AM 6545: A Novel Peripheral CB1 Antagonist

Obesity and other related metabolic disorders are a common problem in the United States. Consequently, several drug therapies have been developed in an attempt to address this problem. Many older appetite suppressants, such as amphetamines, were dangerous and potentially addictive. For the last few years, the endocannabinoid system was investigated as a potential target for appetite suppression. Unfortunately, early cannabinoid CB1 antagonists came with an unacceptable side effect profile of their own, which is largely due to central actions of these drugs. In an attempt to reduce the side effect profile, researchers are investigating peripherally acting cannabinoid antagonists, which do not penetrate the blood brain barrier. This study investigated AM 6545, a novel peripheral cannabinoid antagonist, for its effects on food reinforced instrumental behavior. In the end, the results indicated that AM6545 produced a dose-related suppression of lever pressing for food reinforcement.

Design and implementation of a clinical dashboard

In a large health care system, the importance of accurate information as feedback mechanisms about its performance is necessary on many levels from the senior level management to service level managers for valid decision-making purposes. The implementation of dashboards is one way to remedy the problem of data overload by providing up-to-date, accurate, and concise information. As this health care system seeks to have an organized, systematic review mechanism in place, dashboards are being created in a variety of the hospital service departments to monitor performance indicators. The Infection Control Administration of this health care system is one that does not currently utilize a dashboard but seeks to implement one. ^ The purpose of this project is to research and design a clinical dashboard for the Infection Control Administration. The intent is that the implementation and usefulness of the clinical dashboard translates into improvement in the measurement of health care quality.^

Physician coding for mental illness reimbursement and the need for mental health parity

Many patients with anxiety and depression initially seek treatment from their primary care physicians. Changes in insurance coverage and current mental parity laws, make reimbursement for services a problem. This has led to a coding dilemma for physicians seeking payment for their services. This study seeks to determine first the frequency at which primary care physicians use alternative coding, and secondly, if physicians would change their coding practices, provided reimbursement was assured through changes in mental parity laws. A mail survey was sent to 260 randomly selected primary care physicians, who are family practice, internal medicine, and general practice physicians, and members of the Harris County Medical Society. The survey evaluated the physicians' demographics, the number of patients with psychiatric disorders seen by primary care physicians, the frequency with which physicians used alternative coding, and if mental parity laws changed, the rate at which physicians would use a psychiatric illness diagnosis as the primary diagnostic code. The overall response rate was 23%. Only 47 of the 59 physicians, who responded, qualified for the study and of those 45% used a psychiatric disorder to diagnose patients with a primary psychiatric disorder, 47% used a somatic/symptom disorder, and 8% used a medical diagnosis. From the physicians who would not use a psychiatric diagnosis as a primary ICD-9 code, 88% were afraid of not being reimbursed and 12% were worried about stigma or jeopardizing insurability. If payment were assured using a psychiatric diagnostic code, 81% physicians would use a psychiatric diagnosis as the primary diagnostic code. However, 19% would use an alternative diagnostic code in fear of stigmatizing and/or jeopardizing patients' insurability. Although the sample size of the study design was adequate, our survey did not have an ideal response rate, and no significant correlation was observed. However, it is evident that reimbursement for mental illness continues to be a problem for primary care physicians. The reformation of mental parity laws is necessary to ensure that patients receive mental health services and that primary care physicians are reimbursed. Despite the possibility of improved mental parity legislation, some physicians are still hesitant to assign patients with a mental illness diagnosis, due to the associated stigma, which still plays a role in today's society. ^

Statistical Methods for Differential Expressions of Genes Detected in Multiple-Condition Experiment of Microarray

Most studies of differential gene-expressions have been conducted between two given conditions. The two-condition experimental (TCE) approach is simple in that all genes detected display a common differential expression pattern responsive to a common two-condition difference. Therefore, the genes that are differentially expressed under the other conditions other than the given two conditions are undetectable with the TCE approach. In order to address the problem, we propose a new approach called multiple-condition experiment (MCE) without replication and develop corresponding statistical methods including inference of pairs of conditions for genes, new t-statistics, and a generalized multiple-testing method for any multiple-testing procedure via a control parameter C. We applied these statistical methods to analyze our real MCE data from breast cancer cell lines and found that 85 percent of gene-expression variations were caused by genotypic effects and genotype-ANAX1 overexpression interactions, which agrees well with our expected results. We also applied our methods to the adenoma dataset of Notterman et al. and identified 93 differentially expressed genes that could not be found in TCE. The MCE approach is a conceptual breakthrough in many aspects: (a) many conditions of interests can be conducted simultaneously; (b) study of association between differential expressions of genes and conditions becomes easy; (c) it can provide more precise information for molecular classification and diagnosis of tumors; (d) it can save lot of experimental resources and time for investigators.^

Sobre el concepto de filosofía política en Leo Strauss

Según Leo Strauss, la filosofía política no es más que el intento por responder una pregunta fundamental: la pregunta por el mejor régimen de gobierno que haga posible la “vida buena". Esta pregunta admite dos direcciones distintas como respuesta, y éstas se identifican con lo que el Autor denomina solución clásica y solución moderna al problema de la filosofía política. Sin embargo, sólo la primera puede considerarse una respuesta apropiada al problema, aun cuando debe enfrentar algunas dificultades y contradicciones que en este artículo se analizan en detalle.

