[Invasive meningococcal infections: two cases that demonstrate the broad spectrum in clinical manifestation and outcome]

Invasive meningococcal infections show a broad clinical picture including sepsis and meningitis. Here we report on a case of sepsis and a case of meningitis, two clinical manifestations of meningococcal infections with striking differences in the clinical presentation and outcome. Meningococcal sepsis is characterized by a systemic release of endotoxins, that triggers an intense cytokine response of the host that can lead to shock and multi organ failure and death within hours. Meningococcal meningitis occurs when bacteria breach into the subarachnoidal and ventricular space during bacteremia and mortality is much lower that in sepsis. Thus meningitis may be seen as a consequence of lower pathogenicity and/or more efficient host control of the meningococci compared to sepsis.

Traumatic brain injury (TBI) produces cytoskeletal protein derangements within cortical neurons that can be attenuated by protease inhibition

TBI produces a consistent and extensive loss of neurofilament 68 (NF68) and neurofilament 200 (NF200), key intermediate cytoskeletal proteins found in neurons including axons and dendrites, in cortical samples from injured brain. The presence of low molecular weight NF68 breakdown products (BDPs) strongly suggest that calpain proteolysis at least in part contributes to neurofilament (NF) protein loss following injury. Furthermore, one and two-dimensional gel electrophoresis analyses of NF BDPs obtained from in situ and in vitro tissue also implicated the involvement of calpain 2 mediated proteolysis of neurofilaments following TBI. Immunohistochemical examination of derangements in cytoskeletal proteins following traumatic brain injury in rats indicated that preferential dendritic rather than axonal damage occurs within three hours post-TBI. Although proteolysis of cytoskeletal proteins occurred concurrently with early morphological alterations, evidence of proteolysis preceded the full expression of evolutionary histopathological changes. Furthermore, cytoskeletal immunofluorescence alterations were not restricted to the site of impact. Confocal microscopic investigations of NF68 and NF200 immunofluorescence within injured cortical neurons revealed alterations in neurofilament assembly in the absence of NF derangements detectable at the light microscopic level ($<$15 minutes post-TBI). Collectively immunohistochemistry studies suggest that derangements to neuronal processes are biochemical and evolutionary in nature, and not due solely to mechanical shearing. Importantly, a systemically administered calpain inhibitor (calpain inhibitor 2) significantly reduced NF200, NF68, and spectrin protein loss as well as providing marked preservation of NF proteins in neuronal somata, dendrites, and axons at 24 hours post-TBI. ^

Silence That Can Be Dangerous: A Vignette Study to Assess Healthcare Professionals' Likelihood of Speaking up about Safety Concerns

PURPOSE To investigate the likelihood of speaking up about patient safety in oncology and to clarify the effect of clinical and situational context factors on the likelihood of voicing concerns. PATIENTS AND METHODS 1013 nurses and doctors in oncology rated four clinical vignettes describing coworkers' errors and rule violations in a self-administered factorial survey (65% response rate). Multiple regression analysis was used to model the likelihood of speaking up as outcome of vignette attributes, responder's evaluations of the situation and personal characteristics. RESULTS Respondents reported a high likelihood of speaking up about patient safety but the variation between and within types of errors and rule violations was substantial. Staff without managerial function provided significantly higher levels of decision difficulty and discomfort to speak up. Based on the information presented in the vignettes, 74%-96% would speak up towards a supervisor failing to check a prescription, 45%-81% would point a coworker to a missed hand disinfection, 82%-94% would speak up towards nurses who violate a safety rule in medication preparation, and 59%-92% would question a doctor violating a safety rule in lumbar puncture. Several vignette attributes predicted the likelihood of speaking up. Perceived potential harm, anticipated discomfort, and decision difficulty were significant predictors of the likelihood of speaking up. CONCLUSIONS Clinicians' willingness to speak up about patient safety is considerably affected by contextual factors. Physicians and nurses without managerial function report substantial discomfort with speaking up. Oncology departments should provide staff with clear guidance and trainings on when and how to voice safety concerns.

Fluid-related inclusions in Alpine high-pressure peridotite reveal trace element recycling during subduction-zone dehydration of serpentinized mantle (Cima di Gagnone, Swiss Alps).

Serpentinites release at sub-arc depths volatiles and several fluid-mobile trace elements found in arc magmas. Constraining element uptake in these rocks and defining the trace element composition of fluids released upon serpentinite dehydration can improve our understanding of mass transfer across subduction zones and to volcanic arcs. The eclogite-facies garnet metaperidotite and chlorite harzburgite bodies embedded in paragneiss of the subduction melange from Cima di Gagnone derive from serpentinized peridotite protoliths and are unique examples of ultramafic rocks that experienced subduction metasomatism and devolatilization. In these rocks, metamorphic olivine and garnet trap polyphase inclusions representing the fluid released during high-pressure breakdown of antigorite and chlorite. Combining major element mapping and laser-ablation ICP-MS bulk inclusion analysis, we characterize the mineral content of polyphase inclusions and quantify the fluid composition. Silicates, Cl-bearing phases, sulphides, carbonates, and oxides document post-entrapment mineral growth in the inclusions starting immediately after fluid entrapment. Compositional data reveal the presence of two different fluid types. The first (type A) records a fluid prominently enriched in fluid-mobile elements, with Cl, Cs, Pb, As, Sb concentrations up to 10(3) PM (primitive mantle), similar to 10(2) PM Tit Ba, while Rb, B, Sr, Li, U concentrations are of the order of 10(1) PM, and alkalis are similar to 2 PM. The second fluid (type B) has considerably lower fluid-mobile element enrichments, but its enrichment patterns are comparable to type A fluid. Our data reveal multistage fluid uptake in these peridotite bodies, including selective element enrichment during seafloor alteration, followed by fluid-rock interaction along with subduction metamorphism in the plate interface melange. Here, infiltration of sediment-equilibrated fluid produced significant enrichment of the serpentinites in As, Sb, B, Pb, an enriched trace element pattern that was then transferred to the fluid released at greater depth upon serpentine dehydration (type A fluid). The type B fluid hosted by garnet may record the composition of the chlorite breakdown fluid released at even greater depth. The Gagnone study-case demonstrates that serpentinized peridotites acquire water and fluid-mobile elements during ocean floor hydration and through exchange with sediment-equilibrated fluids in the early subduction stages. Subsequent antigorite devolatilization at subarc depths delivers aqueous fluids to the mantle wedge that can be prominently enriched in sediment-derived components, potentially triggering arc magmatism without the need of concomitant dehydration/melting of metasediments or altered oceanic crust.

