Introdução: Prurigo é uma terminologia de conotação sindrômica que tem o prurido como sintoma incondicional. O sinal é dermatológico, caracteristicamente manifestado por pápulas que se distribuem com relativa simetria pelo tegumento. Do ponto de vista clínico é uma condição de fácil suspeita, mas de difícil conclusão causal. Na Fundação Centro de Controle de Oncologia do Amazonas (FCECON), quadro de prurigo em pacientes oncológicos eram ocasionalmente identificados após início da radioterapia para o tratamento do tumor de base, contexto epidemiológico que não é classicamente relacionado ao prurigo. Objetivos: Descrever os aspectos clínicos, histopatológicos e imunoistoquímicos dos casos pósradioterapia. Métodos: estudo transversal, descritivo, de janeiro de 2006 a dezembro de 2012, com seleção de pacientes com CID de prurigo na FCECON. Serão descritas as características clínicas, histopatológicas e imunoistoquimicas dos casos com pesquisa de DNA viral do EBV, CMV e parvovírus B19. Resultados: Foram 35 mulheres e um homem, com idade média de 47 anos, sempre com queixa de prurido. A pelve sempre foi o campo irradiado com mediana de 28 dias para o surgimento dos sintomas. Foram 34 tumores ginecológicos com 31 casos de colo de útero. Ao todo ocorreram 13.339 lesões (média de 371), com 535 do grupo 1 (vesículas e urticas), 4.934 do grupo 2 (pápulas), 4.218 do grupo 3 (escoriações) e 3.652 do grupo 4 (residuais). Os membros inferiores foram acometidos em todos os casos e em 27 casos houve acometimento dos membros superiores. A histologia das 27 lâminas disponíveis identificou epiderme normal em cinco pacientes, atrofia em dois, espongiose em oito e alteração secundária ao prurido nas demais. Espongiose folicular e/ou espongiose do acrossiríngeo foram identificadas por nove ocasiões. Infiltrado perivascular superficial, profundo e intersticial composto por linfócitos e eosinófilos com distribuição perianexial foi o padrão mais encontrado na derme. O padrão do infiltrado foi de linfócitos T CD4 e ausência de linfócitos CD20 e linfócitos CD56. Não foi identificado DNA viral nas amostras examinadas. Discussão: O quadro de prurigo pós-radioterapia possui as mesmas características clínicoepidemiológicas e histológicas da síndrome EPPER. Histologicamente pode ser inclusa dentro das doenças inflamatórias eosinofílicas da pele, com padrão imunoistoquímico do infiltrado sugestivo de reação de hipersensibilidade mediada por linfócitos no padrão Th2. Como reação a picada de mosquitos foi o diagnóstico histológico de todos os casos, postula-se que o prurigo pós radioterapia, ou síndrome EPPER, seja reação imunológica precipitada pela exposição aos antígenos salivares do mosquito em um ambiente imune induzido pelo efeito abscopal secundário a irradiação pélvica. A natureza do estudo não permite confirmar esta conclusão, que deverá ser fruto de pesquisas futuras. Conclusões: O quadro de prurigo pós radioterapia esteve associado a irradiação da pelve, especialmente de tumores ginecológicos, com predomínio do câncer de colo de útero. Clinicamente semelhante a erupção pruriginosa, polimórfica, eosinofílica associada a radioditerapia (EPPER), pode ser classificado como prurigo agudo. As manifestações clínicas, histológicas e imunoistoquímicas são semelhantes ao quadro de hipersensibilidade a picada de mosquito do padrão celular, mediado por linfócitos Th2, sem evidencia de co-participação viral nos casos examinados / Introduction: Prurigo, a terminology used with a syndromic connotation, is characterized by pruritus, as an unconditional symptom, and papules usually distributed with relative symmetry by the integument. From the clinical point of view, it is a condition of easy suspicion, but of difficult causal conclusion. At the Fundação Centro de Controle de Oncologia do Amazonas (FCECON), prurigo was occasionally identified in cancer patients after radiation therapy for the treatment of the underlying tumor, an epidemiological context that is not classically related to prurigo. Objectives: To describe the clinical, histopathological and immunohistochemical aspects of post-radiotherapy prurigo. Methods: a cross-sectional, descriptive study, from January 2006 to December 2012, with the selection of patients with prurigo as classified by international classification of diseases in FCECON. The clinical, histopathological and immunohistochemical characteristics of the cases with viral DNA screening by RT-PCR EBV, CMV and parvovirus B19 is described. Results: There were 35 women and one man, with an average age of 47 years. Pruritus was always present. The pelvis was invariably the irradiated field with a median of 28 days for the onset of symptoms. There were 34 cases with gynecological tumors with 31 of the uterine cervix. A total of 13,339 lesions (mean of 371), with 535 of group 1 (vesicles and urticas), 4,934 of group 2 (papules), 4,218 of group 3 (excoriations) and 3,652 of group 4 (residual). The lower