Blackfolds, plane waves and minimal surfaces

Minimal surfaces in Euclidean space provide examples of possible non-compact horizon geometries and topologies in asymptotically flat space-time. On the other hand, the existence of limiting surfaces in the space-time provides a simple mechanism for making these configurations compact. Limiting surfaces appear naturally in a given space-time by making minimal surfaces rotate but they are also inherent to plane wave or de Sitter space-times in which case minimal surfaces can be static and compact. We use the blackfold approach in order to scan for possible black hole horizon geometries and topologies in asymptotically flat, plane wave and de Sitter space-times. In the process we uncover several new configurations, such as black helicoids and catenoids, some of which have an asymptotically flat counterpart. In particular, we find that the ultraspinning regime of singly-spinning Myers-Perry black holes, described in terms of the simplest minimal surface (the plane), can be obtained as a limit of a black helicoid, suggesting that these two families of black holes are connected. We also show that minimal surfaces embedded in spheres rather than Euclidean space can be used to construct static compact horizons in asymptotically de Sitter space-times.

Minimal residual disease in cancer therapy - Small things make all the difference

Minimal residual disease (MRD) is a major hurdle in the eradication of malignant tumors. Despite the high sensitivity of various cancers to treatment, some residual cancer cells persist and lead to tumor recurrence and treatment failure. Obvious reasons for residual disease include mechanisms of secondary therapy resistance, such as the presence of mutant cells that are insensitive to the drugs, or the presence of cells that become drug resistant due to activation of survival pathways. In addition to such unambiguous resistance modalities, several patients with relapsing tumors do not show refractory disease and respond again when the initial therapy is repeated. These cases cannot be explained by the selection of mutant tumor cells, and the precise mechanisms underlying this clinical drug resistance are ill-defined. In the current review, we put special emphasis on cell-intrinsic and -extrinsic mechanisms that may explain mechanisms of MRD that are independent of secondary therapy resistance. In particular, we show that studying genetically engineered mouse models (GEMMs), which highly resemble the disease in humans, provides a complementary approach to understand MRD. In these animal models, specific mechanisms of secondary resistance can be excluded by targeted genetic modifications. This allows a clear distinction between the selection of cells with stable secondary resistance and mechanisms that result in the survival of residual cells but do not provoke secondary drug resistance. Mechanisms that may explain the latter feature include special biochemical defense properties of cancer stem cells, metabolic peculiarities such as the dependence on autophagy, drug-tolerant persisting cells, intratumoral heterogeneity, secreted factors from the microenvironment, tumor vascularization patterns and immunosurveillance-related factors. We propose in the current review that a common feature of these various mechanisms is cancer cell dormancy. Therefore, dormant cancer cells appear to be an important target in the attempt to eradicate residual cancer cells, and eventually cure patients who repeatedly respond to anticancer therapy but lack complete tumor eradication.

Synchronous carotid and coronary bypass surgery using minimal extracorporeal circulation does not increase the risk of in-hospital stroke compared to isolated carotid endarterectomy under general anaesthesia

Gebiet: Chirurgie Abstract: Introduction: Carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) could be approached in a combined or a staged fashion. Some crucial studies have shown no significant difference in peri-operative stroke and death rate in combined versus staged CEA/CABG. At present conventional extracorporeal circulation (CECC) is regarded as the gold standard for performing on-pump coronary artery bypass grafting. On contrary, the use of minimized extracorporeal circulation (MECC) for CABG diminishes hemodilution, blood-air contact, foreign surface contact and inflammatory response. At the same time, general anaesthesia (GA) is a potential risk factor for higher perioperative stroke rate after isolated CEA, not only for the ipsilateral but also for the contralateral side especially in case of contralateral high-grade stenosis or occlusion. The aim of the study was to analyze if synchronous CEA/CABG using MECC (CEA/CABG group) allows reducing the perioperative stroke risk to the level of isolated CEA performed under GA (CEA-GA group). – Methods: A retrospective analysis of all patients who underwent CEA at our institution between January 2005 and December 2012 was performed. We compared outcomes between all patients undergoing CEA/CABG to all isolated CEA-GA during the same time period. The CEA/CABG group was additionally compared to a reference group consisting of patients undergoing isolated CEA in local anaesthesia. Primary outcome was in-hospital stroke. – Results: A total of 367 CEAs were performed, from which 46 patients were excluded having either off-pump CABG or other cardiac surgery procedures than CABG combined with CEA. Out of 321 patients, 74 were in the CEA/CABG and 64 in the CEA-GA group. There was a significantly higher rate of symptomatic stenoses among patients in the CEA-GA group (p<0.002). Three (4.1%) strokes in the CEA/CABG group were registered, two ipsilateral (2.7%) and one contralateral (1.4%) to the operated side. In the CEA-GA group 2 ipsilateral strokes (3.1%) occurred. No difference was noticed between the groups (p=1.000). One patient with stroke in each group had a symptomatic stenosis preoperatively. – Conclusions: Outcome with regard to mortality and neurologic injury is very good in both -patients undergoing CEA alone as well as patients undergoing synchronous CEA and CABG using the MECC system. Although the CEA/CABG group showed slightly increased risk of stroke, it can be considered as combined treatment in particular clinical situations.

Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS).

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists.

Minimal invasive extracorporeal circulation should become the standard practice in coronary revascularization surgery†.

We read with great interest the large-scale network meta-analysis by Kowalewski et al. comparing clinical outcomes of patients undergoing coronary artery bypass grafting (CABG) operated on using minimal invasive extracorporeal circulation (MiECC) or off-pump (OPCAB) with those undergoing surgery on conventional cardiopulmonary bypass (CPB) [1]. The authors actually integrated into single study two recently published meta-analysis comparing MiECC and OPCAB with conventional CPB, respectively [2, 3] into a single study. According to the results of this study, MiECC and OPCAB are both strongly associated with improved perioperative outcomes following CABG when compared with CABG performed on conventional CPB. The authors conclude that MiECC may represent an attractive compromise between OPCAB and conventional CPB. After carefully reading the whole manuscript, it becomes evident that the role of MiECC is clearly undervalued. Detailed statistical analysis using the surface under the cumulative ranking probabilities indicated that MiECC represented the safer and more effective intervention regarding all-cause mortality and protection from myocardial infarction, cerebral stroke, postoperative atrial fibrillation and renal dysfunction when compared with OPCAB. Even though no significant statistical differences were demonstrated between MiECC and OPCAB, the superiority of MiECC is obvious by the hierarchy of treatments in the probability analysis, which ranked MiECC as the first treatment followed by OPCAB and conventional CPB. Thus, MiECC does not represent a compromise between OPCAB and conventional CPB, but an attractive dominant technique in CABG surgery. These results are consistent with the largest published meta-analysis by Anastasiadis et al. comparing MiECC versus conventional CPB including a total of 2770 patients. A significant decrease in mortality was observed when MiECC was used, which was also associated with reduced risk of postoperative myocardial infarction and neurological events [4]. Similarly, another recent meta-analysis by Benedetto et al. compared MiECC versus OPCAB and resulted in comparable outcomes between these two surgical techniques [5]. As stated in the text, superiority of MiECC observed in the current network meta-analysis, when compared with OPCAB, could be attributed to the fact that MiECC offers the potential for complete revascularization, whereas OPCAB poses a challenge for unexperienced surgeons; especially when distal marginal branches on the lateral and/or posterior wall of the heart need revascularization. This is reflected by a significantly lower number of distal anastomoses performed in OPCAB when compared with conventional CPB. Therefore, taking into consideration the literature published up to date, including the results of the current article, we advocate that MiECC should be integrated in the clinical practice guidelines as a state-of-the-art technique and become a standard practice for perfusion in coronary revascularization surgery.

Minimal template size for Iris-Recognition

A method to achieve improvement in template size for an iris-recognition system is reported. To achieve this result, the biological characteristics of the human iris have been studied. Processing has been performed by image processing techniques, isolating the iris and enhancing the area of study, after which multi resolution analysis is made. Reduction of the pattern obtained has been obtained via statistical study.

Minimal strong digraphs

We introduce adequate concepts of expansion of a digraph to obtain a sequential construction of minimal strong digraphs. We obtain a characterization of the class of minimal strong digraphs whose expansion preserves the property of minimality. We prove that every minimal strong digraph of order nmayor que=2 is the expansion of a minimal strong digraph of order n-1 and we give sequentially generative procedures for the constructive characterization of the classes of minimal strong digraphs. Finally we describe algorithms to compute unlabeled minimal strong digraphs and their isospectral classes.

