Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial

AIMS The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes. METHODS AND RESULTS Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates. CONCLUSIONS The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.

Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

OBJECTIVE Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. DESIGN HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. RESULTS HLA-A*11:01 (OR = 1.49 [1.18-1.87] P = 7.0*10-4), C*04:01 (OR = 1.34 [1.10-1.63] P = 3.23*10-3), and B*35:01 (OR=1.46 [1.13-1.89] P = 3.64*10-3) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr9 (OR = 1.32 [1.15-1.52] P = 6.95*10-5) and HLA-C-Ser11 (OR=1.34 [1.15-1.57] P = 2.43*10-4). CONCLUSIONS Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons.

Team: Bee Me. A formulative evaluation of a negative eating attitudes and behaviors primary prevention curriculum targeted at 5 th grade elementary school girls

Objective. To evaluate a school-based intervention aimed at the primary prevention of negative eating attitudes and behaviors among preadolescent girls, and to revise curriculum lessons based on quantitative and qualitative findings. ^ Intervention Design. A formative evaluation was conducted on four Team: Bee Me curriculum lessons at a Houston elementary school. Evaluation focused on program satisfaction and short-term effect on knowledge and eating attitudes and behaviors. ^ Results. Sixteen girls participated in the five-day project. Statistically significant improvements in overall knowledge were observed (p<0.05), however only modest changes were observed in eating attitudes and behaviors. Program satisfaction was high among student participants and the teacher who implemented it. Insight for future modifications to this program and for similar interventions was provided by the students and teacher. ^ Conclusions. This program led to positive trends in outcome variables; however longer and more intensive testing of this program is needed to better evaluate its effectiveness.^

Report on the practice based culminating experience as teaching assistant for "Pathology and Public Health" class taught at University of Texas School of Public Health, Houston

Objectives. The objectives of this report were to describe current best standards in online education, class competencies, class objectives, class activities and to compare the class competencies, objectives and activities undertaken with the current best practices in online teaching and to provide a list of recommendations based on the most efficacious practices. ^ Methods. Utilizing the key words- online teaching, national standards, quality, online courses, I: (1) conducted a search on Google to find the best standard for quality online courses; the search yielded National Standards for Quality Online Teaching as the gold standard in online course quality; (2) specified class objectives and competencies as well as major activities undertaken as a part of the class. Utilizing the Southern Regional Education Board evaluation checklist for online courses, I: (1) performed an analysis comparing the class activities, objectives, and competencies with the current best standards; (2) utilized the information obtained from the analysis and class experiences to develop recommendations for the most efficacious online teaching practices. ^ Results. The class met the criteria set by the Southern Regional Education Board for evaluating online classes completely in 75%, partially in 16% and did not meet the criteria in 9% cases. The majority of the parameters in which the class did not meet the standards (4 of 5) were due to technological reasons beyond the scope of the class instructor, teaching assistant and instructional design. ^ Discussion. Successful online teaching requires awareness of technology, good communication, methods, collaboration, reflection and flexibility. Creation of an online community, engaging online learners and utilizing different learning styles and assessment methods promote learning. My report proposes that online teaching should actively engage the students and teachers with multiple interactive strategies as evidenced from current best standards of online education and my “hands-on” work experience. ^ Conclusion. The report and the ideas presented are intended to create a foundation for efficacious practice on the online teaching platform. By following many of the efficacious online practices described in the report and adding from their own experiences, online instructors and teaching assistants can contribute to effective online learning. ^

On-Chip Thermal Monitoring: Design, Placement and Interconnection of Temperature Sensors