limbs were affected in all cases, and in 27 cases there was involvement of the upper limbs. The histology of the 27 available slides identified normal epidermis in five patients, atrophy in two, spongiosis in eight and alteration secondary to pruritus in the others. Follicular spongiosis or spongiosis of the acrosyringium were identified on nine occasions. A superficial, deep and interstitial perivascular infiltrate composed of lymphocytes and eosinophils with perianexial distribution was the most common pattern found in the dermis. The composition of the infiltrate was of CD3 CD4 T lymphocytes and absence of CD20 lymphocytes and CD56 lymphocytes. There were no viral DNA identified in the samples examined. Discussion: Postradiotherapy prurigo has the same clinical-epidemiological and histological characteristics of eosinophilic, polymorphic, pruritic associated with radiotherapy (EPPER) syndrome. Histologically it can be included within the inflammatory eosinophilic diseases of the skin, and the immunohistochemestry pattern of the infiltrate suggests a hypersensitivity reaction mediated by Th2 lymphocytes. Since a reaction to mosquito bites was the clinicopathological diagnosis of all cases, the authors postulate that post-radiation prurigo, or EPPER syndrome, is an immunological reaction precipitated by exposure to the mosquito\'s salivary antigens in an immune environment induced by the abscopal effect secondary to irradiation of the pelvis. The nature of the study does not allow this conclusion, which should be the result of future research. Conclusions: Post-radiation prurigo was associated with irradiation of the pelvis especially to treat gynecological tumors, with cancer of the cervix predominance. Clinically similar to EPPER syndrome, it can be classified as acute prurigo. Clinical, histological and immunohistochemical manifestations are similar to the hypersensitivity of Th2 lymphocytemediated mosquito bites, with no evidence of viral co-participation in the cases examined

Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation and increases the risks of primary non-function, delayed graft function and rejection. Oxidative damage to mitochondria is a key early event in IR injury. The aim of this project was to examine the safety and efficacy of the mitochondria-targeted antioxidant MitoQ in reducing pig and human kidney IR injury using an ex vivo normothermic perfusion (EVNP) system. Over a range of 500 nM to 250 µM using a 150 pig kidneys and 80 declined deceased human kidneys, MitoQ was successfully taken up by pig and human kidneys in a concentration-dependent manner, resulting in stable tissue concentrations over 24 hours of cold storage followed by 6 hours of EVNP. The uptake of MitoQ was increased approximately 2-fold when MitoQ was administered to warm (rather than cold) kidneys and when kidneys were preserved using hypothermic machine perfusion (rather than cold static storage). 50 µM MitoQ, administered to pig kidneys at the end of warm ischaemia, significantly increased renal blood and urine output flow at the end of 6 h EVNP compared to the control group. Creatinine clearance was numerically higher in the 50 µM MitoQ group compared to the control group but the difference did not reach statistical significance. To test the safety and efficacy of MitoQ in human kidney IRI, pairs of declined deceased human kidneys were used, with one kidney in each pair used as control. The total urine output, creatinine clearance and percentage fall of serum creatinine were numerically higher in the 50 µM MitoQ group compared to the control group, although the differences did not reach statistical significance during 3 h of EVNP. There was a significant difference in the renal blood flow between the 50 µM MitoQ group and the control group at the end of the first hour of EVNP. The renal blood flow remained relatively stable during the first hour of EVNP in the 50 µM MitoQ group compared to a significant decrease in renal blood flow in the control group. There was no effect on fractional excretion of sodium or oxidative injury markers (protein carbonyl formation, lipid peroxidation) in pig or human kidneys, which is consistent with previous studies that demonstrated the requirement of >24 hour after reperfusion for manifestation of changes in these parameters. In this thesis, I was able to successfully demonstrate the safety and potential efficacy of MitoQ in ameliorating renal IRI using pig kidneys. While more declined deceased human kidneys need to be analysed to fully explore the potential efficacy of MitoQ in ameliorating renal IRI, this study provides important data that will help inform future studies and ultimately a clinical trial for assessing the efficacy of the mitochondria-targeted antioxidant MitoQ in human kidney transplantation. My findings suggest that MitoQ has the potential to increase the use of marginal kidneys and to improve graft and patient outcomes.

