State of Emergency Medicine in Switzerland: a national profile of emergency departments in 2006

BACKGROUND Emergency departments (EDs) are an essential component of any developed health care system. There is, however, no national description of EDs in Switzerland. Our objective was to establish the number and location of EDs, patient visits and flow, medical staff and organization, and capabilities in 2006, as a benchmark before emergency medicine became a subspecialty in Switzerland. METHODS In 2007, we started to create an inventory of all hospital-based EDs with a preliminary list from the Swiss Society of Emergency and Rescue Medicine that was improved with input from ED physicians nationwide. EDs were eligible if they offered acute care 24 h per day, 7 days per week. Our goal was to have 2006 data from at least 80% of all EDs. The survey was initiated in 2007 and the 80% threshold reached in 2012. RESULTS In 2006, Switzerland had a total of 138 hospital-based EDs. The number of ED visits was 1.475 million visits or 20 visits per 100 inhabitants. The median number of visits was 8,806 per year; 25% of EDs admitted 5,000 patients or less, 31% 5,001-10,000 patients, 26% 10,001-20,000 patients, and 17% >20,000 patients per year. Crowding was reported by 84% of EDs with >20,000 visits/year. Residents with limited experience provided care for 77% of visits. Imaging was not immediately available for all patients: standard X-ray within 15 min (70%), non-contrast head CT scan within 15 min (38%), and focused sonography for trauma (70%); 67% of EDs had an intensive care unit within the hospital, and 87% had an operating room always available. CONCLUSIONS Swiss EDs were significant providers of health care in 2006. Crowding, physicians with limited experience, and the heterogeneity of emergency care capabilities were likely threats to the ubiquitous and consistent delivery of quality emergency care, particularly for time-sensitive conditions. Our survey establishes a benchmark to better understand future improvements in Swiss emergency care.

Iron X-ray fluorescence (XRF) scannings of ODP Holes 165-1001A and 171-1050C

Abstract: Ocean Drilling Program Sites 1001A (Caribbean Sea) and 1050C (western North Atlantic) display obliquity and precession cycles throughout polarity zone C27 of the late Danian stage (earliest Cenozoic time). Sliding-window spectra analysis and direct cycle counting on downhole logs and high-resolution Fe variations at both sites yield the equivalent of 35-36 obliquity cycles. This cycle-tuned duration for polarity chron C27 of 1.45 Ma (applying a modern mean obliquity period of 40.4 ka) is consistent with trends from astronomical tuning of early Danian polarity chron C29 and 40Ar/39Ar age calibration of the Campanian-Maastrichtian magnetic polarity time scale. The cycle-tuned Danian stage (sensu Berggren et al. 1995, in SEPM Special Publications, 54, 129-212) spans 3.65 Ma (65.5-61.85 Ma). Spreading rates on a reference South Atlantic synthetic profile display progressive slowing during the Maastrichtian to Danian stages, then remained relatively constant through late Palaeocene and early Eocene time.

Testing the Weak Equivalence Principle with an antimatter beam at CERN

The goal of the AEgIS experiment is to measure the gravitational acceleration of antihydrogen – the simplest atom consisting entirely of antimatter – with the ultimate precision of 1%. We plan to verify the Weak Equivalence Principle (WEP), one of the fundamental laws of nature, with an antimatter beam. The experiment consists of a positron accumulator, an antiproton trap and a Stark accelerator in a solenoidal magnetic field to form and accelerate a pulsed beam of antihydrogen atoms towards a free-fall detector. The antihydrogen beam passes through a moir ́e deflectometer to measure the vertical displacement due to the gravitational force. A position and time sensitive hybrid detector registers the annihilation points of the antihydrogen atoms and their time-of-flight. The detection principle has been successfully tested with antiprotons and a miniature moir ́e deflectometer coupled to a nuclear emulsion detector.

