Functional and effective connectivity in MEG. Application to the study of epilepsy

Nuestro cerebro contiene cerca de 1014 sinapsis neuronales. Esta enorme cantidad de conexiones proporciona un entorno ideal donde distintos grupos de neuronas se sincronizan transitoriamente para provocar la aparición de funciones cognitivas, como la percepción, el aprendizaje o el pensamiento. Comprender la organización de esta compleja red cerebral en base a datos neurofisiológicos, representa uno de los desafíos más importantes y emocionantes en el campo de la neurociencia. Se han propuesto recientemente varias medidas para evaluar cómo se comunican las diferentes partes del cerebro a diversas escalas (células individuales, columnas corticales, o áreas cerebrales). Podemos clasificarlos, según su simetría, en dos grupos: por una parte, la medidas simétricas, como la correlación, la coherencia o la sincronización de fase, que evalúan la conectividad funcional (FC); mientras que las medidas asimétricas, como la causalidad de Granger o transferencia de entropía, son capaces de detectar la dirección de la interacción, lo que denominamos conectividad efectiva (EC). En la neurociencia moderna ha aumentado el interés por el estudio de las redes funcionales cerebrales, en gran medida debido a la aparición de estos nuevos algoritmos que permiten analizar la interdependencia entre señales temporales, además de la emergente teoría de redes complejas y la introducción de técnicas novedosas, como la magnetoencefalografía (MEG), para registrar datos neurofisiológicos con gran resolución. Sin embargo, nos hallamos ante un campo novedoso que presenta aun varias cuestiones metodológicas sin resolver, algunas de las cuales trataran de abordarse en esta tesis. En primer lugar, el creciente número de aproximaciones para determinar la existencia de FC/EC entre dos o más señales temporales, junto con la complejidad matemática de las herramientas de análisis, hacen deseable organizarlas todas en un paquete software intuitivo y fácil de usar. Aquí presento HERMES (http://hermes.ctb.upm.es), una toolbox en MatlabR, diseñada precisamente con este fin. Creo que esta herramienta será de gran ayuda para todos aquellos investigadores que trabajen en el campo emergente del análisis de conectividad cerebral y supondrá un gran valor para la comunidad científica. La segunda cuestión practica que se aborda es el estudio de la sensibilidad a las fuentes cerebrales profundas a través de dos tipos de sensores MEG: gradiómetros planares y magnetómetros, esta aproximación además se combina con un enfoque metodológico, utilizando dos índices de sincronización de fase: phase locking value (PLV) y phase lag index (PLI), este ultimo menos sensible a efecto la conducción volumen. Por lo tanto, se compara su comportamiento al estudiar las redes cerebrales, obteniendo que magnetómetros y PLV presentan, respectivamente, redes más densamente conectadas que gradiómetros planares y PLI, por los valores artificiales que crea el problema de la conducción de volumen. Sin embargo, cuando se trata de caracterizar redes epilépticas, el PLV ofrece mejores resultados, debido a la gran dispersión de las redes obtenidas con PLI. El análisis de redes complejas ha proporcionado nuevos conceptos que mejoran caracterización de la interacción de sistemas dinámicos. Se considera que una red está compuesta por nodos, que simbolizan sistemas, cuyas interacciones se representan por enlaces, y su comportamiento y topología puede caracterizarse por un elevado número de medidas. Existe evidencia teórica y empírica de que muchas de ellas están fuertemente correlacionadas entre sí. Por lo tanto, se ha conseguido seleccionar un pequeño grupo que caracteriza eficazmente estas redes, y condensa la información redundante. Para el análisis de redes funcionales, la selección de un umbral adecuado para decidir si un determinado valor de conectividad de la matriz de FC es significativo y debe ser incluido para un análisis posterior, se convierte en un paso crucial. En esta tesis, se han obtenido resultados más precisos al utilizar un test de subrogadas, basado en los datos, para evaluar individualmente cada uno de los enlaces, que al establecer a priori un umbral fijo para la densidad de conexiones. Finalmente, todas estas cuestiones se han aplicado al estudio de la epilepsia, caso práctico en el que se analizan las redes funcionales MEG, en estado de reposo, de dos grupos de pacientes epilépticos (generalizada idiopática y focal frontal) en comparación con sujetos control sanos. La epilepsia es uno de los trastornos neurológicos más comunes, con más de 55 millones de afectados en el mundo. Esta enfermedad se caracteriza por la predisposición a generar ataques epilépticos de actividad neuronal anormal y excesiva o bien síncrona, y por tanto, es el escenario perfecto para este tipo de análisis al tiempo que presenta un gran interés tanto desde el punto de vista clínico como de investigación. Los resultados manifiestan alteraciones especificas en la conectividad y un cambio en la topología de las redes en cerebros epilépticos, desplazando la importancia del ‘foco’ a la ‘red’, enfoque que va adquiriendo relevancia en las investigaciones recientes sobre epilepsia. ABSTRACT There are about 1014 neuronal synapses in the human brain. This huge number of connections provides the substrate for neuronal ensembles to become transiently synchronized, producing the emergence of cognitive functions such as perception, learning or thinking. Understanding the complex brain network organization on the basis of neuroimaging data represents one of the most important and exciting challenges for systems neuroscience. Several measures have been recently proposed to evaluate at various scales (single cells, cortical columns, or brain areas) how the different parts of the brain communicate. We can classify them, according to their symmetry, into two groups: symmetric measures, such as correlation, coherence or phase synchronization indexes, evaluate functional connectivity (FC); and on the other hand, the asymmetric ones, such as Granger causality or transfer entropy, are able to detect effective connectivity (EC) revealing the direction of the interaction. In modern neurosciences, the interest in functional brain networks has increased strongly with the onset of new algorithms to study interdependence between time series, the advent of modern complex network theory and the introduction of powerful techniques to record neurophysiological data, such as magnetoencephalography (MEG). However, when analyzing neurophysiological data with this approach several questions arise. In this thesis, I intend to tackle some of the practical open problems in the field. First of all, the increase in the number of time series analysis algorithms to study brain FC/EC, along with their mathematical complexity, creates the necessity of arranging them into a single, unified toolbox that allow neuroscientists, neurophysiologists and researchers from related fields to easily access and make use of them. I developed such a toolbox for this aim, it is named HERMES (http://hermes.ctb.upm.es), and encompasses several of the most common indexes for the assessment of FC and EC running for MatlabR environment. I believe that this toolbox will be very helpful to all the researchers working in the emerging field of brain connectivity analysis and will entail a great value for the scientific community. The second important practical issue tackled in this thesis is the evaluation of the sensitivity to deep brain sources of two different MEG sensors: planar gradiometers and magnetometers, in combination with the related methodological approach, using two phase synchronization indexes: phase locking value (PLV) y phase lag index (PLI), the latter one being less sensitive to volume conduction effect. Thus, I compared their performance when studying brain networks, obtaining that magnetometer sensors and PLV presented higher artificial values as compared with planar gradiometers and PLI respectively. However, when it came to characterize epileptic networks it was the PLV which gives better results, as PLI FC networks where very sparse. Complex network analysis has provided new concepts which improved characterization of interacting dynamical systems. With this background, networks could be considered composed of nodes, symbolizing systems, whose interactions with each other are represented by edges. A growing number of network measures is been applied in network analysis. However, there is theoretical and empirical evidence that many of these indexes are strongly correlated with each other. Therefore, in this thesis I reduced them to a small set, which could more efficiently characterize networks. Within this framework, selecting an appropriate threshold to decide whether a certain connectivity value of the FC matrix is significant and should be included in the network analysis becomes a crucial step, in this thesis, I used the surrogate data tests to make an individual data-driven evaluation of each of the edges significance and confirmed more accurate results than when just setting to a fixed value the density of connections. All these methodologies were applied to the study of epilepsy, analysing resting state MEG functional networks, in two groups of epileptic patients (generalized and focal epilepsy) that were compared to matching control subjects. Epilepsy is one of the most common neurological disorders, with more than 55 million people affected worldwide, characterized by its predisposition to generate epileptic seizures of abnormal excessive or synchronous neuronal activity, and thus, this scenario and analysis, present a great interest from both the clinical and the research perspective. Results revealed specific disruptions in connectivity and network topology and evidenced that networks’ topology is changed in epileptic brains, supporting the shift from ‘focus’ to ‘networks’ which is gaining importance in modern epilepsy research.