Zhu Jian-hui. / "July 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 174-215). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

This thesis deals with the estimation of unobserved variables or states from a time series of noisy observations. Approximate minimum variance filters for a class of discrete time systems with both additive and multiplicative noise, where the measurement might be delayed randomly by one or more sample times, are investigated. The delayed observations are modelled by up to N sample times by using N Bernoulli random variables with values of 0 or 1. We seek to minimize variance over a class of filters which are linear in the current measurement (although potentially nonlinear in past measurements) and present a closed-form solution. An interpretation of the multiplicative noise in both transition and measurement equations in terms of filtering under additive noise and stochastic perturbations in the parameters of the state space system is also provided. This filtering algorithm extends to the case when the system has continuous time state dynamics and discrete time state measurements. The Euler scheme is used to transform the process into a discrete time state space system in which the state dynamics have a smaller sampling time than the measurement sampling time. The number of sample times by which the observation is delayed is considered to be uncertain and a fraction of the measurement sample time. The same problem is considered for nonlinear state space models of discrete time systems, where the measurement might be delayed randomly by one sample time. The linearisation error is modelled as an additional source of noise which is multiplicative in nature. The algorithms developed are demonstrated throughout with simulated examples.

Esta tese versa sobre a síntese de compensadores antiwindup para sistemas lineares contínuos invariantes no tempo, com restrições no atuador e atraso no tempo. Baseados em um funcional Liapunov-Krasovskii e uma condição de setor para a função zona-morta já existentes na literatura, são propostas condições suficientes expressas em LMIs para a existência de compensadores antiwindup para duas classes de sistemas: sistemas com atraso nos estados, e sistemas com atraso na entrada. Em ambos os casos, considera-se a síntese de um compensador de ordem plena para um sistema com um controlador dado a priori desprezando limites do atuador. A síntese dos compensadores antiwindup considera um atuador restrito em amplitude e o sistema sujeito a perturbações limitadas em norma L2. A verificação das condições enunciadas garante a estabilidade da origem em malha fechada, e um conjunto de inicialização dos estados do sistema tolerante à perturbação com norma L2 inferior a um máximo, determinado juntamente com a síntese do compensador antiwindup. Na ausência de perturbação a origem é garantida assintoticamente estável. Para sistemas com atraso no estado, primeiro propõe-se um método para a síntese de compensadores dinâmicos racionais de ordem plena. Este método é baseado no Lema de Projeção. Em seguida, estende-se o resultado, propondo-se um framework genérico que permite a síntese de compensadores racionais e não racionais. Este método é baseado em uma transformação de variáveis linearizante. Para sistemas com atraso na entrada, propõe-se três resultados de síntese de compensadores antiwindup: compensadores estáticos, dinâmicos racionais, e dinâmicos não racionais. Estes métodos são novamente baseados no Lema de Projeção. Em todos os casos, as condições obtidas que garantem a existência de um compensador antiwindup são expressas em forma de LMIs e garantem a estabilidade local da origem. Em seguida, estende-se os resultados para garantir a estabilidade global da origem, nos casos em que a planta é estável em malha aberta. Problemas de otimização são propostos para ambos os métodos para maximizar a tolerância à perturbação e a minimização do ganho L2 da perturbação à saída regulada. Exemplos numéricos ilustram cada método na solução dos problemas de máxima tolerância à perturbação, e minimização do ganho L2 da perturbação à saída regulada. / This thesis verses about antiwindup compensator synthesis for linear time invariant continuous systems, presenting constraints in actuator and time delay. Based on a Liapunov-Krasovskii functional and a sector condition for the dead-zone nonlinearity already castign in literature, it is proposed sufficient conditions expressed in LMI to the existance of an antiwindup compensator for two classes of systems: systems with state delay, and systems with input delay. In both cases it is considered the synthesis of a full order antiwindup compensator for a system with a controller a priori given that disregards the actuator bounds. The synthesis of