Energy and power aware scheduling algorithm modeling for battery powered embedded systems

Energy management has always been recognized as a challenge in mobile systems, especially in modern OS-based mobile systems where multi-functioning are widely supported. Nowadays, it is common for a mobile system user to run multiple applications simultaneously while having a target battery lifetime in mind for a specific application. Traditional OS-level power management (PM) policies make their best effort to save energy under performance constraint, but fail to guarantee a target lifetime, leaving the painful trading off between the total performance of applications and the target lifetime to the user itself. This thesis provides a new way to deal with the problem. It is advocated that a strong energy-aware PM scheme should first guarantee a user-specified battery lifetime to a target application by restricting the average power of those less important applications, and in addition to that, maximize the total performance of applications without harming the lifetime guarantee. As a support, energy, instead of CPU or transmission bandwidth, should be globally managed as the first-class resource by the OS. As the first-stage work of a complete PM scheme, this thesis presents the energy-based fair queuing scheduling, a novel class of energy-aware scheduling algorithms which, in combination with a mechanism of battery discharge rate restricting, systematically manage energy as the first-class resource with the objective of guaranteeing a user-specified battery lifetime for a target application in OS-based mobile systems. Energy-based fair queuing is a cross-application of the traditional fair queuing in the energy management domain. It assigns a power share to each task, and manages energy by proportionally serving energy to tasks according to their assigned power shares. The proportional energy use establishes proportional share of the system power among tasks, which guarantees a minimum power for each task and thus, avoids energy starvation on any task. Energy-based fair queuing treats all tasks equally as one type and supports periodical time-sensitive tasks by allocating each of them a share of system power that is adequate to meet the highest energy demand in all periods. However, an overly conservative power share is usually required to guarantee the meeting of all time constraints. To provide more effective and flexible support for various types of time-sensitive tasks in general purpose operating systems, an extra real-time friendly mechanism is introduced to combine priority-based scheduling into the energy-based fair queuing. Since a method is available to control the maximum time one time-sensitive task can run with priority, the power control and time-constraint meeting can be flexibly traded off. A SystemC-based test-bench is designed to assess the algorithms. Simulation results show the success of the energy-based fair queuing in achieving proportional energy use, time-constraint meeting, and a proper trading off between them. La gestión de energía en los sistema móviles está considerada hoy en día como un reto fundamental, notándose, especialmente, en aquellos terminales que utilizando un sistema operativo implementan múltiples funciones. Es común en los sistemas móviles actuales ejecutar simultaneamente diferentes aplicaciones y tener, para una de ellas, un objetivo de tiempo de uso de la batería. Tradicionalmente, las políticas de gestión de consumo de potencia de los sistemas operativos hacen lo que está en sus manos para ahorrar energía y satisfacer sus requisitos de prestaciones, pero no son capaces de proporcionar un objetivo de tiempo de utilización del sistema, dejando al usuario la difícil tarea de buscar un compromiso entre prestaciones y tiempo de utilización del sistema. Esta tesis, como contribución, proporciona una nueva manera de afrontar el problema. En ella se establece que un esquema de gestión de consumo de energía debería, en primer lugar, garantizar, para una aplicación dada, un tiempo mínimo de utilización de la batería que estuviera especificado por el usuario, restringiendo la potencia media consumida por las aplicaciones que se puedan considerar menos importantes y, en segundo lugar, maximizar las prestaciones globales sin comprometer la garantía de utilización de la batería. Como soporte de lo anterior, la energía, en lugar del tiempo de CPU o el ancho de banda, debería gestionarse globalmente por el sistema operativo como recurso de primera clase. Como primera fase en el desarrollo completo de un esquema de gestión de consumo, esta tesis presenta un algoritmo de planificación de encolado equitativo (fair queueing) basado en el consumo de energía, es decir, una nueva clase de algoritmos de planificación que, en combinación con mecanismos que restrinjan la tasa de descarga de una batería, gestionen de forma sistemática la energía como recurso de primera clase, con el objetivo de garantizar, para una aplicación dada, un tiempo de uso de la batería, definido por el usuario, en sistemas móviles empotrados. El encolado equitativo de energía es una extensión al dominio de la energía del encolado equitativo tradicional. Esta clase de algoritmos asigna una reserva de potencia a cada tarea y gestiona la energía sirviéndola de manera proporcional a su reserva. Este uso proporcional de la energía garantiza que cada tarea reciba una porción de potencia y evita que haya tareas que se vean privadas de recibir energía por otras con un comportamiento más ambicioso. Esta clase de algoritmos trata a todas las tareas por igual y puede planificar tareas periódicas en tiempo real asignando a cada una de ellas una reserva de potencia que es adecuada para proporcionar la mayor de las cantidades de energía demandadas por período. Sin embargo, es posible demostrar que sólo se consigue cumplir con los requisitos impuestos por todos los plazos temporales con reservas de potencia extremadamente conservadoras. En esta tesis, para proporcionar un soporte más flexible y eficiente para diferentes tipos de tareas de tiempo real junto con el resto de tareas, se combina un mecanismo de planificación basado en prioridades con el encolado equitativo basado en energía. En esta clase de algoritmos, gracias al método introducido, que controla el tiempo que se ejecuta con prioridad una tarea de tiempo real, se puede establecer un compromiso entre el cumplimiento de los requisitos de tiempo real y el consumo de potencia. Para evaluar los algoritmos, se ha diseñado en SystemC un banco de pruebas. Los resultados muestran que el algoritmo de encolado equitativo basado en el consumo de energía consigue el balance entre el uso proporcional a la energía reservada y el cumplimiento de los requisitos de tiempo real.