Generación de modelos físicos personalizados y segmentación de la pared arterial y el trombo intraluminal en imágenes de aneurismas aórticos abdominales

Esta tesis doctoral está encuadrada dentro del marco general de la ingeniería biomédica aplicada al tratamiento de las enfermedades cardiovasculares, enfermedades que provocan alrededor de 1.9 millones (40%) de muertes al año en la Unión Europea. En este contexto surge el proyecto europeo SCATh-Smart Catheterization, cuyo objetivo principal es mejorar los procedimientos de cateterismo aórtico introduciendo nuevas tecnologías de planificación y navegación quirúrgica y minimizando el uso de fluoroscopía. En particular, esta tesis aborda el modelado y diagnóstico de aneurismas aórticos abdominales (AAA) y del trombo intraluminal (TIL), allí donde esté presente, así como la segmentación de estas estructuras en imágenes preoperatorias de RM. Los modelos físicos específicos del paciente, construidos a partir de imágenes médicas preoperatorias, tienen múltiples usos, que van desde la evaluación preoperatoria de estructuras anatómicas a la planificación quirúrgica para el guiado de catéteres. En el diagnóstico y tratamiento de AAA, los modelos físicos son útiles a la hora de evaluar diversas variables biomecánicas y fisiológicas de las estructuras vasculares. Existen múltiples técnicas que requieren de la generación de modelos físicos que representen la anatomía vascular. Una de las principales aplicaciones de los modelos físicos es el análisis de elementos finitos (FE). Las simulaciones de FE para AAA pueden ser específicas para el paciente y permiten modelar estados de estrés complejos, incluyendo los efectos provocados por el TIL. La aplicación de métodos numéricos de análisis tiene como requisito previo la generación de una malla computacional que representa la geometría de interés mediante un conjunto de elementos poliédricos, siendo los hexaédricos los que presentan mejores resultados. En las estructuras vasculares, generar mallas hexaédricas es un proceso especialmente exigente debido a la compleja anatomía 3D ramificada. La mayoría de los AAA se encuentran situados en la bifurcación de la arteria aorta en las arterias iliacas y es necesario modelar de manera fiel dicha bifurcación. En el caso de que la sangre se estanque en el aneurisma provocando un TIL, éste forma una estructura adyacente a la pared aórtica. De este modo, el contorno externo del TIL es el mismo que el contorno interno de la pared, por lo que las mallas resultantes deben reflejar esta particularidad, lo que se denomina como "mallas conformadas". El fin último de este trabajo es modelar las estructuras vasculares de modo que proporcionen nuevas herramientas para un mejor diagnóstico clínico, facilitando medidas de riesgo de rotura de la arteria, presión sistólica o diastólica, etc. Por tanto, el primer objetivo de esta tesis es diseñar un método novedoso y robusto para generar mallas hexaédricas tanto de la pared aórtica como del trombo. Para la identificación de estas estructuras se utilizan imágenes de resonancia magnética (RM). Deben mantenerse sus propiedades de adyacencia utilizando elementos de alta calidad, prestando especial atención al modelado de la bifurcación y a que sean adecuadas para el análisis de FE. El método tiene en cuenta la evolución de la línea central del vaso en el espacio tridimensional y genera la malla directamente a partir de las imágenes segmentadas, sin necesidad de reconstruir superficies triangulares. Con el fin de reducir la intervención del usuario en el proceso de generación de las mallas, es también objetivo de esta tesis desarrollar un método de segmentación semiautomática de las distintas estructuras de interés. Las principales contribuciones de esta tesis doctoral son: 1. El diseño, implementación y evaluación de un algoritmo de generación de mallas hexaédricas conformadas de la pared y el TIL a partir de los contornos segmentados en imágenes de RM. Se ha llevado a cabo una evaluación de calidad que determine su aplicabilidad a métodos de FE. Los resultados demuestran que el algoritmo desarrollado genera mallas conformadas de alta calidad incluso en la región de la bifurcación, que son adecuadas para su uso en métodos de análisis de FE. 2. El diseño, implementación y evaluación de un método de segmentación automático de las estructuras de interés. La luz arterial se segmenta de manera semiautomática utilizando un software disponible a partir de imágenes de RM con contraste. Los resultados de este proceso sirven de inicialización para la segmentación automática de las caras interna y externa de la pared aórtica utilizando métodos basado en modelos de textura y forma a partir de imágenes de RM sin contraste. Los resultados demuestran que el algoritmo desarrollado proporciona segmentaciones fieles de las distintas estructuras de interés. En conclusión, el