Recorriendo las Tolderías de Valentín Sayhueque : Reminiscencias de Francisco Moreno 1870-1880

El presente trabajo tiene como objetivo mostrar y analizar las relaciones fronterizas entre indígenas, cronistas, viajeros y agentes del gobierno de Buenos Aires en el período de 1870 a 1880. Se prestará especial atención a las vinculaciones entre estos "mundos" a partir de los viajes que realizó Moreno a los toldos del cacique Valentín Sayhueque y su comunidad en las regiones aledañas al Lago Nahuel Huapi. No se descarta la influencia de otros cronistas de época (Cox y Musters) como tampoco la impronta de personajes centrales en el contexto (Zeballos y Roca). Los viajeros que recorrieron la Patagonia dejaron testimonios claves para comprender el proceso que se dio entre las sociedades indígenas y el Estado nacional argentino a fines del siglo XIX. Su análisis a través de una mirada crítica da la pauta de cómo las sociedades nativas fueron observadas y estudiadas desde el gobierno de Buenos Aires y países extranjeros. La actual Patagonia fue un punto de atracción (y lo sigue siendo), para muchos individuos que no conocen el lugar. Su naturaleza, paisaje, vegetación eran únicos y muy atractivos. Sus tierras eran habitadas por sujetos que no tenían las mismas formas de vida que el resto de las regiones del momento. Habían desarrollado costumbres, formas de comunicación, comercio e intercambio, relaciones sociales, festividades. Cronistas como Francisco Moreno son nodales para adentrarnos al mundo nativo desde otro ángulo, ya que nos muestra las relaciones en el espacio de frontera y los propósitos del gobierno de Buenos Aires en el momento de las campañas militares. Desde el punto de vista metodológico se ha recurrido a la Etnohistoria para abordar nuestro problema desde una óptica diferente y alimentando la investigación en curso

Recorriendo las Tolderías de Valentín Sayhueque : Reminiscencias de Francisco Moreno 1870-1880

El presente trabajo tiene como objetivo mostrar y analizar las relaciones fronterizas entre indígenas, cronistas, viajeros y agentes del gobierno de Buenos Aires en el período de 1870 a 1880. Se prestará especial atención a las vinculaciones entre estos "mundos" a partir de los viajes que realizó Moreno a los toldos del cacique Valentín Sayhueque y su comunidad en las regiones aledañas al Lago Nahuel Huapi. No se descarta la influencia de otros cronistas de época (Cox y Musters) como tampoco la impronta de personajes centrales en el contexto (Zeballos y Roca). Los viajeros que recorrieron la Patagonia dejaron testimonios claves para comprender el proceso que se dio entre las sociedades indígenas y el Estado nacional argentino a fines del siglo XIX. Su análisis a través de una mirada crítica da la pauta de cómo las sociedades nativas fueron observadas y estudiadas desde el gobierno de Buenos Aires y países extranjeros. La actual Patagonia fue un punto de atracción (y lo sigue siendo), para muchos individuos que no conocen el lugar. Su naturaleza, paisaje, vegetación eran únicos y muy atractivos. Sus tierras eran habitadas por sujetos que no tenían las mismas formas de vida que el resto de las regiones del momento. Habían desarrollado costumbres, formas de comunicación, comercio e intercambio, relaciones sociales, festividades. Cronistas como Francisco Moreno son nodales para adentrarnos al mundo nativo desde otro ángulo, ya que nos muestra las relaciones en el espacio de frontera y los propósitos del gobierno de Buenos Aires en el momento de las campañas militares. Desde el punto de vista metodológico se ha recurrido a la Etnohistoria para abordar nuestro problema desde una óptica diferente y alimentando la investigación en curso