Adaptive protection scheme for MVC-encoded stereoscopic video streaming in IP-based networks

We present an adaptive unequal error protection (UEP) strategy built on the 1-D interleaved parity Application Layer Forward Error Correction (AL-FEC) code for protecting the transmission of stereoscopic 3D video content encoded with Multiview Video Coding (MVC) through IP-based networks. Our scheme targets the minimization of quality degradation produced by packet losses during video transmission in time-sensitive application scenarios. To that end, based on a novel packet-level distortion model, it selects in real time the most suitable packets within each Group of Pictures (GOP) to be protected and the most convenient FEC technique parameters, i.e., the size of the FEC generator matrix. In order to make these decisions, it considers the relevance of the packet, the behavior of the channel, and the available bitrate for protection purposes. Simulation results validate both the distortion model introduced to estimate the importance of packets and the optimization of the FEC technique parameter values.

Energy-based Fair Queuing: Energy-centric Processor Scheduling Algorithm for Battery-limited Mobile Systems

Los dispositivos móviles modernos disponen cada vez de más funcionalidad debido al rápido avance de las tecnologías de las comunicaciones y computaciones móviles. Sin embargo, la capacidad de la batería no ha experimentado un aumento equivalente. Por ello, la experiencia de usuario en los sistemas móviles modernos se ve muy afectada por la vida de la batería, que es un factor inestable de difícil de control. Para abordar este problema, investigaciones anteriores han propuesto un esquema de gestion del consumo (PM) centrada en la energía y que proporciona una garantía sobre la vida operativa de la batería mediante la gestión de la energía como un recurso de primera clase en el sistema. Como el planificador juega un papel fundamental en la administración del consumo de energía y en la garantía del rendimiento de las aplicaciones, esta tesis explora la optimización de la experiencia de usuario para sistemas móviles con energía limitada desde la perspectiva de un planificador que tiene en cuenta el consumo de energía en un contexto en el que ésta es un recurso de primera clase. En esta tesis se analiza en primer lugar los factores que contribuyen de forma general a la experiencia de usuario en un sistema móvil. Después se determinan los requisitos esenciales que afectan a la experiencia de usuario en la planificación centrada en el consumo de energía, que son el reparto proporcional de la potencia, el cumplimiento de las restricciones temporales, y cuando sea necesario, el compromiso entre la cuota de potencia y las restricciones temporales. Para cumplir con los requisitos, el algoritmo clásico de fair queueing y su modelo de referencia se extienden desde los dominios de las comunicaciones y ancho de banda de CPU hacia el dominio de la energía, y en base a ésto, se propone el algoritmo energy-based fair queueing (EFQ) para proporcionar una planificación basada en la energía. El algoritmo EFQ está diseñado para compartir la potencia consumida entre las tareas mediante su planificación en función de la energía consumida y de la cuota reservada. La cuota de consumo de cada tarea con restricciones temporales está protegida frente a diversos cambios que puedan ocurrir en el sistema. Además, para dar mejor soporte a las tareas en tiempo real y multimedia, se propone un mecanismo para combinar con el algoritmo EFQ para dar preferencia en la planificación durante breves intervalos de tiempo a las tareas más urgentes con restricciones temporales.Las propiedades del algoritmo EFQ se evaluan a través del modelado de alto nivel y la simulación. Los resultados de las simulaciones indican que los requisitos esenciales de la planificación centrada en la energía pueden lograrse. El algoritmo EFQ se implementa más tarde en el kernel de Linux. Para evaluar las propiedades del planificador EFQ basado en Linux, se desarrolló un banco de pruebas experimental basado en una sitema empotrado, un programa de banco de pruebas multihilo, y un conjunto de pruebas de código abierto. A través de experimentos específicamente diseñados, esta tesis verifica primero las propiedades de EFQ en la gestión de la cuota de consumo de potencia y la planificación en tiempo real y, a continuación, explora los beneficios potenciales de emplear la planificación EFQ en la optimización de la experiencia de usuario para sistemas móviles con energía limitada. Los resultados experimentales sobre la gestión de la cuota de energía muestran que EFQ es más