trabajo realizado en esta tesis doctoral corrobora las hipótesis de investigación postuladas, y pretende servir como aportación para futuros avances en la generación de modelos físicos de geometrías biológicas. ABSTRACT The frame of this PhD Thesis is the biomedical engineering applied to the treatment of cardiovascular diseases, which cause around 1.9 million deaths per year in the European Union and suppose about 40% of deaths per year. In this context appears the European project SCATh-Smart Catheterization. The main objective of this project is creating a platform which improves the navigation of catheters in aortic catheterization minimizing the use of fluoroscopy. In the framework of this project, the specific field of this PhD Thesis is the diagnosis and modeling of abdominal aortic aneurysm (AAAs) and the intraluminal thrombus (ILT) whenever it is present. Patient-specific physical models built from preoperative imaging are becoming increasingly important in the area of minimally invasive surgery. These models can be employed for different purposes, such as the preoperatory evaluation of anatomic structures or the surgical planning for catheter guidance. In the specific case of AAA diagnosis and treatment, physical models are especially useful for evaluating pressures over vascular structures. There are multiple techniques that require the generation of physical models which represent the target anatomy. Finite element (FE) analysis is one the principal applications for physical models. FE simulations for AAA may be patient-specific and allow modeling biomechanical and physiological variables including those produced by ILT, and also the segmentation of those anatomical structures in preoperative MR images. Applying numeric methods requires the generation of a proper computational mesh. These meshes represent the patient anatomy using a set of polyhedral elements, with hexahedral elements providing better results. In the specific case of vascular structures, generating hexahedral meshes is a challenging task due to the complex 3D branching anatomy. Each patient’s aneurysm is unique, characterized by its location and shape, and must be accurately represented for subsequent analyses to be meaningful. Most AAAs are located in the region where the aorta bifurcates into the iliac arteries and it is necessary to model this bifurcation precisely and reliably. If blood stagnates in the aneurysm and forms an ILT, it exists as a conforming structure with the aortic wall, i.e. the ILT’s outer contour is the same as the wall’s inner contour. Therefore, resulting meshes must also be conforming. The main objective of this PhD Thesis is designing a novel and robust method for generating conforming hexahedral meshes for the aortic wall and the thrombus. These meshes are built using largely high-quality elements, especially at the bifurcation, that are suitable for FE analysis of tissue stresses. The method accounts for the evolution of the vessel’s centerline which may develop outside a single plane, and generates the mesh directly from segmented images without the requirement to reconstruct triangular surfaces. In order to reduce the user intervention in the mesh generation process is also a goal of this PhD. Thesis to develop a semiautomatic segmentation method for the structures of interest. The segmentation is performed from magnetic resonance image (MRI) sequences that have tuned to provide high contrast for the arterial tissue against the surrounding soft tissue, so that we determine the required information reliably. The main contributions of this PhD Thesis are: 1. The design, implementation and evaluation of an algorithm for generating hexahedral conforming meshes of the arterial wall and the ILT from the segmented contours. A quality inspection has been applied to the meshes in order to determine their suitability for FE methods. Results show that the developed algorithm generates high quality conforming hexahedral meshes even at the bifurcation region. Thus, these meshes are suitable for FE analysis. 2. The design, implementation and evaluation of a semiautomatic segmentation method for the structures of interest. The lumen is segmented in a semiautomatic way from contrast filled MRI using an available software. The results obtained from this process are used to initialize the automatic segmentation of the internal and external faces of the aortic wall. These segmentations are performed by methods based on texture and shape models from MRI with no contrast. The results show that the algorithm provides faithful segmentations of the structures of interest requiring minimal user intervention. In conclusion, the work undertaken in this PhD. Thesis verifies the investigation hypotheses. It intends to serve as basis for future physical model generation of proper biological anatomies used by numerical methods.

