categories is presented. A Monte Carlo method is used to construct the posterior distribution of the link function. The link function is treated as an arbitrary scalar function. Then the Gauss-Markov theorem is used to determine a function of the link which produces a random vector of coefficients. The posterior distribution of the random vector of coefficients is used to estimate the regression coefficients. The method described is referred to as a Bayesian generalized least square (BGLS) analysis. Two cases involving multinominal logit models are described. Case I involves a cumulative logit model and Case II involves a proportional-odds model. All inferences about the coefficients for both cases are described in terms of the posterior distribution of the regression coefficients. The results from the BGLS method are compared to maximum likelihood estimates of the regression coefficients. The BGLS method avoids the nonlinear problems encountered when estimating the regression coefficients of a generalized linear model. The method is not complex or computationally intensive. The BGLS method offers several advantages over Bayesian approaches. ^

NONLINEAR TIME SERIES/SYSTEM ANALYSIS (STATE-SPACE, DYNAMICS, INTERVENTION, RESILIENCE, KALMAN)

A discussion of nonlinear dynamics, demonstrated by the familiar automobile, is followed by the development of a systematic method of analysis of a possibly nonlinear time series using difference equations in the general state-space format. This format allows recursive state-dependent parameter estimation after each observation thereby revealing the dynamics inherent in the system in combination with random external perturbations.^ The one-step ahead prediction errors at each time period, transformed to have constant variance, and the estimated parametric sequences provide the information to (1) formally test whether time series observations y(,t) are some linear function of random errors (ELEM)(,s), for some t and s, or whether the series would more appropriately be described by a nonlinear model such as bilinear, exponential, threshold, etc., (2) formally test whether a statistically significant change has occurred in structure/level either historically or as it occurs, (3) forecast nonlinear system with a new and innovative (but very old numerical) technique utilizing rational functions to extrapolate individual parameters as smooth functions of time which are then combined to obtain the forecast of y and (4) suggest a measure of resilience, i.e. how much perturbation a structure/level can tolerate, whether internal or external to the system, and remain statistically unchanged. Although similar to one-step control, this provides a less rigid way to think about changes affecting social systems.^ Applications consisting of the analysis of some familiar and some simulated series demonstrate the procedure. Empirical results suggest that this state-space or modified augmented Kalman filter may provide interesting ways to identify particular kinds of nonlinearities as they occur in structural change via the state trajectory.^ A computational flow-chart detailing computations and software input and output is provided in the body of the text. IBM Advanced BASIC program listings to accomplish most of the analysis are provided in the appendix. ^

Estimadores bayesianos de la fiabilidad con muestreo censurado

El estudio de la fiabilidad de componentes y sistemas tiene gran importancia en diversos campos de la ingenieria, y muy concretamente en el de la informatica. Al analizar la duracion de los elementos de la muestra hay que tener en cuenta los elementos que no fallan en el tiempo que dure el experimento, o bien los que fallen por causas distintas a la que es objeto de estudio. Por ello surgen nuevos tipos de muestreo que contemplan estos casos. El mas general de ellos, el muestreo censurado, es el que consideramos en nuestro trabajo. En este muestreo tanto el tiempo hasta que falla el componente como el tiempo de censura son variables aleatorias. Con la hipotesis de que ambos tiempos se distribuyen exponencialmente, el profesor Hurt estudio el comportamiento asintotico del estimador de maxima verosimilitud de la funcion de fiabilidad. En principio parece interesante utilizar metodos Bayesianos en el estudio de la fiabilidad porque incorporan al analisis la informacion a priori de la que se dispone normalmente en problemas reales. Por ello hemos considerado dos estimadores Bayesianos de la fiabilidad de una distribucion exponencial que son la media y la moda de la distribucion a posteriori. Hemos calculado la expansion asint6tica de la media, varianza y error cuadratico medio de ambos estimadores cuando la distribuci6n de censura es exponencial. Hemos obtenido tambien la distribucion asintotica de los estimadores para el caso m3s general de que la distribucion de censura sea de Weibull. Dos tipos de intervalos de confianza para muestras grandes se han propuesto para cada estimador. Los resultados se han comparado con los del estimador de maxima verosimilitud, y con los de dos estimadores no parametricos: limite producto y Bayesiano, resultando un comportamiento superior por parte de uno de nuestros estimadores. Finalmente nemos comprobado mediante simulacion que nuestros estimadores son robustos frente a la supuesta distribuci6n de censura, y que uno de los intervalos de confianza propuestos es valido con muestras pequenas. Este estudio ha servido tambien para confirmar el mejor comportamiento de uno de nuestros estimadores. SETTING OUT AND SUMMARY OF THE THESIS When we study the lifetime of components it's necessary to take into account the elements that don't fail during the experiment, or those that fail by reasons which are desirable to exclude from consideration. The model of random censorship is very usefull for analysing these data. In this model the time to failure and the time censor are random variables. We obtain two Bayes estimators of the reliability function of an exponential distribution based on randomly censored data. We have calculated the asymptotic expansion of the mean, variance and mean square error of both estimators, when the censor's distribution is exponential. We have obtained also the asymptotic distribution of the estimators for the more general case of censor's Weibull distribution. Two large-sample confidence bands have been proposed for each estimator. The results have been compared with those of the maximum likelihood estimator, and with those of two non parametric estimators: Product-limit and Bayesian. One of our estimators has the best behaviour. Finally we have shown by simulation, that our estimators are robust against the assumed censor's distribution, and that one of our intervals does well in small sample situation.