Communication Middleware for Distributed Hard Real-Time Systems in Java

Distributed real-time embedded systems are becoming increasingly important to society. More demands will be made on them and greater reliance will be placed on the delivery of their services. A relevant subset of them is high-integrity or hard real-time systems, where failure can cause loss of life, environmental harm, or significant financial loss. Additionally, the evolution of communication networks and paradigms as well as the necessity of demanding processing power and fault tolerance, motivated the interconnection between electronic devices; many of the communications have the possibility of transferring data at a high speed. The concept of distributed systems emerged as systems where different parts are executed on several nodes that interact with each other via a communication network. Java’s popularity, facilities and platform independence have made it an interesting language for the real-time and embedded community. This was the motivation for the development of RTSJ (Real-Time Specification for Java), which is a language extension intended to allow the development of real-time systems. The use of Java in the development of high-integrity systems requires strict development and testing techniques. However, RTJS includes a number of language features that are forbidden in such systems. In the context of the HIJA project, the HRTJ (Hard Real-Time Java) profile was developed to define a robust subset of the language that is amenable to static analysis for high-integrity system certification. Currently, a specification under the Java community process (JSR- 302) is being developed. Its purpose is to define those capabilities needed to create safety critical applications with Java technology called Safety Critical Java (SCJ). However, neither RTSJ nor its profiles provide facilities to develop distributed realtime applications. This is an important issue, as most of the current and future systems will be distributed. The Distributed RTSJ (DRTSJ) Expert Group was created under the Java community process (JSR-50) in order to define appropriate abstractions to overcome this problem. Currently there is no formal specification. The aim of this thesis is to develop a communication middleware that is suitable for the development of distributed hard real-time systems in Java, based on the integration between the RMI (Remote Method Invocation) model and the HRTJ profile. It has been designed and implemented keeping in mind the main requirements such as the predictability and reliability in the timing behavior and the resource usage. iThe design starts with the definition of a computational model which identifies among other things: the communication model, most appropriate underlying network protocols, the analysis model, and a subset of Java for hard real-time systems. In the design, the remote references are the basic means for building distributed applications which are associated with all non-functional parameters and resources needed to implement synchronous or asynchronous remote invocations with real-time attributes. The proposed middleware separates the resource allocation from the execution itself by defining two phases and a specific threading mechanism that guarantees a suitable timing behavior. It also includes mechanisms to monitor the functional and the timing behavior. It provides independence from network protocol defining a network interface and modules. The JRMP protocol was modified to include two phases, non-functional parameters, and message size optimizations. Although serialization is one of the fundamental operations to ensure proper data transmission, current implementations are not suitable for hard real-time systems and there are no alternatives. This thesis proposes a predictable serialization that introduces a new compiler to generate optimized code according to the computational model. The proposed solution has the advantage of allowing us to schedule the communications and to adjust the memory usage at compilation time. In order to validate the design and the implementation a demanding validation process was carried out with emphasis in the functional behavior, the memory usage, the processor usage (the end-to-end response time and the response time in each functional block) and the network usage (real consumption according to the calculated consumption). The results obtained in an industrial application developed by Thales Avionics (a Flight Management System) and in exhaustive tests show that the design and the prototype are reliable for industrial applications with strict timing requirements. Los sistemas empotrados y distribuidos de tiempo real son cada vez más importantes para la sociedad. Su demanda aumenta y cada vez más dependemos de los