La temperatura es una preocupación que juega un papel protagonista en el diseño de circuitos integrados modernos. El importante aumento de las densidades de potencia que conllevan las últimas generaciones tecnológicas ha producido la aparición de gradientes térmicos y puntos calientes durante el funcionamiento normal de los chips. La temperatura tiene un impacto negativo en varios parámetros del circuito integrado como el retardo de las puertas, los gastos de disipación de calor, la fiabilidad, el consumo de energía, etc. Con el fin de luchar contra estos efectos nocivos, la técnicas de gestión dinámica de la temperatura (DTM) adaptan el comportamiento del chip en función en la información que proporciona un sistema de monitorización que mide en tiempo de ejecución la información térmica de la superficie del dado. El campo de la monitorización de la temperatura en el chip ha llamado la atención de la comunidad científica en los últimos años y es el objeto de estudio de esta tesis. Esta tesis aborda la temática de control de la temperatura en el chip desde diferentes perspectivas y niveles, ofreciendo soluciones a algunos de los temas más importantes. Los niveles físico y circuital se cubren con el diseño y la caracterización de dos nuevos sensores de temperatura especialmente diseñados para los propósitos de las técnicas DTM. El primer sensor está basado en un mecanismo que obtiene un pulso de anchura variable dependiente de la relación de las corrientes de fuga con la temperatura. De manera resumida, se carga un nodo del circuito y posteriormente se deja flotando de tal manera que se descarga a través de las corrientes de fugas de un transistor; el tiempo de descarga del nodo es la anchura del pulso. Dado que la anchura del pulso muestra una dependencia exponencial con la temperatura, la conversión a una palabra digital se realiza por medio de un contador logarítmico que realiza tanto la conversión tiempo a digital como la linealización de la salida. La estructura resultante de esta combinación de elementos se implementa en una tecnología de 0,35 _m. El sensor ocupa un área muy reducida, 10.250 nm2, y consume muy poca energía, 1.05-65.5nW a 5 muestras/s, estas cifras superaron todos los trabajos previos en el momento en que se publicó por primera vez y en el momento de la publicación de esta tesis, superan a todas las implementaciones anteriores fabricadas en el mismo nodo tecnológico. En cuanto a la precisión, el sensor ofrece una buena linealidad, incluso sin calibrar; se obtiene un error 3_ de 1,97oC, adecuado para tratar con las aplicaciones de DTM. Como se ha explicado, el sensor es completamente compatible con los procesos de fabricación CMOS, este hecho, junto con sus valores reducidos de área y consumo, lo hacen especialmente adecuado para la integración en un sistema de monitorización de DTM con un conjunto de monitores empotrados distribuidos a través del chip. Las crecientes incertidumbres de proceso asociadas a los últimos nodos tecnológicos comprometen las características de linealidad de nuestra primera propuesta de sensor. Con el objetivo de superar estos problemas, proponemos una nueva técnica para obtener la temperatura. La nueva técnica también está basada en las dependencias térmicas de las corrientes de fuga que se utilizan para descargar un nodo flotante. La novedad es que ahora la medida viene dada por el cociente de dos medidas diferentes, en una de las cuales se altera una característica del transistor de descarga |la tensión de puerta. Este cociente resulta ser muy robusto frente a variaciones de proceso y, además, la linealidad obtenida cumple ampliamente los requisitos impuestos por las políticas DTM |error 3_ de 1,17oC considerando variaciones del proceso y calibrando en dos puntos. La implementación de la parte sensora de esta nueva técnica implica varias consideraciones de diseño, tales como la generación de una referencia de tensión independiente de variaciones de proceso, que se analizan en profundidad en la tesis. Para la conversión tiempo-a-digital, se emplea la misma estructura de digitalización que en el primer sensor. Para la implementación física de la parte de digitalización, se ha construido una biblioteca de células estándar completamente nueva orientada a la reducción de área y consumo. El sensor resultante de la unión de todos los bloques se caracteriza por una energía por muestra ultra baja (48-640 pJ) y un área diminuta de 0,0016 mm2, esta cifra mejora todos los trabajos previos. Para probar esta afirmación, se realiza una comparación exhaustiva con más de 40 propuestas de sensores en la literatura científica. Subiendo el nivel de abstracción al sistema, la