Methods for the treatment of uncertainty in dynamical systems: Application to diabetes

[EN] Patients suffering from Type 1 Diabetes are not able to secrete insulin, thus, they have to get it administered externally. Current research is focused on developing an artificial pancreas, a control system that automatically administers insulin according to patient's needs. The work presented here aims to improve the efficiency and safety of control algorithms for artificial pancreas. Glucose-insulin models try to mimic the administration of external insulin, the absorption of carbohydrates, and the influence of both of them in blood glucose concentration. However, these processes are infinitely complex and they are characterized by their high variability. The mathematical models used are often a simplified version which does not include all the process variability and, therefore, they do not always match reality. This deficiency on the models can be addressed by considering uncertainty on their parameters and initial conditions. In this way, the exact values are unknown but they can be bounded by intervals that comprehend all the variability of the considered process. When the value of the parameters and initial conditions is known, there is usually just one possible behaviour. However, if they are bounded by intervals, a set of possible solutions exists. In this case, it is interesting to compute a solution envelope that guarantees the inclusion of all the possible behaviours. A common technique to compute this envelope is the monotonicity analysis of the system. Nevertheless, some overestimation is produced if the system is not fully monotone. In this thesis, several methods and approaches have been developed to reduce, or even eliminate, the overestimation in the computation of solution envelopes, while satisfying the inclusion guarantee. Another problem found during the use of an artificial pancreas is that only the subcutaneous glucose concentration can be measured in real time, with some noise in the measurements. The rest of the system states are unknown, but they could be estimated from this set of noisy measurements by state observers, like Kalman filters. A detailed example is shown at the end of this thesis, where an Extended Kalman Filter is used to estimate in real time insulin concentration based on the food ingested and in periodical measurements of subcutaneous glucose.[ES] Los pacientes que sufren de diabetes tipo 1 no son capaces de secretar insulina, por lo que tienen que administrársela externamente. La investigación actual se centra en el desarrollo de un páncreas artificial, un sistema de control que administre automáticamente la insulina en función de las necesidades del paciente. El trabajo que aquí se presenta tiene como objetivo mejorar la eficiencia y la seguridad de los algoritmos de control para el páncreas artificial. Los modelos de glucosa-insulina tratan de emular la administración externa de la insulina, la absorción de carbohidratos y la influencia de ambos en la concentración de glucosa en sangre. El problema es que estos procesos son infinitamente complejos y se caracterizan por su alta variabilidad. Los modelos matemáticos utilizados suelen ser una versión simplificada que no incluye toda la variabilidad del proceso y, por lo tanto, no coinciden con la realidad. Esta deficiencia de los modelos puede subsanarse considerando inciertos sus parámetros y las condiciones iniciales, de manera que se desconoce su valor exacto pero sí podemos englobarlos en ciertos intervalos que comprendan toda la variabilidad del proceso considerado. Cuando los valores de los parámetros y de las condiciones iniciales son conocidos, existe, por lo general, un único comportamiento posible. Sin embargo, si están delimitados por intervalos se obtiene un conjunto de posibles soluciones. En este caso, interesa obtener una envoltura de las soluciones que garantice la inclusión de todos los comportamientos posibles. Una técnica habitual que facilita el cómputo de esta envoltura es el análisis de la monotonicidad del sistema. Sin embargo, si el sistema no es totalmente monótono la envoltura obtenida estará sobrestimada. En esta tesis se han desarrollado varios métodos para reducir, o incluso eliminar, la sobrestimación en el cálculo de envolturas, al tiempo que se satisface la garantía de inclusión. Otro inconveniente con el que nos encontramos durante el uso de un páncreas artificial es que solo es posible medir en tiempo real, con cierto ruido en la medida, la glucosa subcutánea. El resto de los estados del sistema son desconocidos, pero podrían ser estimados a partir de este conjunto limitado de mediciones con ruido utilizando observadores de estado, como el Filtro de Kalman. Un ejemplo detallado se muestra al final de la tesis, donde se estima en tiempo real la concentración de insulina en plasma en función de la comida ingerida y de mediciones periódicas de la glucosa subcutánea con ayuda de un Filtro de Kalman Extendido.[CA] Els pacients que pateixen de diabetis tipus 1 no són capaços de secretar insulina, motiu pel qual han d'administrar-se-la externament. La investigació actual es centra en el desenvolupament d'un pàncrees artificial, un sistema de control que administre automàticament la insulina en funció de les necessitats del pacient. El treball que ací es presenta té com a objectiu millorar l'eficiència i la seguretat dels algorismes de control per al pàncrees artificial. Els models de glucosa-insulina tracten d'emular l'administració externa de la insulina, l'absorció de carbohidrats i la influència d'ambdós factors en la concentració de glucosa en sang. El problema és que estos processos són infinitament complexos i es caracteritzen per la seua alta variabilitat. Els models matemàtics emprats solen ser una versió simplificada que no inclou tota la variabilitat del procés i, per tant, no coincideixen amb la realitat. Esta deficiència dels models pot esmenar-se considerant incerts els seus paràmetres i les condicions inicials, de manera que es desconeix el seu valor exacte però sí podem englobar-los en certs intervals que comprenguen tota la variabilitat del procés considerat. Quan els valors dels paràmetres i de les condicions inicials són coneguts, existeix, en general, un únic comportament possible. No obstant, si estan delimitats per intervals s'obté un conjunt de possibles solucions. En este cas, interessa obtindre un embolcall de les solucions que assegure la inclusió de tots els comportaments possibles. Una tècnica habitual que facilita el còmput d'este embolcall és l'anàlisi de la monotonicitat del sistema. No obstant, si el sistema no és totalment monòton l'embolcall obtingut estarà sobreestimat. En esta tesi s'han desenvolupat diversos mètodes per a reduir, o fins i tot eliminar, la sobreestimació en el càlcul dels embolcalls, al temps que se satisfà la garantia d'inclusió. Altre inconvenient amb què ens trobem durant l'ús d'un pàncrees artificial és que només és possible mesurar en temps real, amb cert soroll en la mesura, la glucosa subcutània. La resta dels estats del sistema són desconeguts, però podrien ser estimats a partir d'este conjunt limitat de mesures amb soroll utilitzant observadors d'estat, com el Filtre de Kalman. Un exemple detallat es mostra al final de la tesi, on s'estima en temps real la concentració d'insulina en plasma en funció del menjar ingerit i de les mesures periòdiques de la glucosa subcutània amb ajuda d'un Filtre de Kalman Estés.Pereda Sebastián, DD. (2015). Methods for the treatment of uncertainty in dynamical systems: Application to diabetes [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/54121TESI