Drifting plasma collection by a positive biased tether wire in LEO-like plasma conditions: current measurement and plasma diagnostic

BETs is a three-year project financed by the Space Program of the European Commission, aimed at developing an efficient deorbit system that could be carried on board any future satellite launched into Low Earth Orbit (LEO). The operational system involves a conductive tape-tether left bare to establish anodic contact with the ambient plasma as a giant Langmuir probe. As a part of this project, we are carrying out both numerical and experimental approaches to estimate the collected current by the positive part of the tether. This paper deals with experimental measurements performed in the IONospheric Atmosphere Simulator (JONAS) plasma chamber of the Onera-Space Environment Department. The JONAS facility is a 9- m3 vacuum chamber equipped with a plasma source providing drifting plasma simulating LEO conditions in terms of density and temperature. A thin metallic cylinder, simulating the tether, is set inside the chamber and polarized up to 1000 V. The Earth's magnetic field is neutralized inside the chamber. In a first time, tether collected current versus tether polarization is measured for different plasma source energies and densities. In complement, several types of Langmuir probes are used at the same location to allow the extraction of both ion densities and electron parameters by computer modeling (classical Langmuir probe characteristics are not accurate enough in the present situation). These two measurements permit estimation of the discrepancies between the theoretical collection laws, orbital motion limited law in particular, and the experimental data in LEO-like conditions without magnetic fields. In a second time, the spatial variations and the time evolutions of the plasma properties around the tether are investigated. Spherical and emissive Langmuir probes are also used for a more extensive characterization of the plasma in space and time dependent analysis. Results show the ion depletion because of the wake effect and the accumulation of- ions upstream of the tether. In some regimes (at large positive potential), oscillations are observed on the tether collected current and on Langmuir probe collected current in specific sites.

Transformación de series numéricas temporales en secuencias simbólicas

El Trabajo de Fin de Grado aborda el tema del Descubrimiento de Conocimiento en series numéricas temporales, abordando el análisis de las mismas desde el punto de vista de la semántica de las series. La gran mayoría de trabajos realizados hasta la fecha en el campo del análisis de series temporales proponen el análisis numérico de los valores de la serie, lo que permite obtener buenos resultados pero no ofrece la posibilidad de formular las conclusiones de forma que se puedan justificar e interpretar los resultados obtenidos. Por ello, en este trabajo se pretende crear una aplicación que permita realizar el análisis de las series temporales desde un punto de vista cualitativo, en contraposición al tradicional método cuantitativo. De esta forma, quedarán recogidos todos los elementos relevantes de la serie temporal que puedan servir de estudio en un futuro. Para abordar el objetivo propuesto se plantea un mecanismo para extraer de la serie temporal la información que resulta de interés para su análisis. Para poder hacerlo, primero se formaliza el conjunto de comportamientos relevantes del dominio, que serán los símbolos a mostrar en la salida de la aplicación. Así, el método que se ha diseñado e implementado transformará una serie temporal numérica en una secuencia simbólica que recoge toda la semántica de la serie temporal de partida y resulta más intuitiva y fácil de interpretar. Una vez que se dispone de un mecanismo para transformar las series numéricas en secuencias simbólicas, se pueden plantear todas las tareas de análisis sobre dichas secuencias de símbolos. En este trabajo, aunque no se entra en este post-análisis de estas series, sí se plantean distintos campos en los que se puede avanzar en el futuro. Por ejemplo, se podría hacer una medida de la similitud entre dos secuencias simbólicas como punto de partida para la tarea de comparación o la creación de modelos de referencia para análisis posteriores de las series temporales. ---ABSTRACT---This Final-year Project deals with the topic of Knowledge Discovery in numerical time series, addressing time series analysis from the viewpoint of the semantics of the series. Most of the research conducted to date in the field of time series analysis recommends analysing the values of the series numerically. This provides good results but prevents the conclusions from being formulated to allow justification and interpretation of the results. Thus, the purpose of this project is to create an application that allows the analysis of time series, from a qualitative point of view rather than a quantitative one. This way, all the relevant elements of the time series will be gathered for future studies. The design of a mechanism to extract the information that is of interest from the time series is the first step towards achieving the proposed objective. To do this, all the key behaviours in the domain are set, which will be the symbols shown in the output. The designed and implemented method transforms a numerical time series into a symbolic sequence that takes in all the semantics of the original time series and is more intuitive and easier to interpret. Once a mechanism for transforming the numerical series into symbolic sequences is created, the symbolic sequences are ready for analysis. Although this project does not cover a post-analysis of these series, it proposes different fields in which research can be done in the future. For instance, comparing two different sequences to measure the similarities between them, or the creation of reference models for further analysis of time series.

