Acute Stroke: Present and Future of Catheter-Based Interventions

Acute ischemic stroke is a major cause of morbidity and mortality in industrialized nations. The sequel of stroke ranges from mild to severe disability and even death. Since the impairment may be permanent, the costs to society from work incapacity and the need for long-term care can be high. Additionally, the burden of suffering associated with the disease may have devastating effects on individuals and families.Following the occlusion of a cerebral vessel, the full extent of the infarction may not become clinically and radiologically apparent until days after. By then, the surrounding watershed zone, or penumbra, either survives or succumbs to necrosis over time. The natural history of this "tissue at risk" is determined by two factors: the collateralization from other vascular territories and the possible occurrence of spontaneous recanalization of the occluded vessel. The current treatment options for acute ischemic stroke are aiming at an early and sustained restoration of flow to the penumbra. The effect of the treatment is therefore time-dependent and the neurologic outcome is a function of the time span between onset of symptoms and recanalization therapy as well as of the recanalization rate associated with a specific treatment.This report summarizes the results of the major trials on catheter-based interventions, either using thrombolytic drugs or novel mechanical approaches being developed to treat patients with acute ischemic stroke.

Factors that determine penumbral tissue loss in acute ischaemic stroke

The goal of acute stroke treatment with intravenous thrombolysis or endovascular recanalization techniques is to rescue the penumbral tissue. Therefore, knowing the factors that influence the loss of penumbral tissue is of major interest. In this study we aimed to identify factors that determine the evolution of the penumbra in patients with proximal (M1 or M2) middle cerebral artery occlusion. Among these factors collaterals as seen on angiography were of special interest. Forty-four patients were included in this analysis. They had all received endovascular therapy and at least minimal reperfusion was achieved. Their penumbra was assessed with perfusion- and diffusion-weighted imaging. Perfusion-weighted imaging volumes were defined by circular singular value decomposition deconvolution maps (Tmax > 6 s) and results were compared with volumes obtained with non-deconvolved maps (time to peak > 4 s). Loss of penumbral volume was defined as difference of post- minus pretreatment diffusion-weighted imaging volumes and calculated in per cent of pretreatment penumbral volume. Correlations between baseline characteristics, reperfusion, collaterals, time to reperfusion and penumbral volume loss were assessed using analysis of covariance. Collaterals (P = 0.021), reperfusion (P = 0.003) and their interaction (P = 0.031) independently influenced penumbral tissue loss, but not time from magnetic resonance (P = 0.254) or from symptom onset (P = 0.360) to reperfusion. Good collaterals markedly slowed down and reduced the penumbra loss: in patients with thrombolysis in cerebral infarction 2 b-3 reperfusion and without any haemorrhage, 27% of the penumbra was lost with 8.9 ml/h with grade 0 collaterals, whereas 11% with 3.4 ml/h were lost with grade 1 collaterals. With grade 2 collaterals the penumbral volume change was -2% with -1.5 ml/h, indicating an overall diffusion-weighted imaging lesion reversal. We conclude that collaterals and reperfusion are the main factors determining loss of penumbral tissue in patients with middle cerebral artery occlusions. Collaterals markedly reduce and slow down penumbra loss. In patients with good collaterals, time to successful reperfusion accounts only for a minor fraction of penumbra loss. These results support the hypothesis that good collaterals extend the time window for acute stroke treatment.

Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model

Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15min on and 15min off) starting 45min after middle cerebral artery occlusion and lasting 4h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans.

Imaging of acute ischemic stroke.

BACKGROUND Over 80% of strokes result from ischemic damage to the brain due to an acute reduction in the blood supply. Around 25-35% of strokes present with large vessel occlusion, and the patients in this category often present with severe neurological deficits. Without early treatment, the prognosis is poor. Stroke imaging is critical for assessing the extent of tissue damage and for guiding treatment. SUMMARY This review focuses on the imaging techniques used in the diagnosis and treatment of acute ischemic stroke, with an emphasis on those involving the anterior circulation. Key Message: Effective and standardized imaging protocols are necessary for clinical decision making and for the proper design of prospective studies on acute stroke. CLINICAL IMPLICATIONS Each minute without treatment spells the loss of an estimated 1.8 million neurons ('time is brain'). Therefore, stroke imaging must be performed in a fast and efficient manner. First, intracranial hemorrhage and stroke mimics should be excluded by the use of computed tomography (CT) or magnetic resonance imaging (MRI). The next key step is to define the extent and location of the infarct core (values of >70 ml, >1/3 of the middle cerebral artery (MCA) territory or an ASPECTS score ≤ 7 indicate poor clinical outcome). Penumbral imaging is currently based on the mismatch concept. It should be noted that the penumbra is a dynamic zone and can be sustained in the presence of good collateral circulation. A thrombus length of >8 mm predicts poor recanalization after intravenous thrombolysis.

Time window for recanalization in basilar artery occlusion: Speculative synthesis.

Basilar artery occlusion (BAO) is one of the most devastating forms of stroke and few patients have good outcomes without recanalization. Most centers apply recanalization therapies for BAO up to 12-24 hours after symptom onset, which is a substantially longer time window than the 4.5 hours used in anterior circulation stroke. In this speculative synthesis, we discuss recent advances in BAO treatment in order to understand why and under which circumstances longer symptom duration might not necrotize the brainstem and turn therapeutic attempts futile. We raise the possibility that distinct features of the posterior circulation, e.g., highly developed, persistent collateral arterial network, reverse filling of the distal basilar artery, and delicate plasma flow siding the clot, might sustain brittle patency of brainstem perforators in the face of stepwise growth of the thrombus. Meanwhile, the tissue clock characterizing the rapid necrosis of a typical anterior circulation penumbra will not start. During this perilous time period, recanalization at any point would salvage the brainstem from eventual necrosis caused by imminent reinforcement and further building up of the clot.