Guaranteed computation methods for compartmental in-series models under uncertainty

The pattern of some real phenomenon can be described by compartmental in-series models. Nevertheless, most of these processes are characterized by their variability, which produces that the exact values of the model parameters are uncertain, although they can be bounded by intervals. The aim of this paper is to compute tight solution envelopes that guarantee the inclusion of all possible behaviors of such processes. Current methods, such as monotonicity analysis, enable us to obtain guaranteed solution envelopes. However, if the model includes nonmonotone compartments or parameters, the computation of solution envelopes may produce a significant overestimation. Our proposal consists of performing a change of variables in which the output is unaltered, and the model obtained is monotone with respect to the uncertain parameters. The monotonicity of the new system allows us to compute the output bounds for the original system without overestimation. These model transformations have been developed for linear and non-linear systems. Furthermore, if the conditions are not completely satisfied, a novel method to compute tight solution envelopes is proposed. The methods exposed in this paper have been applied to compute tight solution envelopes for two different models: a linear system for glucose modeling and a non-linear system for an epidemiological model.This work was partially supported by the Spanish Ministerio de Ciencia e Innovacion through Grant DPI-2010-20764-C02-01, and by the Generalitat Valenciana through Grant GV/2012/085.De Pereda Sebastián, D.; Romero Vivó, S.; Ricarte Benedito, B.; Bondía Company, J. (2013). Guaranteed computation methods for compartmental in-series models under uncertainty. Computers and Mathematics with Applications. 66(9):1595-1605. https://doi.org/10.1016/j.camwa.2013.03.008S1595160566

The 'Portuguese Forestry Community' and Research Fellows abroad between 1915 and 1945