tercera contribución se centra en el modelado de un sistema de monitorización que consiste de un conjunto de sensores distribuidos por la superficie del chip. Todos los trabajos anteriores de la literatura tienen como objetivo maximizar la precisión del sistema con el mínimo número de monitores. Como novedad, en nuestra propuesta se introducen nuevos parámetros de calidad aparte del número de sensores, también se considera el consumo de energía, la frecuencia de muestreo, los costes de interconexión y la posibilidad de elegir diferentes tipos de monitores. El modelo se introduce en un algoritmo de recocido simulado que recibe la información térmica de un sistema, sus propiedades físicas, limitaciones de área, potencia e interconexión y una colección de tipos de monitor; el algoritmo proporciona el tipo seleccionado de monitor, el número de monitores, su posición y la velocidad de muestreo _optima. Para probar la validez del algoritmo, se presentan varios casos de estudio para el procesador Alpha 21364 considerando distintas restricciones. En comparación con otros trabajos previos en la literatura, el modelo que aquí se presenta es el más completo. Finalmente, la última contribución se dirige al nivel de red, partiendo de un conjunto de monitores de temperatura de posiciones conocidas, nos concentramos en resolver el problema de la conexión de los sensores de una forma eficiente en área y consumo. Nuestra primera propuesta en este campo es la introducción de un nuevo nivel en la jerarquía de interconexión, el nivel de trillado (o threshing en inglés), entre los monitores y los buses tradicionales de periféricos. En este nuevo nivel se aplica selectividad de datos para reducir la cantidad de información que se envía al controlador central. La idea detrás de este nuevo nivel es que en este tipo de redes la mayoría de los datos es inútil, porque desde el punto de vista del controlador sólo una pequeña cantidad de datos |normalmente sólo los valores extremos| es de interés. Para cubrir el nuevo nivel, proponemos una red de monitorización mono-conexión que se basa en un esquema de señalización en el dominio de tiempo. Este esquema reduce significativamente tanto la actividad de conmutación sobre la conexión como el consumo de energía de la red. Otra ventaja de este esquema es que los datos de los monitores llegan directamente ordenados al controlador. Si este tipo de señalización se aplica a sensores que realizan conversión tiempo-a-digital, se puede obtener compartición de recursos de digitalización tanto en tiempo como en espacio, lo que supone un importante ahorro de área y consumo. Finalmente, se presentan dos prototipos de sistemas de monitorización completos que de manera significativa superan la características de trabajos anteriores en términos de área y, especialmente, consumo de energía. Abstract Temperature is a first class design concern in modern integrated circuits. The important increase in power densities associated to recent technology evolutions has lead to the apparition of thermal gradients and hot spots during run time operation. Temperature impacts several circuit parameters such as speed, cooling budgets, reliability, power consumption, etc. In order to fight against these negative effects, dynamic thermal management (DTM) techniques adapt the behavior of the chip relying on the information of a monitoring system that provides run-time thermal information of the die surface. The field of on-chip temperature monitoring has drawn the attention of the scientific community in the recent years and is the object of study of this thesis. This thesis approaches the matter of on-chip temperature monitoring from different perspectives and levels, providing solutions to some of the most important issues. The physical and circuital levels are covered with the design and characterization of two novel temperature sensors specially tailored for DTM purposes. The first sensor is based upon a mechanism that obtains a pulse with a varying width based on the variations of the leakage currents on the temperature. In a nutshell, a circuit node is charged and subsequently left floating so that it discharges away through the subthreshold currents of a transistor; the time the node takes to discharge is the width of the pulse. Since the width of the pulse displays an exponential dependence on the temperature, the conversion into a digital word is realized by means of a logarithmic counter that performs both the timeto- digital conversion and the linearization of the output. The structure resulting from this combination of elements is implemented in a 0.35_m technology and is characterized by very reduced area, 10250 