Time-order errors and standard-position effects in duration discrimination: An experimental study and an analysis by the sensation-weighting model

Studies have shown that the discriminability of successive time intervals depends on the presentation order of the standard (St) and the comparison (Co) stimuli. Also, this order affects the point of subjective equality. The first effect is here called the standard-position effect (SPE); the latter is known as the time-order error. In the present study, we investigated how these two effects vary across interval types and standard durations, using Hellström’s sensation-weighting model to describe the results and relate them to stimulus comparison mechanisms. In Experiment 1, four modes of interval presentation were used, factorially combining interval type (filled, empty) and sensory modality (auditory, visual). For each mode, two presentation orders (St–Co, Co–St) and two standard durations (100 ms, 1,000 ms) were used; half of the participants received correctness feedback, and half of them did not. The interstimulus interval was 900 ms. The SPEs were negative (i.e., a smaller difference limen for St–Co than for Co–St), except for the filled-auditory and empty-visual 100-ms standards, for which a positive effect was obtained. In Experiment 2, duration discrimination was investigated for filled auditory intervals with four standards between 100 and 1,000 ms, an interstimulus interval of 900 ms, and no feedback. Standard duration interacted with presentation order, here yielding SPEs that were negative for standards of 100 and 1,000 ms, but positive for 215 and 464 ms. Our findings indicate that the SPE can be positive as well as negative, depending on the interval type and standard duration, reflecting the relative weighting of the stimulus information, as is described by the sensation-weighting model.

Proyectando entre ruinas : lógicas de intervención continua en la arquitectura contemporánea