Re-Ocupación y/o Re-Construcción de estructuras urbanas en desuso y su conexión con el espacio público y el paisaje

Los nuevos comportamientos urbanos nos permiten observar cada vez con más frecuencia en nuestras calles y plazas realidades que siempre habíamos considerado domésticas. Al contrario también pasa, todos los días vivimos en nuestras casas situaciones que implican relacionarnos con personas que no son de nuestro núcleo familiar. El diseño doméstico de nuestras ciudades y el urbanismo del diseño de interiores parecen herramientas oportunas en el mundo que nos ha tocado vivir. Esto nos lleva a pensar que los espacios públicos y privados son términos simplificados, definidos en base a conceptos de propiedad para organizar la ciudad. En cambio, sus usos y vivencias, su gestión y sus comportamientos se han complejizado, distorsionando la terminología convencional hasta hacerla obsoleta. En este contexto, considerado también el marco socioeconómico actual, surgen las “acciones de abajo a arriba” como nuevo paradigma o modelo de renovación urbana, que entienden la involucración del ciudadano como parte activa en el proceso de construcción de la urbe desde la misma gestación del proyecto, frente a las acciones habituales que consideran al usuario como mero receptor de las propuestas. Un ciudadano que parece estar cada vez más radicalizado y una administración que parece asustarse ante el desconcierto que el acercamiento al ciudadano puede acarrear, han ocasionado por un lado, espacios “gueto” de carácter casi anárquico y, por el otro lado, lugares tan institucionalizados que derivan en espacios asociados a la administración y ajenos al ciudadano. Por ello, se considera imprescindible la colaboración entre ambos poderes. De acuerdo con el discurso que precede, dentro de un marco comparativo, se estudian 5 supuestos seleccionados de las ciudades Madrid y Zaragoza. Madrid porque es referencia nacional e internacional en el desarrollo urbano a través de procesos ‘abajo arriba’. Zaragoza porque es una ciudad ‘media’ que históricamente no se ha definido por estrategias urbanas claras, ya sean de carácter social o institucional. Sin embargo, en el momento actual se pueden identificar planteamientos relacionados con la recuperación de construcciones y espacios vacantes que pueden ser determinantes a la hora de alcanzar equilibrios con los intensos procesos institucionales acaecidos en las dos últimas décadas. De los procesos urbanos registrados en cada lugar, desarrollados en construcciones y espacios vacantes, he seleccionado: Construcciones Vacantes Madrid |Tabacalera de Lavapiés Zaragoza | Antiguo I.E.S. Luis Buñuel y antiguo Convento de Mínimos Espacios Vacantes Madrid | Campo de Cebada [solar] Zaragoza | Patio ‘antiguo I.E.S. Luis Buñuel [espacio libre] y plaza Eduardo Ibarra [espacio libre] El proyecto de investigación ha partido de las hipótesis de partida que siguen: UNA… Las ‘acciones de abajo arriba’ o renovación desde abajo no tienen cabida como elementos urbanos aislados sino conectados entre sí, posibilitando la producción de sinergias y la construcción de la ciudad; pudiendo ser consideradas acciones de desarrollo y enlace urbano, pues su objetivo es convertirse en motores del espacio público. Cuestión que es aplicable al resto de los procesos o acciones urbanas [‘horizontales’ o ‘institucionales’] DOS… La capacidad de adaptación manifestada por las ‘acciones de abajo arriba’ implica un marco ideológico de referencia asociado a la importancia de la construcción con mínimos recursos [Re-ocupación y/o Re- Construcción de estructuras urbanas en desuso] en los procesos urbanos descritos, como vía para comprender los concepto sostenibilidad y calidad figurativa de lo construido. Cuestión que es aplicable a la recuperación de aquellos aspectos de la arquitectura que la convierten en necesaria para la sociedad. Y tiene como objetivo: Identificar modelos de sostenibilidad urbana como una estrategia que va de lo individual a lo colectivo y que se transmite fundamentalmente con la acción, mezclando la innovación y la tecnología en múltiples ámbitos, utilizando los recursos naturales e intelectuales de una manera eficiente y entendiendo la inteligencia humana y sobre todo la inteligencia colectiva, como principio y justificación. Se han analizado los siguientes aspectos: sociales [participación ciudadana e implicación de la administración pública], urbanos [conexiones con otros colectivos o espacios urbanos / transformaciones urbanas a través de los procesos de gestión utilizados], constructivos [materiales utilizados en la re-construcción de construcciones y espacios vacantes / sistemas constructivos utilizados] y los relacionados con la sostenibilidad [sostenibilidad económica / sostenibilidad de mantenimiento / sostenibilidad funcional / inteligencia colectiva] El estudio de los aspectos considerados se ha desarrollado con las herramientas metodológicas siguientes: Entrevistas abiertas a expertos: se han obtenido respuestas de 25 personas expertas [5 por cada espacio o construcción vacante] relacionadas con las acciones urbanas sostenibles, la cultura y las relaciones sociales, y que también conocen los lugares y su entorno desde los puntos de vista urbano y construido. Son ‘tipos ideales’ asociados a uno de los cinco poderes que se manifiestan en la ciudad: el poder educativo [la universidad], el poder creativo [la cultura], el poder administrativo [la política], el poder empresarial [la empresa privada] y los usuarios [un usuario activo y representativo de cada lugar elegido que haya intervenido en la gestación del proceso]. Han sido personas que conocían el tejido social y urbano de la ciudad de Zaragoza y Madrid, ya que la herramienta ‘entrevista abierta a expertos’, recoge datos y opiniones planteadas en las construcciones y espacios vacantes ubicados en Zaragoza y Madrid. Entrevistas cerradas a usuarios: como la población de usuarios que se somete a la investigación es infinita o muy grande, resulta imposible o inconveniente realizar la obtención de los datos sobre todos aquellos elementos que la forman. Por lo tanto, he decidido estudiar sólo una parte de la población que denomino ‘tipos ideales’, obteniendo respuestas de 150 usuarios [30 personas por cada espacio o construcción vacante]. La selección de grupos de personas entrevistadas, debe permitir que los resultados