nm2, and power consumption, 1.05-65.5 nW at 5 samples/s, these figures outperformed all previous works by the time it was first published and still, by the time of the publication of this thesis, they outnumber all previous implementations in the same technology node. Concerning the accuracy, the sensor exhibits good linearity, even without calibration it displays a 3_ error of 1.97oC, appropriate to deal with DTM applications. As explained, the sensor is completely compatible with standard CMOS processes, this fact, along with its tiny area and power overhead, makes it specially suitable for the integration in a DTM monitoring system with a collection of on-chip monitors distributed across the chip. The exacerbated process fluctuations carried along with recent technology nodes jeop-ardize the linearity characteristics of the first sensor. In order to overcome these problems, a new temperature inferring technique is proposed. In this case, we also rely on the thermal dependencies of leakage currents that are used to discharge a floating node, but now, the result comes from the ratio of two different measures, in one of which we alter a characteristic of the discharging transistor |the gate voltage. This ratio proves to be very robust against process variations and displays a more than suficient linearity on the temperature |1.17oC 3_ error considering process variations and performing two-point calibration. The implementation of the sensing part based on this new technique implies several issues, such as the generation of process variations independent voltage reference, that are analyzed in depth in the thesis. In order to perform the time-to-digital conversion, we employ the same digitization structure the former sensor used. A completely new standard cell library targeting low area and power overhead is built from scratch to implement the digitization part. Putting all the pieces together, we achieve a complete sensor system that is characterized by ultra low energy per conversion of 48-640pJ and area of 0.0016mm2, this figure outperforms all previous works. To prove this statement, we perform a thorough comparison with over 40 works from the scientific literature. Moving up to the system level, the third contribution is centered on the modeling of a monitoring system consisting of set of thermal sensors distributed across the chip. All previous works from the literature target maximizing the accuracy of the system with the minimum number of monitors. In contrast, we introduce new metrics of quality apart form just the number of sensors; we consider the power consumption, the sampling frequency, the possibility to consider different types of monitors and the interconnection costs. The model is introduced in a simulated annealing algorithm that receives the thermal information of a system, its physical properties, area, power and interconnection constraints and a collection of monitor types; the algorithm yields the selected type of monitor, the number of monitors, their position and the optimum sampling rate. We test the algorithm with the Alpha 21364 processor under several constraint configurations to prove its validity. When compared to other previous works in the literature, the modeling presented here is the most complete. Finally, the last contribution targets the networking level, given an allocated set of temperature monitors, we focused on solving the problem of connecting them in an efficient way from the area and power perspectives. Our first proposal in this area is the introduction of a new interconnection hierarchy level, the threshing level, in between the monitors and the traditional peripheral buses that applies data selectivity to reduce the amount of information that is sent to the central controller. The idea behind this new level is that in this kind of networks most data are useless because from the controller viewpoint just a small amount of data |normally extreme values| is of interest. To cover the new interconnection level, we propose a single-wire monitoring network based on a time-domain signaling scheme that significantly reduces both the switching activity over the wire and the power consumption of the network. This scheme codes the information in the time domain and allows a straightforward obtention of an ordered list of values from the maximum to the minimum. If the scheme is applied to monitors that employ TDC, digitization resource sharing is achieved, producing an important saving in area and power consumption. Two prototypes of complete monitoring systems are presented, they significantly overcome previous works in terms of area and, specially, power consumption.