servicios que proporcionan. Los sistemas de alta integridad constituyen un subconjunto de gran importancia. Se caracterizan por que un fallo en su funcionamiento puede causar pérdida de vidas humanas, daños en el medio ambiente o cuantiosas pérdidas económicas. La necesidad de satisfacer requisitos temporales estrictos, hace más complejo su desarrollo. Mientras que los sistemas empotrados se sigan expandiendo en nuestra sociedad, es necesario garantizar un coste de desarrollo ajustado mediante el uso técnicas adecuadas en su diseño, mantenimiento y certificación. En concreto, se requiere una tecnología flexible e independiente del hardware. La evolución de las redes y paradigmas de comunicación, así como la necesidad de mayor potencia de cómputo y de tolerancia a fallos, ha motivado la interconexión de dispositivos electrónicos. Los mecanismos de comunicación permiten la transferencia de datos con alta velocidad de transmisión. En este contexto, el concepto de sistema distribuido ha emergido como sistemas donde sus componentes se ejecutan en varios nodos en paralelo y que interactúan entre ellos mediante redes de comunicaciones. Un concepto interesante son los sistemas de tiempo real neutrales respecto a la plataforma de ejecución. Se caracterizan por la falta de conocimiento de esta plataforma durante su diseño. Esta propiedad es relevante, por que conviene que se ejecuten en la mayor variedad de arquitecturas, tienen una vida media mayor de diez anos y el lugar ˜ donde se ejecutan puede variar. El lenguaje de programación Java es una buena base para el desarrollo de este tipo de sistemas. Por este motivo se ha creado RTSJ (Real-Time Specification for Java), que es una extensión del lenguaje para permitir el desarrollo de sistemas de tiempo real. Sin embargo, RTSJ no proporciona facilidades para el desarrollo de aplicaciones distribuidas de tiempo real. Es una limitación importante dado que la mayoría de los actuales y futuros sistemas serán distribuidos. El grupo DRTSJ (DistributedRTSJ) fue creado bajo el proceso de la comunidad de Java (JSR-50) con el fin de definir las abstracciones que aborden dicha limitación, pero en la actualidad aun no existe una especificacion formal. El objetivo de esta tesis es desarrollar un middleware de comunicaciones para el desarrollo de sistemas distribuidos de tiempo real en Java, basado en la integración entre el modelo de RMI (Remote Method Invocation) y el perfil HRTJ. Ha sido diseñado e implementado teniendo en cuenta los requisitos principales, como la predecibilidad y la confiabilidad del comportamiento temporal y el uso de recursos. El diseño parte de la definición de un modelo computacional el cual identifica entre otras cosas: el modelo de comunicaciones, los protocolos de red subyacentes más adecuados, el modelo de análisis, y un subconjunto de Java para sistemas de tiempo real crítico. En el diseño, las referencias remotas son el medio básico para construcción de aplicaciones distribuidas las cuales son asociadas a todos los parámetros no funcionales y los recursos necesarios para la ejecución de invocaciones remotas síncronas o asíncronas con atributos de tiempo real. El middleware propuesto separa la asignación de recursos de la propia ejecución definiendo dos fases y un mecanismo de hebras especifico que garantiza un comportamiento temporal adecuado. Además se ha incluido mecanismos para supervisar el comportamiento funcional y temporal. Se ha buscado independencia del protocolo de red definiendo una interfaz de red y módulos específicos. También se ha modificado el protocolo JRMP para incluir diferentes fases, parámetros no funcionales y optimizaciones de los tamaños de los mensajes. Aunque la serialización es una de las operaciones fundamentales para asegurar la adecuada transmisión de datos, las actuales implementaciones no son adecuadas para sistemas críticos y no hay alternativas. Este trabajo propone una serialización predecible que ha implicado el desarrollo de un nuevo compilador para la generación de código optimizado acorde al modelo computacional. La solución propuesta tiene la ventaja que en tiempo de compilación nos permite planificar las comunicaciones y ajustar el uso de memoria. Con el objetivo de validar el diseño e implementación se ha llevado a cabo un exigente proceso de validación con énfasis en: el comportamiento funcional, el uso de memoria, el uso del procesador (tiempo de respuesta de extremo a extremo y en cada uno de los bloques funcionales) y el uso de la red (consumo real conforme al estimado). Los buenos resultados obtenidos en una aplicación industrial desarrollada por Thales Avionics (un sistema de gestión de vuelo) y en las pruebas exhaustivas han demostrado que el diseño y el prototipo son fiables para aplicaciones industriales con estrictos requisitos temporales.

