Projeto de um Multiplicador Divisor Anal´ogico em tecnologia CMOS para uso em controlador fuzzy tipo-2 intervalar

The main objective of the presented study is the design of a analog multiplier-divider as integrant part of the type-reducer circuit of type-2 fuzzy controller chip. The proposed circuit is a multiplier/divider which operates in current mode, in the CMOS technology with a supply voltage of 1.8 V.The circuit simulation was performed in PSPICE software with simulation model provided by AMS (Austria Mikro Systems International) in CMOS technology 0.35μm

Prevenção da repetição de episódos de reação tipo 2 da Hanseníase com o uso da talidomida na dose de 100mg/dia

Introdução: A hanseníase é doença crônica que pode ter seu curso interrompido por episódios reacionais tipo 1 e 2 ou ENH, sendo que estes podem ser repetitivos, com conseqüentes danos ao paciente.A talidomida é a medicação de eleição para o controle, desde 1965. Objetivo: Evitar repetição de episódios reacionais. Material e Método: Após o controle da reação com dose tradicional, utilizou-se 100mg/d, pelo período de seis meses, com acompanhamento por seis meses após a suspensão. Resultados: Foram avaliados 42 pacientes MB, 39 (92,85%) da forma V e 3(7,15%) da D, que apresentaram ENH, como primeiro episódio ou repetição, 33(78,6%) do sexo masculino e9(21,4%) do feminino. As idades variaram de 18 a 84 anos, predomínio acima de 49 anos.Não se observou repetição em 100% dos pacientes durante o uso dessa dose.Durante a observação clinica, 33(78,6%)continuaram sem apresentar reação e9(21,4%), todos da forma V,a apresentaram, de forma leve,sem sinais e sintomas, controlada com antinflamatórios não hormonais. Não houve efeitos adversos. Conclusões: sugere-se o uso da talidomida, 100mg/ dia, como manutenção, que foi efetiva, impedindo a repetição das reações tipo 2.

Insulin analogues in the treatment of diabetes in pregnancy

Pregnancy affects both maternal and fetal metabolism, and even in non-diabetic women, it exerts a diabetogenic effect. Among pregnant women, 2% to 14% develop gestational diabetes. Pregnancy can also occur in women with preexisting diabetes, which may predispose the fetus to many alterations in organogenesis, restrict growth, and the mother, to some diabetes-related complications, such as retinopathy and nephropathy, or to acceleration of the course of these complications, if they are already present. Women with gestational diabetes generally start their treatment with diet and lifestyle changes; when these changes are not enough for optimal glycemic control, insulin therapy must then be considered. Women with type 2 diabetes using oral hypoglycemic agents are advised to change to insulin therapy. Those with preexisting type 1 diabetes should start intensive glycemic control. As basal insulin analogues have frequently been used off-label in pregnant women, there is a need to evaluate their safety and efficacy. The aim of this review is to report the use of both short- and long-acting insulin analogues during pregnancy and to enable clinicians, obstetricians, and endocrinologists to choose the best insulin treatment for their patients.

Estudio etiopatogénico del circovirus porcino tipo 2 asociado a virus y bacterias en una infección natural