sean representativos de la población total de usuarios. Además, la elección de ‘tipos ideales’ se ha identificado con los vecinos de los núcleos urbanos [o barrios] en los que se ubican las construcciones o espacios vacantes analizados. Observación estructurada: recoger información a través de la observación me ha permitido conocer las actuaciones y comportamientos de los ciudadanos en el medio urbano. Esto ha facilitado el estudio del medio a nivel práctico, valorando el uso que la sociedad da a las construcciones y a los espacios vacantes analizados. Es importante posicionar la estrategia en relación con el tema de investigación propuesto. Una estrategia que dibuje un panorama plural, desarrollado a través de herramientas sociales y constructivas que permitan que la arquitectura hable de cosas parecidas a lo que interesa a la ciudadanía. Para ello, propuse un catálogo de herramientas arquitectónicas que han permitido evaluar todas las propuestas. Un contexto de estrategias comunes que han descrito con los mismos códigos las distintas actuaciones analizadas. Estas herramientas tocan diferentes campos de interés. Desde las partes más tectónicas y constructivas, hasta las más ligadas con el desarrollo urbanístico y social. Acciones de participación colectiva: Experiencias o laboratorios urbanos participados por los alumnos del grado de arquitectura de la UNIZAR y los agentes sociales. Las acciones son una herramienta propositiva. Investigar y analizar proponiendo ha permitido que el análisis del contexto pueda llegar a capas de mucha más profundidad. No se ha trabajado estableciendo jerarquías de profesores y alumnos, sino que se ha intentado posibilitar la conexión de distintos agentes que trabajan coordinadamente durante el tiempo que han durado las acciones. Por un lado esto ha permite que cada integrante haya aportado al grupo lo que mejor sabe hacer y de la misma manera, que cada uno pueda aprender aquello de lo que tenga más ganas… y reflexionar sobre determinados aspectos objeto del análisis. Una vez interpretados los resultados, obtenidos a través de las herramientas metodológicas referenciadas, se ha concluido lo que sigue: Respecto de la Hipótesis de partida UNO LAS ACCIONES ‘ABAJO ARRIBA’ han revelado que no se puede entender ningún proceso de gestión urbana fuera de la participación ciudadana. El ‘ESPACIO LIBRE’ de una ciudad necesita lugares de autogestión, espacios de cogestión, movimientos de ‘arriba abajo’ y también modelos que todavía no sabemos ni que existen. LAS ACCIONES INSTITUCIONALES ‘ARRIBA ABAJO’ han demostrado que no han presentado permeabilidad ni relación con las circulaciones de entorno. Tampoco han tenido en cuenta a otras muchas personas, ‘usuarios productores’, a las que les interesan los procesos de búsqueda y las fórmulas de conexión más interactivas. Respecto de la hipótesis de partida DOS LAS ACCIONES ‘ABAJO ARRIBA’ han revelado que el ‘derecho a la ciudad’, paradigma defendido por Lefebvre desde el cual se piensa el urbanismo ciudadano, en estos supuestos podría entenderse como el ‘derecho a la infraestructura’. El ESPACIO LIBRE es infraestructura y se quiere para infraestructurar los derechos de cada uno. Y aunque también es verdad que estas acciones son simples destellos, han hecho visible otro paradigma de gestión y propuesta urbana que puede ser predominante en un futuro próximo. LAS ACCIONES INSTITUCIONALES ‘ARRIBA ABAJO’ han revelado que las intervenciones estuvieron enfocadas únicamente a la resolución de los procesos constructivos y a la incorporación del programa como un dato ‘problema’ que era necesario resolver para evitar la afección al diseño. ABSTRACT The new urban ways of behaviour let us watch more and more frequently in our streets and squares, realities that we had always considered as domestic. This also happens the other way round. Every day we have to go through situations at home which imply relationships with people who don’t belong to our family circle. The domestic design of our cities and the urban planning of indoor design seem to be adequate tools in the world we have to live in. This leads us to think that public and private spaces are simplified terms, defined according to concepts of property in order to organise the city. On the other hand, its uses and the experiences of people, its management and ways of behaviour is now more complex, changing the conventional terminology that has become outdated. In this context, ‘bottom-up’ actions arise as a new paradigm or model of urban renewal. These actions consider the active role of social participation in the process of building up the city from the very beginning, in comparison with the former way of acting that considered the user as mere receptor of the proposals. A citizen who seems to become more and more radical, and an administration that seems to be afraid of the unknown, have created both almost anarchic ghetto spaces and, on the other hand, spaces which have been so institutionalised that derive into areas associated to the administration but alienated from the citizen. For this reason, cowork of both forces is considered as crucial. In accordance with the above mentioned ideas and within a comparative framework, five situations chosen from the cities of Madrid and Zaragoza are studied. Madrid because is a national and international reference in urban development that uses “bottom-up” processes. Zaragoza because is a “medium-size” city that, historically, has not been defined by clear social or institutional urban strategies. Nevertheless, at the present time we can identify approaches on the recovery of constructions and empty areas that may be determining for reaching a balance with the intense institutional processes that have taken place in the two last decades. From the urban processes registered in every place and developed in vacant areas and constructions, I have chosen: Vacant constructions Madrid | Lavapiés Tobacco Factory Zaragoza | Old Secondary School Luis Buñuel and old Convent of the Minimos Vacant areas Madrid | Campo de Cebada [non-built site]. Zaragoza | Old courtyard of the secondary school and Eduardo Ibarra square [free space] The research project has been issued from the following starting hypotheses: ONE… “Bottom-up actions” or renewal from below have no place as isolated urban elements but as connected parts that can produce synergies and