Toward reduction of artifacts in fused images

Most fusion satellite image methodologies at pixel-level introduce false spatial details, i.e.artifacts, in the resulting fusedimages. In many cases, these artifacts appears because image fusion methods do not consider the differences in roughness or textural characteristics between different land covers. They only consider the digital values associated with single pixels. This effect increases as the spatial resolution image increases. To minimize this problem, we propose a new paradigm based on local measurements of the fractal dimension (FD). Fractal dimension maps (FDMs) are generated for each of the source images (panchromatic and each band of the multi-spectral images) with the box-counting algorithm and by applying a windowing process. The average of source image FDMs, previously indexed between 0 and 1, has been used for discrimination of different land covers present in satellite images. This paradigm has been applied through the fusion methodology based on the discrete wavelet transform (DWT), using the à trous algorithm (WAT). Two different scenes registered by optical sensors on board FORMOSAT-2 and IKONOS satellites were used to study the behaviour of the proposed methodology. The implementation of this approach, using the WAT method, allows adapting the fusion process to the roughness and shape of the regions present in the image to be fused. This improves the quality of the fusedimages and their classification results when compared with the original WAT method

An example of integration between en economic and an hydrologic model in the framework of water resource management problems

Growing scarcity, increasing demand and bad management of water resources are causing weighty competition for water and consequently managers are facing more and more pressure in an attempt to satisfy users? requirement. In many regions agriculture is one of the most important users at river basin scale since it concentrates high volumes of water consumption during relatively short periods (irrigation season), with a significant economic, social and environmental impact. The interdisciplinary characteristics of related water resources problems require, as established in the Water Framework Directive 2000/60/EC, an integrated and participative approach to water management and assigns an essential role to economic analysis as a decision support tool. For this reason, a methodology is developed to analyse the economic and environmental implications of water resource management under different scenarios, with a focus on the agricultural sector. This research integrates both economic and hydrologic components in modelling, defining scenarios of water resource management with the goal of preventing critical situations, such as droughts. The model follows the Positive Mathematical Programming (PMP) approach, an innovative methodology successfully used for agricultural policy analysis in the last decade and also applied in several analyses regarding water use in agriculture. This approach has, among others, the very important capability of perfectly calibrating the baseline scenario using a very limited database. However one important disadvantage is its limited capacity to simulate activities non-observed during the reference period but which could be adopted if the scenario changed. To overcome this problem the classical methodology is extended in order to simulate a more realistic farmers? response to new agricultural policies or modified water availability. In this way an economic model has been developed to reproduce the farmers? behaviour within two irrigation districts in the Tiber High Valley. This economic model is then integrated with SIMBAT, an hydrologic model developed for the Tiber basin which allows to simulate the balance between the water volumes available at the Montedoglio dam and the water volumes required by the various irrigation users.

Categorical Missing Data Imputation Using Fuzzy Neural Networks with Numerical and Categorical Inputs

There are many situations where input feature vectors are incomplete and methods to tackle the problem have been studied for a long time. A commonly used procedure is to replace each missing value with an imputation. This paper presents a method to perform categorical missing data imputation from numerical and categorical variables. The imputations are based on Simpson’s fuzzy min-max neural networks where the input variables for learning and classification are just numerical. The proposed method extends the input to categorical variables by introducing new fuzzy sets, a new operation and a new architecture. The procedure is tested and compared with others using opinion poll data.

Making Transport Safer: V2V-Based Automated Emergency Braking System

An important goal in the field of intelligent transportation systems (ITS) is to provide driving aids aimed at preventing accidents and reducing the number of traffic victims. The commonest traffic accidents in urban areas are due to sudden braking that demands a very fast response on the part of drivers. Attempts to solve this problem have motivated many ITS advances including the detection of the intention of surrounding cars using lasers, radars or cameras. However, this might not be enough to increase safety when there is a danger of collision. Vehicle to vehicle communications are needed to ensure that the other intentions of cars are also available. The article describes the development of a controller to perform an emergency stop via an electro-hydraulic braking system employed on dry asphalt. An original V2V communication scheme based on WiFi cards has been used for broadcasting positioning information to other vehicles. The reliability of the scheme has been theoretically analyzed to estimate its performance when the number of vehicles involved is much higher. This controller has been incorporated into the AUTOPIA program control for automatic cars. The system has been implemented in Citroën C3 Pluriel, and various tests were performed to evaluate its operation.

Using combined static analysis and profiling for logic program execution time estimation

Predicting statically the running time of programs has many applications ranging from task scheduling in parallel execution to proving the ability of a program to meet strict time constraints. A starting point in order to attack this problem is to infer the computational complexity of such programs (or fragments thereof). This is one of the reasons why the development of static analysis techniques for inferring cost-related properties of programs (usually upper and/or lower bounds of actual costs) has received considerable attention.

Análisis estático de sistemas de membranas para la determinación de reglas activas