Evaluation of preisach model of hysteresis to model superconductors

The Large Hadron Collider is the world’s largest and most powerful particle accelerator. The project is divided in phases. The first one goes from 2009 until 2020. The second phase will consist of the implementation of upgrades. One of the upgrades is to increase the ratio of collision, the luminosity. This objective is the main of one of the most important projects which is carrying out the upgrades: Hi-Lumi LHC project. Increasing luminosity could be done by using a new material in the superconductor magnets placed at the interaction points: Nb3Sn, instead of NbTi, the one being used right now. Before implementing it many aspects should be analysed. One of them is the induction magnetic field quality. The tool used so far has been ROXIE, software developed at CERN by S. Russenschuck. One of the main features of the programme is the time-transient analysis, which is based on three mathematical models. It is quite precise for fields above 1.5 Tesla. However, they are not very accurate for lower fields. Therefore the aim of this project is to evaluate a more accurate model: Classical Preisach Model of Hysteresis, in order to better analyse induced field quality in the new material Nb3Sn. Resumen: El Gran Colisionador de Hadrones es el mayor acelerador de partículas circular del mundo. Se trata de uno de los mayores proyectos de investigación. La primera fase de funcionamiento comprende desde 2009 a 2020, cuando comenzará la siguiente fase. Durante el primer periodo se han pensado mejoras para que puedan ser implementadas en la segunda fase. Una de ellas es el aumento del ratio de las colisiones entre protones por choque. Este es el principal objetivo de uno de los proyectos que está llevando a cabo las mejoras a ser implementadas en 2020: Hi- Lumi LHC. Se cambiarán los imanes superconductores de NbTi de las dos zonas principales de interacción, y se sustituirán por imanes de Nb3Sn. Esta sustituciónn conlleva un profundo estudio previo. Entre otros, uno de los factores a analizar es la calidad del campo magnético. La herramienta utilizada es el software desarrollado por S. Russenschuck en el CERN llamado ROXIE. Está basado en tres modelos de magnetización, los cuales son precisos para campos mayores de 1.5 T. Sin embargo, no lo son tanto para campos menores. Con este proyecto se pretende evaluar la implementación de un cuarto modelo, el modelo clásico de histéresis de Preisach que permita llevar a cabo un mejor análisis de la calidad del campo inducido por el futuro material a utilizar en algunos de los imanes.

"Deporte inclusivo en la escuela": diseño y análisis de un programa de intervencion para promover la inclusión del alumnado con discapacidad en Educación Física

