An ICT-based closed-loop model to improve care for heart failure patients

Durante las últimas décadas se ha producido un fenómeno global de envejecimiento en la población. Esta tendencia se puede observar prácticamente en todos los países del mundo y se debe principalmente a los avances en la medicina, y a los descensos en las tasas de fertilidad y mortalidad. El envejecimiento de la población tiene un gran impacto en la salud de los ciudadanos, y a menudo es la causa de aparición de enfermedades crónicas. Este tipo de enfermedades supone una amenaza y una carga importantes para la sociedad, especialmente en aspectos como la mortalidad o los gastos en los sistemas sanitarios. Entre las enfermedades cardiovasculares, la insuficiencia cardíaca es probablemente la condición con mayor prevalencia y afecta a 23-26 millones de personas en todo el mundo. Normalmente, la insuficiencia cardíaca presenta un mal pronóstico y una tasa de supervivencia bajas, en algunos casos peores que algún tipo de cáncer. Además, suele ser la causa de hospitalizaciones frecuentes y es una de las enfermedades más costosas para los sistemas sanitarios. La tendencia al envejecimiento de la población y la creciente incidencia de las enfermedades crónicas están llevando a una situación en la que los sistemas de salud no son capaces de hacer frente a la demanda de la sociedad. Los servicios de salud existentes tendrán que adaptarse para ser efectivos y sostenibles en el futuro. Es necesario identificar nuevos paradigmas de cuidado de pacientes, así como mecanismos para la provisión de servicios que ayuden a transformar estos sistemas sanitarios. En este contexto, esta tesis se plantea la búsqueda de soluciones, basadas en las Tecnologías de la Información y la Comunicación (TIC), que contribuyan a realizar la transformación en los sistemas sanitarios. En concreto, la tesis se centra en abordar los problemas de una de las enfermedades con mayor impacto en estos sistemas: la insuficiencia cardíaca. Las siguientes hipótesis constituyen la base para la realización de este trabajo de investigación: 1. Es posible definir un modelo basado en el paradigma de lazo cerrado y herramientas TIC que formalice el diseño de mejores servicios para pacientes con insuficiencia cardíaca. 2. El modelo de lazo cerrado definido se puede utilizar para definir un servicio real que ayude a gestionar la insuficiencia cardíaca crónica. 3. La introducción, la adopción y el uso de un servicio basado en el modelo definido se traducirá en mejoras en el estado de salud de los pacientes que sufren insuficiencia cardíaca. a. La utilización de un sistema basado en el modelo de lazo cerrado definido mejorará la experiencia del usuario de los pacientes. La definición del modelo planteado se ha basado en el estándar ISO / EN 13940- Sistema de conceptos para dar soporte a la continuidad de la asistencia. Comprende un conjunto de conceptos, procesos, flujos de trabajo, y servicios como componentes principales, y representa una formalización de los servicios para los pacientes con insuficiencia cardíaca. Para evaluar el modelo definido se ha definido un servicio real basado en el mismo, además de la implementación de un sistema de apoyo a dicho servicio. El diseño e implementación de dicho sistema se realizó siguiendo la metodología de Diseño Orientado a Objetivos. El objetivo de la evaluación consistía en investigar el efecto que tiene un servicio basado en el modelo de lazo cerrado sobre el estado de salud de los pacientes con insuficiencia cardíaca. La evaluación se realizó en el marco de un estudio clínico observacional. El análisis de los resultados ha comprendido métodos de análisis cuantitativos y cualitativos. El análisis cuantitativo se ha centrado en determinar el estado de salud de los pacientes en base a datos objetivos (obtenidos en pruebas de laboratorio o exámenes médicos). Para realizar este análisis se definieron dos índices específicos: el índice de estabilidad y el índice de la evolución del estado de salud. El análisis cualitativo ha evaluado la autopercepción del estado de salud de los pacientes en términos de calidad de vida, auto-cuidado, el conocimiento, la ansiedad y la depresión, así como niveles de conocimiento. Se ha basado en los datos recogidos mediante varios cuestionarios o instrumentos estándar (i.e. EQ-5D, la Escala de Ansiedad y Depresión (HADS), el Cuestionario de Cardiomiopatía de Kansas City (KCCQ), la Escala Holandesa de Conocimiento de Insuficiencia Cardíaca (DHFKS), y la Escala Europea de Autocuidado en Insuficiencia Cardíaca (EHFScBS), así como cuestionarios dedicados no estandarizados de experiencia de usuario. Los resultados obtenidos en ambos análisis, cuantitativo y cualitativo, se compararon con el fin de evaluar la correlación entre el estado de salud objetivo y subjetivo