An investigation of the performance of a new Mechanical thrombectomy device using Bond Graph modelling: application to the extraction of blood clots in the middle cerebral artery

A number of thrombectomy devices using a variety of methods have now been developed to facilitate clot removal. We present research involving one such experimental device recently developed in the UK, called a ‘GP’ Thrombus Aspiration Device (GPTAD). This device has the potential to bring about the extraction of a thrombus. Although the device is at a relatively early stage of development, the results look encouraging. In this work, we present an analysis and modeling of the GPTAD by means of the bond graph technique; it seems to be a highly effective method of simulating the device under a variety of conditions. Such modeling is useful in optimizing the GPTAD and predicting the result of clot extraction. The aim of this simulation model is to obtain the minimum pressure necessary to extract the clot and to verify that both the pressure and the time required to complete the clot extraction are realistic for use in clinical situations, and are consistent with any experimentally obtained data. We therefore consider aspects of rheology and mechanics in our modeling.

Probabilistic Atlas Based Segmentation Using Affine Moment Descriptors and Graph-Cuts

We show a procedure for constructing a probabilistic atlas based on affine moment descriptors. It uses a normalization procedure over the labeled atlas. The proposed linear registration is defined by closed-form expressions involving only geometric moments. This procedure applies both to atlas construction as atlas-based segmentation. We model the likelihood term for each voxel and each label using parametric or nonparametric distributions and the prior term is determined by applying the vote-rule. The probabilistic atlas is built with the variability of our linear registration. We have two segmentation strategy: a) it applies the proposed affine registration to bring the target image into the coordinate frame of the atlas or b) the probabilistic atlas is non-rigidly aligning with the target image, where the probabilistic atlas is previously aligned to the target image with our affine registration. Finally, we adopt a graph cut - Bayesian framework for implementing the atlas-based segmentation.

Refined second law of thermodynamics for fast random processes

We establish a refined version of the Second Law of Thermodynamics for Langevin stochastic processes describing mesoscopic systems driven by conservative or non-conservative forces and interacting with thermal noise. The refinement is based on the Monge-Kantorovich optimal mass transport and becomes relevant for processes far from quasi-stationary regime. General discussion is illustrated by numerical analysis of the optimal memory erasure protocol for a model for micron-size particle manipulated by optical tweezers.

A constitutive model for the in-plane mechanical behavior of nonwoven fabrics

A constitutive model is presented for the in-plane mechanical behavior of nonwoven fabrics. The model is developed within the context of the finite element method and provides the constitutive response for a mesodomain of the fabric corresponding to the area associated to a finite element. The model is built upon the ensemble of three blocks, namely fabric, fibers and damage. The continuum tensorial formulation of the fabric response rigorously takes into account the effect of fiber rotation for large strains and includes the nonlinear fiber behavior. In addition, the various damage mechanisms experimentally observed (bond and fiber fracture, interfiber friction and fiber pull-out) are included in a phenomenological way and the random nature of these materials is also taken into account by means of a Monte Carlo lottery to determine the damage thresholds. The model results are validated with recent experimental results on the tensile response of smooth and notched specimens of a polypropylene nonwoven fabric.