eficaz que el planificador de Linux-CFS en la gestión de energía, logrando un reparto proporcional de la energía del sistema independientemente de en qué dispositivo se consume la energía. Los resultados experimentales en la planificación en tiempo real demuestran que EFQ puede lograr de forma eficaz, flexible y robusta el cumplimiento de las restricciones temporales aunque se dé el caso de aumento del el número de tareas o del error en la estimación de energía. Por último, un análisis comparativo de los resultados experimentales sobre la optimización de la experiencia del usuario demuestra que, primero, EFQ es más eficaz y flexible que los algoritmos tradicionales de planificación del procesador, como el que se encuentra por defecto en el planificador de Linux y, segundo, que proporciona la posibilidad de optimizar y preservar la experiencia de usuario para los sistemas móviles con energía limitada. Abstract Modern mobiledevices have been becoming increasingly powerful in functionality and entertainment as the next-generation mobile computing and communication technologies are rapidly advanced. However, the battery capacity has not experienced anequivalent increase. The user experience of modern mobile systems is therefore greatly affected by the battery lifetime,which is an unstable factor that is hard to control. To address this problem, previous works proposed energy-centric power management (PM) schemes to provide strong guarantee on the battery lifetime by globally managing energy as the first-class resource in the system. As the processor scheduler plays a pivotal role in power management and application performance guarantee, this thesis explores the user experience optimization of energy-limited mobile systemsfrom the perspective of energy-centric processor scheduling in an energy-centric context. This thesis first analyzes the general contributing factors of the mobile system user experience.Then itdetermines the essential requirements on the energy-centric processor scheduling for user experience optimization, which are proportional power sharing, time-constraint compliance, and when necessary, a tradeoff between the power share and the time-constraint compliance. To meet the requirements, the classical fair queuing algorithm and its reference model are extended from the network and CPU bandwidth sharing domain to the energy sharing domain, and based on that, the energy-based fair queuing (EFQ) algorithm is proposed for performing energy-centric processor scheduling. The EFQ algorithm is designed to provide proportional power shares to tasks by scheduling the tasks based on their energy consumption and weights. The power share of each time-sensitive task is protected upon the change of the scheduling environment to guarantee a stable performance, and any instantaneous power share that is overly allocated to one time-sensitive task can be fairly re-allocated to the other tasks. In addition, to better support real-time and multimedia scheduling, certain real-time friendly mechanism is combined into the EFQ algorithm to give time-limited scheduling preference to the time-sensitive tasks. Through high-level modelling and simulation, the properties of the EFQ algorithm are evaluated. The simulation results indicate that the essential requirements of energy-centric processor scheduling can be achieved. The EFQ algorithm is later implemented in the Linux kernel. To assess the properties of the Linux-based EFQ scheduler, an experimental test-bench based on an embedded platform, a multithreading test-bench program, and an open-source benchmark suite is developed. Through specifically-designed experiments, this thesis first verifies the properties of EFQ in power share management and real-time scheduling, and then, explores the potential benefits of employing EFQ scheduling in the user experience optimization for energy-limited mobile systems. Experimental results on power share management show that EFQ is more effective than the Linux-CFS scheduler in managing power shares and it can achieve a proportional sharing of the system power regardless of on which device the energy is spent. Experimental results on real-time scheduling demonstrate that EFQ can achieve effective, flexible and robust time-constraint compliance upon the increase of energy estimation error and task number. Finally, a comparative analysis of the experimental results on user experience optimization demonstrates that EFQ is more effective and flexible than traditional processor scheduling algorithms, such as those of the default Linux scheduler, in optimizing and preserving the user experience of energy-limited mobile systems.