La arquitectura de José M. García de Paredes ideario de una obra

Acercarse a las obras de José M. García de Paredes, y mirarlas como un conjunto de ideas que nos indican una manera de pensar y de hacer arquitectura, nos explica un ideario que persiste en el tiempo. Tomando prestado el término “explicar” en el sentido que Stravinski le da en su Poética musical1: desplegar, desarrollar, describir una cosa, descubrir y aclarar su génesis, se comprueban las relaciones que cosas aparentemente dispersas tienen entre si, cómo se originan las obras para saber cómo determinan la arquitectura, una vez que ésta tiene vida propia y uso, pasado el tiempo. El motivo de esta tesis se encuentra en el orden, análisis y estudio de su archivo, realizado a partir del año 1990. García de Paredes, titulado en Madrid, fue arquitecto entre 1950 y 1990 y se inició en la arquitectura en un tiempo tan complejo como el actual. No fue un teórico de la arquitectura, si bien conoció en profundidad su teoría y dejó escritos y reflexiones sobre la manera de abordar el proyecto. Quizás no fue un arquitecto radicalmente innovador y sus obras son silenciosas, aunque muchas encierran planteamientos rotundos que permanecen voluntariamente en penumbra. Sin embargo sus obras son nítidas, tienen el valor de la coherencia y son valiosas por el conocimiento y por los valores que transmiten. Han cumplido su objetivo y ahora son parte de los lugares para los que se construyeron y parte de la vida de las personas para las que se proyectaron. En gran medida, poseen ya la pátina del tiempo. Su obra, no muy extensa, aúna ideas necesarias para abordar la práctica del proyecto y para llegar a ese voluntario resultado final en el que la arquitectura sea, además de una expresión personal, una actividad social capaz de hacer mejor la vida de las personas. Mirar la arquitectura de García de Paredes a través del estudio de todas las cuestiones que intervienen en ella y convertir su conocimiento en un instrumento útil de trabajo en el proyecto, es el objetivo de esta tesis. Así se analizan determinadas obras para exponer temas de antes y de ahora, ideas que son a la vez antiguas y contemporáneas. Este ideario sobre la arquitectura de García de Paredes no pertenece sólo a un tiempo, pues la bella utilidad social de la arquitectura y cómo llegar a ella a través del conocimiento y de la economía intelectual, sigue vigente. Y este objetivo tiene claramente una segunda lectura, pues al poner en valor el ideario de su obra, la presente tesis constituye tanto un homenaje como un agradecimiento al arquitecto. Sintetizar este ideario ha necesitado tanto del tiempo para organizar un archivo como de la práctica de la arquitectura para constatarlo. Durante una década, entre 1981 y 1990, trabajé en el estudio de José M. García de Paredes, con la mirada enfocada hacia los proyectos que entonces se desarrollaban en su estudio. En esos años, la música y las secciones de las salas de concierto llenaban las mesas de dibujo. En 1990, tras su inesperada marcha, me encontré con un legado de documentos que constituyen un fragmento de la arquitectura contemporánea española, que encierran la explicación de proyectos y planteamientos que son respuesta clara a la realidad de su momento. La preparación entonces de la documentación para las tres monografías sobre su obra me llevó a ordenar, clasificar y a documentar los fondos del estudio de manera sistemática y cronológicamente. Los documentos, conservados en archivadores y tubos sin numerar, desvelaban una obra en un momento en el cual el escenario de fondo del debate sobre arquitectura era ético. De manera casi artesanal y próximo de un grupo coherente de arquitectos, algunos vinculados también a las artes plásticas, García de Paredes utiliza los medios materiales a su alcance, interpretando la realidad de una forma personal, alejada de la frialdad del movimiento moderno estricto, con una voluntad de mejorarla y de prescindir de todo aquello que no fuera necesario. Las obras dan respuesta a esa realidad de tal manera que la transforman, como si de un “mágico realismo” se tratara. Estos documentos con olor a antiguo, más que narrar una historia, explican la manera en que se ha hecho esa historia, cómo las biografías y los acontecimientos se entrelazan para llegar al conocido resultado final. Y de un primer análisis, disponiéndolos a la vista de un mismo tiempo, va surgiendo otro interés que no es el de explicar su obra sino el de observar el proceso de trabajo de un arquitecto para desvelar un método de proyecto. Sobre el método de trabajo de un músico, Azorín se pregunta en su artículo “Vida imaginaria de Falla”: “Es fácil ver trabajar a un pintor, no es tan fácil ver enfrascado en su labor a un literato, aunque en las redacciones solamos ver cómo escribe un poeta que hace artículos para un periódico. ¿Pero cómo imaginamos a un músico en su tarea?. ¿Cómo escribe un músico?. ¿Es que siente de pronto un arrebato lírico y un poco desmelenado, los músicos deben llevar el pelo largo, se sienta al piano y comienza a tañer como una inspirada pitonisa?. ¿es que se levanta a media noche y, arrebatado por la inspiración y a la luz de la luna, si la hay, escribe febrilmente esas garrapatitas que vemos en los hilos telegráficos de la música?" Manuel de Falla en una carta le responde: “Nada de eso, mi querido amigo, mi trabajo de compositor no es tan misterioso como usted imagina: podría compararse al de un escritor que fuera a la vez arquitecto”. ¿Y cómo trabaja un arquitecto?. La complejidad del proceso arquitectónico nos presenta sin embargo resultados finales que sólo a través de una observación minuciosa permiten entrever el recorrido desde el pensamiento hasta la obra acabada. El escritor narra lo que ve o imagina y el arquitecto construye y da forma a esa realidad o a esos deseos y para ello debe mirar, escuchar y debe saber hacer. Analizar este proceso nos lleva inexorablemente a desvelar las claves que hacen valiosas determinadas arquitecturas. En junio de 1986 García de Paredes escribe el texto “Tres paisajes con arquitecturas”4. El texto describe tres paisajes culturales diferentes en distintos tiempos. El primero que describe es el Madrid neoclásico y el significado que tiene en este paisaje el Museo del Prado. El segundo paisaje se denomina “Alhambra versus Carlos V” y en él relata un delicado escenario donde se entrelazan distintas cuestiones relativas a la intervención en lugares históricos. En el tercer paisaje “Paisaje con Ruinas” tras describir las hermosas ruinas físicas del pasado concluye con una reflexión: “Hay ruinas y ruinas… Pero quizá no sean estas las verdaderas ruinas de nuestro tiempo. Qué clase de ruina