La Educación Física se muestra, a priori, como un área idónea para trabajar intervenciones educativas para facilitar la inclusión de alumnos con discapacidad. Sin embargo, poco se conoce sobre el potencial que presentan los deportes adaptados y paralímpicos como contenido para fomentar la sensibilización y concienciación del alumnado sin discapacidad, especialmente en situaciones inclusivas de práctica. Por otro lado, la actitud del docente y su formación se presentan como claves en este contexto, ya que es quien en última instancia selecciona los contenidos a trabajar. Entendemos que en EF disponemos de una ocasión única en el curriculum para fomentar la participación activa y efectiva del alumno con discapacidad en clase (especialmente a nivel de desarrollo de la competencia motriz, entre otras), si bien esto depende de factores relacionados con los dos agentes anteriores. Es por todo ello que la Educación Física, como protagonista y como contenido, se muestra como un contexto adecuado para la investigación de los procesos de inclusión de alumnos con discapacidad en el ámbito educativo. Este trabajo de investigación pretende arrojar luz a los interrogantes que condicionan y limitan este contexto, desde una perspectiva multidisciplinar, con distintas metodologías, sobre los tres agentes indicados. La falta de consenso en la literatura en cuanto a las características y tipo de intervenciones eficaces para facilitar esta sensibilización del alumnado, unido a que es un ámbito relativamente reciente como tema de investigación, nos ha impulsado a trabajar en esta línea. El primer objetivo de este trabajo de investigación fue diseñar e implementar un programa de sensibilización y concienciación hacia la discapacidad basado en los deportes adaptados en el área de Educación Física para alumnos de secundaria y bachillerato. Inicialmente, se realizó una búsqueda bibliográfica tanto a nivel nacional como internacional, con el fin de definir las características principales que aporta la literatura científica en este aspecto. Apoyándonos por un lado, en el programa educativo Paralympic School Day (CPI, 2004) y por otro, en la citada revisión, desarrollamos un planteamiento inicial de estructura y fases. Dicho proyecto, fue presentado al Comité Paralímpico Español y a las federaciones deportivas españolas para personas con discapacidad, con la finalidad de recabar su apoyo institucional en forma de aval y recursos no solo a nivel económico sino también como apoyo logístico y de difusión. Tras su aprobación y gracias también al apoyo de la UPM, la Fundación Sanitas y Liberty Seguros, se procedió a diseñar el programa. Para el desarrollo de los materiales didácticos se contactó con expertos en la materia de EF y Actividad Física Adaptada tanto del ámbito educativo (profesores de educación secundaria y profesorado universitario) como del deportivo a nivel nacional. A su vez, se comenzó a difundir entre el profesorado de los centros con el fin de detectar su interés en participar durante el curso académico (2012-2013) en el programa “Deporte Inclusivo en la Escuela”. Con la finalización del desarrollo de los materiales didácticos, se visitó a los centros educativos para presentar el dossier informativo donde se explicaba el programa, así como las características y fases para su implementación. El programa está fundamentado en la Teoría del Contacto (Allport, 1954) y basado en los deportes adaptados y paralímpicos, planteado con una metodología inclusiva, seleccionando la información, la simulación y el contacto directo como estrategias para el fomento de la sensibilización y concienciación hacia la inclusión. En la reunión celebrada en la Facultad de Ciencias de la Actividad Física y del Deporte (INEF-UPM) en febrero de 2013, se coordinó junto con el profesorado la implementación del programa en cada uno de los 13 centros educativos, con acciones concretas como la adecuación de la propuesta didáctica en la planificación anual del profesor, el préstamo de material o la ponencia del deportista paralímpico entre otras cuestiones. Para la consecución del objetivo 2 de este trabajo, analizar el efecto del programa en los distintos agentes implicados en el mismo, alumnos sin discapacidad, profesorado de EF y alumnos con discapacidad, se calendarizó la toma de datos y la administración de las diferentes herramientas metodológicas para antes (pretest) como después de la intervención (posttets). En el caso de los alumnos sin discapacidad (N= 1068), se analizó el efecto de la intervención sobre la actitud hacia la inclusión, utilizando el cuestionario “Children Attitude Integrated Physical Education-Revised” (CAIPE-R; Block, 1995) de carácter cuantitativo tras su validación y adaptación al contexto español. Los resultados mostraron cambios significativos positivos en la actitud el grupo que mantuvo un contacto no estructurado con alumnos con discapacidad. En esta muestra también se midió la actitud hacia el juego cooperativo con compañeros con discapacidad en clases de EF usando el cuestionario “Children's Beliefs Toward Cooperative Playing With Peers With Disabilities in Physical Education” (CBIPPD-MPE; Obrusnikova, Block, y Dillon, 2010). El desarrollo de un sistema de categorías fundamentado en la Teoría del Comportamiento Planificado (Azjen, 1991) sirvió como base para el análisis de las creencias del alumnado sin discapacidad. Tras la intervención, las creencias conductuales emergentes se mantuvieron, excepto en el caso de los factores identificados como obstáculos de la inclusión. En el caso de las creencias normativas también se mantuvieron tras la intervención y respecto a las creencias de control, los alumnos identificaron al profesor como principal agente facilitador de la inclusión. En el caso de los profesores de EF participantes en el programa (N=18), se analizó el efecto del programa en su actitud hacia la inclusión de alumnos con discapacidad en EF con el cuestionario “Attitud toward inclusion of individual with physical disabilities in Physical Education” (ATISDPE-R; Kudláèek, Válková, Sherrill, Myers, y French, 2002). Los resultados mostraron que no se produjeron diferencias significativas tras la intervención en la actitud general, encontrando algunas diferencias en determinados ítems relacionados con los beneficios de la inclusión en los alumnos sin discapacidad relacionados con los docentes con experiencia previa con discapacidad y en EF antes de la intervención. La otra dimensión analizada fue el efecto de la intervención en la autoeficacia del profesor en la enseñanza de la EF en condiciones inclusivas, habiendo utilizado el cuestionario "Self-efficacy in teaching PE under inclusive conditions" (SEIPE; Hutzler, Zach, y Gafni, 2005). Los resultados en este caso muestran diferencias significativas positivas en cuestiones relacionadas como sentirse capaces de mejorar las condiciones óptimas de enseñanza con alumnos con discapacidad física como movilidad reducida severa y amputación y discapacidad visual tanto en situaciones deportivas, como juegos o actividades fuera del centro educativo a favor de los docentes. En cuanto al género, los hombres obtuvieron valores superiores a las mujeres en relación a sentirse más capaces de incluir a alumnos con discapacidad física tanto en juegos durante el recreo como en la enseñanza de técnica deportiva. Los profesores con menos de 10 años de docencia mostraron valores más positivos en cuanto a sentirse capaces de incluir a un alumno con discapacidad fisica en deportes durante su tiempo libre. El análisis del diario del profesor muestra por un lado, las tendencias emergentes como principales elementos facilitadores u obstaculizadores de la inclusión en EF, identificando al propio alumno sin discapacidad, el propio profesor, los contenidos, los materiales y la organización. Por otro lado, el análisis de los contenidos propuestos en el programa. En el caso de los alumnos con discapacidad (N=22), se analizó el impacto del programa de intervención en el autoconcepto, con el cuestionario "Autoconcepto forma 5" (AF5; F. García y Musitu, 2001). Se encontraron diferencias significativas a favor de las mujeres antes de la intervención en la dimensión familiar, mientras que los hombres obtuvieron valores más altos en las dimensiones social y físico. En cuanto a la edad, se encontraron diferencias significativas antes de la intervención, con valores superiores en los alumnos más jóvenes (12-14 años) en la dimensión físico, mientras que los alumnos mayores (15-17 años) mostraron valores más altos en la dimensión social del cuestionario. Respeto al tipo de discapacidad, los alumnos con discapacidad motórica mostraron mejores valores que los que tienen discapacidad auditiva para la dimensión físico antes de la intervención. En cuanto al autoconcepto general, las diferencias significativas positivas se producen en la dimensión académica. En cuanto al efecto del programa en la autoestima de los alumnos con discapacidad, se utilizó la Escala de "Autoestima de Rosenberg" (Rosenberg, 1989), no obteniendo diferencias significativas en cuanto el género. Apareciendo diferencias significativas antes de la intervención en el caso de la variable edad en los alumnos más jóvenes, en cuanto a que desearían valorarse más, y en los alumnos con discapacidad auditiva en que no se sienten muy orgullosos de ellos mismos. Se produce una mejora en la autoestima general en cuanto a que se sienten menos inútiles tras la intervención. En relación al objetivo 3 de este trabajo, tras el análisis de los resultados y haber discutido los mismos con los autores de referencia, emergió la propuesta de orientaciones tanto para los programa de intervención en EF para la sensibilización y concienciación del alumnado hacia la inclusión como de cara a la formación específica del profesorado, como clave en este tipo de intervenciones. Creemos que el programa “Deporte Inclusivo Escuela” se convierte en un elemento transformador de la realidad, ya que responde a las necesidades detectadas a la luz de esta investigación y que vienen a dar respuesta a los distintos agentes implicados en su desarrollo. Por un lado, atiende la demanda del ámbito educativo en cuanto a las necesidades de formación