de los pacientes. Los resultados de la validación demostraron que el modelo propuesto tiene efectos positivos en el cuidado de los pacientes con insuficiencia cardíaca y contribuye a mejorar su estado de salud. Asimismo, ratificaron al modelo como instrumento válido para la definición de servicios mejorados para la gestión de esta enfermedad. ABSTRACT During the last decades we have witnessed a global aging phenomenon in the population. This can be observed in practically every country in the world, and it is mainly caused by the advances in medicine, and the decrease of mortality and fertility rates. Population aging has an important impact on citizens’ health and it is often the cause for chronic diseases, which constitute global burden and threat to the society in terms of mortality and healthcare expenditure. Among chronic diseases, Chronic Heart Failure (CHF) or Heart Failure (HF) is probably the one with highest prevalence, affecting between 23 and 26 million people worldwide. Heart failure is a chronic, long-term and serious condition with very poor prognosis and worse survival rates than some type of cancers. Additionally, it is often the cause of frequent hospitalizations and one of the most expensive conditions for the healthcare systems. The aging trends in the population and the increasing incidence of chronic diseases are leading to a situation where healthcare systems are not able to cope with the society demand. Current healthcare services will have to be adapted and redefined in order to be effective and sustainable in the future. There is a need to find new paradigms for patients’ care, and to identify new mechanisms for services’ provision that help to transform the healthcare systems. In this context, this thesis aims to explore new solutions, based on ICT, that contribute to achieve the needed transformation within the healthcare systems. In particular, it focuses on addressing the problems of one of the diseases with higher impact within these systems: Heart Failure. The following hypotheses represent the basis to the elaboration of this research: 1. It is possible to define a model based on a closed-loop paradigm and ICT tools that formalises the design of enhanced healthcare services for chronic heart failure patients. 2. The described closed-loop model can be exemplified in a real service that supports the management of chronic heart failure disease. 3. The introduction, adoption and use of a service based on the outlined model will result in improvements in the health status of patients suffering heart failure. 4. The user experience of patients when utilizing a system based on the defined closed-loop model will be enhanced. The definition of the closed-loop model for health care support of heart failure patients have been based on the standard ISO/EN 13940 System of concepts to support continuity of care. It includes a set of concept, processes and workflows, and services as main components, and it represent a formalization of services for heart failure patients. In order to be validated, the proposed closed-loop model has been instantiated into a real service and a supporting IT system. The design and implementation of the system followed the user centred design methodology Goal Oriented Design. The validation, that included an observational clinical study, aimed to investigate the effect that a service based on the closed-loop model had on heart failure patients’ health status. The analysis of results comprised quantitative and qualitative analysis methods. The quantitative analysis was focused on determining the health status of patients based on objective data (obtained in lab tests or physical examinations). Two specific indexes where defined and considered in this analysis: the stability index and the health status evolution index. The qualitative analysis assessed the self-perception of patients’ health status in terms of quality of life, self-care, knowledge, anxiety and depression, as well as knowledge levels. It was based on the data gathered through several standard instruments (i.e. EQ-5D, the Hospital Anxiety and Depression Scale, the Kansas City Cardiomyopathy Questionnaire, the Dutch Heart Failure Knowledge Scale, and the European Heart Failure Self-care Behaviour Scale) as well as dedicated non-standardized user experience questionnaires. The results obtained in both analyses, quantitative and qualitative, were compared in order to assess the correlation between the objective and subjective health status of patients. The results of the validation showed that the proposed model contributed to improve the health status of the patients and had a positive effect on the patients’ care. It also proved that the model is a valid instrument for designing enhanced healthcare services for heart failure patients.