producirá nuestra modesta arquitectura del siglo XX?. Nuestro legado no debería leerse en clave de piedras como las de otras épocas que no disponían de otro lenguaje que el de construir para los tiempos. Sin embargo es posible que surjan otras claves, quizá aún no bien conocidas, que sean para las generaciones futuras de tan clara lectura como la de este tercer Paisaje”. Encontrar esas claves contemporáneas, es el objeto de este paseo por las obras y escritos de García de Paredes. Mirar, suprimido el tiempo, los planos, dibujos, escritos, libros y fotografías del archivo del arquitecto, ordenando y comprendiendo los motivos que propiciaron cada obra, nos lleva a pensar que la arquitectura de cada momento es sólo un desplazamiento de los anteriores. Nada ahora es completamente distinto de lo que era entonces y la arquitectura de antes puede ser interpretada, más allá de aspectos formales, por otras generaciones, desdibujándose el tiempo donde pretendemos ordenarla. Este legado de claves conceptuales nos es útil ahora para conocer lo que permanece en la arquitectura pensando en cuestiones actuales a través de papeles antiguos. El legado de esa “modesta arquitectura” no se debe leer pues en clave de “piedras”, como expresaba García de Paredes. Gran parte de sus obras se construyen con materiales sencillos y la lectura de su valor no es directa. Sin embargo explican en qué momento la arquitectura pasa a ser un hecho capaz de transmitir intenciones ocultas y convertirse en una actividad social en sintonía con la realidad. Desvelar esta colección de ideas para enfocar cuestiones de arquitectura, en el convencimiento de que este ideario es tan válido hoy como entonces, nos acerca a ese utópico método de trabajo del arquitecto. En este ciclo abierto se han seleccionado determinadas obras que permiten plantear mejor las cuestiones que ilustran su razón de ser y así pues se suceden lugares y personas, números y geometrías, música, artes plásticas y arquitecturas. ABSTRACT Looking at the work of José M. García de Paredes as a set of ideas that outline a way of imagining and producing architecture, explains a vision that has persisted in time. Employing the word “explain” in the same sense as Stravinsky in his Poetics of Music: deploying, developing and describing something, discovering and clarifying its origins as a way of observing the relationships between things and the way designs originate in order to understand how they determine the architecture, once it has a life and use of its own after time has passed. This thesis is based on an analysis of the archives of José M. Garcia de Paredes, which began in 1990. After graduating from the Madrid School in 1950 —an equally complex time as today— he continued to practise architecture until 1990. He was not an architectural theorist but he had a deep understanding of theory and left essays and ideas on the way to tackle projects. Although he may not have been a radically innovative architect and his work may seem subdued, much of it embodies categorical approaches, which are deliberately overshadowed. Nevertheless, his work is sharp, consistent and is valuable for the knowledge and values it transmits. It has served its purpose, it now forms part of the places for which it was built and has become part of the lives of the people it was designed for. To a large extent, his buildings already show the patina of time. While not large in number, they bring together the ideas needed to put a project into practice and arrive at an end result in which the architecture is also a personal expression, a social activity that makes life better for people. The discourse takes a new look at the architecture of Garcia de Paredes through an analysis of all the issues involved in order to turn the resulting knowledge into a useful tool for project work. It therefore now, ideas that are old but at the same time contemporary. This vision time. The beautiful social utility of his architecture and the way he arrived at it through knowledge and intellectual economy still remain valid. The synthesis of this vision has required much time to organize the archive and also a professional architectural practice to put it into perspective. The preserved documents reveal a body of work that was designed at a time when ethics shaped the underlying scenario of the Relación de architectural debate. The architect used the material resources at his disposal in an almost craftsman-like way, in the company of a congruent group of architects. He interpreted reality in a personal way, removed from the coldness of the strict Modern Movement, striving to improve it and strip off anything that was unnecessary. His buildings responded to their context in such a way that transformed it, as if they were “magical realism”. Another line of analysis emerged from an initial analysis, with all the documents in view at the same time: not to explain his work but rather to study the design process of an architect in order to discover a method. In 1986, García de Paredes wrote “Three landscapes with architectures”, which describes three cultural landscapes in different times. After describing the beauty of the physical ruins of the past, the third landscape, “Landscape with Ruins”, concludes with this observation: “There are ruins and ruins ... But these might not be the real ruins of our time. What kind of ruin will be produced by our modest 20th century architecture? Our legacy should not be interpreted in the key of mere stones, like those of past eras which had access to no other language than construction for all times. Other keys, perhaps not yet familiar, may well emerge and be as legible for future generations as this third Landscape”. This tour of the work and writings of Garcia de Paredes is aimed at discovering these contemporary keys. The legacy of such keys can now help us to know what endures in architecture; thinking about current issues through the perspective of old papers. Having set aside the time factor, looking at the drawings, essays, books and photographs from the architect’s archives, organising and understanding the reasons that gave rise to each work, I now believe that the architecture of each moment is only previous work that has been shifted. Nothing is completely different now from what it was back then. The architecture of the past can be interpreted by other generations, looking beyond the aspects of form, blurring the time factor when we want to order it. For this purpose I have selected particular works that permit a better enunciation of the issues that illustrate their rationale, hence the succession of places and people, numbers and geometries, music, art and architectures.