Multiobjective optimization applied to structural sizing of low cost university-class microsatellite projects

In recent years, there has been continuing interest in the participation of university research groups in space technology studies by means of their own microsatellites. The involvement in such projects has some inherent challenges, such as limited budget and facilities. Also, due to the fact that the main objective of these projects is for educational purposes, usually there are uncertainties regarding their in orbit mission and scientific payloads at the early phases of the project. On the other hand, there are predetermined limitations for their mass and volume budgets owing to the fact that most of them are launched as an auxiliary payload in which the launch cost is reduced considerably. The satellite structure subsystem is the one which is most affected by the launcher constraints. This can affect different aspects, including dimensions, strength and frequency requirements. In this paper, the main focus is on developing a structural design sizing tool containing not only the primary structures properties as variables but also the system level variables such as payload mass budget and satellite total mass and dimensions. This approach enables the design team to obtain better insight into the design in an extended design envelope. The structural design sizing tool is based on analytical structural design formulas and appropriate assumptions including both static and dynamic models of the satellite. Finally, a Genetic Algorithm (GA) multiobjective optimization is applied to the design space. The result is a Pareto-optimal based on two objectives, minimum satellite total mass and maximum payload mass budget, which gives a useful insight to the design team at the early phases of the design.

Virtual Excursions: a new way to explore science in class

The educational platform Virtual Science Hub (ViSH) has been developed as part of the GLOBAL excursion European project. ViSH (http://vishub.org/) is a portal where teachers and scientist interact to create virtual excursions to science infrastructures. The main motivation behind the project was to connect teachers - and in consequence their students - to scientific institutions and their wide amount of infrastructures and resources they are working with. Thus the idea of a hub was born that would allow the two worlds of scientists and teachers to connect and to innovate science teaching. The core of the ViSH?s concept design is based on virtual excursions, which allow for a number of pedagogical models to be applied. According to our internal definition a virtual excursion is a tour through some digital context by teachers and pupils on a given topic that is attractive and has an educational purpose. Inquiry-based learning, project-based and problem-based learning are the most prominent approaches that a virtual excursion may serve. The domain specific resources and scientific infrastructures currently available on the ViSH are focusing on life sciences, nano-technology, biotechnology, grid and volunteer computing. The virtual excursion approach allows an easy combination of these resources into interdisciplinary teaching scenarios. In addition, social networking features support the users in collaborating and communicating in relation to these excursions and thus create a community of interest for innovative science teaching. The design and development phases were performed following a participatory design approach. An important aspect in this process was to create design partnerships amongst all actors involved, researchers, developers, infrastructure providers, teachers, social scientists, and pedagogical experts early in the project. A joint sense of ownership was created and important changes during the conceptual phase were implemented in the ViSH due to early user feedback. Technology-wise the ViSH is based on the latest web technologies in order to make it cross-platform compatible so that it works on several operative systems such as Windows, Mac or Linux and multi-device accessible, such as desktop, tablet and mobile devices. The platform has been developed in HTML5, the latest standard for web development, assuring that it can run on any modern browser. In addition to social networking features a core element on the ViSH is the virtual excursions editor. It is a web tool that allows teachers and scientists to create rich mash-ups of learning resources provided by the e-Infrastructures (i.e. remote laboratories and live webcams). These rich mash-ups can be presented in either slides or flashcards format. Taking advantage of the web architecture supported, additional powerful components have been integrated like a recommendation engine to provide personalized suggestions about educational content or interesting users and a videoconference tool to enhance real-time collaboration like MashMeTV (http://www.mashme.tv/).

Assesing the usefulness of the ACM/IEEE-CS Computing Curricula for the design of Computer-Related Engineering Curricula, an experience in Telematics

This paper presents the rationale to build up a Telematics Engineering curriculum. Telematics is a strongly computing oriented area; then, the authors have initially intended to apply the common requirements described in the computing curricula elaborated by the ACM/EEEE-CS Joint Curriculum Task Force. This experience has revealed some problematic aspects in the ACM/IEEE-CS proposal. From the analysis of these problems, a model to guide the selection and specially the approach of the Telematics curriculum contents is proposed. This model can be easily generalized to other strongly computing oriented curricula, whose number is growing everyday

Enhancing K-12 science education through a multi-device web tool to facilitate content integration and e-infrastructure access

An effective K-12 science education is essential to succeed in future phases of the curriculum and the e-Infrastructures for education provide new opportunities to enhance it. This paper presents ViSH Viewer, an innovative web tool to consume educational content which aims to facilitate e-Science infrastructures access through a next generation learning object called "Virtual Excursion". Virtual Excursions provide a new way to explore science in class by taking advantage of e-Infrastructure resources and their integration with other educational contents, resulting in the creation of a reusable, interoperable and granular learning object. In order to better understand how this tool can allow teachers and students a joyful exploration of e-Science, we also present three Virtual Excursion examples. Details about the design, development and the tool itself are explained in this paper as well as the concept, structure and metadata of the new learning object.