Los cambios percibidos hacia finales del siglo XX y a principios del nuevo milenio, nos ha mostrado que la crisis cultural de la que somos participes refleja también una crisis de los modelos universales. Nuestra situación contemporánea, parece indicar que ya no es posible formular un sistema estético para atribuirle una vigencia universal e intemporal más allá de su estricta eficacia puntual. La referencia organizada, delimitada, invariable y específica que ofrecía cualquier emplazamiento, en tanto preexistencia, reflejaba una jerarquía del sistema formal basado en lo extensivo: la medida, las normas, el movimiento, el tiempo, la modulación, los códigos y las reglas. Sin embargo, actualmente, algunos aspectos que permanecían latentes sobre lo construido, emergen bajo connotaciones intensivas, transgrediendo la simple manifestación visual y expresiva, para centrase en las propiedades del comportamiento de la materia y la energía como determinantes de un proceso de adaptación en el entorno. A lo largo del todo el siglo XX, el desarrollo de la relación del proyecto sobre lo construido ha sido abordado, casi en exclusiva, entre acciones de preservación o intervención. Ambas perspectivas, manifestaban esfuerzos por articular un pensamiento que diera una consistencia teórica, como soporte para la producción de la acción aditiva. No obstante, en las últimas décadas de finales de siglo, la teoría arquitectónica terminó por incluir pensamientos de otros campos que parecen contaminar la visión sesgada que nos refería lo construido. Todo este entramado conceptual previo, aglomeraba valiosos intentos por dar contenido a una teoría que pudiese ser entendida desde una sola posición argumental. Es así, que en 1979 Ignasi Solá-Morales integró todas las imprecisiones que referían una actuación sobre una arquitectura existente, bajo el termino de “intervención”, el cual fue argumentado en dos sentidos: El primero referido a cualquier tipo de actuación que se puede hacer en un edificio, desde la defensa, preservación, conservación, reutilización, y demás acciones. Se trata de un ámbito donde permanece latente el sentido de intensidad, como factor común de entendimiento de una misma acción. En segundo lugar, más restringido, la idea de intervención se erige como el acto crítico a las ideas anteriores. Ambos representan en definitiva, formas de interpretación de un nuevo discurso. “Una intervención, es tanto como intentar que el edificio vuelva a decir algo o lo diga en una determinada dirección”. A mediados de 1985, motivado por la corriente de revisión historiográfica y la preocupación del deterioro de los centros históricos que recorría toda Europa, Solá-Morales se propone reflexionar sobre “la relación” entre una intervención de nueva arquitectura y la arquitectura previamente existente. Relación condicionada estrictamente bajo consideraciones lingüísticas, a su entender, en sintonía con toda la producción arquitectónica de todo el siglo XX. Del Contraste a la Analogía, resumirá las transformaciones en la concepción discursiva de la intervención arquitectónica, como un fenómeno cambiante en función de los valores culturales, pero a su vez, mostrando una clara tendencia dialógica entres dos categorías formales: El Contraste, enfatizando las posibilidades de la novedad y la diferencia; y por otro lado la emergente Analogía, como una nueva sensibilidad de interpretación del edificio antiguo, donde la semejanza y la diversidad se manifiestan simultáneamente. El aporte reflexivo de los escritos de Solá-Morales podría ser definitivo, si en las últimas décadas antes del fin de siglo, no se hubiesen percibido ciertos cambios sobre la continuidad de la expresión lingüística que fomentaba la arquitectura, hacia una especie de hipertrofia figurativa. Entre muchos argumentos: La disolución de la consistencia compositiva y el estilo unitario, la incorporación volumétrica del proyecto como dispositivo reactivo, y el cambio de visión desde lo retrospectivo hacia lo prospectivo que sugiere la nueva conservación. En este contexto de desintegración, el proyecto, en tanto incorporación o añadido sobre un edificio construido, deja de ser considerado como un apéndice volumétrico subordinado por la reglas compositivas y formales de lo antiguo, para ser considerado como un organismo de orden reactivo, que produce en el soporte existente una alteración en su conformación estructural y sistémica. La extensión, antes espacial, se considera ahora una extensión sensorial y morfológica con la implementación de la tecnología y la hiper-información, pero a su vez, marcados por una fuerte tendencia de optimización energética en su rol operativo, ante el surgimiento del factor ecológico en la producción contemporánea. En una sociedad, como la nuestra, que se está modernizando intensamente, es difícil compartir una adecuada sintonía con las formas del pasado. Desde 1790, fecha de la primera convención francesa para la conservación de monumentos, la escala de lo que se pretende preservar es cada vez más ambiciosa, tanto es así, que al día de hoy el repertorio de lo que se conserva incluye prácticamente todas las tipologías del entorno construido. Para Koolhaas, el intervalo entre el objeto y el momento en el cual se decide su conservación se ha reducido, desde dos milenios en 1882 a unas décadas hoy en día. En breve este lapso desaparecerá, demostrando un cambio radical desde lo retrospectivo hacia lo prospectivo, es decir, que dentro de poco habrá que decidir que es lo que se conserva antes de construir. Solá-Morales, en su momento, distinguió la relación entre lo nuevo y lo antiguo, entre el contraste y la analogía. Hoy casi tres décadas después, el objetivo consiste en evaluar si el modelo de intervención arquitectónica sobre lo construido se ha mantenido desde entonces o si han aparecido nuevas formas de posicionamiento del proyecto sobre lo construido. Nuestro trabajo pretende demostrar el cambio de enfoque proyectual con la preexistencia y que éste tiene estrecha relación con la incorporación de nuevos conceptos, técnicas, herramientas y necesidades que imprimen el contexto cultural, producido por el cambio de siglo. Esta suposición nos orienta a establecer un paralelismo arquitectónico entre los modos de relación en que se manifiesta lo nuevo, entre una posición comúnmente asumida (Tópica), genérica y ortodoxa, fundamentada en lo visual y expresivo de las últimas décadas del siglo XX, y una realidad emergente (Heterotópica), extraordinaria y heterodoxa que estimula lo inmaterial y que parece emerger con creciente intensidad en el siglo XXI. Si a lo largo de todo el siglo XX, el proyecto de intervención arquitectónico, se debatía entre la continuidad y discontinuidad de las categorías formales marcadas por la expresión del edificio preexistente, la nueva intervención contemporánea, como dispositivo reactivo en el paisaje y en el territorio, demanda una absoluta continuidad, ya no visual, expresiva, ni funcional, sino una continuidad fisiológica de adaptación y cambio con la propia dinámica del territorio, bajo nuevas reglas de juego y desplegando planes y estrategias operativas (proyectivas) desde su propia lógica y contingencia. El objeto de esta investigación es determinar los nuevos modos de continuidad y las posibles lógicas de producción que se manifiestan dentro de la Intervención Arquitectónica, intentando superar lo aparente de su relación física y visual, como resultado de la incorporación del factor operativo desplegado por el nuevo dispositivo contemporáneo. Creemos que es acertado mantener la senda connotativa que marca la denominación intervención arquitectónica, por aglutinar conceptos y acercamientos teóricos previos que han ido evolucionando en el tiempo. Si bien el término adolece de mayor alcance operativo desde su formulación, una cualidad que infieren nuestras lógicas contemporáneas, podría ser la reformulación y consolidación de un concepto de intervención más idóneo con nuestros tiempos, anteponiendo un procedimiento lógico desde su propia necesidad y contingencia. Finalmente, nuestro planteamiento inicial aspira a constituir un nueva forma de reflexión que nos permita comprender las complejas implicaciones que infiere la nueva arquitectura sobre la preexistencia, motivada por las incorporación de factores externos al simple juicio formal y expresivo preponderante a finales del siglo XX. Del mismo modo, nuestro camino propuesto, como alternativa, permite proyectar posibles sendas de prospección, al considerar lo preexistente como un ámbito que abarca la totalidad del territorio con dinámicas emergentes de cambio, y con ellas, sus lógicas de intervención.Abstract The perceived changes towards the end of the XXth century and at the beginning of the new milennium have shown us that the cultural crisis in which we participate also reflects a crisis of the universal models. The difference between our contemporary situation and the typical situations of modern orthodoxy and post-modernistic fragmentation, seems to indicate that it is no longer possible to formulate a valid esthetic system, to assign a universal and eternal validity to it beyond its strictly punctual effectiveness; which is even subject to questioning because of the continuous transformations that take place in time and in the sensibility of the subject itself every time it takes over the place. The organised reference that any location offered, limited, invariable and specific, while pre-existing, reflected a hierarchy of the formal system based on the applicable: measure, standards, movement, time, modulation, codes and rules. Authors like Marshall Mc Luhan, Paul Virilio, or Marc Augé anticipated a reality where the conventional system already did not seem to respond to the new architectural requests in which information, speed, disappearance and the virtual had blurred the traditional limits of place; pre-existence did no longer possess a specific delimitation and, on the contrary, they expect to reach a global scale. Currently, some aspects that stayed latent relating to the constructed, surface from intensive connotations, transgressing the simple visual and expressive manifestation in order to focus on the traits of the behaviour of material and energy as determinants of a process of adaptation to the surroundings. Throughout the entire Century, the development of the relation of the project relating to the constructed has been addressed, almost exclusively, in preservational or interventianal actions. Both perspectives