One of the areas of greatest interest to a researcher in the field of the history of technology are studies done on the process of appropriating new scientific theories and technologies in countries that can be classified as peripheral in terms of their scientific output. Peripheral countries have been usually classified as those whose academic community is distanced from advanced centers in terms of the research they produce and that have participated to a lesser extent in the process of technical development [SAIZ 2003, 223-245]. This article will attempt to reflect on the process of international technology transfer in the 20th Century, specifically between 1915 and 1946. During this period, the achievement and spread of technological innovations were vital to the development of Portuguese forestry. In less developed European countries such as Portugal, the transfer of foreign technical knowledge was more important than that generated within the nation itself. External technological transfer became an essential factor, without which there would have been no push toward the professionalization of this new profession. Portugal was a country in the periphery of European science and technology. This situation has translated into an external technological dependence in several economic sectors. Reports on travels of learning have become one of the main sources for research in Science and Technology History. The new works of these young engineers will be taken as a valid, albeit only partial, indicator of the direction and structure of the processes of innovation in the Portuguese forestry. Among other things, the degree of Portuguese dependence upon external technology, as well as which countries played an essential role in the transfer of technology; and which scientific specialties depended most on foreign technology can be ascertained. One of the most serious problems confronting any researcher interested in forestry innovation is the evaluation of travels’ importance as a technological indicator of investment tendencies in new technologies. The various means of innovation in an economy are well-known: advances in productive processes can be invented and incorporated, just as they can be imported directly from another country using foreign technicians in their construction. Only innovations that are applied, put into practice and remain productive can be considered as such. From our point of view, new technologies brought by forestry students from abroad are not only a partial technical indicator, but are also, depending on whether or not they are put in practice, an important indicator of those tendencies in new technologies. In general, the decision to send Portuguese students to international technological centers is based on expected profits from the new techniques to be imported, and how complex the new technology is. Taking into account the advantage that travels of learning provide as a source of study (as a consequence of the existence of some kind of travel reports), it is surprising that they have not been used more often as raw material for forest history research. Here, as already mentioned, we can draw valid conclusions and extrapolate them to the process of forestry renewal in Portugal. This permits an understanding of the nature and direction of technological changes, the structure of the transfer and the importance of outside technology. This study is based on a sample of articles found in various agronomy and forestry reviews. Bulletins has served, from its inception, as the agronomy and forestry students' official bulletin (Boletim Agros), in which travel reports were customarily published. With time we will look for all the foresters’ information in the Arquivo Histórico do Instituto Camões. We will study the cases of the following fellows: Mário Azevedo Gomes (USA, 1915), Joaquim Vieira Natividade (UK, 1931), Francisco Santos Hall (USA and Germany, 1931), Francisco Caldeira Cabral (Germany, 1936), Francisco Mimoso Flores (USA, 1936) and Carlos Manuel Baeta Neves (Spain, 1946)

The rod domain is not essential for the function of plectin in maintaining tissue integrity

This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.-- et al.Epidermolysis bullosa simplex associated with late-onset muscular dystrophy (EBS-MD) is an autosomal recessive disorder resulting from mutations in the plectin gene. The majority of these mutations occur within the large exon 31 encoding the central rod domain and leave the production of a low-level rodless plectin splice variant unaffected. To investigate the function of the rod domain, we generated rodless plectin mice through conditional deletion of exon 31. Rodless plectin mice develop normally without signs of skin blistering or muscular dystrophy. Plectin localization and hemidesmosome organization are unaffected in rodless plectin mice. However, superresolution microscopy revealed a closer juxtaposition of the C-terminus of plectin to the integrin β4 subunit in rodless plectin keratinocytes. Wound healing occurred slightly faster in rodless plectin mice than in wild-type mice, and keratinocytes migration was increased in the absence of the rod domain. The faster migration of rodless plectin keratinocytes is not due to altered biochemical properties because, like full-length plectin, rodless plectin is a dimeric protein. Our data demonstrate that rodless plectin can functionally compensate for the loss of full-length plectin in mice. Thus the low expression level of plectin rather than the absence of the rod domain dictates the development of EBS-MD.This work was supported financially by grants from DEBRA UK and the Netherlands Organization for Scientific Research (NWO/ALW). J.M.d.P. was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (Grant BFU2012-32847).Peer Reviewe

Aproximación a los procesos de desigualdad e integración social. Dispositivos de regulación y "Determinación Política" de las necesidades

En esta intervención queremos presentar la perspectiva que en Colectivo Ioé hemos elaborado a lo largo de varias investigaciones sociológicas sobre la desigualdad e integración social. Primero planteamos una postura metodológica respecto al análisis de las carencias sociales, cuestionando los análisis habituales que se focalizan sólo sobre la descripción de los colectivos carenciales o en la pura aproximación económica, y destacando la importancia de los mecanismos institucionales e ideológicos. Después se presenta un desarrollo concreto de tal metodología mostrando, por un lado, la persistencia y desarrollo de la desigualdad social en España y, a continuación, un análisis de las actuales formas institucionales de "gestión de la pobreza". Se pone el acento en su función homogeneizadora, que pretende reconducir el conflicto social colectivo bien hacia pautas de comportamiento "normalizado" o bien hacia conductas "desviadas" de los individuos. En tercer lugar, se desarrolla un breve análisis del panorama ideológico español contemporáneo, que muestra el predominio de "visiones del mundo" que contemplan la exclusión y marginalidad social como un fenómeno a gestionar profesionalmente, al margen de cualquier reflexión sobre el funcionamiento del sistema social que las genera. Desde esta mentalidad, entendemos, no puede trascenderse la pura "gestión de la pobreza" en la medida en que se asume acríticamente el marco institucional descrito en el apartado anterior. Los elementos propuestos anteriormente articulan nuestra perspectiva de análisis pero, en difinitiva, el reto fundamental es, según nuestra perspectiva, enfrentar el cuarto y último punto: la repolitización de la vida social frente a la mera gestión de la desigualdad