Contribuciones en sistemas de adquisición de datos inteligentes para entornos de fusión por confinamiento magnético

Los sistemas de adquisición de datos utilizados en los diagnósticos de los dispositivos de fusión termonuclear se enfrentan a importantes retos planteados en los dispositivos de pulso largo. Incluso en los dispositivos de pulso corto, en los que se analizan los datos después de la descarga, existen aún una gran cantidad de datos sin analizar, lo cual supone que queda una gran cantidad de conocimiento por descubrir dentro de las bases de datos existentes. En la última década, la comunidad de fusión ha realizado un gran esfuerzo para mejorar los métodos de análisis off‐line para mejorar este problema, pero no se ha conseguido resolver completamente, debido a que algunos de estos métodos han de resolverse en tiempo real. Este paradigma lleva a establecer que los dispositivos de pulso largo deberán incluir dispositivos de adquisición de datos con capacidades de procesamiento local, capaces de ejecutar avanzados algoritmos de análisis. Los trabajos de investigación realizados en esta tesis tienen como objetivo determinar si es posible incrementar la capacidad local de procesamiento en tiempo real de dichos sistemas mediante el uso de GPUs. Para ello durante el trascurso del periodo de experimentación realizado se han evaluado distintas propuestas a través de casos de uso reales elaborados para algunos de los dispositivos de fusión más representativos como ITER, JET y TCV. Las conclusiones y experiencias obtenidas en dicha fase han permitido proponer un modelo y una metodología de desarrollo para incluir esta tecnología en los sistemas de adquisición para diagnósticos de distinta naturaleza. El modelo define no sólo la arquitectura hardware óptima para realizar dicha integración, sino también la incorporación de este nuevo recurso de procesamiento en los Sistemas de Control de Supervisión y Adquisición de Datos (SCADA) utilizados en la comunidad de fusión (EPICS), proporcionando una solución completa. La propuesta se complementa con la definición de una metodología que resuelve las debilidades detectadas, y permite trazar un camino de integración de la solución en los estándares hardware y software existentes. La evaluación final se ha realizado mediante el desarrollo de un caso de uso representativo de los diagnósticos que necesitan adquisición y procesado de imágenes en el contexto del dispositivo internacional ITER, y ha sido testeada con éxito en sus instalaciones. La solución propuesta en este trabajo ha sido incluida por la ITER IO en su catálogo de soluciones estándar para el desarrollo de sus futuros diagnósticos. Por otra parte, como resultado y fruto de la investigación de esta tesis, cabe destacar el acuerdo llevado a cabo con la empresa National Instruments en términos de transferencia tecnológica, lo que va a permitir la actualización de los sistemas de adquisición utilizados en los dispositivos de fusión. ABSTRACT Data acquisition systems used in the diagnostics of thermonuclear fusion devices face important challenges due to the change in the data acquisition paradigm needed for long pulse operation. Even in shot pulse devices, where data is mainly analyzed after the discharge has finished , there is still a large amount of data that has not been analyzed, therefore producing a lot of buried knowledge that still lies undiscovered in the data bases holding the vast amount of data that has been generated. There has been a strong effort in the fusion community in the last decade to improve the offline analysis methods to overcome this problem, but it has proved to be insufficient unless some of these mechanisms can be run in real time. In long pulse devices this new paradigm, where data acquisition devices include local processing capabilities to be able to run advanced data analysis algorithms, will be a must. The research works done in this thesis aim to determining whether it is possible to increase local capacity for real‐time processing of such systems by using GPUs. For that, during the experimentation period, various proposals have been evaluated through use cases developed for several of the most representative fusion devices, ITER, JET and TCV. Conclusions and experiences obtained have allowed to propose a model, and a development methodology, to include this technology in systems for diagnostics of different nature. The model defines not only the optimal hardware architecture for achieving this integration, but also the incorporation of this new processing resource in one of the Systems of Supervision Control and Data Acquisition (SCADA) systems more relevant at the moment in the fusion community (EPICS), providing a complete solution. The final evaluation has been performed through a use case developed for a generic diagnostic requiring image acquisition and processing for the international ITER device, and has been successfully tested in their premises. The solution proposed in this thesis has been included by the ITER IO in his catalog of standard solutions for the development of their future diagnostics. This has been possible thanks to the technologic transfer agreement signed with xi National Instruments which has permitted us to modify and update one of their core software products targeted for the acquisition systems used in these devices.

Analytical study of the thermal behaviour and stability of a small satellite

In this work the thermal analysis of a small satellite orbiting around the Earth has been approached by direct integration of the heat balance equations of a two-node reduced model, obtaining a linearized second order ODE problem, similar in form to the classical case of the forced vibration of a damped system. As the thermal loads (solar radiation, albedo, etc.) are harmonic, the problem is solved by means of Fourier analysis methods. Research on that field can be directly applied to the analysis of thermal problems and the results obtained are satisfactory. Working on the frequency domain streamlines the analysis, simplifies the study and facilitates the experimental testing. The transfer functions are obtained for the two-node case but the study can be extended to an n-node model.

Relationship between residual stresses and mechanical behavior in ceramic composites