Esta tesis doctoral se enmarca dentro de la computación con membranas. Se trata de un tipo de computación bio-inspirado, concretamente basado en las células de los organismos vivos, en las que se producen múltiples reacciones de forma simultánea. A partir de la estructura y funcionamiento de las células se han definido diferentes modelos formales, denominados P sistemas. Estos modelos no tratan de modelar el comportamiento biológico de una célula, sino que abstraen sus principios básicos con objeto de encontrar nuevos paradigmas computacionales. Los P sistemas son modelos de computación no deterministas y masivamente paralelos. De ahí el interés que en los últimos años estos modelos han suscitado para la resolución de problemas complejos. En muchos casos, consiguen resolver de forma teórica problemas NP-completos en tiempo polinómico o lineal. Por otra parte, cabe destacar también la aplicación que la computación con membranas ha tenido en la investigación de otros muchos campos, sobre todo relacionados con la biología. Actualmente, una gran cantidad de estos modelos de computación han sido estudiados desde el punto de vista teórico. Sin embargo, el modo en que pueden ser implementados es un reto de investigación todavía abierto. Existen varias líneas en este sentido, basadas en arquitecturas distribuidas o en hardware dedicado, que pretenden acercarse en lo posible a su carácter no determinista y masivamente paralelo, dentro de un contexto de viabilidad y eficiencia. En esta tesis doctoral se propone la realización de un análisis estático del P sistema, como vía para optimizar la ejecución del mismo en estas plataformas. Se pretende que la información recogida en tiempo de análisis sirva para configurar adecuadamente la plataforma donde se vaya a ejecutar posteriormente el P sistema, obteniendo como consecuencia una mejora en el rendimiento. Concretamente, en esta tesis se han tomado como referencia los P sistemas de transiciones para llevar a cabo el estudio de dicho análisis estático. De manera un poco más específica, el análisis estático propuesto en esta tesis persigue que cada membrana sea capaz de determinar sus reglas activas de forma eficiente en cada paso de evolución, es decir, aquellas reglas que reúnen las condiciones adecuadas para poder ser aplicadas. En esta línea, se afronta el problema de los estados de utilidad de una membrana dada, que en tiempo de ejecución permitirán a la misma conocer en todo momento las membranas con las que puede comunicarse, cuestión que determina las reglas que pueden aplicarse en cada momento. Además, el análisis estático propuesto en esta tesis se basa en otra serie de características del P sistema como la estructura de membranas, antecedentes de las reglas, consecuentes de las reglas o prioridades. Una vez obtenida toda esta información en tiempo de análisis, se estructura en forma de árbol de decisión, con objeto de que en tiempo de ejecución la membrana obtenga las reglas activas de la forma más eficiente posible. Por otra parte, en esta tesis se lleva a cabo un recorrido por un número importante de arquitecturas hardware y software que diferentes autores han propuesto para implementar P sistemas. Fundamentalmente, arquitecturas distribuidas, hardware dedicado basado en tarjetas FPGA y plataformas basadas en microcontroladores PIC. El objetivo es proponer soluciones que permitan implantar en dichas arquitecturas los resultados obtenidos del análisis estático (estados de utilidad y árboles de decisión para reglas activas). En líneas generales, se obtienen conclusiones positivas, en el sentido de que dichas optimizaciones se integran adecuadamente en las arquitecturas sin penalizaciones significativas. Summary Membrane computing is the focus of this doctoral thesis. It can be considered a bio-inspired computing type. Specifically, it is based on living cells, in which many reactions take place simultaneously. From cell structure and operation, many different formal models have been defined, named P systems. These models do not try to model the biological behavior of the cell, but they abstract the basic principles of the cell in order to find out new computational paradigms. P systems are non-deterministic and massively parallel computational models. This is why, they have aroused interest when dealing with complex problems nowadays. In many cases, they manage to solve in theory NP problems in polynomial or lineal time. On the other hand, it is important to note that membrane computing has been successfully applied in many researching areas, specially related to biology. Nowadays, lots of these computing models have been sufficiently characterized from a theoretical point of view. However, the way in which they can be implemented is a research challenge, that it is still open nowadays. There are some lines in this way, based on distributed architectures or dedicated hardware. All of them are trying to approach to its non-deterministic and parallel character as much as possible, taking into account viability and efficiency. In this doctoral thesis it is proposed carrying out a static analysis of the P system in order to optimize its performance in a computing platform. The general idea is that after data are collected in analysis time, they are used for getting a suitable configuration of the computing platform in which P system is going to be performed. As a consequence, the system throughput will improve. Specifically, this thesis has made use of Transition P systems for carrying out the study in static analysis. In particular, the static analysis proposed in this doctoral thesis tries to achieve that every membrane can efficiently determine its active rules in every evolution step. These rules are the ones that can be applied depending on the system configuration at each computational step. In this line, we are going to tackle the problem of the usefulness states for a membrane. This state will allow this membrane to know the set of membranes with which communication is possible at any time. This is a very important issue in determining the set of rules that can be applied. Moreover, static analysis in this thesis is carried out taking into account other properties such as membrane structure, rule antecedents, rule consequents and priorities among rules. After collecting all data in analysis time, they are arranged in a decision tree structure, enabling membranes to obtain the set of active rules as efficiently as possible in run-time system. On the other hand, in this doctoral thesis is going to carry out an overview of hardware and software architectures, proposed by different authors in order to implement P systems, such as distributed architectures, dedicated hardware based on PFGA, and computing platforms based on PIC microcontrollers. The aim of this overview is to propose solutions for implementing the results of the static analysis, that is, usefulness states and decision trees for active rules. In general, conclusions are satisfactory, because these optimizations can be properly integrated in most of the architectures without significant penalties.