showed efforts in order to express a thought that would give a theoretical consistency as a base for the production of the additive action. Nevertheless, the last decades of the Century, architectural theory ended up including thoughts from other fields that seem to contaminate the biased vision 15 which the constructed related us. Ecology, planning, philosophy, global economy, etc, suggest new approaches to the construction of the contemporary city; but this time with a determined idea of change and continuous transformation, that enriches the panorama of thought and architectural practice, at the same time, according to some, it puts disciplinary specification at risk, given that there is no architecture without destruction, the constructed organism requires mutation in order to adjust to the change of shape. All of this previous conceptual framework gathered valuable intents to give importance to a theory that could be understood solely from an argumental position. Thusly, in 1979 Ignasi Solá-Morales integrated all of the imprecisions that referred to an action in existing architecture under the term of “Intervention”, which was explained in two ways: The first referring to any type of intervention that can be carried out in a building, regarding protection, conservation, reuse, etc. It is about a scope where the meaning of intensity stays latent as a common factor of the understanding of a single action. Secondly, more limitedly, the idea of intervention is established as the critical act to the other previous ideas such as restauration, conservation, reuse, etc. Both ultimately represent ways of interpretation of a new speech. “An intervention, is as much as trying to make the building say something again or that it be said in a certain direction”. Mid 1985, motivated by the current of historiographical revision and the concerns regarding the deterioration of historical centres that traversed Europe, Solá-Morales decides to reflect on “the relationship” between an intervention of the new architecture and the previously existing architecture. A relationship determined strictly by linguistic considerations, to his understanding, in harmony with all of the architectural production of the XXth century. From Contrast to Analogy would summarise transformations in the discursive perception of architectural intervention, as a changing phenomenon depending on cultural values, but at the same time, showing a clear dialogical tendency between two formal categories: Contrast, emphasising the possibilities of novelty and difference; and on the other hand the emerging Analogy, as a new awareness of interpretation of the ancient building, where the similarity and diversity are manifested simultaneously. For Solá-Morales the analogical procedure is not based on the visible simultaneity of formal orders, but on associations that the subject establishes throughout time. Through analogy it is tried to overcome the simple visual relationship with the antique, to focus on its spacial, physical and geographical nature. If the analogical attempt guides an opening towards a new continuity; it still persists in the connection of dimensional, typological and figurative factors, subordinate to the formal hierarchy of the preexisting subjects. 16 The reflexive contribution of Solá-Morales’ works could be final, if in the last decades before the end of the century there had not been certain changes regarding linguistic expression, encouraged by architecture, towards a kind of figurative hypertrophy, amongst many arguments we are in this case interested in three moments: The dissolution of the compositional consistency and the united style, the volumetric incorporation of the project as a reactive mechanism, and the change of the vision from retrospective towards prospective that the new conservation suggests. The recurrence to the history of architecture and its recognisable forms, as a way of perpetuating memory and establishing a reference, dissolved any instinct of compositive unity and style, provoking permanent relationships to tend to disappear. The composition and coherence lead to suppose a type of discontinuity of isolated objects in which only possible relationships could appear; no longer as an order of certain formal and compositive rules, but as a special way of setting elements in a specific work. The new globalised field required new forms of consistency between the project and the pre-existent subject, motivated amongst others by the higher pace of market evolution, increase of consumer tax and the level of information and competence between different locations; aspects which finally made stylistic consistence inefficient. In this context of disintegration, the project, in incorporation as well as added to a constructed building, stops being considered as a volumetric appendix subordinate to compositive and formal rules of old, to be considered as an organism of reactive order, that causes a change in the structural and systematic configuration of the existing foundation. The extension, previsouly spatial, is now considered a sensorial and morphological extension, with the implementation of technology and hyper-information, but at the same time, marked by a strong tendency of energetic optimization in its operational role, facing the emergence of the ecological factor in contemporary production. The technological world turns into a new nature, a nature that should be analysed from ecological terms; in other words, as an event of transition in the continuous redistribution of energy. In this area, effectiveness is not only determined by the capacity of adaptation to changing conditions, but also by its transforming capacity “expressly” in order to change an environment. In a society, like ours, that is modernising intensively, it is difficult to share an adecuate agreement with the forms of the past. From 1790, the date of the first French convention for the conservation of monuments, the scale of what is expexted to be preserved is more and more ambitious, so much so that nowadays the repertoire of that what is conserved includes practically all typologies of the constructed surroundings. For Koolhaas, the ínterval between the object and the moment when its conservation is decided has been reduced, from two 17 milennia in 1882 to a few decades nowadays. Shortly this lapse will disappear, showing a radical change of retrospective towards prospective, that is to say, that soon it will be necessary to decide what to conserve before constructing. The shapes of cities are the result of the continuous incorporation of architecture, and perhaps that only through architecture the response to the universe can be understood, the continuity of what has already been constructed. Our work is understood also within that system, modifying the field of action and leaving the road ready for the next movement of those that will follow after us. Continuity does not mean conservatism, continuity means being conscient of the transitory value of our answers to specific needs, accepting the change that we have received. That what has been constructed to remain and last, should cause future interventions to be integrated in it. It is necessary to accept continuity as a rule. Solá-Morales, in his time, distinguished between the relationship with new and old, between contrast and analogy. Today, almost three decades later, the objective consists of evaluating whether the model of architectural intervention in the constructed has been maintained since then or if new ways of positioning the project regarding the constructed have appeared. Our work claims to show the change of the approach of projects with pre-existing subjects and that this has got a close relation to the incorporation of new concepts, techniques, tools and necessities that impress the cultural context, caused by the change of centuries. This assumption guides us to establish a parallelism between the forms of connection where that what is new is manifested between a commonly assumed (topical), generic and orthodox position, based on that what is visual and expressive in the last decades of the XXth century, and an emerging (heterotopical), extraordinary and heterodox reality that stimulates the immaterial and that seems to emerge with growing intensity in the XXIst century. If throughout the XXth century the project of architectural intervention was considered from the continuity and discontinuity of formal categories, marked by the expression of the pre-existing building, the new contemporary intervention, as a reactive device in the landscape and territory, demands an absolute continuity. No longer a visual, expressive or functional one but a morphological continuity of adaptation and change with its own territorial dynamics, under new game rules and unfolding new operative (projective) strategies from its own logic and contingency. 18 The aim of this research is to determine new forms of continuity and the possible logic of production that are expressed in the Architectural Intervention, trying to overcome the obviousness of its physical and visual relationship, at the beginning of this new century, as a result of the incorporation of the operative factor that the new architectural device unfolds. We think it is correct to maintain the connotative path that marks the name architectural intervention by bringing previous concepts and theorical approaches that have been evolving through time together. If the name suffers from a wider operational range because of its formulation, a quality that our contemporary logic provokes, the reformulation and consolidation of an interventional concept could be more suitable for our times, giving preference to a logical method from its own necessity and contingency. It seems that now time shapes the topics, it is no longer about materialising a certain time but about expressing the changes that its new temporality generates. Finally, our initial approach aspires to form a new way of reflection that permits us to understand the complex implications that the new architecture submits the pre-existing subject to, motivated by the incorporation of factors external to simple formal and expressive judgement, prevailing at the end of the XXth century. In the same way, our set road, as an alternative, permits the contemplation of possible research paths, considering that what is pre-existing as an area that spans the whole territory with emerging changing dynamics and, with them, their interventional logics.