HF spectrum activity prediction model based on HMM for cognitive radio applications

Although most of the research on Cognitive Radio is focused on communication bands above the HF upper limit (30 MHz), Cognitive Radio principles can also be applied to HF communications to make use of the extremely scarce spectrum more efficiently. In this work we consider legacy users as primary users since these users transmit without resorting to any smart procedure, and our stations using the HFDVL (HF Data+Voice Link) architecture as secondary users. Our goal is to enhance an efficient use of the HF band by detecting the presence of uncoordinated primary users and avoiding collisions with them while transmitting in different HF channels using our broad-band HF transceiver. A model of the primary user activity dynamics in the HF band is developed in this work to make short-term predictions of the sojourn time of a primary user in the band and avoid collisions. It is based on Hidden Markov Models (HMM) which are a powerful tool for modelling stochastic random processes and are trained with real measurements of the 14 MHz band. By using the proposed HMM based model, the prediction model achieves an average 10.3% prediction error rate with one minute-long channel knowledge but it can be reduced when this knowledge is extended: with the previous 8 min knowledge, an average 5.8% prediction error rate is achieved. These results suggest that the resulting activity model for the HF band could actually be used to predict primary users activity and included in a future HF cognitive radio based station.

A fitting algorithm for random modeling the PLC channel

The characteristics of the power-line communication (PLC) channel are difficult to model due to the heterogeneity of the networks and the lack of common wiring practices. To obtain the full variability of the PLC channel, random channel generators are of great importance for the design and testing of communication algorithms. In this respect, we propose a random channel generator that is based on the top-down approach. Basically, we describe the multipath propagation and the coupling effects with an analytical model. We introduce the variability into a restricted set of parameters and, finally, we fit the model to a set of measured channels. The proposed model enables a closed-form description of both the mean path-loss profile and the statistical correlation function of the channel frequency response. As an example of application, we apply the procedure to a set of in-home measured channels in the band 2-100 MHz whose statistics are available in the literature. The measured channels are divided into nine classes according to their channel capacity. We provide the parameters for the random generation of channels for all nine classes, and we show that the results are consistent with the experimental ones. Finally, we merge the classes to capture the entire heterogeneity of in-home PLC channels. In detail, we introduce the class occurrence probability, and we present a random channel generator that targets the ensemble of all nine classes. The statistics of the composite set of channels are also studied, and they are compared to the results of experimental measurement campaigns in the literature.

Molecular basis of salt tolerance in Physcomitrella Patens model plant: potassium homeostasis and physiological roles of chx transporters