En este trabajo, materiales de tipo alúmina/Y-TZP (ZrO2 tetragonal, estabilizada con 3 mol. % Y2O3), como sistema cerámico popular por sus mejoradas propiedades mecánicas en comparación con las cerámicas de alúmina puras, han sido estudiados en términos de propiedades mecánicas y tensiones residuales. El novedoso método de colado en cinta, consistente en el apilamiento de cintas de cerámica verde a temperatura ambiente y el uso de bajas presiones, se ha escogido para la presente investigación con el fin de poder aprovechar al máximo el futuro desarrollo de materiales laminados de alúmina-óxido de circonio. Se han determinado las propiedades de los materiales obtenidos por este nuevo método de procesamiento comparándolas con las de los materiales obtenidos por “slip casting”, con el fin de analizar si el método propuesto afecta a la microestructura y, por tanto, a las propiedades mecánicas y tensiones residuales propias de estos materiales. Para analizar la idoneidad del proceso de fabricación, utilizado para evitar la presencia de discontinuidades en las intercaras entre las láminas así como otros fenómenos que puedan interferir con las propiedades mecánicas, se estudiaron materiales cerámicos con la misma composición en cintas. Por otra parte también se analizó el efecto de la adición de óxido de circonio sobre la aparición de tensiónes residuales en cerámicas Al2O3/Y-TZP, teniendo en cuenta su notable influencia sobre las propiedades microestructurales y mecánicas de los materiales, así como el requisito de co-sinterización de capas con diferentes materiales compuestos en materiales laminados. La caracterización del material incluye la determinación de la densidad, el análisis de la microestructura, la obtención de las propiedades mecánicas (módulo de elasticidad, dureza, resistencia a la flexión y tenacidad de fractura) así como de las tensiones residuales. En combinación con otros métodos de medida tradicionales, la nanoindentación también se empleó como una técnica adicional para la medida del módulo de elasticidad y de la dureza. Por otro lado, diferentes técnicas de difracción con neutrones, tanto las basadas en longitud de onda constante (CW) como en tiempo de vuelo (TOF), han sido empleadas para la medición fiable de la deformación residual a través del grosor en muestras a granel. Las tensiones residuales fueron determinadas con elevada precisión, aplicando además métodos de análisis apropiados, como por ejemplo el refinamiento de Rietveld. Las diferentes fases en cerámicas sinterizadas, especialmente las de zirconia, se examinaron con detalle mediante el análisis de Rietveld, teniendo en cuenta el complicado polimorfismo del Óxido de Zirconio (ZrO2) así como las posibles transformaciones de fase durante el proceso de fabricación. Los efectos del contenido de Y-TZP en combinación con el nuevo método de procesamiento sobre la microestructura, el rendimiento mecánico y las tensiones residuales de los materiales estudiados (Al2O3/Y-TZP) se resumen en el presente trabajo. Finalmente, los mecanismos de endurecimiento, especialmente los relacionados con las tensiones residuales, son igualmente discutidos. In present work, Alumina/Y-TZP (tetragonal ZrO2 stabilized with 3 mol% Y2O3) materials, as an popular ceramic system with improved mechanical properties compared with the pure alumina ceramics, have been studied in terms of mechanical properties and residual stresses. The novel tape casting method, which involved the stacking of green ceramics tapes at room temperature and using low pressures, is selected for manufacturing and investigation, in order to take full advantage of the future development of alumina-zirconia laminated materials. Features of materials obtained by the new processing method are determined and compared with those of materials obtained by conventional slip casting in a plaster mold, in order to study whether the proposed method of processing affects microstructure and thereby the mechanical properties and residual stresses characteristics of materials. To analyse the adequacy of the manufacturing process used to avoid the presence of discontinuities at the interfaces between the sheets and other phenomena that interfere with the mechanical properties, ceramic materials with the same composition in tapes were investigated. Moreover, the effect of addition of zirconia on residual stress development of Al2O3/Y-TZP ceramics were taken into investigations, considering its significantly influence on the microstructure and mechanical properties of materials as well as the requirement of co-sintering of layers with different composites in laminated materials. The characterization includes density, microstructure, mechanical properties (elastic modulus, hardness, flexure strength and fracture toughness) and residual stresses. Except of the traditional measurement methods, nanoindentation technique was also used as an additional measurement of the elastic modulus and hardness. Neutron diffraction, both the constant-wavelength (CW) and time-of-flight (TOF) neutron diffraction techniques, has been used for reliable through-thickness residual strain measurement in bulk samples. Residual stresses were precisely determined combined with appropriate analysis methods, e.g. the Rietveld refinement. The phase compositions in sintered ceramics especially the ones of zirconia were accurately examined by Rietveld analysis, considering the complex polymorph of ZrO2 and the possible phase transformation during manufacturing process. Effects of Y-TZP content and the new processing method on the microstructure, mechanical performance and residual stresses were finally summarized in present studied Al2O3/Y-TZP materials. The toughening mechanisms, especially the residual stresses related toughening, were theoretically discussed.