Quasiperiodic Graphs: Structural Design, Scaling and Entropic Properties

A novel class of graphs, here named quasiperiodic, are const ructed via application of the Horizontal Visibility algorithm to the time series generated along the quasiperiodic route to chaos. We show how the hierarchy of mode-locked regions represented by the Far ey tree is inherited by their associated graphs. We are able to establish, via Renormalization Group (RG) theory, the architecture of the quasiperiodic graphs produced by irrational winding numbers with pure periodic continued fraction. And finally, we demonstrate that the RG fixed-point degree distributions are recovered via optimization of a suitably defined graph entropy

"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.

Design and demonstration of an electronically scanned reflectarray antenna at 100 GHz using multiresonant cells based on liquid crystals

The design, fabrication and measured results are presented for a reconfigurable reflectarray antenna based on liquid crystals (LC) which operates above 100 GHz. The antenna has been designed to provide beam scanning capabilities over a wide angular range, a large bandwidth and reduced Side-Lobe Level. Measured radiation patterns are in good agreement with simulations, and show that the antenna generates an electronically steerable beam in one plane over an angular range of 55º in the frequency band from 96 to 104 GHz. The Side Lobes Level is lower than -13 dB for all the scan angles and -18 dB is obtained over 16% of the scan range. The measured performance is significantly better than previously published results for this class of electronically tunable antenna, and moreover verifies the accuracy of the proposed procedure for LC modeling and antenna design.

The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1

The bryostatins are a unique family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa. Although the biochemical basis for their therapeutic activity is not known, these macrolactones exhibit high affinities for protein kinase C (PKC) isozymes, compete for the phorbol ester binding site on PKC, and stimulate kinase activity in vitro and in vivo. Unlike the phorbol esters, they are not first-stage tumor promoters. The design, computer modeling, NMR solution structure, PKC binding, and functional assays of a unique class of synthetic bryostatin analogs are described. These analogs (7b, 7c, and 8) retain the putative recognition domain of the bryostatins but are simplified through deletions and modifications in the C4-C14 spacer domain. Computer modeling of an analog prototype (7a) indicates that it exists preferentially in two distinct conformational classes, one in close agreement with the crystal structure of bryostatin 1. The solution structure of synthetic analog 7c was determined by NMR spectroscopy and found to be very similar to the previously reported structures of bryostatins 1 and 10. Analogs 7b, 7c, and 8 bound strongly to PKC isozymes with Ki = 297, 3.4, and 8.3 nM, respectively. Control 7d, like the corresponding bryostatin derivative, exhibited weak PKC affinity, as did the derivative, 9, lacking the spacer domain. Like bryostatin, acetal 7c exhibited significant levels of in vitro growth inhibitory activity (1.8–170 ng/ml) against several human cancer cell lines, providing an important step toward the development of simplified, synthetically accessible analogs of the bryostatins.

Design of compounds that increase the absorption of polar molecules

Hydrophilic drugs are often poorly absorbed when administered orally. There has been considerable interest in the possibility of using absorption enhancers to promote absorption of polar molecules across membrane surfaces. The bile acids are one of the most widely investigated classes of absorption enhancers, but there is disagreement about what features of bile acid enhancers are responsible for their efficacy. We have designed a class of glycosylated bile acid derivatives to evaluate how increasing the hydrophilicity of the steroid nucleus affects the ability to transport polar molecules across membranes. Some of the glycosylated molecules are significantly more effective than taurocholate in promoting the intestinal absorption of a range of drugs, showing that hydrophobicity is not a critical parameter in transport efficacy, as previously suggested. Furthermore, the most effective glycosylated compound is also far less damaging to membranes than the best bile acid absorption promoters, presumably because it is more hydrophilic. The results reported here show that it is possible to decouple absorption-promoting activity from membrane damage, a finding that should spark interest in the design of new compounds to facilitate the delivery of polar drugs.