Dynamic gamma frequency feedback coupling between higher and lower order visual cortices underlies perceptual completion in humans

To perceive a coherent environment, incomplete or overlapping visual forms must be integrated into meaningful coherent percepts, a process referred to as ?Gestalt? formation or perceptual completion. Increasing evidence suggests that this process engages oscillatory neuronal activity in a distributed neuronal assembly. A separate line of evidence suggests that Gestalt formation requires top-down feedback from higher order brain regions to early visual cortex. Here we combine magnetoencephalography (MEG) and effective connectivity analysis in the frequency domain to specifically address the effective coupling between sources of oscillatory brain activity during Gestalt formation. We demonstrate that perceptual completion of two-tone ?Mooney? faces induces increased gamma frequency band power (55?71 Hz) in human early visual, fusiform and parietal cortices. Within this distributed neuronal assembly fusiform and parietal gamma oscillators are coupled by forward and backward connectivity during Mooney face perception, indicating reciprocal influences of gamma activity between these higher order visual brain regions. Critically, gamma band oscillations in early visual cortex are modulated by top-down feedback connectivity from both fusiform and parietal cortices. Thus, we provide a mechanistic account of Gestalt perception in which gamma oscillations in feature sensitive and spatial attention-relevant brain regions reciprocally drive one another and convey global stimulus aspects to local processing units at low levels of the sensory hierarchy by top-down feedback. Our data therefore support the notion of inverse hierarchical processing within the visual system underlying awareness of coherent percepts.

La reutilización de efluentes depurados en España: retrospectiva, desarrollo del marco normativo, estudio de las tecnologías de regeneración frente a los biorreactores de membrana y sus costes en función del uso