Viviendas productivas

El presente trabajo recoge los resultados de una investigación sobre la «vivienda productiva», es decir, de la casa como lugar de trabajo. Dicha investigación se ha ocupado de explorar cómo influyen las cotidianeidades doméstico-laborales actuales —junto con sus arquitecturas y los urbanismos que estas generan— en la sociedad, en especial en temas sociales centrales como la construcción de las subjetividades, y de una vida en comunidad. Asimismo, explora cómo podrían influir en un futuro. La hipótesis sobre la que se trabaja, y que finalmente se intenta demostrar, consiste en que, en la territorialidad múltiple de lo laboral, la vivienda, como plataforma doméstica multiusos, productiva y reproductiva de la que muchas personas disponen, desempeña un papel nodal, y es posible que en el futuro su papel sea aún más importante y más visible. La vivienda productiva funciona como una infraestructura urbana desde la cual se construyen diferentes tipos de bienes materiales e inmateriales, pero sobre todo formas de relación, sociales y productivas con otros, además de imaginarios y afectos. La vivienda como infraestructura productiva y reproductiva es tanto «fábrica fundamental de lo social», como nos enseña Silvia Federici, como «fábrica de lo urbano». El trabajo en casa, como parte de diferentes dinámicas «dispersas» del trabajo que se dan en la actualidad, presenta tanto problemáticas y desafíos importantes, como capitales y posibilidades sociales. Por un lado, puede facilitar una absorción de tipo «24/7» vinculada a las lógicas de producción dispersa y consumo dominantes además de la que se da por las dinámicas patriarcales tradicionales, y en múltiples casos situaciones de evidente asimetría y de explotación laboral. También puede propiciar situaciones socialmente extendidas o impuestas de soledad y aislamiento. Sin embargo, está asimismo vinculado al surgimiento de espacios de experimentación tanto en soledad como en compañía, de cooperación y de intercambio, además de a la evidente posibilidad de construir rutinas propias y, por tanto, una subjetividad laboral propia. Por otro lado, frente a la idea general y homogénea del trabajador casero como un sujeto mayoritariamente aislado de su entorno, las jornadas de trabajo de los trabajadores caseros estudiados presentan una gran diversidad. Estas pueden conllevar aislamiento y exclusión, así como acompañar diferentes formas de construcción de una ciudadanía activa, tanto en solitario, como mediante formas de participación activa en la construcción de una vida en comunidad. En esta investigación se analizan, pues, desafíos y oportunidades de estas espacialidades del trabajo y, a través de este análisis, se indaga en el papel de los marcos físicos, organizativos y simbólicos actuales para la vivienda y para la ciudad pensada desde los trabajadores caseros. Al mismo tiempo se exploran nuevos tipos de vivienda y urbanismos que puedan quizás acompañar procesos sociales de inclusión, así como de emancipación, cooperación e intercambio y, en general, nuevas formas de vecindad y bienestar compartido en los ámbitos doméstico-productivos. Metodológicamente, las singularidades presentes en las realidades estudiadas invitan además a explorar protocolos de análisis, métodos de diseño, de gestión y gobierno que, desde lo micro, puedan dialogar con lo cotidiano y sus singularidades. Diego Barajas, autor de la tesis, es arquitecto dedicado a la práctica, a la investigación y la docencia. Su trabajo se focaliza en explorar el carácter mediador de la arquitectura frente a lo cotidiano y sus microrrealidades. Es profesor de proyectos de urbanismo en la IE School of Architecture y es miembro de Husos, una plataforma de investigación y diseño orientada a la innovación en arquitectura y urbanismo, con sede en Madrid. Es el autor del libro Dispersion, A Study of Global Mobility and the Dynamics of a Fictional Urbanism (Episode Publishers, Róterdam, 2003). Sus trabajos teóricos y de investigación han aparecido en libros y revistas internacionales tales como The Domestic and The Foreign in Architecture (010 Publishers, 2008), Public Spheres, a Europan Discussion (Europan9, 2007), Photoespaña 05 (La Fábrica, Madrid, 2005), Domus, Volume, Abitare, Architese, Plot, y Summa+. Su trabajo se ha expuesto en la Bienal de Venecia (selección principal), la Bienal de Róterdam, la Fundación Tapies, Photoespaña, entre otros y es parte de la colección permanente del FRAC Centre en Orleans y del Historisch Museum de Róterdam entre otros. Antes de estudiar en Róterdam, se gradúa con Honores en la Universidad de los Andes en 1999 y su tesis de grado de arquitectura recibe la máxima distinción como proyecto de Grado Meritorio. ABSTRACT The present study records an investigation into the «productive house», or the home as a workplace. This investigation looks at how working from home, its architectures, and the urban dynamics generated around it influence daily life and the construction of society. It also explores what influences home-based work might have in the future, particularly in central themes such as the biopolitical construction of subjectivities and community life. The central hypothesis revolves around the idea that the home, as a multi-use infrastructure that most of us have access to, plays a fundamental role in the contemporary work sphere, due to —or even in spite of— the omnipresence of work in practically every moment and area of our daily lives, and might play a main role in the future. The home functions as a kind of hub from which we create different kinds of material and immaterial goods, but above all relationships with others, both social and productive, as well as imaginaries and affections. The home, as a machine for production and reproduction, is as much a main «factory of the social» as Silvia Federici describes it, as a «factory of the urban». Working from home, as one of several «dispersed» work dynamics that are part of the contemporary world of work, presents as many important problematics and challenges as it does possibilities and social capital. On the one hand, it can contribute to kind of «24/7» absorption linked both to the logistics of the current dispersed production and consumption, and to that of traditional patriarchal dynamics, and in some cases even clearly asymmetrical situations that exploit the workforce. It can also lead to the socially widespread phenomena of isolation and loneliness, at times imposed upon home-based workers. However, by the same token, it is also linked to the growth of experimental spaces of cooperation and exchange, both solitary and in company, as well as the clear possibility of constructing individualised routines and, therefore, a personal laboural subjectivity. On the other hand, contrary to the generalised, homogenous idea of a home-based worker who is mostly isolated from his or her environment, the working days of those we studied went hand in hand with different ways of building subjectivities. This could be as much in exclusion and isolation as through building an active citizenship, at times in solitary and at times actively participating in the construction of communal life. In this investigation, therefore, the challenges and opportunities of the home as workplace have been analysed, and through this analysis we have inquired into the role of current physical, organisational and symbolic frameworks for the home and for the city from the perspective of home workers. At the same time we have explored new types of homes and of town planning that could perhaps accompany social processes of diversity and inclusion as well as emancipation, cooperation and exchange and, in general, new forms of shared welfare in productive domestic environments. Methodologically, the singularities present in the cases studied also invite us to explore protocols of analysis, methods of design, management and government that, from the micro level, could dialogue with the peculiarities of day-to-day life. The author of this thesis, Diego Barajas, is an architect dedicated to practice, investigation and teaching. His work is focussed on exploring the mediating nature of architecture and the built environment in terms of daily life and its microrealities. He is professor of urban projects at the IE School of Architecture and member of Husos, a platform for investigation and town planning based in Madrid. He is the author of the book Dispersion, A Study of Global Mobility and the Dynamics of a Fictional Urbanism (Episode Publishers, Rotterdam, 2003) and his theoretical works and investigations have appeared in books such as The Domestic and The Foreign in Architecture (010 Publishers, 2008), Public Spheres, a Europan Discussion (Europan9, 2007), Photoespaña 05 (La Fábrica, Madrid, 2005), and in international magazines such as Domus, Volume, Abitare, Architese, Plot and Summa+. His work has been exhibited in places such as the Venice Biennial (main selection), the Rotterdam Biennial, the Tapies Foundation and Photoespaña, among others, and forms part of the permanent collection of the FRAC Centre in Orleans and the Historisch Museum of Rotterdam. Before studying in Rotterdam, he graduated with Honours from the University of the Andes in 1999, and his architecture degree thesis received the maximum distinction of Meritorious Graduation Project.