del profesorado, sensibilización y concienciación del alumnado sin discapacidad, además de facilitar oportunidades de participación activa al alumno con discapacidad en las sesiones de EF. Por otro lado, satisface la demanda por parte de las instituciones deportivas del ámbito de la discapacidad en cuanto a la promoción y difusión de los deportes adaptados y paralímpicos. Por último, desde el ámbito universitario, se muestra como un recurso en la formación del alumnado del grado en Ciencias de la Actividad Física y del Deporte, por su participación directa con la discapacidad. Por estos motivos, este trabajo se muestra como un punto de partida adecuado para seguir avanzando en la investigación en esta área. ABSTRACT Physical Education (PE) seems a priori, as a suitable area to work educational interventions to facilitate the inclusion of students with disabilities. However, little is known about the potential that have adapted and Paralympic sports as content to raise awareness of students without disabilities, especially in inclusive practice context. On the other hand, teachers’ attitude and their training are presented as key in this context because it is who selects the content to work. We understand that PE have a unique opportunity in the curriculum to encourage active and effective participation of students with disabilities in class (especially at motor competence development, etc.), although this depends on factors related to the two agents. For these reasons that the PE, as actors and as content is displayed as a context for investigating the processes of inclusion of students with disabilities in education. This research aims to shed light on the questions that condition and limit this context, from a multidisciplinary perspective, with different methodologies on the three agents mentioned. The lack of accord in the literature regarding the characteristics and type of effective facilitators of awareness of students, and that is a new area as a research topic, has prompted us to work in this topic research. The first aim of this research was to design and implement a program of awareness towards disability based on adapted sports in the area of physical education for middle and high school students. Initially, a literature search was performed both nationally and internationally, in order to define the main features that brings the scientific literature in this area. On the one hand, we supported in the Paralympic School Day (IPC, 2004) educative program and on the other hand, in that review, we developed an initial approach to structure and phases. The project was presented to the Spanish Paralympic Committee and the Spanish Sports Federations for people with disabilities, in order to obtain institutional support in the form of guarantees and resources not only in economic terms but also as logistical support and dissemination. Thanks to the support of Fundación Sanitas, Liberty Seguros and Politechnical University of Madrid, we proceeded to design the program. For the development of teaching resources it was contacted experts in the field of Adapted Physical Activity and physical education and both the field of education (high school teachers and university professors) as the adapted sport national. In turn, it began to spread among the teachers of the schools in order to identify their interest in participating in the academic year (2012-2013) in the "Inclusive Sport in School" program. With the completion of the development of educational materials to schools he was visited to present the briefing where the program, as well as features and steps for its implementation are explained. The program is based on the Contact Theory (Allport, 1954) and based on adapted and Paralympic sports, raised with an inclusive approach, selecting strategies for promoting awareness and awareness to inclusion like information, contact and simulation of disability. At the meeting held at the Faculty of Sciences of Physical Activity and Sport (INEF-UPM) in February 2013, it was coordinated with the teachers implementing the program in each of the 13 schools with concrete actions such as adequacy of methodological approach in the annual planning of the teacher, the loan or the presentation of materials Paralympian among other issues. To achieve the objective 2 of this paper, to analyze the effect of the program on the various actions involved it, students without disabilities, PE teachers and students with disabilities, the date for management of the different methodological tools for before (pretest) and after the intervention (posttets). For students without disabilities (N= 1068), the effect of the intervention on the attitude towards inclusion was analyzed, using the quantitative questionnaire "Integrated Physical Education Attitude Children-Revised" (CAIPE-R; Block, 1995), after validation and adaptation to the Spanish context. The results showed significant positive changes in the attitude of the group with no structured contact with students with disabilities. This shows the beliefs towards the cooperative play was with peers with disabilities in PE classes also measured, using the questionnaire "Children's Beliefs Toward Cooperative Playing With Peers With Disabilities in Physical Education" (CBIPPD-MPE; Obrusnikova, Block, and Dillon, 2010). The development of a system of categories based on the Theory of Planned Behavior (Azjen, 1991) served as the basis for analysis of the beliefs of students without disabilities. After surgery, emerging behavioral beliefs remained, except in the case of the factors identified as barriers to inclusion. In the case of normative beliefs also they remained after surgery and regarding control beliefs, students identified the teacher as the main facilitator of inclusion. Regarding PE teachers participating in the program (N = 18), the effect of the program was analyzed their attitude toward inclusion of students with disability in PE with the questionnaire "Toward Attitude inclusion of Individual with in Physical Education "(ATISDPE-R; Kudláèek, Válková, Sherrill, Myers, and French, 2002). The results showed no significant difference occurred after surgery in the general attitude, finding some differences in certain related benefits of inclusion in students without disability relating to teachers with previous experience with disability in PE before intervention. The other dimension was analyzed the effect of the intervention on self-efficacy of teachers in the teaching of PE in inclusive terms, having used the questionnaire "Self-efficacy in PE teaching even under conditions" (SEIPE; Hutzler, Zach, and Gafni, 2005). The results showed significant differences positive in issues like being able to enhance the optimal conditions for teaching students with physical disabilities as amputation and severe visual impairment in both sports situations, such as games or activities outside the school to for teachers. Regard to gender, men earned higher values regarding women about feel more able to include students with physical disabilities in both games during recess and teaching sports technique. Teachers with less than 10 years of teaching showed more positive values as you feel able to include a student with physical disabilities in sports during their leisure time. The analysis of daily teacher shows on the one hand, emerging trends as key facilitators or barrier of the inclusion elements in PE, identifying the students without disabilities themselves, the professor, contents, materials and organization. Furthermore, the analysis of daily teacher about the contents proposed in the program. In the case of students with disabilities (N=22), the impact of the intervention program on self-concept was analyzed, with the questionnaire "Self-concept form 5" (AF5, F. Garcia and Musitu, 2001). The women showed significant differences before the intervention in family dimension, while men scored higher values in the social and physical dimensions were found. In terms of age, significant differences were found before the intervention, with higher values in younger students (12-14 years) in the physical dimension, while older children (15-17 years) showed higher values the social dimension of the questionnaire. Respect disabilities, students with motor disabilities showed better values than those with hearing impairment to the physical dimension before surgery. As for the general self-concept, positive significant differences occur in the academic dimension. As for the effect of the program on self-esteem of students with disabilities Scale "Rosenberg Self-Esteem" (Rosenberg, 1989) was used, not getting significant differences in gender. Only appear significant difference before the intervention in the case of younger students as they wish to be valued more, and students with hearing disabilities who do not feel very proud of themselves. Improved self-esteem generally occurs in that they feel less useless after surgery. With regard to the aim 3 of this research, after analyzing the results and have discussed them with the authors, it emerged the proposal of guidelines for both intervention program EF for sensitization and awareness of students towards inclusion as in the face of specific training for teachers, as key in such interventions. We believe that "Inclusive Sport Schools" program becomes a transforming element of reality, as it responds to the needs identified in the light of this research and come to respond to the various elements involved in its development. On the one hand, it meets the demand of the education sector in terms of the needs of teacher training, awareness of students without disability, and facilitates opportunities for students with disabilities for active participation in PE class. On the other hand, it meets the demand of sports institutions in the field of disability regarding the promotion and dissemination of adapted and Paralympic sports. Finally, it is shown as a resource from the university level for the training of degree in Physical Activity and Sport Science students, by its direct involvement with disability. For these reasons, this work is shown as a good starting point to further advance research in this area.