La reutilización de efluentes depurados siempre ha sido una opción en lugares con déficit coyuntural o estructural de recursos hídricos, se haya o no procedido a la regulación y planificación de esta práctica. La necesidad se crea a partir de las demandas de una zona, normalmente riego agrícola, que ven un mejor desarrollo de su actividad por contar con este recurso. España es el país de la UE que más caudal reutiliza, y está dentro de los diez primeros a nivel mundial. La regulación de esta práctica por el RD 1620/2007, ayudó a incorporar la reutilización de efluentes depurados a la planificación hidrológica como parte de los programas de medidas, con objeto de mitigar presiones, como son las extracciones de agua superficial y subterránea, o mejoras medioambientales evitando un vertido. El objeto de este trabajo es conocer la situación de la reutilización de efluentes depurados en España, los diferentes escenarios y planteamientos de esta actividad, el desarrollo del marco normativo y su aplicabilidad, junto a los tratamientos que permiten alcanzar los límites de calidad establecidos en la normativa vigente, en función de los distintos usos. Además, se aporta un análisis de costes de las distintas unidades de tratamiento y tipologías de líneas de regeneración, tanto de las utilizadas después de un tratamiento secundario como de otras opciones de depuración, como son los biorreactores de membrana (MBRs). Para el desarrollo de estos objetivos, en primer lugar, se aborda el conocimiento de la situación de la reutilización en España a través de una base de datos diseñada para cubrir todos los aspectos de esta actividad: datos de la estación depuradora de aguas residuales (EDAR), de la estación regeneradora (ERA), caudales depurados, reutilizados, volúmenes utilizados y ubicación de los distintos usos, tipos de líneas de tratamiento, calidades del agua reutilizada, etc. Las principales fuentes de información son las Confederaciones Hidrográficas (CCHH) a través de las concesiones de uso del agua depurada, las entidades de saneamiento y depuración de las distintas comunidades autónomas (CCAA), ayuntamientos, Planes Hidrológicos de Cuenca (PHC) y visitas a las zonas más emblemáticas. Además, se revisan planes y programas con el fin de realizar una retrospectiva de cómo se ha ido consolidando y desarrollando esta práctica en las distintas zonas de la geografía española. Se han inventariado 322 sistemas de reutilización y 216 tratamientos de regeneración siendo el más extendido la filtración mediante filtro arena seguido de una desinfección mediante hipoclorito, aunque este tratamiento se ha ido sustituyendo por un físico-químico con decantación lamelar, filtro de arena y radiación ultravioleta, tratamiento de regeneración convencional (TRC), y otros tratamientos que pueden incluir membranas, tratamientos de regeneración avanzados (TRA), con dosificación de hipoclorito como desinfección residual, para adaptarse al actual marco normativo. El uso más extendido es el agrícola con el 70% del caudal total reutilizado, estimado en 408 hm3, aunque la capacidad de los tratamientos de regeneración esperada para 2015, tras el Plan Nacional de Reutilización de Aguas (PNRA), es tres veces superior. Respecto al desarrollo normativo, en las zonas donde la reutilización ha sido pionera, las administraciones competentes han ido desarrollando diferentes recomendaciones de calidad y manejo de este tipo de agua. El uso agrícola, y en zonas turísticas, el riego de campos de golf, fueron los dos primeros usos que tuvieron algún tipo de recomendación incluso reglamentación. Esta situación inicial, sin una normativa a nivel estatal ni recomendaciones europeas, creó cierta incertidumbre en el avance de la reutilización tanto a nivel de concesiones como de planificación. En la actualidad sigue sin existir una normativa internacional para la reutilización y regeneración de efluentes depurados. Las recomendaciones de referencia a nivel mundial, y en concreto para el uso agrícola, son las de la OMS (Organización Mundial de la Salud) publicadas 1989, con sus posteriores revisiones y ampliaciones (OMS, 2006). Esta norma combina tratamientos básicos de depuración y unas buenas prácticas basadas en diferentes niveles de protección para evitar problemas sanitarios. Otra normativa que ha sido referencia en el desarrollo del marco normativo en países donde se realiza esta práctica, son las recomendaciones dadas por la Agencia Medioambiente Estadunidense (USEPA, 2012) o las publicadas por el Estado de California (Título 22, 2001). Estas normas establecen unos indicadores y valores máximos dónde el tratamiento de regeneración es el responsable de la calidad final en función del uso. Durante 2015, la ISO trabajaba en un documento para el uso urbano donde se muestra tanto los posibles parámetros que habría que controlar como la manera de actuar para evitar posibles riesgos. Por otro lado, la Comisión Europea (CE) viene impulsando desde el 2014 la reutilización de aguas depuradas dentro del marco de la Estrategia Común de Implantación de la Directiva Marco del Agua, y fundamentalmente a través del grupo de trabajo de “Programas de medidas”. Para el desarrollo de esta iniciativa se está planteando sacar para 2016 una guía de recomendaciones que podría venir a completar el marco normativo de los distintos Estados Miembros (EM). El Real Decreto 1620/2007, donde se establece el marco jurídico de la reutilización de efluentes depurados, tiende más a la filosofía implantada por la USEPA, aunque la UE parece más partidaria de una gestión del riesgo, donde se establecen unos niveles de tolerancia y unos puntos de control en función de las condiciones socioeconómicas de los distintos Estados, sin entrar a concretar indicadores, valores máximos o tratamientos. Sin embargo, en la normativa estadounidense se indican una serie de tratamientos de regeneración, mientras que, en la española, se hacen recomendaciones a este respecto en una Guía sin validez legal. Por tanto, queda sin regular los procesos para alcanzar estos estándares de calidad, pudiendo ser éstos no apropiados para esta práctica. Es el caso de la desinfección donde el uso de hipoclorito puede generar subproductos indeseables. En la Guía de recomendaciones para la aplicación del RD, publicada por el Ministerio de Agricultura y Medioambiente (MAGRAMA) en 2010, se aclaran cuestiones frecuentes sobre la aplicación del RD, prescripciones técnicas básicas para los sistemas de reutilización, y buenas prácticas en función del uso. Aun así, el RD sigue teniendo deficiencias en su aplicación siendo necesaria una revisión de la misma, como en las frecuencias de muestreo incluso la omisión de algunos parámetros como huevos de nematodos que se ha demostrado ser inexistentes tras un tratamiento de regeneración convencional. En este sentido, existe una tendencia a nivel mundial a reutilizar las aguas con fines de abastecimiento, incluir indicadores de presencia de virus o protozoos, o incluir ciertas tecnologías como las membranas u oxidaciones avanzadas para afrontar temas como los contaminantes emergentes. Otro de los objetivos de este trabajo es el estudio de tipologías de tratamiento en función de los usos establecidos en el RD 1620/2007 y sus costes asociados, siendo base de lo establecido a este respecto en la Guía y PNRA anteriormente indicados. Las tipologías de tratamiento propuestas se dividen en líneas con capacidad de desalar y las que no cuentan con una unidad de desalación de aguas salobres de ósmosis inversa o electrodiálisis reversible. Se realiza esta división al tener actuaciones en zonas costeras donde el agua de mar entra en los colectores, adquiriendo el agua residual un contenido en sales que es limitante en algunos usos. Para desarrollar este objetivo se han estudiado las unidades de tratamiento más implantadas en ERAs españolas en cuanto a fiabilidad para conseguir determinada calidad y coste, tanto de implantación como de explotación. El TRC, tiene un coste de implantación de 28 a 48 €.m-3.d y de explotación de 0,06 a 0,09 €. m-3, mientras que, si se precisara desalar, este coste se multiplica por diez en la implantación y por cinco en la explotación. En caso de los usos que requieren de TRA, como los domiciliarios o algunos industriales, los costes serían de 185 a 398 €.m-3.d en implantación y de 0,14 a 0,20 €.m-3 en explotación. En la selección de tecnologías de regeneración, la capacidad del tratamiento en relación al coste es un indicador fundamental. Este trabajo aporta curvas de tendencia coste-capacidad que sirven de herramienta de selección frente a otros tratamientos de regeneración de reciente implantación como son los MBR, u otros como la desalación de agua de mar o los trasvases entre cuencas dentro de la planificación hidrológica. En España, el aumento de las necesidades de agua de alta calidad en zonas con recursos escasos, aumento de zonas sensibles como puntos de captación para potables, zonas de baño o zonas de producción piscícola, y en ocasiones, el escaso terreno disponible para la implantación de nuevas plantas depuradoras (EDARs), han convertido a los MBRs, en una opción dentro del marco de la reutilización de aguas depuradas. En este trabajo, se estudia esta tecnología frente a los TRC y TRA, aportando igualmente curvas de tendencia coste-capacidad, e identificando cuando esta opción tecnológica puede ser más competitiva frente a los otros tratamientos de regeneración. Un MBR es un tratamiento de depuración de fangos activos donde el decantador secundario es sustituido por un sistema de membranas de UF o MF. La calidad del efluente, por tanto, es la misma que el de una EDAR seguida de un TRA. Los MBRs aseguran una calidad del efluente para todos los usos establecidos en el RD, incluso dan un efluente que permite ser directamente tratado por las unidades de desalación de OI o EDR. La implantación de esta tecnología en España ha tenido un crecimiento exponencial, pasando de 13 instalaciones de menos de 5.000 m3. d-1 en el 2006, a más de 55 instalaciones en operación o construcción a finales del 2014, seis de ellas con capacidades por encima de los 15.000 m3. d-1. Los sistemas de filtración en los MBR son los que marcan la operación y diseño de este tipo de instalaciones. El sistema más implantado en España es de membrana de fibra hueca (MFH), sobre todo para instalaciones de gran capacidad, destacando Zenon que cuenta con el 57% de la capacidad total instalada. La segunda casa comercial con mayor número de plantas es Kubota, con membranas de configuración placa plana (MPP), que cuenta con el 30 % de la capacidad total instalada. Existen otras casas comerciales implantadas en MBR españoles como son Toray, Huber, Koch o Microdym. En este documento se realiza la descripción de los sistemas de filtración de todas estas casas comerciales, aportando información de sus características, parámetros de diseño y operación más relevantes. El estudio de 14 MBRs ha posibilitado realizar otro de los objetivos de este trabajo, la estimación de los costes de explotación e implantación de este tipo de sistemas frente a otras alternativas de tratamiento de regeneración. En este estudio han participado activamente ACA y ESAMUR, entidades públicas de saneamiento y depuración de Cataluña y Murcia respectivamente, que cuentan con una amplia experiencia en la explotación de este tipo de sistemas. Este documento expone los problemas de operación encontrados y sus posibles soluciones, tanto en la explotación como en los futuros diseños de este tipo de