The Escherichia coli MG1655 in silico metabolic genotype: Its definition, characteristics, and capabilities

The Escherichia coli MG1655 genome has been completely sequenced. The annotated sequence, biochemical information, and other information were used to reconstruct the E. coli metabolic map. The stoichiometric coefficients for each metabolic enzyme in the E. coli metabolic map were assembled to construct a genome-specific stoichiometric matrix. The E. coli stoichiometric matrix was used to define the system's characteristics and the capabilities of E. coli metabolism. The effects of gene deletions in the central metabolic pathways on the ability of the in silico metabolic network to support growth were assessed, and the in silico predictions were compared with experimental observations. It was shown that based on stoichiometric and capacity constraints the in silico analysis was able to qualitatively predict the growth potential of mutant strains in 86% of the cases examined. Herein, it is demonstrated that the synthesis of in silico metabolic genotypes based on genomic, biochemical, and strain-specific information is possible, and that systems analysis methods are available to analyze and interpret the metabolic phenotype.

Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits

We examined the role of cyclooxygenase-2 (COX-2) in the late phase of ischemic preconditioning (PC). A total of 176 conscious rabbits were used. Ischemic PC (six cycles of 4-min coronary occlusions/4-min reperfusions) resulted in a rapid increase in myocardial COX-2 mRNA levels (+231 ± 64% at 1 h; RNase protection assay) followed 24 h later by an increase in COX-2 protein expression (+216 ± 79%; Western blotting) and in the myocardial content of prostaglandin (PG)E2 and 6-keto-PGF1α (+250 ± 85% and +259 ± 107%, respectively; enzyme immunoassay). Administration of two unrelated COX-2 selective inhibitors (NS-398 and celecoxib) 24 h after ischemic PC abolished the ischemic PC-induced increase in tissue levels of PGE2 and 6-keto-PGF1α. The same doses of NS-398 and celecoxib, given 24 h after ischemic PC, completely blocked the cardioprotective effects of late PC against both myocardial stunning and myocardial infarction, indicating that COX-2 activity is necessary for this phenomenon to occur. Neither NS-398 nor celecoxib lowered PGE2 or 6-keto-PGF1α levels in the nonischemic region of preconditioned rabbits, indicating that constitutive COX-1 activity was unaffected. Taken together, these results demonstrate that, in conscious rabbits, up-regulation of COX-2 plays an essential role in the cardioprotection afforded by the late phase of ischemic PC. Therefore, this study identifies COX-2 as a cardioprotective protein. The analysis of arachidonic acid metabolites strongly points to PGE2 and/or PGI2 as the likely effectors of COX-2-dependent protection. The recognition that COX-2 mediates the antistunning and antiinfarct effects of late PC impels a reassessment of current views regarding this enzyme, which is generally regarded as detrimental.

CluSTr: a database of clusters of SWISS-PROT+TrEMBL proteins

The CluSTr (Clusters of SWISS-PROT and TrEMBL proteins) database offers an automatic classification of SWISS-PROT and TrEMBL proteins into groups of related proteins. The clustering is based on analysis of all pairwise comparisons between protein sequences. Analysis has been carried out for different levels of protein similarity, yielding a hierarchical organisation of clusters. The database provides links to InterPro, which integrates information on protein families, domains and functional sites from PROSITE, PRINTS, Pfam and ProDom. Links to the InterPro graphical interface allow users to see at a glance whether proteins from the cluster share particular functional sites. CluSTr also provides cross-references to HSSP and PDB. The database is available for querying and browsing at http://www.ebi.ac.uk/clustr.