antiwindup compensators considers an actuator constrained in amplitude and a system subjected to norm-L2 bounded disturbances. Once the casted conditions are verified, it is assured the closed loop origin stability; a set for the initial states of the system tolerating disturbances up to a maximum L2 norm, which is also determined along the antiwindup compensator synthesis procedure. In the absence of disturbance the origin is assuredly asymptotically stable. For state delay systems, first it is proposed a method for designing full order rational antiwindup compensators. This method is based on the Projection Lemma. Afterwards, results are extended proposing a generic framework allowing the synthesis of rational and nonrational compensators of different topologies. This method is based on a linearizing variable transformation. For input delay systems, it is proposed three synthesis results: static, rational dynamic and nonrational dynamic compensators. These methods are based on the Projection Lemma. In all cases, the conditions obtained assuring the existance of an antiwindup compensator are expressed by means of LMIs that, once verified, assure the origin local stability. Then, the conditions are extended for the global stability case, when the system is open loop stable. Optimization problems are proposed for both methods to maximize the disturbance tolerance and the minimization of the L2-gain of the disturbance to the regulated output. Numerical examples are presented to illustrate each method in the solution of the problems of maximum disturbance tolerance, and minimization of L2-gain from the disturbance to the regulated output.

A possibilidade do controle feminino sobre a reprodução, de escolha ou não pela maternidade, do número de filhos e de quando tê-los, se coloca como um fenômeno que vem se consolidando ao longo do tempo, acompanhando as diversas transformações na família, no casamento, na maternidade e na paternidade. Cresce, nesse contexto, o número de mulheres que postergam a maternidade para idades cada vez mais avançadas. Tal fenômeno vem muitas vezes carregado de idealizações e de desconhecimento, o que pode gerar a ilusão de um controle que não necessariamente equivale às vivências reais. O objetivo geral desta tese é o de investigar o fenômeno do adiamento da maternidade, na sociedade atual, com base nas vivências de mulheres de dois diferentes grupos que optaram por ter o primeiro filho depois dos trinta e cinco anos: aquelas que conseguiram e aquelas que não, seja porque ainda estivessem tentando, seja porque houvessem desistido. Como objetivo específico, pretende-se pensar a influência dos fatores conjugalidade, carreira profissional e história de vida, nas famílias de origem na determinação desse tipo de escolha. Para tanto, foram realizadas, a partir de uma metodologia clínico-qualitativa, a aplicação das pranchas 1, 2, 7MF, 10 e 16 do TAT, além de uma entrevista semidirigida, com oito mulheres quatro pertencentes a cada grupo com idades entre trinta e seis e quarenta e um anos, em um relacionamento estável, com mais de oito anos de escolaridade, habitantes da região metropolitana de São Paulo. Os dados foram analisados de acordo com o referencial psicanalítico, levando-se em conta, também, aspectos históricos e psicossociais que influenciam o fenômeno. Os resultados são apresentados de acordo com as seguintes categorias de análise: a experiência do adiamento da maternidade; a maternidade, como experiência para aquelas que se tornaram mães, e como experiência projetada, para aquelas que não se tornaram mães; conjugalidade; carreira profissional; relação com a própria mãe e conjugalidade dos pais; e a questão do poder. Conclui-se que o fenômeno do adiamento da maternidade, na sociedade contemporânea, mostra-se complexo e imerso em uma multiplicidade de significados. Em meio às especificidades de cada caso, algumas aproximações puderam ser feitas entre as experiências das mulheres dos dois grupos, especialmente no que diz respeito à valorização e idealização da conjugalidade, percebida inclusive como mais importante que o desenvolvimento de uma carreira profissional, bem como a possibilidade de integração dos aspectos que concernem ao poder em relação ao corpo e ao controle da reprodução por meio dos binômios: onipotência/impotência e elementos femininos/masculinos puros na mulher contemporânea, de um ponto de vista winnicottiano. As divergências mais marcantes entre os dois grupos se referem sobretudo à relação estabelecida com as próprias mães, além da conjugalidade dos pais. A postergação da maternidade, fenômeno tão atual e com potencial para mobilizar tantas angústias e sofrimentos, pode ser vivenciada pelas mulheres contemporâneas de maneira mais ou menos saudável ou criativa, com uma maior ou menor