LAICIDADE E ECUMENICIDADE DA IGREJA O Pensamento Eclesiológico de John Wesley

A presente investigação se concentra na eclesiologia prática, experimental e funcional de John Wesley, examinando não apenas o que se encontra explícito em seus escritos sobre a igreja, mas também o que está implícito na práxis social e missionária dos primeiros metodistas. Antes, porém, é traçado um panorama das discussões em torno da concepção wesleyana de igreja, desenvolvidas, sobretudo, nos últimos cinqüenta anos. O valor dessas pesquisas é reconhecido, pois elas ajudaram a criar certa convergência em torno dos principais temas da visão de Wesley. Entretanto, em boa parte delas, nota-se esforço em enquadrar a fragmentada reflexão wesleyana em algum esquema de interpretação previamente definido. De conservador e defensor da Igreja estabelecida a cismático radical, quase todas as qualificações lhe foram atribuídas. É certo que Wesley assimilou a contribuição de várias correntes, o que oferece justa dimensão da complexidade de sua teologia, resistente a explicações simplistas. Nem sempre, porém, se indaga sobre o que determinou as suas preferências. Aqui é sustentada a tese de que não foi o apego a princípios considerados ortodoxos, mas o encontro com o povo que levou Wesley à abertura crescente para uma compreensão da igreja, ao mesmo, sensível ao sofrimento dos excluídos da sociedade inglesa, e flexível para se ajustar a conjunturas em mutação constante. Ele rompeu com a eclesiologia hierárquica, em que foi formado, e pôs em prática uma concepção fundamentalmente laica de igreja. Quebrou o monopólio do clero e tornou realidade o sacerdócio de todos os crentes, tanto de homens quanto de mulheres. Rejeitou o individualismo e valorizou a vida comunitária responsável. Desfez a interpretação paroquialista e exclusivista de igreja e abraçou a ecumenicidade como caráter essencial da Igreja de Cristo. Enfim, centralizou-se na via salutis, na renovação de toda a criação, pela graça de Deus com a participação humana responsável, e relativizou a própria Igreja.

LAICIDADE E ECUMENICIDADE DA IGREJA O Pensamento Eclesiológico de John Wesley

A presente investigação se concentra na eclesiologia prática, experimental e funcional de John Wesley, examinando não apenas o que se encontra explícito em seus escritos sobre a igreja, mas também o que está implícito na práxis social e missionária dos primeiros metodistas. Antes, porém, é traçado um panorama das discussões em torno da concepção wesleyana de igreja, desenvolvidas, sobretudo, nos últimos cinqüenta anos. O valor dessas pesquisas é reconhecido, pois elas ajudaram a criar certa convergência em torno dos principais temas da visão de Wesley. Entretanto, em boa parte delas, nota-se esforço em enquadrar a fragmentada reflexão wesleyana em algum esquema de interpretação previamente definido. De conservador e defensor da Igreja estabelecida a cismático radical, quase todas as qualificações lhe foram atribuídas. É certo que Wesley assimilou a contribuição de várias correntes, o que oferece justa dimensão da complexidade de sua teologia, resistente a explicações simplistas. Nem sempre, porém, se indaga sobre o que determinou as suas preferências. Aqui é sustentada a tese de que não foi o apego a princípios considerados ortodoxos, mas o encontro com o povo que levou Wesley à abertura crescente para uma compreensão da igreja, ao mesmo, sensível ao sofrimento dos excluídos da sociedade inglesa, e flexível para se ajustar a conjunturas em mutação constante. Ele rompeu com a eclesiologia hierárquica, em que foi formado, e pôs em prática uma concepção fundamentalmente laica de igreja. Quebrou o monopólio do clero e tornou realidade o sacerdócio de todos os crentes, tanto de homens quanto de mulheres. Rejeitou o individualismo e valorizou a vida comunitária responsável. Desfez a interpretação paroquialista e exclusivista de igreja e abraçou a ecumenicidade como caráter essencial da Igreja de Cristo. Enfim, centralizou-se na via salutis, na renovação de toda a criação, pela graça de Deus com a participação humana responsável, e relativizou a própria Igreja.

Region-dependent dynamics of cAMP response element-binding protein phosphorylation in the basal ganglia

The cAMP response element-binding protein (CREB) is an activity-dependent transcription factor that is involved in neural plasticity. The kinetics of CREB phosphorylation have been suggested to be important for gene activation, with sustained phosphorylation being associated with downstream gene expression. If so, the duration of CREB phosphorylation might serve as an indicator for time-sensitive plastic changes in neurons. To screen for regions potentially involved in dopamine-mediated plasticity in the basal ganglia, we used organotypic slice cultures to study the patterns of dopamine- and calcium-mediated CREB phosphorylation in the major subdivisions of the striatum. Different durations of CREB phosphorylation were evoked in the dorsal and ventral striatum by activation of dopamine D1-class receptors. The same D1 stimulus elicited (i) transient phosphorylation (≤15 min) in the matrix of the dorsal striatum; (ii) sustained phosphorylation (≤2 hr) in limbic-related structures including striosomes, the nucleus accumbens, the fundus striati, and the bed nucleus of the stria terminalis; and (iii) prolonged phosphorylation (up to 4 hr or more) in cellular islands in the olfactory tubercle. Elevation of Ca2+ influx by stimulation of L-type Ca2+ channels, NMDA, or KCl induced strong CREB phosphorylation in the dorsal striatum but not in the olfactory tubercle. These findings differentiate the response of CREB to dopamine and calcium signals in different striatal regions and suggest that dopamine-mediated CREB phosphorylation is persistent in limbic-related regions of the neonatal basal ganglia. The downstream effects activated by persistent CREB phosphorylation may include time-sensitive neuroplasticity modulated by dopamine.