KH domain: one motif, two folds

The K homology (KH) module is a widespread RNA-binding motif that has been detected by sequence similarity searches in such proteins as heterogeneous nuclear ribonucleoprotein K (hnRNP K) and ribosomal protein S3. Analysis of spatial structures of KH domains in hnRNP K and S3 reveals that they are topologically dissimilar and thus belong to different protein folds. Thus KH motif proteins provide a rare example of protein domains that share significant sequence similarity in the motif regions but possess globally distinct structures. The two distinct topologies might have arisen from an ancestral KH motif protein by N- and C-terminal extensions, or one of the existing topologies may have evolved from the other by extension, displacement and deletion. C-terminal extension (deletion) requires β-sheet rearrangement through the insertion (removal) of a β-strand in a manner similar to that observed in serine protease inhibitors serpins. Current analysis offers a new look on how proteins can change fold in the course of evolution.

Comparison of circumsporozoite proteins from avian and mammalian malarias: biological and phylogenetic implications.

The circumsporozoite (CS) protein of malaria parasites (Plasmodium) covers the surface of sporozoites that invade hepatocytes in mammalian hosts and macrophages in avian hosts. CS genes have been characterized from many Plasmodium that infect mammals; two domains of the corresponding proteins, identified initially by their conservation (region I and region II), have been implicated in binding to hepatocytes. The CS gene from the avian parasite Plasmodium gallinaceum was characterized to compare these functional domains to those of mammalian Plasmodium and for the study of Plasmodium evolution. The P. gallinaceum protein has the characteristics of CS proteins, including a secretory signal sequence, central repeat region, regions of charged amino acids, and an anchor sequence. Comparison with CS signal sequences reveals four distinct groupings, with P. gallinaceum most closely related to the human malaria Plasmodium falciparum. The 5-amino acid sequence designated region I, which is identical in all mammalian CS and implicated in hepatocyte invasion, is different in the avian protein. The P. gallinaceum repeat region consists of 9-amino acid repeats with the consensus sequence QP(A/V)GGNGG(A/V). The conserved motif designated region II-plus, which is associated with targeting the invasion of liver cells, is also conserved in the avian protein. Phylogenetic analysis of the aligned Plasmodium CS sequences yields a tree with a topology similar to the one obtained using sequence data from the small subunit rRNA gene. The phylogeny using the CS gene supports the proposal that the human malaria P. falciparum is significantly more related to avian parasites than to other parasites infecting mammals, although the biology of sporozoite invasion is different between the avian and mammalian species.

Estudo de metodologias de controle de qualidade do Mo-99 utilizado no preparo de geradores de Mo-99/Tc-99m

O 99mTc é o radionuclídeo mais utilizado em medicina nuclear. No Brasil os geradores de 99Mo/99mTc são produzidos exclusivamente pelo Centro de Radiofarmácia do IPEN-CNEN/SP, com 99Mo importado de diferentes fornecedores. O 99Mo (t1/2 = 66 h), por ser um produto de fissão do 235U, pode conter impurezas radionuclídicas prejudiciais à saúde humana. Dessa forma, para que o gerador seja utilizado de forma segura, é necessário que o 99Mo seja avaliado por ensaios de controle de qualidade e atenda à alguma especificação descrita em farmacopeia. A Farmacopeia Europeia (FE) apresenta monografia, com parâmetros (identificação, pureza radioquímica e pureza radionuclídica), métodos de análise, e limites, para avaliação da qualidade da solução de [99Mo] na forma de molibdato de sódio, que é utilizada como matéria-prima no preparo dos geradores de 99Mo/99mTc. No entanto, observa-se uma dificuldade na implementação e execução dos métodos por parte dos produtores de geradores, com pouca literatura sobre o assunto, provavelmente devido à falta de praticidade dos métodos propostos e à extensa lista de reagentes utilizados. Nesse trabalho foram avaliados vários parâmetros de qualidade do 99Mo descritos na monografia da FE. Foram estudados métodos de separação do 99Mo de suas impurezas radionuclídicas por extração em fase sólida (SPE) e por TLC. Após separação por SPE, foi proposta a quantificação de metais por ICP-OES para avaliar a porcentagem de retenção de Mo e a porcentagem de recuperação de Ru e Te e Sr em diversos tipos de cartuchos, em substituição ao uso de radiotraçadores. Observou-se que a marca de cartucho de SPE para separação do 99Mo recomendada pela FE apresentou baixa recuperação para Ru, quando comparado aos outros cartuchos de troca aniônica disponíveis no mercado. Amostras de 99Mo de diferentes fornecedores mundiais foram analisadas. Observou-se que é possível realizar a quantificação de 103Ru em amostras de 99Mo mesmo com tempos de decaimento acima de 4 semanas. Um método alternativo de separação do 99Mo do 131I por TLC apresentou resultados promissores. Não foi feita a quantificação das impurezas radionuclídicas emissoras beta e alfa. Todas as amostras analisadas apresentaram resultados dentro das especificações da FE para pureza radioquímica (>95%) e pureza radionuclídica.