Sistemas radiolarios: geometrías y arquitecturas derivadas

Uno de los temas más importantes dentro del debate contemporáneo, es el que se refiere a la sostenibilidad a largo plazo de la sociedad tal y como la entendemos hoy. El ser humano está recuperando la sensibilidad perdida que le concebía como una pieza más dentro del ciclo natural de la vida. Por fin hemos entendido que no podemos ser auto suficientes e independientes del entorno natural que nos rodea. Más allá del respeto y del cuidado, está abierta la puerta del conocimiento infinito que nos brinda la naturaleza a todos los niveles y a todas las escalas. Dentro de la disciplina arquitectónica han existido ejemplos como Antoni Gaudí o Frei Otto que han referenciado su obra en el mundo Natural, encontrando en él las estrategias y bases para el diseño arquitectónico. Sin embargo han sido una minoría dentro del enorme elenco de arquitectos defensores del ángulo recto. En las últimas décadas, la tendencia está cambiando. No nos referimos tanto a la sensibilidad creciente por conseguir una mayor eficiencia energética que ha llevado a una puesta en valor de la arquitectura vernácula, trasladando su sabiduría a las estrategias bioclimáticas. Nos referimos a un caso específico dentro del amplio abanico de formas arquitectónicas que han aparecido gracias a la incorporación de las herramientas computacionales en el diseño y la producción. Las arquitecturas que nos interesan son las que aprovechan estas técnicas para analizar e interpretar las estrategias complejas y altamente eficientes que encontramos en la naturaleza, y trasladarlas a la disciplina arquitectónica. Esta tendencia que se enmarca dentro de la Biomímesis o Biomimética es conocida con el nombre de Bioarquitectura. La presente tesis trata de morfología y sobre todo de morfogénesis. El término morfología se refiere al estudio de una forma concreta que nos permite entender un caso específico, nuestro foco de atención se centra sin embargo en la morfogénesis, es decir, en el estudio de los procesos de generación de esas formas, para poder reproducir patrones y generar abanicos de casos adaptables y reconfigurables. El hecho de estudiar la forma no quiere decir que ésta sea una tesis “formalista” con la connotación peyorativa y gestual que se le suele atribuir a este término. La investigación concibe el concepto de forma como lo hace el mundo natural: forma como síntesis de eficiencia. No hay ninguna forma natural gratuita, que no cumpla una función determinada y que no se desarrolle con el mínimo material y gaste la mínima energía posible. Este afán por encontrar la “forma eficaz” es lo que nos hace traspasar la frontera de la arquitectura formalista. El camino de investigación morfológica se traza, como el título de la tesis indica, siguiendo el hilo conductor concreto de los radiolarios. Estos microorganismos unicelulares poseen unos esqueletos tan complejos que para poder entender su morfología es necesario establecer un amplio recorrido que abarca más de 4.000 años de conocimiento humano. Desde el descubrimiento de los sólidos platónicos, poliedros que configuran muchas de las formas globales de estos esqueletos; hasta la aplicación de los algoritmos generativos, que permiten entender y reproducir los patrones de comportamiento que existen detrás de los sistemas de compactación y teselación irregular de los esqueletos radiolarios. La tesis no pretende plantear el problema desde un punto de vista biológico, ni paleontológico, aunque inevitablemente en el primer capítulo se realiza un análisis referenciado del estado del conocimiento científico actual. Sí se analizan en mayor profundidad cuestiones morfológicas y se tratan los diferentes posicionamientos desde los cuales estos microorganismos han servido de referencia en la disciplina arquitectónica. Además encontramos necesario analizar otros patrones naturales que comparten estrategias generativas con los esqueletos radiolarios. Como ya hemos apuntado, en el segundo capítulo se aborda un recorrido desde las geometrías más básicas a las más complejas, que tienen relación con las estrategias de generación de las formas detectadas en los microorganismos. A su vez, el análisis de estas geometrías se intercala con ejemplos de aplicaciones dentro de la arquitectura, el diseño y el arte. Finalizando con un cronograma que sintetiza y relaciona las tres vías de investigación abordadas: natural, geométrica y arquitectónica. Tras los dos capítulos centrales, el capítulo final recapitula las estrategias analizadas y aplica el conocimiento adquirido en la tesis, mediante la realización de diferentes prototipos que abarcan desde el dibujo analítico tradicional, a la fabricación digital y el diseño paramétrico, pasando por modelos analógicos de escayola, barras metálicas, resina, silicona, látex, etc. ABSTRACT One of the most important issues in the contemporary debate, is the one concerning the long-term sustainability of society as we understand it today. The human being is recovering the lost sensitivity that conceived us as part of the natural cycle of life. We have finally understood that we cannot be self-sufficient and independent of the natural environment which surrounds us. Beyond respect and care, we’ll find that the gateway to the infinite knowledge that nature provides us at all levels and at all scales is open. Within the architectural discipline, there have been remarkable examples such as Antoni Gaudí or Frei Otto who have inspired their work in the natural world. Both, found in nature the strategies and basis of their architectural designs. However, they have been a minority within the huge cast of architects defenders of the right angle. In recent decades, the trend is changing. We are not referring to the growing sensitivity in trying to achieve energy efficiency that has led to an enhancement of vernacular architecture, transferring its wisdom to bioclimatic strategies. We refer to a specific case within the wide range of architectural forms that have appeared thanks to the integration of computer tools in both design and production processes. We are interested in architectures that exploit these techniques to analyse and interpret the complex and highly efficient strategies found in nature, and shift them to the discipline of architecture. This trend, which is being implemented in the framework of the Biomimicry or biomimetics, is called Bioarchitecture. This thesis deals with morphology and more specifically with morphogenesis. Morphology is the study of a concrete form that allows us to understand a specific case. However, our focus is centered in morphogenesis or, in other words, the study of the processes of generation of these forms, in order to replicate patterns and generate a range of adaptable and reconfigurable cases. The fact of studying shapes does not mean that this is a “formalistic” thesis with the pejorative connotation that is often attributed to this term. This study conceives the concept of shape as Nature does: as a synthesis of efficiency. There is no meaningless form in nature. Furthermore, forms and shapes in nature play a particular role and are developed with minimum energetic consumption. This quest to find the efficient shape is what makes us go beyond formalistic architecture. The road of morphological investigation is traced, as the title of the thesis suggests, following the thread of radiolaria. These single-cell microorganisms possess very complex skeletons, so to be able to understand their morphology we must establish a wide spectrum which spans throughout more than 4.000 years of human knowledge. From the discovery of the platonic solids, polyhedrons which configure a huge range of global shapes of these skeletons, through the application of generative algorithms which allow us to understand and recreate the behavioral patterns behind the systems of compression and irregular tessellation of the radiolarian skeletons. The thesis does not pretend to lay out the problem from a biological, paleontological standpoint, although inevitably the first chapter is developed through an analysis in reference to the current state of the science. A deeper analysis of morphological aspects and different positionings is taken into account where these microorganisms have served as reference in the architectonic discipline. In addition we find necessary to analyse other natural patterns which share generative strategies with radiolarian skeletons. Aforementioned, in the second chapter an itinerary of the most basic geometries to the more complex ones is addressed. These are related, in this chapter, to the generative strategies of the shapes found in microorganisms. At the same time, the analysis of these geometries is placed among examples of applications inside the fields of architecture, design and the arts. To come to an end, a time chart synthesizes and relates the three investigation paths addressed: natural, geometrical and architectonic. After the two central chapters, the final chapter summarises the strategies analysed and applies the knowledge acquired throughout the thesis. This final chapter is shaped by the realization of different prototypes which range from traditional analytical drawings, to digital fabrication and parametric design, going through plaster analogical models, metal bars, resin, silicone, latex, etc.

Rho-dependent Regulation of Cell Spreading by the Tetraspan Membrane Protein Gas3/PMP22

Gas3/PMP22 plays a crucial role in regulating myelin formation and maintenance, and different genetic alterations in gas3/PMP22 are responsible for a set of human peripheral neuropathies. We have previously demonstrated that Gas3/PMP22 could regulate susceptibility to apoptosis in NIH3T3 cells but not in REF 52 cells. In this report we demonstrate that when the apoptotic response triggered by gas3/PMP22 was counteracted by Bcl-2 coexpression, morphological changes were observed. Time-lapse analysis confirmed that Gas3/PMP22 can modulate cell spreading, and this effect was strengthened after inhibition of phosphoinositide 3-kinase. Using the active form of the small GTPase RhoA, we have been able to dissect the different Gas3/PMP22 biological activities. RhoA counteracted the Gas3/PMP22-dependent morphological response but was unable to neutralize the apoptotic response. Treatment of NIH3T3 cells with cytotoxic necrotizing factor 1, which activates endogenous Rho, also counteracted Gas3/PMP22-mediated cell shape and spreading changes. Treatment of REF 52 cells, which are unresponsive to Gas3/PMP22 overexpression, with the C3 exoenzyme, inhibiting Rho activity, renders REF 52 cells responsive to Gas3/PMP22 overexpression for cell shape and spreading changes. Finally, assembly of stress fibers and focal adhesions complexes, in response to lysophosphatidic acid–induced endogenous Rho activation, was impaired in Gas3/PMP22-overexpressing cells. We hypothesize that cell shape and spreading regulated by Gas3/PMP22 through the Rho GTPase might have an important role during Schwann cells differentiation and myelinization.