Role of the cotransporter KCC2 in cortical excitatory synapse development and febrile seizure susceptibility

Le co-transporteur KCC2 spécifique au potassium et chlore a pour rôle principal de réduire la concentration intracellulaire de chlore, entraînant l’hyperpolarisation des courants GABAergic l’autorisant ainsi à devenir inhibiteur dans le cerveau mature. De plus, il est aussi impliqué dans le développement des synapses excitatrices, nommées aussi les épines dendritiques. Le but de notre projet est d’étudier l’effet des modifications concernant l'expression et la fonction de KCC2 dans le cortex du cerveau en développement dans un contexte de convulsions précoces. Les convulsions fébriles affectent environ 5% des enfants, et ce dès la première année de vie. Les enfants atteints de convulsions fébriles prolongées et atypiques sont plus susceptibles à développer l’épilepsie. De plus, la présence d’une malformation cérébrale prédispose au développement de convulsions fébriles atypiques, et d’épilepsie du lobe temporal. Ceci suggère que ces pathologies néonatales peuvent altérer le développement des circuits neuronaux irréversiblement. Cependant, les mécanismes qui sous-tendent ces effets ne sont pas encore compris. Nous avons pour but de comprendre l'impact des altérations de KCC2 sur la survenue des convulsions et dans la formation des épines dendritiques. Nous avons étudié KCC2 dans un modèle animal de convulsions précédemment validé, qui combine une lésion corticale à P1 (premier jour de vie postnatale), suivie d'une convulsion induite par hyperthermie à P10 (nommés rats LHS). À la suite de ces insultes, 86% des rats mâles LHS développent l’épilepsie à l’âge adulte, au même titre que des troubles d’apprentissage. À P20, ces animaux presentent une augmentation de l'expression de KCC2 associée à une hyperpolarisation du potentiel de réversion de GABA. De plus, nous avons observé des réductions dans la taille des épines dendritiques et l'amplitude des courants post-synaptiques excitateurs miniatures, ainsi qu’un déficit de mémoire spatial, et ce avant le développement des convulsions spontanées. Dans le but de rétablir les déficits observés chez les rats LHS, nous avons alors réalisé un knock-down de KCC2 par shARN spécifique par électroporation in utero. Nos résultats ont montré une diminution de la susceptibilité aux convulsions due à la lésion corticale, ainsi qu'une restauration de la taille des épines. Ainsi, l’augmentation de KCC2 à la suite d'une convulsion précoce, augmente la susceptibilité aux convulsions modifiant la morphologie des épines dendritiques, probable facteur contribuant à l’atrophie de l’hippocampe et l’occurrence des déficits cognitifs. Le deuxième objectif a été d'inspecter l’effet de la surexpression précoce de KCC2 dans le développement des épines dendritiques de l’hippocampe. Nous avons ainsi surexprimé KCC2 aussi bien in vitro dans des cultures organotypiques d’hippocampe, qu' in vivo par électroporation in utero. À l'inverse des résultats publiés dans le cortex, nous avons observé une diminution de la densité d’épines dendritiques et une augmentation de la taille des épines. Afin de confirmer la spécificité du rôle de KCC2 face à la région néocorticale étudiée, nous avons surexprimé KCC2 dans le cortex par électroporation in utero. Cette manipulation a eu pour conséquences d’augmenter la densité et la longueur des épines synaptiques de l’arbre dendritique des cellules glutamatergiques. En conséquent, ces résultats ont démontré pour la première fois, que les modifications de l’expression de KCC2 sont spécifiques à la région affectée. Ceci souligne les obstacles auxquels nous faisons face dans le développement de thérapie adéquat pour l’épilepsie ayant pour but de moduler l’expression de KCC2 de façon spécifique.