plantas. El trabajo concluye que los MBRs son una opción más para la reutilización de efluentes depurados, siendo ventajosos en costes, tanto de implantación como de explotación, respecto a EDARs seguidas de TRA en capacidades por encima de los 10.000 m3.d-1. ABSTRACT The reuse of treated effluent has always been an option in places where a situational or structural water deficit exists, whether regulatory and/or planning efforts are completed or not. The need arises from the demand of a sector, commonly agricultural irrigation, which benefits of this new resource. Within the EU, Spain is ahead in the annual volume of reclaimed water, and is among the top ten countries at a global scale. The regulation of this practice through the Royal Decree 1620/2007 has helped to incorporate the water reuse to the hydrological plans as a part of the programme of measures to mitigate pressures such as surface or ground water extraction, or environmental improvements preventing discharges. The object of this study is to gain an overview of the state of the water reuse in Spain, the different scenarios and approaches to this activity, the development of the legal framework and its enforceability, together with the treatments that achieve the quality levels according to the current law, broken down by applications. Additionally, a cost analysis of technologies and regeneration treatment lines for water reclamation is performed, whereas the regeneration treatment is located after a wastewater treatment or other options such as membrane bioreactors (MBR). To develop the abovementioned objectives, the state of water reuse in Spain is studied by means of a database designed to encompass all aspects of the activity: data from the wastewater treatment plants (WWTP), from the water reclamation plants (WRP), the use of reclaimed water, treated water and reclaimed water annual volumes and qualities, facilities and applications, geographic references, technologies, regeneration treatment lines, etc. The main data providers are the River Basin authorities, through the concession or authorization for water reuse, (sanitary and wastewater treatment managers from the territorial governments, local governments, Hydrological Plans of the River Basins and field visits to the main water reuse systems. Additionally, a review of different plans and programmes on wastewater treatment or water reuse is done, aiming to put the development and consolidation process of this activity in the different regions of Spain in perspective. An inventory of 322 reuse systems and 216 regeneration treatments has been gathered on the database, where the most extended regeneration treatment line was sand filtration followed by hypochlorite disinfection, even though recently it is being replaced by physical–chemical treatment with a lamella settling system, depth sand filtration, and a disinfection with ultraviolet radiation and hypochlorite as residual disinfectant, named conventional regeneration treatment (CRT), and another treatment that may include a membrane process, named advanced regeneration treatment (ART), to adapt to legal requirements. Agricultural use is the most extended, accumulating 70% of the reclaimed demand, estimated at 408 hm3, even though the expected total capacity of WRPs for 2015, after the implementation of the National Water Reuse Plan (NWRP) is three times higher. According to the development of the water reuse legal framework, there were pioneer areas where competent authorities developed different quality and use recommendations for this new resource. Agricultural use and golf course irrigation in touristic areas were the first two uses with recommendations and even legislation. The initial lack of common legislation for water reuse at a national or European level created some doubts which affected the implementation of water reuse, both from a planning and a licensing point of view. Currently there is still a lack of common international legislation regarding water reuse, technologies and applications. Regarding agricultural use, the model recommendations at a global scale are those set by the World Health Organization published in 1989, and subsequent reviews and extensions about risk prevention (WHO, 2006). These documents combine wastewater treatments with basic regeneration treatments reinforced by good practices based on different levels of protection to avoid deleterious health effects. Another relevant legal reference for this practices has been the Environmental Protection Agency of the US (USEPA, 2012), or those published by the State of California (Title 22, 2001). These establish indicator targets and maximum thresholds where regeneration treatment lines are responsible for the final quality according to the different uses. During 2015, the ISO has worked on a document aimed at urban use, where the possible parameters to be monitored together with risk prevention have been studied. On the other hand, the European Commission has been promoting the reuse of treated effluents within the Common Implementation Strategy of the Water Framework Directive, mainly through the work of the Programme of Measures Working Group. Within this context, the publication of a recommendation guide during 2016 is intended, as a useful tool to fill in the legal gaps of different Member States on the matter. The Royal Decree 1620/2007, where the water reuse regulation is set, resembles the principles of the USEPA more closely, even though the EU shows a tendency to prioritize risk assessment by establishing tolerance levels and thresholds according to socioeconomic conditions of the different countries, without going into details of indicators, maximum thresholds or treatments. In contrast, in the US law, regeneration treatments are indicated, while in the Spanish legislation, the only recommendations to this respect are compiled in a non-compulsory guide. Therefore, there is no regulation on the different treatment lines used to achieve the required quality standards, giving room for inappropriate practices in this respect. This is the case of disinfection, where the use of hypochlorite may produce harmful byproducts. In the recommendation Guide for the application of the Royal Decree (RD), published by the Ministry of Agriculture and Environment (MAGRAMA) in 2010, clarifications of typical issues that may arise from the application of the RD are given, as well as basic technical parameters to consider in reuse setups, or good practices according to final use. Even so, the RD still presents difficulties in its application and requires a review on issues such as the sampling frequency of current quality parameters or even the omission of nematode eggs indicator, which have been shown to be absent after CRT. In this regard, there is a global tendency to employ water reuse for drinking water, including indicators for the presence of viruses and protozoans, or to include certain technologies such as membranes or advanced oxidation processes to tackle problems like emerging pollutants. Another of the objectives of this study is to provide different regeneration treatment lines to meet the quality requirements established in the RD 1620/2007 broken down by applications, and to estimate establishment and operational costs. This proposal has been based on what is established in the above mentioned Guide and NWRP. The proposed treatment typologies are divided in treatment trains with desalination, like reverse osmosis or reversible electrodialisis, and those that lack this treatment for brackish water. This separation is done due to coastal facilities, where sea water may permeate the collecting pipes, rising salt contents in the wastewater, hence limiting certain uses. To develop this objective a study of the most common treatment units set up in Spanish WRPs is conducted in terms of treatment train reliability to obtain an acceptable relationship between the required quality and the capital and operational costs. The CRT has an establishment cost of 28 to 48 €.m-3.d and an operation cost of 0.06 to 0.09 €.m-3, while, if desalination was required, these costs would increase tenfold for implementation and fivefold for operation. In the cases of uses that require ART, such as residential or certain industrial uses, the costs would be of 185 to 398 €.m-3.d for implementation and of 0.14 to 0.20 €.m-3 for operation. When selecting regeneration treatment lines, the relation between treatment capacity and cost is a paramount indicator. This project provides cost-capacity models for regeneration treatment trains. These may serve as a tool when selecting between different options to fulfill water demands with MBR facilities, or others such as sea water desalination plants or inter-basin water transfer into a water planning framework. In Spain, the requirement for high quality water in areas with low resource availability, the increasing number of sensitive zones, such as drinking water extraction, recreational bathing areas, fish protected areas and the lack of available land to set up new WWTPs, have turned MBRs into a suitable option for water reuse. In this work this technology is analyzed in contrast to CRT and ART, providing cost-capacity models, and identifying when and where this treatment option may outcompete other regeneration treatments. An MBR is an activated sludge treatment where the secondary settling is substituted by a membrane system of UF or MF. The quality of the effluent is, therefore, comparable to that of a WWTP followed by an ART. MBRs ensure a sufficient quality level for the requirements of the different uses established in the RD, even producing an effluent that can be directly treated in OI or EDR processes. The implementation of this technology in Spain has grown exponentially, growing from 13 facilities with less than 5000 m3.d-1 in 2006 to above 55 facilities operating by the end of 2014, 6 of them with capacities over 15000 m3.d-1. The membrane filtration systems for MBR are the ones that set the pace of operation and design of this type of facilities. The most widespread system in Spain is the hollow fiber membrane configuration, especially on high flow capacities, being Zenon commercial technology, which mounts up to 57% of the total installed capacity, the main contributor. The next commercial technology according to plant number is Kubota, which uses flat sheet membrane configuration, which mounts up to 30% of the total installed capacity. Other commercial technologies exist within the Spanish MBR context, such as Toray, Huber, Koch or Microdym. In this document an analysis of all of these membrane filtration systems is done, providing information about their characteristics and relevant design and operation parameters. The study of 14 full scale running MBRs has enabled to pursue another of the objectives of this work: the estimation of the implementation and operation costs of this type of systems in contrast to other regeneration alternatives. Active participation of ACA and ESAMUR, public wastewater treatment and reuse entities of Cataluña and Murcia respectively, has helped attaining this objective. A number of typical operative problems and their possible solutions are discussed, both for operation and plant design purposes. The conclusion of this study is that MBRs are another option to consider for water reuse, being advantageous in terms of both implementation and operational costs, when compared with WWTPs followed by ART, when considering flow capacities above 10000 m3.d-1.