PTSD, Depression, and Substance Abuse Symptoms in Women Exposed to Intimate Partner Abuse

The present study explores relationships among several established correlates of trauma in women exposed to intimate partner abuse (IPA), including PTSD, depression, and dissociation symptoms as well as alcohol use as well as other trauma-related variables, such as social support and violence exposure. Two analysis methods were utilized: variable-oriented methods, which examine relationships between variables, and person-oriented analysis methods, which examine groupings of participants within a larger sample (N = 233). Results of the variable-oriented analyses indicated positive links among depression, PTSD, dissociation, and alcohol use in women exposed to IPA, as well as positive links between the aforementioned psychological symptoms and exposure to violence. Social support was related to decreased psychological symptoms. Person-oriented analyses indicated the presence of four unique profiles of women within the larger study sample: Profile 1 (n = 21), which was labeled High Dissociation, Low Depression/PTSD; Profile 2 (n = 150), which was labeled Low Symptoms, High Social Support, Profile 3 (n = 41); which was labeled Low Dissociation, High Depression/PTSD; and Profile 4 (n = 22), which was labeled High Symptoms, Low Social Support. This research supports previous findings about the relationships among several variables related to IPA as well as suggests the need for careful consideration of differences among women within the larger context of research, advocacy, and clinical interventions related to IPA.

Extractive text summarization: can we use the same techniques for any text?

In this paper we address two issues. The first one analyzes whether the performance of a text summarization method depends on the topic of a document. The second one is concerned with how certain linguistic properties of a text may affect the performance of a number of automatic text summarization methods. For this we consider semantic analysis methods, such as textual entailment and anaphora resolution, and we study how they are related to proper noun, pronoun and noun ratios calculated over original documents that are grouped into related topics. Given the obtained results, we can conclude that although our first hypothesis is not supported, since it has been found no evident relationship between the topic of a document and the performance of the methods employed, adapting summarization systems to the linguistic properties of input documents benefits the process of summarization.

Catchment characteristics and soil and water chemistry of the San Francisco basin and subbasins, Ecuador

In this study, the Mean Transit Time and Mixing Model Analysis methods are combined to unravel the runoff generation process of the San Francisco River basin (73.5 km**2) situated on the Amazonian side of the Cordillera Real in the southernmost Andes of Ecuador. The montane basin is covered with cloud forest, sub-páramo, pasture and ferns. Nested sampling was applied for the collection of streamwater samples and discharge measurements in the main tributaries and outlet of the basin, and for the collection of soil and rock water samples. Weekly to biweekly water grab samples were taken at all stations in the period April 2007-November 2008. Hydrometric data, Mean Transit Time and Mixing Model Analysis allowed preliminary evaluation of the processes controlling the runoff in the San Francisco River basin. Results suggest that flow during dry conditions mainly consists of lateral flow through the C-horizon and cracks in the top weathered bedrock layer, and that all subcatchments have an important contribution of this deep water to runoff, no matter whether pristine or deforested. During normal to low precipitation intensities, when antecedent soil moisture conditions favour water infiltration, vertical flow paths to deeper soil horizons with subsequent lateral subsurface flow contribute most to streamflow. Under wet conditions in forested catchments, streamflow is controlled by near surface lateral flow through the organic horizon. Exceptionally, saturation excess overland flow occurs. By absence of the litter layer in pasture, streamflow under wet conditions originates from the A horizon, and overland flow.

Data compilation of ESOP

The work in this sub-project of ESOP focuses on the advective and convective transforma-tion of water masses in the Greenland Sea and its neighbouring areas. It includes observational work on the sub-mesoscale and analysis of hydrographic data up to the gyre-scale. Observations of active convective plumes were made with a towed chain equipped with up to 80 CTD sensors, giving a horizontal and vertical resolution of the hydrographic fields of a few metres. The observed scales of the penetrative convective plumes compare well with those given by theory. On the mesoscale the structure of homogeneous eddies formed as a result of deep convection was observed and the associated mixing and renewal of the intermediate layers quantified. The relative importance and efficiency of thermal and haline penetrative convection in relation to the surface boundary conditions (heat and salt fluxes and ice cover) and the ambient stratification are studied using the multi year time series of hydro-graphic data in the central Greenland Sea. The modification of the water column of the Greenland Sea gyre through advection from and mixing with water at its rim is assessed on longer time scales. The relative contributions are quantified using modern water mass analysis methods based on inverse techniques. Likewise the convective renewal and the spreading of the Arctic Intermediate Water from its formation area is quantified. The aim is to budget the heat and salt content of the water column, in particular of the low salinity surface layer, and to relate its seasonal and interannual variability to the lateral fluxes and the fluxes at the air-sea-ice interface. This will allow to estimate residence times for the different layers of the Greenland Sea gyre, a quantity important for the description of the Polar Ocean carbon cycle.