El suelo salino impone un estrés abiótico importante que causa graves problemas en la agricultura ya que la mayoría de los cultivos se ven afectados por la salinidad debido a efectos osmóticos y tóxicos. Por ello, la contaminación y la escasez de agua dulce, la salinización progresiva de tierras y el aumento exponencial de la población humana representan un grave problema que amenaza la seguridad alimentaria mundial para las generaciones futuras. Por lo tanto, aumentar la tolerancia a la salinidad de los cultivos es un objetivo estratégico e ineludible para garantizar el suministro de alimentos en el futuro. Mantener una óptima homeostasis de K+ en plantas que sufren estrés salino es un objetivo importante en el proceso de obtención de plantas tolerantes a la salinidad. Aunque el modelo de la homeostasis de K+ en las plantas está razonablemente bien descrito en términos de entrada de K+, muy poco se sabe acerca de los genes implicados en la salida de K+ o de su liberación desde la vacuola. En este trabajo se pretende aclarar algunos de los mecanismos implicados en la homeostasis de K+ en plantas. Para ello se eligió la briofita Physcomitrella patens, una planta no vascular de estructura simple y de fase haploide dominante que, entre muchas otras cualidades, hacen que sea un modelo ideal. Lo más importante es que no sólo P. patens es muy tolerante a altas concentraciones de Na+, sino que también su posición filogenética en la evolución de las plantas abre la posibilidad de estudiar los cambios claves que, durante el curso de la evolución, se produjeron en las diversas familias de los transportadores de K+. Se han propuesto varios transportadores de cationes como candidatos que podrían tener un papel en la salida de K+ o su liberación desde la vacuola, especialmente miembros de la familia CPA2 que contienen las familias de transportadores KEA y CHX. En este estudio se intenta aumentar nuestra comprensión de las funciones de los transportadores de CHX en las células de las plantas usando P. patens, como ya se ha dicho. En esta especie, se han identificado cuatro genes CHX, PpCHX1-4. Dos de estos genes, PpCHX1 y PpCHX2, se expresan aproximadamente al mismo nivel que el gen PpACT5, y los otros dos genes muestran una expresión muy baja. La expresión de PpCHX1 y PpCHX2 en mutantes de Escherichia coli defectivos en el transporte de K+ restauraron el crecimiento de esta cepa en medios con bajo contenido de K+, lo que viii sugiere que la entrada de K+ es energizada por un mecanismo de simporte con H+. Por otra parte, estos transportadores suprimieron el defecto asociado a la mutación kha1 en Saccharomyces cerevisiae, lo que sugiere que podrían mediar un antiporte en K+/H+. La proteína PpCHX1-GFP expresada transitoriamente en protoplastos de P. patens co-localizó con un marcador de Golgi. En experimentos similares, la proteína PpCHX2-GFP localizó aparentemente en la membrana plasmática y tonoplasto. Se construyeron las líneas mutantes simples de P. patens ΔPpchx1 y ΔPpchx2, y también el mutante doble ΔPpchx2 ΔPphak1. Los mutantes simples crecieron normalmente en todas las condiciones ensayadas y mostraron flujos de entrada normales de K+ y Rb+; la mutación ΔPpchx2 no aumentó el defecto de las plantas ΔPphak1. En experimentos a largo plazo, las plantas ΔPpchx2 mostraron una retención de Rb+ ligeramente superior que las plantas silvestres, lo que sugiere que PpCHX2 promueve la transferencia de Rb+ desde la vacuola al citosol o desde el citosol al medio externo, actuando en paralelo con otros transportadores. Sugerimos que transportadores de K+ de varias familias están involucrados en la homeostasis de pH de orgánulos ya sea mediante antiporte K+/H+ o simporte K+-H+.ix ABSTRACT Soil salinity is a major abiotic stress causing serious problems in agriculture as most crops are affected by it. Moreover, the contamination and shortage of freshwater, progressive land salinization and exponential increase of human population aggravates the problem implying that world food security may not be ensured for the next generations. Thus, a strategic and an unavoidable goal would be increasing salinity tolerance of plant crops to secure future food supply. Maintaining an optimum K+ homeostasis in plants under salinity stress is an important trait to pursue in the process of engineering salt tolerant plants. Although the model of K+ homeostasis in plants is reasonably well described in terms of K+ influx, very little is known about the genes implicated in K+ efflux or release from the vacuole. In this work, we aim to clarify some of the mechanisms involved in K+ homeostasis in plants. For this purpose, we chose the bryophyte plant Physcomitrella patens, a nonvascular plant of simple structure and dominant haploid phase that, among many other characteristics, makes it an ideal model. Most importantly, not only P. patens is very tolerant to high concentrations of Na+, but also its phylogenetic position in land plant evolution opens the possibility to study the key changes that occurred in K+ transporter families during the course of evolution. Several cation transporter candidates have been proposed to have a role in K+ efflux or release from the vacuole especially members of the CPA2 family which contains the KEA and CHX transporter families. We intended in this study to increase our understanding of the functions of CHX transporters in plant cells using P. patens, in which four CHX genes have been identified, PpCHX1-4. Two of these genes, PpCHX1 and PpCHX2, are expressed at approximately the same level as the PpACT5 gene, but the other two genes show an extremely low expression. PpCHX1 and PpCHX2 restored growth of Escherichia coli mutants on low K+-containing media, suggesting they mediated K+ uptake that may be energized by symport with H+. In contrast, these genes suppressed the defect associated to the kha1 mutation in Saccharomyces cerevisiae, which suggest that they might mediate K+/H+ antiport. PpCHX1-GFP protein transiently expressed in P. patens protoplasts co-localized with a Golgi marker. In similar experiments, the PpCHX2-GFP protein appeared to localize to tonoplast and plasma x membrane. We constructed the ΔPpchx1 and ΔPpchx2 single mutant lines, and the ΔPpchx2 ΔPphak1 double mutant. Single mutant plants grew normally under all the conditions tested and exhibited normal K+ and Rb+ influxes; the ΔPpchx2 mutation did not increase the defect of ΔPphak1 plants. In long-term experiments, ΔPpchx2 plants showed a slightly higher Rb+ retention than wild type plants, which suggests that PpCHX2 mediates the transfer of Rb+ from either the vacuole to the cytosol or from the cytosol to the external medium in parallel with other transporters. We suggest that K+ transporters of several families are involved in the pH homeostasis of organelles by mediating either K+/H+ antiport or K+-H+ symport.

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.

A random utility based multiregional input-output approach to estimate the impact of a new highway on the regional distribution of jobs

This paper addresses the economic impact assessment of the construction of a new road on the regional distribution of jobs. The paper summarizes different existing model approaches considered to assess economic impacts through a literature review. Afterwards, we present the development of a comprehensive approach for analyzing the interaction of new transport infrastructure and the economic impact through an integrated model. This model has been applied to the construction of the motorway A-40 in Spain (497 Km.) which runs across three regions without passing though Madrid City. This may in turn lead to the relocation of labor and capital due to the improvement of accessibility of markets or inputs. The result suggests the existence of direct and indirect effects in other regions derived from the improvement of the transportation infrastructure, and confirms the relevance of road freight transport in some regions. We found that the changes in regional employment are substantial for some regions (increasing or decreasing jobs), but a t the same time negligible in other regions. As a result,the approach provides broad guidance to national governments and other transport-related parties about the impacts of this transport policy.