Alternative neural circuitry that might be impaired in the development of Alzheimer disease

It is well established that some individuals with normal cognitive capacity have abundant senile plaques in their brains. It has been proposed that those individuals are resilient or have compensation factors to prevent cognitive decline. In this comment, we explore an alternative mechanism through which cognitive capacity is maintained. This mechanism could involve the impairment of alternative neural circuitry. Also, the proportion of molecules such as A? or tau protein present in different areas of the brain could be important.

A peptide that inhibits hydroxyapatite growth is in an extended conformation on the crystal surface

Proteins play an important role in the biological mechanisms controlling hard tissue development, but the details of molecular recognition at inorganic crystal interfaces remain poorly characterized. We have applied a recently developed homonuclear dipolar recoupling solid-state NMR technique, dipolar recoupling with a windowless sequence (DRAWS), to directly probe the conformation of an acidic peptide adsorbed to hydroxyapatite (HAP) crystals. The phosphorylated hexapeptide, DpSpSEEK (N6, where pS denotes phosphorylated serine), was derived from the N terminus of the salivary protein statherin. Constant-composition kinetic characterization demonstrated that, like the native statherin, this peptide inhibits the growth of HAP seed crystals when preadsorbed to the crystal surface. The DRAWS technique was used to measure the internuclear distance between two 13C labels at the carbonyl positions of the adjacent phosphoserine residues. Dipolar dephasing measured at short mixing times yielded a mean separation distance of 3.2 ± 0.1 Å. Data obtained by using longer mixing times suggest a broad distribution of conformations about this average distance. Using a more complex model with discrete α-helical and extended conformations did not yield a better fit to the data and was not consistent with chemical shift analysis. These results suggest that the peptide is predominantly in an extended conformation rather than an α-helical state on the HAP surface. Solid-state NMR approaches can thus be used to determine directly the conformation of biologically relevant peptides on HAP surfaces. A better understanding of peptide and protein conformation on biomineral surfaces may provide design principles useful for the modification of orthopedic and dental implants with coatings and biological growth factors that are designed to enhance biocompatibility with surrounding tissue.

NADPH-oxidase and a hydrogen peroxide-sensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines

Pulmonary neuroepithelial bodies (NEB) are widely distributed throughout the airway mucosa of human and animal lungs. Based on the observation that NEB cells have a candidate oxygen sensor enzyme complex (NADPH oxidase) and an oxygen-sensitive K+ current, it has been suggested that NEB may function as airway chemoreceptors. Here we report that mRNAs for both the hydrogen peroxide sensitive voltage gated potassium channel subunit (KH2O2) KV3.3a and membrane components of NADPH oxidase (gp91phox and p22phox) are coexpressed in the NEB cells of fetal rabbit and neonatal human lungs. Using a microfluorometry and dihydrorhodamine 123 as a probe to assess H2O2 generation, NEB cells exhibited oxidase activity under basal conditions. The oxidase in NEB cells was significantly stimulated by exposure to phorbol esther (0.1 μM) and inhibited by diphenyliodonium (5 μM). Studies using whole-cell voltage clamp showed that the K+ current of cultured fetal rabbit NEB cells exhibited inactivating properties similar to KV3.3a transcripts expressed in Xenopus oocyte model. Exposure of NEB cells to hydrogen peroxide (H2O2, the dismuted by-product of the oxidase) under normoxia resulted in an increase of the outward K+ current indicating that H2O2 could be the transmitter modulating the O2-sensitive K+ channel. Expressed mRNAs or orresponding protein products for the NADPH oxidase membrane cytochrome b as well as mRNA encoding KV3.3a were identified in small cell lung carcinoma cell lines. The studies presented here provide strong evidence for an oxidase-O2 sensitive potassium channel molecular complex operating as an O2 sensor in NEB cells, which function as chemoreceptors in airways and in NEB related tumors. Such a complex may represent an evolutionary conserved biochemical link for a membrane bound O2-signaling mechanism proposed for other cells and life forms.

Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-xL

Fas activation triggers apoptosis in many cell types. Studies with anti-Fas antibodies have produced conflicting results on Fas signaling, particularly the role of the Bcl-2 family in this process. Comparison between physiological ligand and anti-Fas antibodies revealed that only extensive Fas aggregation, by membrane bound FasL or aggregated soluble FasL consistently triggered apoptosis, whereas antibodies could act as death agonists or antagonists. Studies on Fas signaling in cell lines and primary cells from transgenic mice revealed that FADD/MORT1 and caspase-8 were required for apoptosis. In contrast, Bcl-2 or Bcl-xL did not block FasL-induced apoptosis in lymphocytes or hepatocytes, demonstrating that signaling for cell death induced by Fas and the pathways to apoptosis regulated by the Bcl-2 family are distinct.