Programa de doctorado: Sanidad y patología animal

Patologie da Porcine Circovirus tipo 2 (PCV2) nel suino

The main work involved the PMWS (Post-weaning multisystemic Wasting Syndrome), caused by PCV-2 (Porcine Circovirus type 2) that involved post-weaned pigs. Merial Italy has funded a study activity in which groups of 3-5 animals were sampled for lungs, tracheo-bronchial and superficial inguinal lymph nodes, ileum and tonsils. The protocol applied can be identified as a more diagnostic potential on the individual than on the group. PNP. Another investigation has been conducted to study proliferative and necrotizing pneumonia (PNP), a form of interstitial pneumonia in weaning and post-weaning pigs characterized by hypertrophy and hyperplasia of type II pneumocytes, coagulative necrosis and granular debris within alveolar spaces. Many studies suggest porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) as the main causes of the disease, but Aujeszky disease virus (ADV) and swine influenza virus (SIV) are also considered. An immunohistochemical study was carried out to evaluate the role of these viruses in PNP lesions in Italy. PNP results primarily associated with PRRSV, even if co-infection is characterized by more severe histological features. Reproductive pathology. A major risk factor for PCV2 infection is a viraemic episode taking place in pregnant sows with low antibody titer which is transmitted by specific PCV2 products of conception. PCV2 can infect the fetus even by vehicles through infected semen or ova, or as a result of infection of the genital tract. An investigation was carried out to identify the presence and localization of PCV2 in the genital tracts of sows experimentally infected with PCV2 and in their fetuses. The results obtained suggest that: conventional sows can be infected by intrauterine exposition; low antibody titres increase the probability of infection; PCV2 infection close to insemination time reduces the pregnancy rate; placental lesions may represent an additional cause of fetal suffering.

Ruolo del Porcine Circovirus tipo 2 (PCV2) nella patologia riproduttiva del suino

La tesi è organizzata in 4 capitoli: -nel primo vengono brevemente riferite le patologie associate all’infezione da PCV2 con particolare riferimento all’iter diagnostico ed al ruolo rivestito dall’esame istologico e dalla identificazione dell’agente eziologico in situ contestualmente alle lesioni istologiche; -nel secondo viene presentato un iter diagnostico originale da applicare in condizioni di campo, qualora si voglia accertare la presenza del PCV2 nei tessuti dei prodotti di natimortalità/aborto del suino. In specifico si riferisce all’applicazione del protocollo in 2 aziende ed i risultati vengono analizzati per una revisione critica del protocollo impiegato; -nel terzo vengono presentati i risultati di un protocollo di infezione con PCV2 per via genitale tramite seme infetto. Scrofe convenzionali sono state sincronizzate per l’estro e fecondate con un’unica dose di seme PCV2 negativo alla PCR (gruppo controlli) o sperimentalmente esposto al PCV2 (gruppo infette). I risultati vengono analizzati in funzione delle ripercussioni che l’infezione precoce in gravidanza può produrre sulla scrofa (mancata gravidanza, ritorno in calore), sui feti e sugli invogli fetali. Viene stabilito il ruolo protettivo degli anticorpi circolanti al momento dell’infezione, stante l’evenienza che un basso titolo anticorpale si associa a viremia prolungata e maggiore numero di feti positivi al virus; -nel quarto viene presentato un esperimento sovrapponibile a quello riferito nel capitolo 3, però con la presenza anche di un gruppo di soggetti convenzionali vaccinati ed infettati con PCV2 durante la fecondazione artificiale usando seme sperimentalmente esposto al virus. Nella discussione dei risultati vengono enfatizzati 2 aspetti importanti nell’epidemiologia dell’infezione da PCV2: la eliminazione di virus è fortemente ridotta dalla vaccinazione, con conseguenze verosimilmente positive sulla circolazione del virus negli effettivi dell’allevamento; l’esposizione uterina è protetta dalla vaccinazione, stante la bassa percentuale di placente infette nel gruppo dei soggetti vaccinati rispetto a quelli non vaccinati e nei controlli.

Sistema de control borroso en lazo cerrado para terapias con insulina en diabetes tipo I