Model of human rhythmic activities on structures

Crowd induced dynamic loading in large structures, such as gymnasiums or stadiums, is usually modelled as a series of harmonic loads which are defined in terms of their Fourier coefficients. Different values of these Fourier coefficients that were obtained from full scale measurements can be found in codes. Recently, an alternative has been proposed, based on random generation of load time histories that take into account phase lags among individuals inside the crowd. Generally the testing is performed on platforms or structures that can be considered rigid because their natural frequencies are higher than the excitation frequencies associated with crowd loading. In this paper we shall present the testing done on a structure designed to be a gymnasium, which has natural frequencies within that range. In this test the gym slab was instrumented with acceleration sensors and different people jumped on a force plate installed on the floor. Test results have been compared with predictions based on the two abovementioned load modelling alternatives and a new methodology for modelling jumping loads has been proposed in order to reduce the difference between experimental and numerical results at high frequency range.

A new label fusion method using graph cuts: application to hippocampus segmentation

The aim of this paper is to develop a probabilistic modeling framework for the segmentation of structures of interest from a collection of atlases. Given a subset of registered atlases into the target image for a particular Region of Interest (ROI), a statistical model of appearance and shape is computed for fusing the labels. Segmentations are obtained by minimizing an energy function associated with the proposed model, using a graph-cut technique. We test different label fusion methods on publicly available MR images of human brains.

Modelos para el análisis dinámico y la predicción a corto plazo de los precios de la electricidad en mercados liberalizados

En esta tesis se va a describir y aplicar de forma novedosa la técnica del alisado exponencial multivariante a la predicción a corto plazo, a un día vista, de los precios horarios de la electricidad, un problema que se está estudiando intensivamente en la literatura estadística y económica reciente. Se van a demostrar ciertas propiedades interesantes del alisado exponencial multivariante que permiten reducir el número de parámetros para caracterizar la serie temporal y que al mismo tiempo permiten realizar un análisis dinámico factorial de la serie de precios horarios de la electricidad. En particular, este proceso multivariante de elevada dimensión se estimará descomponiéndolo en un número reducido de procesos univariantes independientes de alisado exponencial caracterizado cada uno por un solo parámetro de suavizado que variará entre cero (proceso de ruido blanco) y uno (paseo aleatorio). Para ello, se utilizará la formulación en el espacio de los estados para la estimación del modelo, ya que ello permite conectar esa secuencia de modelos univariantes más eficientes con el modelo multivariante. De manera novedosa, las relaciones entre los dos modelos se obtienen a partir de un simple tratamiento algebraico sin requerir la aplicación del filtro de Kalman. De este modo, se podrán analizar y poner al descubierto las razones últimas de la dinámica de precios de la electricidad. Por otra parte, la vertiente práctica de esta metodología se pondrá de manifiesto con su aplicación práctica a ciertos mercados eléctricos spot, tales como Omel, Powernext y Nord Pool. En los citados mercados se caracterizará la evolución de los precios horarios y se establecerán sus predicciones comparándolas con las de otras técnicas de predicción. ABSTRACT This thesis describes and applies the multivariate exponential smoothing technique to the day-ahead forecast of the hourly prices of electricity in a whole new way. This problem is being studied intensively in recent statistics and economics literature. It will start by demonstrating some interesting properties of the multivariate exponential smoothing that reduce drastically the number of parameters to characterize the time series and that at the same time allow a dynamic factor analysis of the hourly prices of electricity series. In particular this very complex multivariate process of dimension 24 will be estimated by decomposing a very reduced number of univariate independent of exponentially smoothing processes each characterized by a single smoothing parameter that varies between zero (white noise process) and one (random walk). To this end, the formulation is used in the state space model for the estimation, since this connects the sequence of efficient univariate models to the multivariate model. Through a novel way, relations between the two models are obtained from a simple algebraic treatment without applying the Kalman filter. Thus, we will analyze and expose the ultimate reasons for the dynamics of the electricity price. Moreover, the practical aspect of this methodology will be shown by applying this new technique to certain electricity spot markets such as Omel, Powernext and Nord Pool. In those markets the behavior of prices will be characterized, their predictions will be formulated and the results will be compared with those of other forecasting techniques.