Role of the cotransporter KCC2 in cortical excitatory synapse development and febrile seizure susceptibility

Le co-transporteur KCC2 spécifique au potassium et chlore a pour rôle principal de réduire la concentration intracellulaire de chlore, entraînant l’hyperpolarisation des courants GABAergic l’autorisant ainsi à devenir inhibiteur dans le cerveau mature. De plus, il est aussi impliqué dans le développement des synapses excitatrices, nommées aussi les épines dendritiques. Le but de notre projet est d’étudier l’effet des modifications concernant l'expression et la fonction de KCC2 dans le cortex du cerveau en développement dans un contexte de convulsions précoces. Les convulsions fébriles affectent environ 5% des enfants, et ce dès la première année de vie. Les enfants atteints de convulsions fébriles prolongées et atypiques sont plus susceptibles à développer l’épilepsie. De plus, la présence d’une malformation cérébrale prédispose au développement de convulsions fébriles atypiques, et d’épilepsie du lobe temporal. Ceci suggère que ces pathologies néonatales peuvent altérer le développement des circuits neuronaux irréversiblement. Cependant, les mécanismes qui sous-tendent ces effets ne sont pas encore compris. Nous avons pour but de comprendre l'impact des altérations de KCC2 sur la survenue des convulsions et dans la formation des épines dendritiques. Nous avons étudié KCC2 dans un modèle animal de convulsions précédemment validé, qui combine une lésion corticale à P1 (premier jour de vie postnatale), suivie d'une convulsion induite par hyperthermie à P10 (nommés rats LHS). À la suite de ces insultes, 86% des rats mâles LHS développent l’épilepsie à l’âge adulte, au même titre que des troubles d’apprentissage. À P20, ces animaux presentent une augmentation de l'expression de KCC2 associée à une hyperpolarisation du potentiel de réversion de GABA. De plus, nous avons observé des réductions dans la taille des épines dendritiques et l'amplitude des courants post-synaptiques excitateurs miniatures, ainsi qu’un déficit de mémoire spatial, et ce avant le développement des convulsions spontanées. Dans le but de rétablir les déficits observés chez les rats LHS, nous avons alors réalisé un knock-down de KCC2 par shARN spécifique par électroporation in utero. Nos résultats ont montré une diminution de la susceptibilité aux convulsions due à la lésion corticale, ainsi qu'une restauration de la taille des épines. Ainsi, l’augmentation de KCC2 à la suite d'une convulsion précoce, augmente la susceptibilité aux convulsions modifiant la morphologie des épines dendritiques, probable facteur contribuant à l’atrophie de l’hippocampe et l’occurrence des déficits cognitifs. Le deuxième objectif a été d'inspecter l’effet de la surexpression précoce de KCC2 dans le développement des épines dendritiques de l’hippocampe. Nous avons ainsi surexprimé KCC2 aussi bien in vitro dans des cultures organotypiques d’hippocampe, qu' in vivo par électroporation in utero. À l'inverse des résultats publiés dans le cortex, nous avons observé une diminution de la densité d’épines dendritiques et une augmentation de la taille des épines. Afin de confirmer la spécificité du rôle de KCC2 face à la région néocorticale étudiée, nous avons surexprimé KCC2 dans le cortex par électroporation in utero. Cette manipulation a eu pour conséquences d’augmenter la densité et la longueur des épines synaptiques de l’arbre dendritique des cellules glutamatergiques. En conséquent, ces résultats ont démontré pour la première fois, que les modifications de l’expression de KCC2 sont spécifiques à la région affectée. Ceci souligne les obstacles auxquels nous faisons face dans le développement de thérapie adéquat pour l’épilepsie ayant pour but de moduler l’expression de KCC2 de façon spécifique.