capacidade de integração da ambivalência, a depender dos recursos psíquicos individuais e do legado geracional / The womans option to control her fertility, to choose motherhood or not, to choose the number of children and the time to have them, is a phenomenon that has been establishing itself over time, following diverse transformations in the family and the marriage, as well as in motherhood and fatherhood. In this context, there has been an increase in the number of women who delay childbirth until later in life. Many times, such phenomenon comes loaded with idealization and lack of knowledge, which may generate an illusion of control that does not necessarily equate with the real experience. The general objective of this thesis is to investigate the phenomenon of delayed motherhood in current society from the perspective of two different groups of women who delayed childbirth to later than thirty-five years of age: those who had already succeeded and those who hadnt yet and either gave up or kept trying. The specific objective is to reflect on the influence of the following factors in determining the choice of delayed childbirth: marital situation, professional career and history of families of origin. For this purpose, it was used a clinical-qualitative methodology that included the application of pictures 1, 2, 7GF, 10 and 16 of the TAT (Thematic apperception test) and of semi-directed interviews with eight women (four from each group) with ages ranging from thirty-six to forty-one years, who were in a steady relationship, had more than eight years of schooling, and resided in the metropolitan region of São Paulo. The data are analyzed in accordance to the psychoanalytical referential, taking into account historical and psychosocial aspects that influence the phenomenon. The results are presented in accordance to the following categories of analysis: the experience of delayed childbirth; the experience of motherhood for those who became mothers and the projected experience for those who did not become mothers; marital life; professional career; relationship with their own mother; their parents marital life; and the power issue. The conclusion is that the phenomenon of delayed motherhood in contemporary society reveals itself as complex and immersed in a multiplicity of meanings. Among the specificities of each case, some proximity between the experiences of the women of the two different groups could be established particularly with regard to the attributed value and idealization of the marital relationship, perceived as more important than the development of a professional career; and with regard to the integration of the power aspects that refer to the body and the control of fertility, by means of the binomials: omnipotence/impotence and pure masculine/feminine elements in the contemporary woman, from a Winnicottian point of view. The remarkable divergences between the two groups referred especially to the relationship established with their own mothers and the marital life of their parents. The delayed motherhood, a current phenomenon with potential to stir much distress and suffering, can be experienced deeply by the contemporary women in a more or less healthy or creative way, to a greater or lesser degree of integration of their capacity for sustaining ambivalence, depending on the individual psychic resources and his/hers generational legacy

In the Romantic period, expanded tonality offers a creative challenge to composers as they explore new ways of establishing the hierarchy of pitches and utilizing the chromatic and diatonic resources. Prominent compositional techniques of this period include the use of linear harmony with less clearly defined root movements, the structural placement of dominant function, new approaches that redefine tonal stability, motivic treatment that generates harmony and form, flexible treatment of rhythm and meter, and functional treatment of chromatic pitches. This study explores the ways in which characteristics of the Romantic period are influenced by the upper/lower leading tone and the effects of compositional treatment on the expansion of tonality. In addition, this study includes two supportive concepts: (1) the wedge and toggle switch by David Witten and (2) The Neapolitan Complex by Christopher Wintle. In describing techniques in expanded tonality, excerpts from compositions by Robert Schumann and Johannes Brahms (both prominent composers of the Romantic period) are used to establish the significance of these techniques. In the fourth movement of Sonata in E minor "Undine," by Carl Reinecke, the structural treatment of the upper/lower leading tones to tonic and dominant are very prominent features that contribute significantly to the development of the concepts in this study.