Lo intermedio como lugar : lo intersticial, lo fronterizo y lo impreciso en la arquitectura contemporánea

1. Nuestra investigación se centra en el estudio de los “ámbitos o espacios intermedios” en momentos de la arquitectura contemporánea, en un período de transición entre finales de los años 80 y nuestros días. Pretendemos analizar cómo se presenta el ámbito intermedio en el objeto o lugar arquitectónico y su función o relación con el entorno cercano, desde el proyecto hasta su repercusión en la experiencia vivida. 2. El concepto de intermedio entendido como ámbito o espacio intersticial, fronterizo y ambivalente (o multivalente), atraviesa en la presente investigación el campo de la etimología, de la ciencia, del pensamiento y del arte, para detenerse en la arquitectura actual, llevándose a cabo una indagación concreta en el proceso de concepción, en la propuesta formal, espacial y funcional, así como en la percepción y demás experiencias o vivencias en el lugar arquitectónico. 3. En primer lugar nos proponemos estudiar y explorar el concepto de “intermedio” en sus características, funciones y ubicaciones dentro de la cultura contemporánea, detectando sus antecedentes culturales más importantes, para a continuación aplicarlo reflexivamente a obras significativas de arquitectura. La investigación se enfoca en la modalidad figural (imprecisa) de lo intermedio (en alusión al “figural” deleuziano), cuyas metáforas base son lo translúcido, la penumbra y la espuma, vinculadas al actual paradigma cultural de la complejidad (C. Jencks). A continuación se analizan las relaciones o implicaciones de dicha modalidad figural en obras de arquitectos como Eisenman, Holl, Tschumi, Ito, Fujimoto, Van Berkel y Bos, y Siza, comprobando su valor operativo y poniendo de manifiesto su sentido e importancia en la actualidad y en la disciplina. El estudio tiene como trasfondo el concepto de in-between de la obra de Eisenman, y utiliza conceptos de la filosofía del límite de Trías como algunos de sus principales fundamentos. 4. En cada una de las obras de arquitectura presentadas esta modalidad imprecisa se traduce en un ámbito o espacio intermedio figural específico. Son obras en las que real y virtual, matricial y objetual, arquitectura y territorio, existente y nuevo, colectivo e individual, social e íntimo, interior y exterior, y demás usos y funciones se entrelazan o funden. Son arquitecturas cuya geometría ya no se encuentra tan determinada por aspectos bi o tridimensionales del dibujo o de la construcción. A través de la manipulación de estas geometrías más o menos complejas, dinámicas e intersticiales, estas obras reflejan (o intuyen) las premisas del actual Zeitgeist: un cambio de esquemas de objetos a relaciones basado en un pensamiento más holístico, transdisciplinar, sistémico o complejo (E. Morin), y una nueva conciencia colectiva sobre la realidad que anuncia la crisis de la percepción, el cambio de paradigma y nuevos valores (F. Capra). Emerge otra forma de sentir y percibir el mundo, los lugares y los espacios, que poco a poco está cambiando el modo de pensar y dibujar la arquitectura, y consecuentemente de interaccionar con ella. 5. El sentido del espacio intermedio figural, emerge en las cada vez más complejas cualidades morfológico-espaciales y funcionales de una parte importante de la arquitectura actual. Arquitectura, geometría y tecnología informática están más entrelazadas que nunca, y de un modo más libre, para así poder indagar en nuevas formas de pensar y crear lugares en que los “espacios intermedios” que investigamos son un testimonio. El espacio arquitectónico se vuelve afectivo e interactivo, un lugar intermedio figural, formalizado por espacialidades intersticiales que parecen aludir a lo líquido, donde la forma es más matriz que configuración, el espacio más espacialidad que compartimiento, la función más versátil y multivalente que específica o autónoma, y la perplejidad, la imaginación y la evocación se entrecruzan y vuelven patentes. 6. La arquitectura de los lugares intermedios valora no solamente el “plano”, la “configuración” y la “transparencia”, sino sobre todo el “espacio” y la “relación” en sus interrelaciones con los usuarios y demás contextos. De la identidad a la relacionalidad, de la representación a la presentación, es una arquitectura que propone “otros espacios” que más que espacios son topografías y espacialidades intersticiales, de tensión, transición, transformación, relación, intercambio e interacción. Son lugares intermedios reales y virtuales, que se sirven tanto de la morfología como de la topología para conquistar nuevas espacialidades, pretendiendo salir de la estricta operación de “forming”/”morphing”/formación/”conformación” para explorar la de “spacing”/espaciamiento. Son lugares que se basan en conceptos como la zona de indiscernibilidad de Deleuze, la imagen- flujo de Buci-Glucksmann, la suspensión-entre de Sloterdijk, o el espacio no-objetivo al que se refiere José Gil, plasmándose en la arquitectura contemporánea como tropos de lo intersticial. 