LAICIDADE E ECUMENICIDADE DA IGREJA O Pensamento Eclesiológico de John Wesley

A presente investigação se concentra na eclesiologia prática, experimental e funcional de John Wesley, examinando não apenas o que se encontra explícito em seus escritos sobre a igreja, mas também o que está implícito na práxis social e missionária dos primeiros metodistas. Antes, porém, é traçado um panorama das discussões em torno da concepção wesleyana de igreja, desenvolvidas, sobretudo, nos últimos cinqüenta anos. O valor dessas pesquisas é reconhecido, pois elas ajudaram a criar certa convergência em torno dos principais temas da visão de Wesley. Entretanto, em boa parte delas, nota-se esforço em enquadrar a fragmentada reflexão wesleyana em algum esquema de interpretação previamente definido. De conservador e defensor da Igreja estabelecida a cismático radical, quase todas as qualificações lhe foram atribuídas. É certo que Wesley assimilou a contribuição de várias correntes, o que oferece justa dimensão da complexidade de sua teologia, resistente a explicações simplistas. Nem sempre, porém, se indaga sobre o que determinou as suas preferências. Aqui é sustentada a tese de que não foi o apego a princípios considerados ortodoxos, mas o encontro com o povo que levou Wesley à abertura crescente para uma compreensão da igreja, ao mesmo, sensível ao sofrimento dos excluídos da sociedade inglesa, e flexível para se ajustar a conjunturas em mutação constante. Ele rompeu com a eclesiologia hierárquica, em que foi formado, e pôs em prática uma concepção fundamentalmente laica de igreja. Quebrou o monopólio do clero e tornou realidade o sacerdócio de todos os crentes, tanto de homens quanto de mulheres. Rejeitou o individualismo e valorizou a vida comunitária responsável. Desfez a interpretação paroquialista e exclusivista de igreja e abraçou a ecumenicidade como caráter essencial da Igreja de Cristo. Enfim, centralizou-se na via salutis, na renovação de toda a criação, pela graça de Deus com a participação humana responsável, e relativizou a própria Igreja.

Advanced handover procedure for cellular communication systems

Third Generation cellular communication systems are expected to support mixed cell architecture in which picocells, microcells and macrocells are used to achieve full coverage and increase the spectral capacity. Supporting higher numbers of mobile terminals and the use of smaller cells will result in an increase in the number of handovers, and consequently an increase in the time delays required to perform these handovers. Higher time delays will generate call interruptions and forced terminations, particularly for time sensitive applications like real-time multimedia and data services. Currently in the Global System for Mobile communications (GSM), the handover procedure is initiated and performed by the fixed part of the Public Land Mobile Network (PLMN). The mobile terminal is only capable of detecting candidate base stations suitable for the handover; it is the role of the network to interrogate a candidate base station for a free channel. Handover signalling is exchanged via the fixed network and the time delay required to perform the handover is greatly affected by the levels of teletraffic handled by the network. In this thesis, a new handover strategy is developed to reduce the total time delay for handovers in a microcellular system. The handover signalling is diverted from the fixed network to the air interface to prevent extra delays due to teletraffic congestion, and to allow the mobile terminal to exchange signalling directly with the candidate base station. The new strategy utilises Packet Reservation Multiple Access (PRMA) technique as a mechanism to transfer the control of the handover procedure from the fixed network to the mobile terminal. Simulation results are presented to show a dramatic reduction in the handover delay as compared to those obtained using fixed channel allocation and dynamic channel allocation schemes.

The preimplantation embryo:handle with care

The past decade has seen considerable advances in our understanding of intrinsic developmental mechanisms associated with gametogenesis and embryogenesis and accompanying applications in the fields of reproductive medicine, embryonic stem cell biology, and nuclear reprogramming. However, a new focus has recently emerged concerning the homeostatic regulation of embryonic cells, how this is set, and how it may influence the longitudinal progression and optimization of the developmental program and indeed the phenotype of the offspring. Attention has been drawn to the preimplantation stage of development as a sensitive "window" when in vitro and in vivo manipulations, such as culture conditions or maternal diet, may have critical consequences. In this article, we review how changes in environmental conditions, mediated via a range of epigenetic, cellular, and metabolic mechanisms in the preimplantation embryo, may alter the pattern of cell division, gene expression, morphology, and potential. We consider how fetal and postnatal phenotype may become susceptible to the plasticity of the preimplantation embryo and the risks for adult health and physiology. Copyright © 2008 by Thieme Medical Publishers, Inc.

Dynamic capabilities and strategic paradox: a case study

Today’s business leaders must constantly review and develop their firm’s abilities to adapt to and benefit from external changes. Dynamic capabilities are the capacity of an organization to purposefully create, extend or modify its resource base. They enable it to exploit business, technological and market opportunities and adapt to market changes, an ability more often observed in highly dynamic industries, such as consumer electronics or telecommunications. Using the case study method, this article identifies dynamic capabilities in traditional, less dynamic industries when faced with a sudden drop of revenue. Four distinct routines emerge, namely structure and practices enduring time-sensitive strategic decision-making by the tice, and a culture encouraging learning and coevolving. Seemingly strategic paradox objectives encourage the management team to question the status quo and, when managed well, transform the tensions between old and new into an ability to advance superior ideas faster.