the construction of the city, and that can also be considered as actions producing urban development and links. This can also be applied to the rest of urban processes or actions [‘horizontal’ or ‘institutional’]. TWO… The capacity of adaptation shown by “bottom-up actions” implies an ideological framework of reference which is related to the importance of construction with minimal resources (re-occupation and/or reconstruction of urban structures in disuse) in the above mentioned urban processes, as a way for understanding the concepts of sustainability and the representational quality of what has been constructed. This can also be applied to the recovery of those architectural aspects that make architecture necessary for society. And its objective is: Identify models of urban sustainability as a strategy going from the individual to the collective, which are mainly transferred by action and that mix innovation and technology in many fields. Models that use natural and intellectual resources in an efficient way, and understand human intelligence and, above all, collective intelligence, as principle and justification. The following aspects have been analysed: social [civic participation and involvement of the public Administration], urban [connections with other collectives or urban spaces / urban transformation by the processes of administration used], constructive [materials used for the re-construction of empty spaces / construction systems used] and those focusing on sustainability [economic sustainability /maintenance sustainability /functional sustainability / collective intelligence]. For researching into the above mentioned aspects, the following methodological tools have been developed: Open interviews with experts: answers from 25 experts have been obtained [five for every vacant space or empty construction] on sustainable urban actions, culture and social relations, who also know the places and their environment from an urban and constructive point of view. These are “ideal types” linked to one of the five powers acting in the city: the educational power [University], the creative power [culture], the administration power [politics], the corporate power [private companies] and the users [an active and representative user for every place selected during the establishment of the process]. They were people who knew the social and urban fabric of Zaragoza and Madrid, since the “open interview for experts” tool collects data and points of view set out in vacant constructions and spaces of Zaragoza and Madrid. Close interviews with users: as the number of users targeted for the research is very big or infinite, it is impossible or inconvenient to get data from all its constituent parts. Therefore, I have decided to research into the part of the population that I call “ideal types”, obtaining answers from 150 users [30 people for every empty space or construction]. The selection of the groups of people interviewed must produce results which are representative of the total population of users. Furthermore, the election of “ideal types” has been identified with the inhabitants of urban areas [or city districts] in which the vacant spaces or constructions analysed are located. A structured observation: I have known the actions and ways of behaving of the citizens in the urban environment by means of collecting information after observation. Therefore, the practical research into the target environment has been easier by valuing the use that society gives to the empty constructions and spaces analysed. It is important to position the strategy with respect to the research subject proposed. It involves a strategy able to get an overview of a plural landscape, developed by social and constructive tools, allowing architecture to talk about topics which are interesting for city dwellers. Therefore, I proposed a set of architectural tools to evaluate all the proposals. A context of common strategies describing the different actions analysed by using the same codes. These tools focus on different fields of interests, from the most tectonic and constructive parts, to the most related to urban and social development. Actions on collective participation: experiences or urban laboratories shared by the students of architecture of the University of Zaragoza and social agents. The actions are a proactive tool. Researching and analysing by means of proposing, has allowed me to analyse the context and much deeper layers. This work has not been done by establishing ranks of professors and student, but trying to get an interaction between the different agents who work in close coordination during the implementation of the actions. This has allowed every agent to contribute the group what they do the best, and also every individual has had the possibility to learn what s/he prefers…, thinking about the different aspects targeted by the analysis. Once the different methodological tools have been interpreted, this is the conclusion: With regard to the initial hypothesis ONE “BOTTOM-UP” ACTIONS have proven that no process of urban management can be understood outside civic participation. The “FREE SPACE” of a city needs self-managed places, co-managed spaces, “up-bottom” movements, and also models whose existence is still ignored. “UP-BOTTOM” INSTITUTIONAL ACTIONS have proven that they have not presented neither permeability nor relation with local ideas. They have also disregarded many other people, the “usersproducers”, who are interested in the most interactive means of searching and connecting processes. With regard to the initial hypothesis TWO Under these premises, “BOTTOM-UP” ACTIONS have shown that the “right to the city”, a paradigm defended by Lefebvre and from which citizen-focused urbanism is conceived, could be considered as a “right to the infrastructures”. A FREE SPACE is an infrastructure and must be used to “infrastructure” the rights of every citizen. And, even though it is true that these actions are mere flashes, they have made visible another paradigm of management and urban proposal that can be prevailing in a near future. “UP-BOTTOM” INSTITUTIONAL ACTIONS have revealed that the interventions have only focused on resolving construction processes and the incorporation of the program as a “problem” data that was necessary to resolve in order to avoid its influence on the design.