La diabetes mellitus es un trastorno del metabolismo de los carbohidratos producido por la insuficiente o nula producción de insulina o la reducida sensibilidad a esta hormona. Es una enfermedad crónica con una mayor prevalencia en los países desarrollados debido principalmente a la obesidad, la vida sedentaria y disfunciones en el sistema endocrino relacionado con el páncreas. La diabetes Tipo 1 es una enfermedad autoinmune en la que son destruidas las células beta del páncreas, que producen la insulina, y es necesaria la administración de insulina exógena. Un enfermo de diabetes Tipo 1 debe seguir una terapia con insulina administrada por la vía subcutánea que debe estar adaptada a sus necesidades metabólicas y a sus hábitos de vida, esta terapia intenta imitar el perfil insulínico de un páncreas no patológico. La tecnología actual permite abordar el desarrollo del denominado “páncreas endocrino artificial”, que aportaría precisión, eficacia y seguridad para los pacientes, en cuanto a la normalización del control glucémico y reducción del riesgo de hipoglucemias. Permitiría que el paciente no estuviera tan pendiente de su enfermedad. El páncreas artificial consta de un sensor continuo de glucosa, una bomba de infusión de insulina y un algoritmo de control, que calcula la insulina a infusionar usando la glucosa como información principal. Este trabajo presenta un método de control en lazo semi-cerrado mediante un sistema borroso experto basado en reglas. La regulación borrosa se fundamenta en la ambigüedad del lenguaje del ser humano. Esta incertidumbre sirve para la formación de una serie de reglas que representan el pensamiento humano, pero a la vez es el sistema que controla un proceso, en este caso el sistema glucorregulatorio. Este proyecto está enfocado en el diseño de un controlador borroso que haciendo uso de variables como la glucosa, insulina y dieta, sea capaz de restaurar la función endocrina del páncreas de forma tecnológica. La validación del algoritmo se ha realizado principalmente mediante experimentos en simulación utilizando una población de pacientes sintéticos, evaluando los resultados con estadísticos de primer orden y algunos más específicos como el índice de riesgo de Kovatchev, para después comparar estos resultados con los obtenidos por otros métodos de control anteriores. Los resultados demuestran que el control borroso (FBPC) mejora el control glucémico con respecto a un sistema predictivo experto basado en reglas booleanas (pBRES). El FBPC consigue reducir siempre la glucosa máxima y aumentar la mínima respecto del pBRES pero es en terapias desajustadas, donde el FBPC es especialmente robusto, hace descender la glucosa máxima 8,64 mg/dl, el uso de insulina es 3,92 UI menor, aumenta la glucosa mínima 3,32 mg/dl y lleva al rango de glucosa 80 – 110 mg/dl 15,33 muestras más. Por lo tanto se puede concluir que el FBPC realiza un mejor control glucémico que el controlador pBRES haciéndole especialmente efectivo, robusto y seguro en condiciones de desajustes de terapia basal y con gran capacidad de mejora futura. SUMMARY The diabetes mellitus is a metabolic disorder caused by a poor or null insulin secretion or a reduced sensibility to insulin. Diabetes is a chronic disease with a higher prevalence in the industrialized countries, mainly due to obesity, the sedentary life and endocrine disfunctions connected with the pancreas. Type 1 diabetes is a self-immune disease where the beta cells of the pancreas, which are the responsible of secreting insulin, are damaged. Hence, it is necessary an exogenous delivery of insulin. The Type 1 diabetic patient has to follow a therapy with subcutaneous insulin administration which should be adjusted to his/her metabolic needs and life style. This therapy tries to mimic the insulin profile of a non-pathological pancreas. Current technology lets the development of the so-called endocrine artificial pancreas that would provide accuracy, efficiency and safety to patients, in regards to the glycemic control normalization and reduction of the risk of hypoglycemic. In addition, it would help the patient not to be so concerned about his disease. The artificial pancreas has a continuous glucose sensor, an insulin infusion pump and a control algorithm, that calculates the insulin infusion using the glucose as main information. This project presents a method of control in semi-closed-loop, through an expert fuzzy system based on rules. The fuzzy regulation is based on the human language ambiguity. This uncertainty serves for construction of some rules that represent the human language besides it is the system that controls a process, in this case the glucoregulatory system. This project is focus on the design of a fuzzy controller that, using variables like glucose insulin and diet, will be able to restore the pancreas endocrine function with technology. The algorithm assessment has mainly been done through experiments in simulation using a population of synthetic patients, evaluating the results with first order statistical parameters and some other more specific such as the Kovatchev risk index, to compare later these results with the ones obtained in others previous methods of control. The results demonstrate that the fuzzy control (FBPC) improves the glycemic control connected with a predictive expert system based on Booleans rules (pBRES). The FBPC is always able to reduce the maximum level of glucose and increase the minimum level as compared with pBRES but it is in unadjusted therapies where FBPC is especially strong, it manages to decrease the maximum level of glucose and insulin used by 8,64 mg/dl and 3,92 UI respectively, also increases the value of minimum glucose by 3,32 mg/dl, getting 15,33 samples more inside the 80-110 mg/dl glucose rank. Therefore we can conclude that FBPC achieves a better glycemic control than the controller pBRES doing it especially effective, robust and safe in conditions of mismatch basal therapy and with a great capacity for future improvements.