7. Son los lugares intermedios de la arquitectura actual, de espacialidad háptica, más “afectiva”, generativa e interactiva, donde ese ámbito intermedio transforma y es transformado, “afecta”, “con-mueve” (nos hace mover/accionar) y evoca otros lugares, otras posibilidades de espacio habitable u ocupable. Emerge lo intermedio como lugar, algo que anuncia y exhibe, de manera paradigmática y manifiesta, el monumento de Eisenman en Berlín. ABSTRACT 1. Our research focuses on the study of “in-between spaces or environments” at particular times in contemporary architecture, in a transition period from the end of the 1980’s through to today. We aim to analyse how in-between environments are presented in the architectural object or place and their function or their relationship with the nearby surroundings, from the project through to the experience had. 2. In this research, the in-between concept, understood as an interstitial, border and ambivalent (or multi-purpose) environment or space, is assessed from the viewpoint of etymology, science, thought and art, to conclude in current architecture, with specific exploration of the conception process, of the formal, spatial and functional proposal, together with the perception and other experiences in the architectural place. 3. Firstly, we aim to study and explore the “in-between” concept as regards its features, functions and locations within contemporary culture, revealing its most important cultural background, to then apply it reflexively to important works of architecture. The research focuses on the figural (imprecise) mode of in-between (in allusion to Deleuze’s “figural” approach) whose base metaphors are the translucent, semi-darkness and foam, linked to the current cultural paradigm of complexity (C. Jenks). We then go on to assess the relationships or implications of said figural mode in architectural works by Eisenman, Holl, Tschumi, Ito, Fujimoto, Van Berkel and Bos, and Siza, verifying their operational worth and revealing their meaning and importance today and in this discipline. The backdrop of the study is the in-between concept of Eisenman’s work and it also uses concepts from the philosophy of the limit of Trías as its main underpinnings. 4. In each of the architectural works presented, this imprecise mode is translated into a specific in-between environment or space. They are works in which real and virtual, matricial and objectual, architecture and territory, existing and new, collective and individual, social and intimate, interior and exterior and other uses and functions all intertwine or blend together. They are architectures the geometry of which is not so much determined by bi- or tri-dimensional aspects of the drawing or construction. Through the manipulation of these more or less complex, dynamic and interstitial geometries, these works reflect (or insinuate) the premises of the current Zeitgeist: A change in the scheme of objects to relationships towards a more holistic, transdisciplinary, systemic or complex thought (E. Morin), and a new collective conscience about the reality which announces the crisis of perception, the change in paradigm and new values (F. Capra). Another way of feeling and perceiving the world, places and spaces, which little by little is changing the way of thinking and drawing architecture and hence of interacting with it. 5. The meaning of figural in-between space emerges in the increasingly complex, morphological-spatial and functional qualities of a large part of architecture today. Architecture, geometry and computer technology are more than ever intertwined in a freer way to inquire into other ways of thinking and making places, where the “in-between” spaces we research are a testimony. Architectural space becomes affective and interactive, a figural in-between place, formed by interstitial spatiality which seems to allude to something liquid, where shape is more matrix than configuration, space more spatiality than compartment, its function more versatile and multi-purpose than specific or autonomous, and perplexity, imagination and evocation criss-cross each other, becoming obvious. 6. The architecture of in-between places values not only “flat”, “configuration” and “transparency”, but above all “space” and the “relationship” in its interrelations with users and other contexts. From identity to relationality, from representation to presentation, it is an architecture that proposes “other spaces”, which more than spaces are topographies and interstitial spatialities, of tension, transition, transformation, relation, exchange and interaction. They are real and virtual in-between places, that take in both morphology and topology to conquer new spatialities, aiming to depart from the strict “forming”/”morphing” operation in order to explore “spacing”. They are places that derive both from Deleuze’s indiscernibility zone concept, from Buci-Glucksmann´s image-flow concept, from Sloterdijk’s suspension-between, and from the non-objective space referred to by José Gil, and they are embodied in contemporary architecture as tropes of the interstitial. 