Metodologías de modelado, monitorización y asistencia robótica en neurorrehabilitación funcional de extremidad superior

La Organización Mundial de la Salud (OMS) prevé que para el año 2020, el Daño Cerebral Adquirido (DCA) estará entre las 10 causas más comunes de discapacidad. Estas lesiones, dadas sus consecuencias físicas, sensoriales, cognitivas, emocionales y socioeconómicas, cambian dramáticamente la vida de los pacientes y sus familias. Las nuevas técnicas de intervención precoz y el desarrollo de la medicina intensiva en la atención al DCA han mejorado notablemente la probabilidad de supervivencia. Sin embargo, hoy por hoy, las lesiones cerebrales no tienen ningún tratamiento quirúrgico que tenga por objetivo restablecer la funcionalidad perdida, sino que las terapias rehabilitadoras se dirigen hacia la compensación de los déficits producidos. Uno de los objetivos principales de la neurorrehabilitación es, por tanto, dotar al paciente de la capacidad necesaria para ejecutar las Actividades de Vida Diaria (AVDs) necesarias para desarrollar una vida independiente, siendo fundamentales aquellas en las que la Extremidad Superior (ES) está directamente implicada, dada su gran importancia a la hora de la manipulación de objetos. Con la incorporación de nuevas soluciones tecnológicas al proceso de neurorrehabilitación se pretende alcanzar un nuevo paradigma centrado en ofrecer una práctica personalizada, monitorizada y ubicua con una valoración continua de la eficacia y de la eficiencia de los procedimientos y con capacidad de generar conocimientos que impulsen la ruptura del paradigma de actual. Los nuevos objetivos consistirán en minimizar el impacto de las enfermedades que afectan a la capacidad funcional de las personas, disminuir el tiempo de incapacidad y permitir una gestión más eficiente de los recursos. Estos objetivos clínicos, de gran impacto socio-económico, sólo pueden alcanzarse desde una apuesta decidida en nuevas tecnologías, metodologías y algoritmos capaces de ocasionar la ruptura tecnológica necesaria que permita superar las barreras que hasta el momento han impedido la penetración tecnológica en el campo de la rehabilitación de manera universal. De esta forma, los trabajos y resultados alcanzados en la Tesis son los siguientes: 1. Modelado de AVDs: como paso previo a la incorporación de ayudas tecnológicas al proceso rehabilitador, se hace necesaria una primera fase de modelado y formalización del conocimiento asociado a la ejecución de las actividades que se realizan como parte de la terapia. En particular, las tareas más complejas y a su vez con mayor repercusión terapéutica son las AVDs, cuya formalización permitirá disponer de modelos de movimiento sanos que actuarán de referencia para futuros desarrollos tecnológicos dirigidos a personas con DCA. Siguiendo una metodología basada en diagramas de estados UML se han modelado las AVDs 'servir agua de una jarra' y 'coger un botella' 2. Monitorización ubícua del movimiento de la ES: se ha diseñado, desarrollado y validado un sistema de adquisición de movimiento basado en tecnología inercial que mejora las limitaciones de los dispositivos comerciales actuales (coste muy elevado e incapacidad para trabajar en entornos no controlados); los altos coeficientes de correlación y los bajos niveles de error obtenidos en los corregistros llevados a cabo con el sistema comercial BTS SMART-D demuestran la alta precisión del sistema. También se ha realizado un trabajo de investigación exploratorio de un sistema de captura de movimiento de coste muy reducido basado en visión estereoscópica, habiéndose detectado los puntos clave donde se hace necesario incidir desde un punto de vista tecnológico para su incorporación en un entorno real 3. Resolución del Problema Cinemático Inverso (PCI): se ha diseñado, desarrollado y validado una solución al PCI cuando el manipulador se corresponde con una ES humana estudiándose 2 posibles alternativas, una basada en la utilización de un Perceptrón Multicapa (PMC) y otra basada en sistemas Artificial Neuro-Fuzzy Inference Systems (ANFIS). La validación, llevada a cabo utilizando información relativa a los modelos disponibles de AVDs, indica que una solución basada en un PMC con 3 neuronas en la capa de entrada, una capa oculta también de 3 neuronas y una capa de salida con tantas neuronas como Grados de Libertad (GdLs) tenga el modelo de la ES, proporciona resultados, tanto de precisión como de tiempo de cálculo, que la hacen idónea para trabajar en sistemas con requisitos de tiempo real 4. Control inteligente assisted-as-needed: se ha diseñado, desarrollado y validado un algoritmo de control assisted-as-needed para una ortesis robótica con capacidades de actuación anticipatoria de la que existe un prototipo implementado en la actualidad. Los resultados obtenidos demuestran cómo el sistema es capaz de adaptarse al perfil disfuncional del paciente activando la ayuda en instantes anteriores a la ocurrencia de movimientos incorrectos. Esta estrategia implica un aumento en la participación del paciente y, por tanto, en su actividad muscular, fomentándose los procesos la plasticidad cerebral responsables del reaprendizaje o readaptación motora 5. Simuladores robóticos para planificación: se propone la utilización de un simulador robótico assisted-as-needed como herramienta de planificación de sesiones de rehabilitación personalizadas y con un objetivo clínico marcado en las que interviene una ortesis robotizada. Los resultados obtenidos evidencian como, tras la ejecución de ciertos algoritmos sencillos, es posible seleccionar automáticamente una configuración para el algoritmo de control assisted-as-needed que consigue que la ortesis se adapte a los criterios establecidos desde un punto de vista clínico en función del paciente estudiado. Estos resultados invitan a