Traditionally, working memory and its neural underpinnings have been studied in the visual domain. A rich and diverse amount of research has investigated the lateral prefrontal cortex (lPFC) as a primary area for visual working memory, while another line of research has found the neurotransmitter acetylcholine (ACh) to be involved. This dissertation used auditory cues and found similar patterns of activity for processing auditory working memory information within a task compared to visual working memory processes. The first two experimental chapters demonstrated that the cholinergic system is involved in auditory working memory in a comparable fashion to its role in visual working memory. In chapter 2, blocking ACh impaired performance on an auditory working memory task in a dose dependent manner. Chapter 3 investigated the specificity of the effect of blocking ACh by administering an ACh agonist (physostigmine) at the same time as an ACh antagonist (scopolamine). When both drugs were administered together performance on the delayed matching-to-sample task (DMTS) task improved compared to performance on scopolamine alone. These results support the hypothesis that ACh is involved in auditory working memory. Chapter 4 investigated the neural correlates of auditory working memory in area 46 and found that this region of the lPFC contains neurons that are responsive to auditory working memory components in a very similar way to how it this region encodes information during visual working memory tasks. Neurons in the lPFC are responsive to visual or auditory cues, the delay portion of tasks, the wait time (i.e. decision making period), response, and reward times. This type of coding provides support for the theories that position the lPFC as a key player in recognition and working memory regardless of modality.

The goal of this thesis is to extend the delayed Kalman filter so it can be used with non-linear systems and that it can handle randomized delays on the measurements. In the particular case of this study, the filter is used to estimates the states of an unmanned aerial system. The outputs of the filter are used to point an antenna and a camera towards a UAS. Different scenarios are simulated for the purpose of comparing the efficiency of this technique in various situations.

<p>During the last years, drugs that prolong the repolarisation phase of the myocardial action potential, due to inhibition of the rapid component of the delayed-rectifying potassium channel (I_Kr) have been in focus. In addition to arrhythmogenic potential, selective Ikr-blockers have also been shown to be embryotoxic and teratogenic in animal studies. The aim of this thesis was to investigate a theory that these developmental toxic results from pharmacologically induced episodes of embryonic cardiac arrhythmias leading to hypoxia related damage in the embryo. Almokalant (ALM) was used as a model compound for selective Ikr-blockers. ALM induced embryonic cardiac arrhythmia, and in similarity with results obtained by maternal hypoxia, ALM induced embryonic death and growth retardation in both rats, and mice. </p><p>The theory of a hypoxia-related mechanism was strengthened by the results that ALM induce phase specific external and visceral defects (e.g. cleft lip/palate, distal digital, cardiovascular, and urogenital defects), and that the skeletal defects (not shown before) showed a clear trend; the later the treatment the more caudal was the site of the defect, which is in accordance with results from maternal hypoxia induced by e.g. lowering of the O₂ content in the air. The spin trapping agent PBN decreased almokalant induced malformations, suggesting that the defects mainly are caused by reoxygenation damage after episodes of severe embryonic dysrhythmia, rather than "pure hypoxia".</p><p>Sotalol was tested in a third species, the rabbit who expresses functional I_Kr channels both in the embryo and in the adult, where it induced developmental toxicity, and indicating that the embryo is more sensitive than the adult towards arrhythmia caused by I_Kr-blockers. </p>