Tid1/Rdh54 promotes colocalization of Rad51 and Dmc1 during meiotic recombination

Two RecA homologs, Rad51 and Dmc1, assemble as cytologically visible complexes (foci) at the same sites on meiotic chromosomes. Time course analysis confirms that co-foci appear and disappear as the single predominant form. A large fraction of co-foci are eliminated in a red1 mutant, which is expected as a characteristic of the interhomolog-specific recombination pathway. Previous studies suggested that normal Dmc1 loading depends on Rad51. We show here that a mutation in TID1/RDH54, encoding a RAD54 homolog, reduces Rad51-Dmc1 colocalization relative to WT. A rad54 mutation, in contrast, has relatively little effect on RecA homolog foci except when strains also contain a tid1/rdh54 mutation. The role of Tid1/Rdh54 in coordinating RecA homolog assembly may be very direct, because Tid1/Rdh54 is known to physically bind both Dmc1 and Rad51. Also, Dmc1 foci appear early in a tid1/rdh54 mutant. Thus, Tid1 may normally act with Rad51 to promote ordered RecA homolog assembly by blocking Dmc1 until Rad51 is present. Finally, whereas double-staining foci predominate in WT nuclei, a subset of nuclei with expanded chromatin exhibit individual Rad51 and Dmc1 foci side-by-side, suggesting that a Rad51 homo-oligomer and a Dmc1 homo-oligomer assemble next to one another at the site of a single double-strand break (DSB) recombination intermediate.

Mechanical behavior in living cells consistent with the tensegrity model

Alternative models of cell mechanics depict the living cell as a simple mechanical continuum, porous filament gel, tensed cortical membrane, or tensegrity network that maintains a stabilizing prestress through incorporation of discrete structural elements that bear compression. Real-time microscopic analysis of cells containing GFP-labeled microtubules and associated mitochondria revealed that living cells behave like discrete structures composed of an interconnected network of actin microfilaments and microtubules when mechanical stresses are applied to cell surface integrin receptors. Quantitation of cell tractional forces and cellular prestress by using traction force microscopy confirmed that microtubules bear compression and are responsible for a significant portion of the cytoskeletal prestress that determines cell shape stability under conditions in which myosin light chain phosphorylation and intracellular calcium remained unchanged. Quantitative measurements of both static and dynamic mechanical behaviors in cells also were consistent with specific a priori predictions of the tensegrity model. These findings suggest that tensegrity represents a unified model of cell mechanics that may help to explain how mechanical behaviors emerge through collective interactions among different cytoskeletal filaments and extracellular adhesions in living cells.

Muscarinic acetylcholine receptor down-regulation limits the extent of inhibition of cell cycle progression in Chinese hamster ovary cells.

Cellular desensitization is believed to be important for growth control but direct evidence is lacking. In the current study we compared effects of wild-type and down-regulation-resistant mutant m3 muscarinic receptors on Chinese hamster ovary (CHO-K1) cell desensitization, proliferation, and transformation. We found that down-regulation of m3 muscarinic acetylcholine receptors was the principal mechanism of desensitization of receptor-activated inositol phosphate phospholipid hydrolysis in these cells. Activation of wild-type and mutant receptors inhibited anchorage-independent growth as assayed by colony formation in agar. However, the potency for inhibition of anchorage-independent growth was greater for cells expressing the mutant receptor. Activation of either receptor also initially inhibited anchorage-dependent cell proliferation in randomly growing populations. Rates of DNA synthesis and cell division were profoundly reduced by carbachol in cells expressing either receptor at early time points. Analysis of cell cycle parameters indicated that cell cycle progression was inhibited at transitions from G1 to S and G2/M to G1 phases. However, mutant receptor effects on anchorage-dependent growth were sustained, whereas wild-type receptor effects were transient. Thus, receptor down-regulation restored cell cycle progression. In contrast, activation of either receptor blocked entry into the cell cycle from quiescence, and this response was not reduced by receptor down-regulation. Therefore, activation of m3 muscarinic acetylcholine receptors inhibited CHO cell anchorage-dependent and -independent growth. In anchored cells carbachol inhibited the cell cycle at three distinct points. Inhibitions at two of these points were eliminated by wild-type receptor down-regulation while the other was not. These results directly demonstrate that desensitization mechanisms can act as principal determinants of cellular growth responses.

Lineage specification of neuronal precursors in the mouse spinal cord.

We have investigated the differentiation potential of precursor cells within the developing spinal cord of mice and have shown that spinal cord cells from embryonic day 10 specifically give rise to neurons when plated onto an astrocytic monolayer, Ast-1. These neurons had the morphology of motor neurons and > 83% expressed the motor neuron markers choline acetyltransferase, peripherin, calcitonin gene-related peptide, and L-14. By comparison, < 10% of the neurons arising on monolayers of other neural cell lines or 3T3 fibroblasts had motor neuron characteristics. Cells derived from dorsal, intermediate, and ventral regions of the spinal cord all behaved similarly and gave rise to motor neuron-like cells when plated onto Ast-1. By using cells that expressed the lacZ reporter gene, it was shown that > 93% of cells present on the Ast-1 monolayers were motor neuron-like. Time-lapse analysis revealed that the precursors on the Ast-1 monolayers gave rise to neurons either directly or following a single cell division. Together, these results indicate that precursors in the murine spinal cord can be induced to differentiate into the motor neuron phenotype by factors produced by Ast-1 cells, suggesting that a similar factor(s) produced by cells akin to Ast-1 may regulate motor neuron differentiation in vivo.

Doseamento microbiológico de neomicina e bacitracina - desenvolvimento e validação de método rápido em microplacas

Os ensaios microbiológicos são utilizados para avaliar a atividade antimicrobiana desde a descoberta do uso dos antibióticos. Apesar dos ensaios microbiológicos serem amplamente empregados para determinação da potência de antibióticos em formas farmacêuticas, uma vez que fornecem a medida da atividade biológica, apresentam limitações quanto a baixa reprodutibilidade e tempo de análise. O objetivo deste trabalho foi desenvolver, otimizar e validar ensaio colorimétrico rápido em microplaca para determinar a potência da neomicina e bacitracina em produtos farmacêuticos. Metodologias de análise fatorial e análise de superfície de resposta foram utilizadas no desenvolvimento e otimização da escolha do microrganismo, da composição do meio de cultura, da proporção de inóculo, e das concentrações de cloreto de trifeniltetrazólio e dos antibióticos. Os métodos otimizados foram validados pela avaliação da linearidade, precisão, exatidão e robustez. Análise estatística mostrou equivalência entre o método de difusão em ágar e o método colorimétrico rápido em microplaca para ambos antibióticos. Além disso, o ensaio em microplaca apresentou vantagens em relação à reprodutibilidade, sensibilidade, tempo de incubação e quantidades necessárias de meio de cultura e soluções para ambos os antibióticos.