Contribución al estudio de las negaciones, autocontradicción, t-normas y t-conormas en los conjuntos borrosos de tipo 2

Los conjuntos borrosos de tipo 2 (T2FSs) fueron introducidos por L.A. Zadeh en 1975 [65], como una extensión de los conjuntos borrosos de tipo 1 (FSs). Mientras que en estos últimos el grado de pertenencia de un elemento al conjunto viene determinado por un valor en el intervalo [0, 1], en el caso de los T2FSs el grado de pertenencia de un elemento es un conjunto borroso en [0,1], es decir, un T2FS queda determinado por una función de pertenencia μ : X → M, donde M = [0, 1][0,1] = Map([0, 1], [0, 1]), es el conjunto de las funciones de [0,1] en [0,1] (ver [39], [42], [43], [61]). Desde que los T2FSs fueron introducidos, se han generalizado a dicho conjunto (ver [39], [42], [43], [61], por ejemplo), a partir del “Principio de Extensión” de Zadeh [65] (ver Teorema 1.1), muchas de las definiciones, operaciones, propiedades y resultados obtenidos en los FSs. Sin embargo, como sucede en cualquier área de investigación, quedan muchas lagunas y problemas abiertos que suponen un reto para cualquiera que quiera hacer un estudio profundo en este campo. A este reto se ha dedicado el presente trabajo, logrando avances importantes en este sentido de “rellenar huecos” existentes en la teoría de los conjuntos borrosos de tipo 2, especialmente en las propiedades de autocontradicción y N-autocontradicción, y en las operaciones de negación, t-norma y t-conorma sobre los T2FSs. Cabe destacar que en [61] se justifica que las operaciones sobre los T2FSs (Map(X,M)) se pueden definir de forma natural a partir de las operaciones sobre M, verificando las mismas propiedades. Por tanto, por ser más fácil, en el presente trabajo se toma como objeto de estudio a M, y algunos de sus subconjuntos, en vez de Map(X,M). En cuanto a la operación de negación, en el marco de los conjuntos borrosos de tipo 2 (T2FSs), usualmente se emplea para representar la negación en M, una operación asociada a la negación estándar en [0,1]. Sin embargo, dicha operación no verifica los axiomas que, intuitivamente, debe verificar cualquier operación para ser considerada negación en el conjunto M. En este trabajo se presentan los axiomas de negación y negación fuerte en los T2FSs. También se define una operación asociada a cualquier negación suprayectiva en [0,1], incluyendo la negación estándar, y se estudia, junto con otras propiedades, si es negación y negación fuerte en L (conjunto de las funciones de M normales y convexas). Además, se comprueba en qué condiciones se cumplen las leyes de De Morgan para un extenso conjunto de pares de operaciones binarias en M. Por otra parte, las propiedades de N-autocontradicción y autocontradicción, han sido suficientemente estudiadas en los conjuntos borrosos de tipo 1 (FSs) y en los conjuntos borrosos intuicionistas de Atanassov (AIFSs). En el presente trabajo se inicia el estudio de las mencionadas propiedades, dentro del marco de los T2FSs cuyos grados de pertenencia están en L. En este sentido, aquí se extienden los conceptos de N-autocontradicción y autocontradicción al conjunto L, y se determinan algunos criterios para verificar tales propiedades. En cuanto a otras operaciones, Walker et al. ([61], [63]) definieron dos familias de operaciones binarias sobre M, y determinaron que, bajo ciertas condiciones, estas operaciones son t-normas (normas triangulares) o t-conormas sobre L. En este trabajo se introducen operaciones binarias sobre M, unas más generales y otras diferentes a las dadas por Walker et al., y se estudian varias