profundizar en el desarrollo de algoritmos más avanzados de selección de parámetros a partir de baterías de simulaciones Estos trabajos han servido para corroborar las hipótesis de investigación planteadas al inicio de la misma, permitiendo, asimismo, la apertura de nuevas líneas de investigación. Summary The World Health Organization (WHO) predicts that by the year 2020, Acquired Brain Injury (ABI) will be among the ten most common ailments. These injuries dramatically change the life of the patients and their families due to their physical, sensory, cognitive, emotional and socio-economic consequences. New techniques of early intervention and the development of intensive ABI care have noticeably improved the survival rate. However, in spite of these advances, brain injuries still have no surgical or pharmacological treatment to re-establish the lost functions. Neurorehabilitation therapies address this problem by restoring, minimizing or compensating the functional alterations in a person disabled because of a nervous system injury. One of the main objectives of Neurorehabilitation is to provide patients with the capacity to perform specific Activities of the Daily Life (ADL) required for an independent life, especially those in which the Upper Limb (UL) is directly involved due to its great importance in manipulating objects within the patients' environment. The incorporation of new technological aids to the neurorehabilitation process tries to reach a new paradigm focused on offering a personalized, monitored and ubiquitous practise with continuous assessment of both the efficacy and the efficiency of the procedures and with the capacity of generating new knowledge. New targets will be to minimize the impact of the sicknesses affecting the functional capabilitiies of the subjects, to decrease the time of the physical handicap and to allow a more efficient resources handling. These targets, of a great socio-economic impact, can only be achieved by means of new technologies and algorithms able to provoke the technological break needed to beat the barriers that are stopping the universal penetration of the technology in the field of rehabilitation. In this way, this PhD Thesis has achieved the following results: 1. ADL Modeling: as a previous step to the incorporation of technological aids to the neurorehabilitation process, it is necessary a first modelling and formalization phase of the knowledge associated to the execution of the activities that are performed as a part of the therapy. In particular, the most complex and therapeutically relevant tasks are the ADLs, whose formalization will produce healthy motion models to be used as a reference for future technological developments. Following a methodology based on UML state-chart diagrams, the ADLs 'serving water from a jar' and 'picking up a bottle' have been modelled 2. Ubiquitous monitoring of the UL movement: it has been designed, developed and validated a motion acquisition system based on inertial technology that improves the limitations of the current devices (high monetary cost and inability of working within uncontrolled environments); the high correlation coefficients and the low error levels obtained throughout several co-registration sessions with the commercial sys- tem BTS SMART-D show the high precision of the system. Besides an exploration of a very low cost stereoscopic vision-based motion capture system has been carried out and the key points where it is necessary to insist from a technological point of view have been detected 3. Inverse Kinematics (IK) problem solving: a solution to the IK problem has been proposed for a manipulator that corresponds to a human UL. This solution has been faced by means of two different alternatives, one based on a Mulilayer Perceptron (MLP) and another based on Artificial Neuro-Fuzzy Inference Systems (ANFIS). The validation of these solutions, carried out using the information regarding the previously generated motion models, indicate that a MLP-based solution, with an architecture consisting in 3 neurons in the input layer, one hidden layer of 3 neurons and an output layer with as many neurons as the number of Degrees of Freedom (DoFs) that the UL model has, is the one that provides the best results both in terms of precission and in terms of processing time, making in idoneous to be integrated within a system with real time restrictions 4. Assisted-as-needed intelligent control: an assisted-as-needed control algorithm with anticipatory actuation capabilities has been designed, developed and validated for a robotic orthosis of which there is an already implemented prototype. Obtained results demonstrate that the control system is able to adapt to the dysfunctional profile of the patient by triggering the assistance right before an incorrect movement is going to take place. This strategy implies an increase in the participation of the patients and in his or her muscle activity, encouraging the neural plasticity processes in charge of the motor learning 5. Planification with a robotic simulator: in this work a robotic simulator is proposed as a planification tool for personalized rehabilitation sessions under a certain clinical criterium. Obtained results indicate that, after the execution of simple parameter selection algorithms, it is possible to automatically choose a specific configuration that makes the assisted-as-needed control algorithm to adapt both to the clinical criteria and to the patient. These results invite researchers to work in the development of more complex parameter selection algorithms departing from simulation batteries Obtained results have been useful to corroborate the hypotheses set out at the beginning of this PhD Thesis. Besides, they have allowed the creation of new research lines in all the studied application fields.