Análise da correlação entre índices radiomorfométricos de densidade óssea, perfil de qualidade óssea em software de implante, quociente de estabilidade e torque de inserção em implantes

A qualidade óssea, bem como a estabilidade inicial dos implantes, está diretamente relacionada com o sucesso das reabilitações na implantodontia. O presente estudo teve como objetivo analisar a correlação entre índices radiomorfométricos de densidade óssea por meio de radiografias panorâmicas, perfil de qualidade óssea com o auxílio de Tomografia Computadorizada de Feixe Cônico (TCFC) com o uso do software de imagens OsiriX, Análise da Frequência de Ressonância (RFA) e Torque de Inserção do implante. Foram avaliados 160 implantes de 72 indivíduos, com média etária de 55,5 (±10,5) anos. Nas radiografias panorâmicas foram obtidos os índices IM, IPM e ICM, e nas tomografias computadorizadas de feixe cônico, os valores de pixels e a espessura da cortical da crista óssea alveolar, além da estabilidade primária por meio do torque de inserção e análise da frequência de ressonância. Os resultados foram analisados pelo coeficiente de correlação de Spearman, para p<= 0,01 foi obtido entre o torque de inserção e valores de pixels (0.330), o torque de inserção e a espessura da cortical da crista alveolar (0.339), o torque de inserção e o ISQ vestibulo-lingual (0.193), os valores de pixels e espessura da cortical da crista alveolar (0.377), as duas direções vestíbulo-lingual e mesio-distal do ISQ (0.674), o ISQ vestíbulo-lingual e a espessura da cortical da crista alveolar (0.270); os índices radiomorfométricos foram correlacionados entre eles e para p<= 0,05 foi obtido entre torque de inserção e ISQ mesio-distal (0.131), entre o ISQ vestibulo-lingual e os valores de pixels (0.156) e ISQ mesio-distal e IPMI esquerdo (0.149) e ISQ mesio-distal e IPMS esquerdo (0.145). Existe correlação entre a TCFC, o torque de inserção e a RFA na avaliação da qualidade óssea. É possível utilizar, pré-cirurgicamente, os exames de TCFC para avaliar a qualidade e quantidade óssea, tendo em vista as correlações obtidas neste estudo.

Avaliação da percepção sobre interdisciplinaridade nas unidades de saúde USF Paranapiacaba, US Vila Helena e CEO Vila Guilherme

É necessário compreender que o indivíduo, no processo saúde-doença, precisa receber atenção completa, que envolva várias disciplinas atuando de forma conjunta, numa visão que envolve integralidade de ações (Saupe et al., 2007; Salvador et al., 2011). Uma das principais características dos serviços de saúde hoje em dia no país é o atendimento feito por equipes multiprofissionais, cujo entrosamento, entendimento e troca de saberes entre seus membros levam à interdisciplinaridade (Salvador et al., 2011), tema central deste trabalho de pesquisa. Atendimento interdisciplinar envolve trabalho recíproco, criando relações sociais horizontais, contrariamente ao que ocorre no modelo de assistência tradicional, hegemônico. Exige que o saber do outro seja ouvido e pensado, inclusive dos indivíduos e das comunidades assistidos (Leite; Veloso, 2008). Este estudo, do tipo quali-quantitativo, tem por objetivo analisar as percepções que trabalhadores e usuários de três unidades de saúde, com estratégias distintas de atendimento, apresentam sobre interdisciplinaridade. Busca-se destacar dificuldades e possíveis meios facilitadores para sua prática diária na perspectiva de profissionais de saúde e usuários dessas três unidades de saúde. Foram aplicados questionários com perguntas fechadas semiestruturadas e abertas, cujos resultados foram submetidos à análise quantitativa, pela técnica descritiva de análise de frequência, e análise qualitativa pela técnica hermenêutica dialética, conforme preconizada por Minayo (2004). À luz dessa modalidade qualitativa de pesquisa aplicada aos profissionais surgiram três categorias: Meios para aumento da interdisciplinaridade; Fatores que afetam a interdisciplinaridade, subdivididos em Incentivadores, Desmotivadores e Ambíguos; e Resultados da interdisciplinaridade. Em relação aos usuários, as categorias emergentes foram: Desinteresse; Visão assistencial individualista e Vantagens da interdisciplinaridade. Os resultados encontrados foram: todas as categorias profissionais sentiram falta de outros profissionais em grupos educativos. A ausência mais sentida foi assistente social (18,75%). A estratégia interdisciplinar mais lembrada foi \"reuniões\" (38,6%). Falta noção de que é necessário trocar informações de forma efetiva, compreensível e satisfatória para todos. Mostrou-se importante aproveitar esses momentos para discutir protocolos e rotinas. Instrumento relevante para aumentar as trocas entre os profissionais foi a capacitação (13,6%) que melhora o relacionamento em equipe ao diminuir inseguranças. Trocas de informações em equipe multidisciplinar podem transformála em interdisciplinar. Pertencimento foi fato importante para a interdisciplinaridade, assim como dialogar, tolerar, respeitar, ouvir, ser flexível e enxergar o que está além de si, com interação social, horizontal. Número reduzido de profissionais, tomar conhecimento dos resultados das decisões em equipe e corresponsabilidade também foram fatores de destaque. Mais de 70% dos usuários relatou não participar de grupos educativos, evidenciando o curativismo. Os usuários valorizaram o atendimento por mais de um profissional. Acolhimento prescinde da ação interdisciplinar. Nenhum modo de atendimento foi sugerido pelos usuários. A interdisciplinaridade favorece a relação entre a equipe e o usuário, diminui espera e aumenta resolução. Na US Vila Helena, a interdisciplinaridade prescindiu de reuniões de equipe para acontecer.

Search for ultrahigh energy neutrinos in highly inclined events at the Pierre Auger Observatory

The Surface Detector of the Pierre Auger Observatory is sensitive to neutrinos of all flavors above 0.1 EeV. These interact through charged and neutral currents in the atmosphere giving rise to extensive air showers. When interacting deeply in the atmosphere at nearly horizontal incidence, neutrinos can be distinguished from regular hadronic cosmic rays by the broad time structure of their shower signals in the water-Cherenkov detectors. In this paper we present for the first time an analysis based on down-going neutrinos. We describe the search procedure, the possible sources of background, the method to compute the exposure and the associated systematic uncertainties. No candidate neutrinos have been found in data collected from 1 January 2004 to 31 May 2010. Assuming an E-2 differential energy spectrum the limit on the single-flavor neutrino is E(2)dN/dE < 1.74 x 10(-7)GeVcm(-2)s(-1)sr(-1) at 90% C.L. in the energy range 1 x 10(17) eV < E < 1 x 10(20)eV.