La participación ciudadana. Algunos apuntes a partir del Barómetro Social de España

At the level of proclaimed principles, one of the hallmarks of Western democracy is public participation in political, economic and cultural life. In practice, however, the daily management of these areas is provided by professional politicians, transnational corporations and media oligopolies. This paper seeks to collect in a broad sense the forms of citizen participation in the field of politics. While indirect participation through the electoral process has been remarkable in the last three decades, direct intervention in the public sphere is very limited, except for a more active social minority or, in exceptional cases, of collective mobilization. Both the data from the Social Barometer of Spain as well as quantitative and qualitative surveys of public opinion suggest that we live more in a technocratic or plutocratic society rather than a democratic one. The political model established in Spain in recent decades provides an ambivalent institutional framework for public participation: on the one hand, it affirms the right of participation and sets out some concrete ways that did not exist previously; on the other, the emphasis on delegation (representation mechanisms) imposes restrictions on direct participation in public affairs.En el nivel de los principios proclamados, una de las señas de identidad de las democracias occidentales es la participación de la población en la vida política, económica y cultural. En la práctica, sin embargo, la gestión cotidiana de esas esferas corre a cargo de profesionales de la política, corporaciones transnacionales y oligopolios mediáticos. El presente texto trata de recoger las formas de participación de la ciudadanía en el ámbito de la política en un sentido amplio. Si bien la participación indirecta, a través de procesos electorales, ha sido notable durante las tres últimas décadas, la intervención directa en la esfera pública es muy limitada, salvo para una minoría social más activa o en casos excepcionales de movilización colectiva. Tanto los datos aportados por el Barómetro social de España como los sondeos cuantitativos y cualitativos de opinión pública apuntan a que vivimos en una sociedad tecnocrática o plutocrática, más que democrática. El modelo político establecido en España en las últimas décadas ofrece un marco institucional ambivalente para la participación ciudadana: por un lado, se afirma el derecho a la participación y se establecen algunos cauces concretos que antes no existían; por otro, el énfasis en la delegación (mecanismos de representación) impone unos límites precisos a la participación directa en los asuntos públicos

Evolución histórica de la vivienda de protección pública en Madrid

El problema del alojamiento de la población obrera en España se intentó solucionar a partir de 1853 con diversas medidas legislativas, con escaso resultado. Tras la promulgación de la primera Ley de casas baratas (1911) se inició la intervención pública que alcanzaría su máximo desarrollo en la década 1960-1970 y que estaría acompañada numerosas iniciativas de promotores privados (cajas de ahorros, empresas, instituciones religiosas). A pesar de ello permanecerían hasta casi finales del siglo XX la autoconstrucción o el barraquismo como formas de alojamiento obrero

Os desafios da nova política migratória brasileira diante do fluxo migratório haitiano

This article analyzes the Brazilian State's responses to the arrival of the south migratory flows to Brazil. The study empirically focuses on Haitian migration in Brazil. We argued the Brazilian migration policies have focused until now mainly in the reception process of immigrants. The New Migration Law (13.445/2017) and Regulatory Resolutions have allowed a regulated entry of Haitian immigrants in Brazil. However, the qualitative research conducted with Haitians in Brasília and Curitiba in 2018-1019, named “Immigration and economic crisis. Haitian return migration and circularity tactics” has showed there are still pending challenges, which the policies has not tackled. In sum, this study showed that in Brazil up to now the integration mechanisms have not developed at the same pace as the flow management rules.Diante da chegada dos novos fluxos migratórios do Sul Global para o Brasil, este artigo analisa as respostas do Estado brasileiro ao caso específico da migração haitiana. Argumentamos que a produção de políticas de gestão migratória no Brasil tem focado na recepção de imigrantes. A formulação da Lei de Migração (13.445/2017) regulamentada pelo decreto 9.199/17, as Resoluções Normativas e as Portarias Interministeriais, permitem a entrada regular dos imigrantes haitianos em território nacional. No entanto, através do estudo qualitativo realizado no marco da pesquisa “Imigração e crise econômica. As táticas migratórias de retorno e circularidade dos haitiana”, com os haitianos em Brasília e Curitiba em 2018-2019 foi revelado que as estruturas e os mecanismos de integração não se desenvolveram no mesmo ritmo das regras de gerenciamento de fluxo. A construção de políticas migratórias para além do novo marco legal segue sendo um desafio pendente para os formuladores de políticas de migração no Brasil