The minimal overlap rule: restrictions on mergers for creditors’ consensus

As it is known, there is no rule satisfying additivity in the complete domain of bankruptcy problems. This paper proposes a notion of partial additivity in this context, to be called μ-additivity. We find out that this property, together with two quite compelling axioms, equal treatment of equals and continuity, identify the minimal overlap rule, introduced by O’Neill (Math. Soc. Sci. 2:345–371, 1982).

Application of self-quenched JH consensus primers for real-time quantitative PCR of IGH gene to minimal residual disease evaluation in multiple myeloma.

Monitoring multiple myeloma patients for relapse requires sensitive methods to measure minimal residual disease and to establish a more precise prognosis. The present study aimed to standardize a real-time quantitative polymerase chain reaction (PCR) test for the IgH gene with a JH consensus self-quenched fluorescence reverse primer and a VDJH or DJH allele-specific sense primer (self-quenched PCR). This method was compared with allele-specific real-time quantitative PCR test for the IgH gene using a TaqMan probe and a JH consensus primer (TaqMan PCR). We studied nine multiple myeloma patients from the Spanish group treated with the MM2000 therapeutic protocol. Self-quenched PCR demonstrated sensitivity of >or=10(-4) or 16 genomes in most cases, efficiency was 1.71 to 2.14, and intra-assay and interassay reproducibilities were 1.18 and 0.75%, respectively. Sensitivity, efficiency, and residual disease detection were similar with both PCR methods. TaqMan PCR failed in one case because of a mutation in the JH primer binding site, and self-quenched PCR worked well in this case. In conclusion, self-quenched PCR is a sensitive and reproducible method for quantifying residual disease in multiple myeloma patients; it yields similar results to TaqMan PCR and may be more effective than the latter when somatic mutations are present in the JH intronic primer binding site.

Minimal residual disease monitoring in multiple myeloma: a comparison between allelic-specific oligonucleotide real-time quantitative polymerase chain reaction and flow cytometry.

BACKGROUND AND OBJECTIVES: Minimal residual disease (MRD) studies are useful in multiple myeloma (MM). However, the definition of the best technique and clinical utility are still unresolved issues. The aim of this study was to analyze and compare the clinical utility of MRD studies in MM with two different techniques: allelic-specific oligonucleotide real-time quantitative PCR (ASO-RQ-PCR), and flow cytometry (FCM). DESIGN AND METHODS: Bone marrow samples from 32 MM patients who had achieved complete response after transplantation were evaluated by ASO-RQ-PCR, using TaqMan technology, and multiparametric FCM. RESULTS: ASO-RQ-PCR was only applicable in 75% of patients for a variety of technical reasons, while FCM was applicable in up to 90%. Therefore, simultaneous PCR/FCM analysis was possible in only 24 patients. The number of residual tumor cells identified by both techniques was very similar (mean=0.29%, range=0.001-1.61%, correlation coefficient=0.861). However, RQ-PCR was able to detect residual myelomatous cells in 17 patients while FCM only did so in 11; thus, 6 cases were FCM negative but PCR positive, all of them displaying a very low number of clonal cells (median=0.014%, range=0.001-0.11). Using an MRD threshold of 0.01% (10(-4)) two risk groups with significantly different progression-free survival could be identified by either PCR (34 vs. 15m, p=0.04) or FCM (27 vs. 10m, p=0.05). INTERPRETATION AND CONCLUSIONS: Although MRD evaluation by ASO-RQ-PCR is slightly more sensitive and specific than FCM, it is applicable in a lower proportion of MM patients and is more time-consuming, while both techniques provide similar prognostic information.

Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.