7. They are the in-between places in architecture today, of haptic spatiality, more “affective”, generative and interactive, where that in-between environment transforms and is transformed, “affects”, “moves” (it makes us move/act) and evokes other places, other possibilities of habitable or occupiable space. The in-between emerges as a place, which paradigmatically and declaredly, Eisenman´s monument in Berlin announces and exhibits. RESUMO 1. A investigação centra-se no estudo dos “âmbitos ou espaços intermédios” em momentos da arquitectura contemporânea, no período de transição entre os finais dos anos 80 e os nossos dias. Pretende-se analisar como se apresenta o âmbito intermédio no objecto ou lugar arquitectónico e sua função ou relação com o meio envolvente, desde o projecto até à sua repercussão na experiencia vivenciada. 2. O conceito de intermédio entendido como âmbito ou espaço intersticial, fronteiriço e ambivalente (ou multivalente), atravessa na presente investigação o campo da etimologia, da ciência, do pensamento e da arte, para deter-se na arquitectura actual, realizando-se uma indagação concreta no processo de concepção, na proposta formal, espacial e funcional, assim como na percepção e demais experiencias ou vivencias no lugar arquitectónico. 3. Em primeiro lugar, explora-se o conceito de “intermédio” nas suas características, funções e concretizações na cultura contemporânea, detectando os seus antecedentes culturais mais importantes, para em seguida aplicá-lo reflexivamente a obras significativas de arquitectura. A investigação centra-se na modalidade figural (imprecisa) do intermédio (alusão ao figural deleuziano) cujas metáforas base são o translúcido, a penumbra e a espuma, relacionadas com o actual paradigma da complexidade (C. Jencks). Em seguida analisam-se as relações ou implicações da referida modalidade figural em obras de arquitectos como Eisenman, Holl, Tschumi, Ito, Fujimoto, Van Berkel e Bos, e Siza, como modo de comprovar o seu valor operativo e revelar o seu sentido e importância na actualidade e na disciplina. O estudo tem como referencia o conceito de in-between da obra de Eisenman, e utiliza conceitos da filosofia do limite de Trias como alguns dos seus principais fundamentos. 4. Em cada uma das obras de arquitectura apresentadas esta modalidade imprecisa traduz-se num âmbito ou espaço intermédia figural especifico. São obras nas quais real e virtual, matricial e objectual, arquitectura e território, existente e novo, colectivo e individual, social e intimo, interior e exterior, e outros usos e funções se entrelaçam ou fundem. São arquitecturas cuja geometria já não está tão determinada por aspectos bi ou tridimensionais do desenho ou da construção. Através do uso destas geometrias mais ou menos complexas, dinâmicas e intersticiais, estas obras reflectem (ou intuem) as premissas do actual zeitgeist: uma mudança de esquemas de objectos a relações para um pensamento mais holístico, transdisciplinar, sistémico ou complexo (E. Morin) e uma nova consciência colectiva sobre a realidade, que anuncia a crise da percepção, a mudança de paradigma e novos valores (F. Capra). Emerge uma outra forma de sentir e perceber o mundo, os lugares e os espaços, que gradualmente vai alterando o modo de pensar e desenhar a arquitectura, e consequentemente de interagir com ela. 5. O sentido do espaço intermédio figural, emerge nas cada vez mais complexas qualidades morfológico-espaciais e funcionais de uma parte importante da arquitectura actual. Cada vez mais, arquitectura, geometria e tecnologia informática, relacionam-se de um modo mais livre para indagar outras formas de pensar e fazer lugares, onde os espaços intermédios que investigamos são um testemunho. O espaço arquitectónico torna-se afectivo e interactivo, um lugar intermédio figural, formalizado por espacialidades intersticiais que parecem aludir ao estado liquido, onde a forma é mais matriz que configuração, o espaço mais espacialidade que compartimento, a função mais versátil e multivalente que especifica ou autónoma, e a perplexidade, a imaginação e a evocação entrecruzam-se e tornam-se patentes. 6. A arquitectura dos lugares intermédios valoriza não só o “plano”, a “configuração” e a “transparência”, mas sobretudo o” espaço” e a ”relação” nas suas inter-relações com os utentes e restante contextos. Da identidade à relacionalidade, da representação à apresentação, é uma arquitectura que propõe “outros espaços”, que além de espaços são topografias e espacialidades intersticiais, de tensão, transição, transformação, relação, intercambio e interacção. São lugares intermédios reais e virtuais que utilizam tanto a morfologia como a topologia para conquistar novas espacialidades, pretendendo ultrapassar a estrita operação de “forming”/“morphing”/formação para explorar a de “spacing”/espaçamento. São lugares que se apoiam tanto no conceito de zona de indescernibilidade de Deleuze, como na de imagem-fluxo de Buci-Glucksmann como no de suspensão–entre de Sloterdijk ou de espaço-não objectivo que refere José Gil, e se plasmam na arquitectura contemporânea como tropos do intersticial. 7. São os lugares intermédios da arquitectura actual, de espacialidade háptica, mais “afectiva”, generativa e interactiva, onde esse âmbito intermédio transforma e é transformado, “afecta”, ”co-move “(nos faz mover/agir) e evoca outros lugares, outras possibilidades de espaço habitável ou ocupável. Emerge o intermédio como lugar que, paradigmática e manifestamente, o monumento de Eisenmann em Berlim, anuncia e exibe.

Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress

Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1–10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported.

N-tert-butyl-alpha-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia.

Recent results have demonstrated that the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) reduces infarct size due to middle cerebral artery occlusion (MCAO), even when given after ischemia. The objective of the present study was to explore whether PBN influences recovery of energy metabolism. MCAO of 2-hr duration was induced in rats by an intraluminal filament technique. Brains were frozen in situ at the end of ischemia and after 1, 2, and 4 hr of recirculation. PBN was given 1 hr after recirculation. Neocortical focal and perifocal ("penumbra") areas were sampled for analyses of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glycogen, glucose, and lactate. The penumbra showed a moderate-to-marked decrease and the focus showed a marked decrease in PCr and ATP concentrations, a decline in the sum of adenine nucleotides, near-depletion of glycogen, and an increase in lactate concentration after 2 hr of ischemia. Recirculation for 1 hr led to only a partial recovery of energy state, with little further improvement after 2 hr and signs of secondary deterioration after 4 hr, particularly in the focus. After 4 hr of recirculation, PBN-treated animals showed pronounced recovery of energy state, with ATP and lactate contents in both focus and penumbra approaching normal values. Although an effect of PBN on mitochondria cannot be excluded, the results suggest that PBN acts by preventing a gradual compromise of microcirculation. The results justify a reevaluation of current views on the pathophysiology of focal ischemic damage and suggest that a therapeutic window of many hours exists in stroke.

La aplicación de stop-motion en arquitectura: materia y luz

Se inicia un análisis de los procesos de trabajo de stop-motion porque ayudan a comprender las diferentes escalas en arquitectura donde las maquetas se convierten en futuros prototipos de infraestructuras de edificios o de paisaje. Stop motion es una técnica de animación fotograma a fotograma de objetos estáticos mediante la manipulación de figuras de plastilina en entornos fijos con cambios de luz, color y sonido. Igual que dicha técnica reúne lo mejor del rodaje tradicional -story board, escenografía, fotografía, personajes, iluminación- la animación de maquetas de interiores sintetiza micro-procesos de mayor repercusión -habitaciones con cambios de humedad, de temperatura, de ventilación y de iluminación- incorporando efectos especiales que son procesados digitalmente en post-producción. Se construyen varios prototipos de habitación con parámetros fijos como el tamaño y la posición de la cámara y otros variables como los materiales, los personajes y la iluminación. Representan un mundo en miniatura que intenta aportar un acercamiento sensorial y atmosférico analizando la magia y la fantasía que Junichirô Tanizaki describe en la penumbra de las construcciones tradicionales japonesas y estudiando las imperfecciones de los escenarios que Tim Burton manipula en su películas de animación con una textura que las tecnologías digitales no pueden igualar. El objetivo es utilizar una escala micro para realizar unos modelos interiores donde las condiciones atmosféricas están controladas y reducidas, y tomar datos que se podrían aplicar a un proceso de modelado a escala intermedia para testar prototipos de edificios como el túnel de viento; o, finalmente, a una escala macro con maquetas de un sector de la costa o de un río donde los fenómenos meteorológicos son los protagonistas para simular inundaciones y diseñar futuras medidas de prevención y seguridad.

A Experiência como ordenação da realidade: uma estratégia orgânica para a educação científica

Knowledge is understanding. According to the philosopher Gaston Bachelard our immediate contact with the reality is only worth as confusing and provisional data. This phenomenological contact requires inventory and classification. For this reason our first reading on any phenomenon is limited to a basic levels of reality. Elements such as dynamics, functioning or detailed characteristics of what is observed can only be accessed at higher levels of reality, explains the physicist Werner Heisenberg. The ideas woven by these two great intellectuals oxygenates the notion that a well-made thinking does not require only observation and description of the nature, but assigns value and meaning to the knowledge. Based on these ideas and on the cognitive horizon brought by the complexity sciences, this research aims to nurture a reflection on our understanding of the world built from a rational perspective of experience, as an organic sequence of research. This arguments, over the study, describes how the experience is able to oxygenate a well-made thinking, as the concept created by Edgar Morin and expanded by Conceição Almeida. I argue that the experience as a path of investigative research allows one to ventures in the shadows of the unknown to access upper layers of reality. The experience is, therefore, an organic strategy for a well-made thinking - A nutritious mud that oxygenates, regulates, repairs and configures the quality of understanding. As a thread to discuss this ideas I've used my professional journey over a year and a half as a Natural Sciences' teacher on the Federal University of Rio Grande do Norte, where I could see how experiences helped on breaking a simplified understanding of the world. I chose to work with the research problems developed by 398 students over these three semesters. The problems were essential to the questioning of the phenomena that once seemed obvious or uninteresting, bringing out operational reasons and dynamics of the observed structures. Experience, in this sense, is the founder of dynamic thinking, as the need to deconstruct the phenomena's first impressions, assigning value and meaning to gestated knowledge.

Tenecteplase and alteplase in acute ischaemic stroke thrombolysis: clinical and imaging study