propiedades de las mismas, con el objeto de deducir nuevas t-normas y t-conormas sobre L. ABSTRACT Type-2 fuzzy sets (T2FSs) were introduced by L.A. Zadeh in 1975 [65] as an extension of type-1 fuzzy sets (FSs). Whereas for FSs the degree of membership of an element of a set is determined by a value in the interval [0, 1] , the degree of membership of an element for T2FSs is a fuzzy set in [0,1], that is, a T2FS is determined by a membership function μ : X → M, where M = [0, 1][0,1] is the set of functions from [0,1] to [0,1] (see [39], [42], [43], [61]). Later, many definitions, operations, properties and results known on FSs, have been generalized to T2FSs (e.g. see [39], [42], [43], [61]) by employing Zadeh’s Extension Principle [65] (see Theorem 1.1). However, as in any area of research, there are still many open problems which represent a challenge for anyone who wants to make a deep study in this field. Then, we have been dedicated to such challenge, making significant progress in this direction to “fill gaps” (close open problems) in the theory of T2FSs, especially on the properties of self-contradiction and N-self-contradiction, and on the operations of negations, t-norms (triangular norms) and t-conorms on T2FSs. Walker and Walker justify in [61] that the operations on Map(X,M) can be defined naturally from the operations onMand have the same properties. Therefore, we will work onM(study subject), and some subsets of M, as all the results are easily and directly extensible to Map(X,M). About the operation of negation, usually has been employed in the framework of T2FSs, a operation associated to standard negation on [0,1], but such operation does not satisfy the negation axioms on M. In this work, we introduce the axioms that a function inMshould satisfy to qualify as a type-2 negation and strong type-2 negation. Also, we define a operation on M associated to any suprajective negation on [0,1], and analyse, among others properties, if such operation is negation or strong negation on L (all normal and convex functions of M). Besides, we study the De Morgan’s laws, with respect to some binary operations on M. On the other hand, The properties of self-contradiction and N-self-contradiction have been extensively studied on FSs and on the Atanassov’s intuitionistic fuzzy sets (AIFSs). Thereon, in this research we begin the study of the mentioned properties on the framework of T2FSs. In this sense, we give the definitions about self-contradiction and N-self-contradiction on L, and establish the criteria to verify these properties on L. Respect to the t-norms and t-conorms, Walker et al. ([61], [63]) defined two families of binary operations on M and found that, under some conditions, these operations are t-norms or t-conorms on L. In this work we introduce more general binary operations on M than those given by Walker et al. and study which are the minimum conditions necessary for these operations satisfy each of the axioms of the t-norm and t-conorm.

Nuevas operaciones binarias sobre los conjuntos borrosos de tipo 2

Walker et al. ([19], [20]) definieron dos familias de operaciones binarias sobre M (conjunto de las funciones de [0,1] en [0,1]), y determinaron que, bajo ciertas condiciones, estas operaciones son tnormas (normas triangulares) o t-conormas sobre L (subconjunto de las funciones normales y convexas de M). En este trabajo se introducen dos operaciones binarias sobre M, diferentes a las dadas por Walker et al., y se estudian varias propiedades de las mismas, con el objeto de deducir nuevas t-normas y t-conormas sobre L y sobre M.