Introduction: Intravenous thrombolysis in acute ischaemic stroke with alteplase improves clinical outcomes, but it has limited efficacy and is associated with increased risk of intracranial haemorrhage. An improved tissue plasminogen activator, tenecteplase, was evidenced to be at least equally effective with lower risk of haemorrhage in acute myocardial infarction thrombolysis. To date, two completed phase II randomised controlled studies comparing tenecteplase and alteplase in acute ischaemic strokes showed variable results. Methods: A literature review of thrombolytic agents used in myocardial infarction and acute ischaemic stroke was performed, followed by a retrospective investigation of the bolus-to- infusion delay of alteplase administration. The main focus of this thesis is the report of our single centre phase II randomised controlled trial that compared tenecteplase (0.25mg/kg, maximum 25mg) and alteplase (0.9mg/kg, maximum 90mg, 10% as the initial bolus, following by one hour infusion with the rest of the dose) in acute ischaemic stroke thrombolysis using advanced imaging as biomarkers. Imaging comprised baseline computed tomography (CT), CT perfusion (CTP) and CT angiography (CTA), and CT+CTA at 24-48 hours. The primary end-point was penumbral salvage (CTP-defined penumbra volume minus follow-up CT infarct volume). A sub-study of coagulation and fibrinolysis analysis of the two agents was performed by comparing a group of coagulation variables measured pre-treatment, 3-12 hours, and 24±3 hours post thrombolysis. An individual patient data (IPD) meta-analysis was carried out using all three completed tenecteplase/alteplase comparison studies in stroke thrombolysis. We compared clinical outcomes including modified Rankin scale at 3 months, early neurological improvement at 24 hours, intracerebral haemorrhage rate and mortality at 3 months between all three tenecteplase doses (0.1mg/kg, 0.25 mg/kg, and 0.4mg/kg) examined and standard alteplase. Imaging outcomes including penumbra salvage, recanalisation rates were also compared using the data from the two studies that had advance imaging carried out. Results: Delay between the initial bolus and the subsequent infusion in administration of alteplase is common. This may reduce the likelihood of achieving a good functional outcome. Among the 104 patients recruited in ATTEST trial, 71 contributed to the imaging primary outcome. No significant differences were observed for penumbral salvage [68 (SD 28) % tenecteplase vs 68 (SD 23) % alteplase], mean difference 1% (95% confidence interval -10%, 12%, p=0·81) or for any secondary end-point. The SICH incidence (1/52, 2% vs 2/51, 4%, by SITS-MOST definition, p=0·55; by ECASS-2 definition, 3/52, 6% tenecteplase vs 4/51, 8% alteplase, p=0.59) did not differed significantly. There was a trend towards lower ICH risk in the tenecteplase group (8/52 tenecteplase, 15% vs 14/51 alteplase, 29%, p=0·091). Compared to baseline, alteplase caused significant hypofibrinogenaemia (p=0.002), prolonged Prothrombin Time (PT) (p=0.011), hypoplasminogenaemia (p=0.001) and lower Factor V (p=0.002) at 3-12 hours after administration with persistent hypofibrinogenaemia at 24h (p=0.011), while only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (p<0.001) and fibrinogen (p=0.002) compared with alteplase. In a pooled analysis, tenecteplase 0.25mg/kg had the greatest odds to achieve early neurological improvement (OR [95%CI] 3.3 [1.5, 7.2], p=0.093), excellent functional outcome (mRS 0-1) at three months (OR [95%CI] 1.9 [0.8, 4.4], p= 0.28), with reduced odds of ICH (OR [95%CI] 0.6 [0.2, 1.8], P=0.43) compared with alteplase. Only 19 patients were treated with tenecteplase 0.4mg/kg, which showed increased odds of SICH compared with alteplase (OR [95% CI] 6.2 [0.7, 56.3]). In the two studies where advanced imaging was performed, the imaging outcomes did not differ in the IPD analysis. Conclusion: Tenecteplase 0.25 mg/kg has the potential to be a better alternative to alteplase. It can be given as a single bolus, does not cause disruption to systemic coagulation, and is possibly safer and more effective in clot lysis. Further phase III study to compare tenecteplase and alteplase in acute ischaemic stroke is warranted.

Un grato desfile de nubes

Nada es real sino hasta tanto tú lo haces existir como real. Nada se mueve si tú no le das el movimiento. Nada tiene sentido hasta que tú no le das el sentido. Nada se siente hasta que tú no lo haces sentir al que te sueña o te busca entre los bosque de rocío. Nadie conoce una ciudad sino eres tú quien se la exhibe como una ciudad de tentáculos melancólicos o inalcanzable en la irritación que te provoca. Nadie conoce un misterio sino se relaciona con quienes lo tienen o lo llevan como una visión. Y así, eso que indico, es para mí, lo que realiza y desarrolla totalmente, con una obsesión sin medida, el poeta Raúl Mejía. Y en todo este libro: Un grato desfile de nubes, es lo que leernos como tras de un cristal opaco o en una habitación en penumbra en la que solo entra la luz por el dintel de la puerta, o de un ocaso tras la calcinada hermosura que ha ocurrido o se ha sucedido desde el mediodía: Detesto que vean en mí a un modelo/De abyecciones y beatitudes/Que solo complican mi laxitud y silencio.

“Dar a volta à história”: do século XIX à Pós-Graduação em Artes Visuais e Género da Universidade de Évora

Comparar visibilidades e invisibilidades, relacionar diferentes tipos de periferias, estudar trajetórias deslembradas e entrelaçar outras mais conhecidas, comparando diferentes geografias, a portuguesa e a eslava, foram os objetivos da comunicação que agora se verte em artigo. Maria Guilhermina Silva Reis, Zoé Wauthelet Batalha Reis, Maria da Glória Ribeiro da Cruz foram três artistas portuguesas do século XIX e início do XX, cujos percursos desembocaram praticamente na invisibilidade. Marie Bashkirtseff, pintora de origem ucraniana, Aurélia de Sousa, pintora portuguesa e Anna Bilińska-Bohdanowicz, pintora polaca, têm os seus retratos na história e aqui serão justamente lembradas. Cotejando invisibilidades, aponta-se o caso atual da Pós-Graduação em Artes Visuais e Género da Universidade de Évora, pioneira no contexto académico português, mas conservada na penumbra. Porque é forte a convicção de que algo se pode fazer neste campo extremamente sensível da visibilidade em Arte, é o momento de “dar a volta à história”…