A dor crônica de joelho secundária a osteoartrite é uma patologia comum com a progressão da idade e que vem aumentando sua prevalência a medida que se elevam a expectativa de vida e os índices de obesidade e sobrepeso. A consequência desses sintomas se reflete de maneira direta sobre a capacidade de realização de atividades diárias, a qualidade do sono e a capacidade laboral do indivíduo. O impacto psicológico, social e econômico da dor crônica de joelho representam um desafio de saúde pública, demandando tratamento eficiente e custo-efetivo. As terapias farmacológicas com frequência apresentam benefício limitado associado a diversos efeitos colaterais. Os procedimentos invasivos não cirúrgicos, como a injeção intraarticular de ácido hialurônico, representam uma alternativa em casos refratários ao tratamento clínico, sendo utilizados como terapia complementar, entretanto apresentam benefício limitado e insuficiente para o controle da dor em casos severos. Os procedimentos cirúrgicos, como a artroplastia total do joelho, habitualmente apresentam resultados satisfatórios na doença avançada, contudo são limitadas pelo seu alto custo, risco cirúrgico inerente e pequena capacidade resolutiva diante da alta prevalência. O bloqueio dos nervos geniculados é uma técnica recentemente descrita, de fácil realização e com mínima invasão necessitando ser estudada para que possa ser aplicada no manejo clínico. Neste estudo foram selecionados pacientes com osteoartrite moderada e severa, que apresentavam dor refratária ao tratamento clínico otimizado. Foram selecionados 16 pacientes e um total de 22 joelhos foram avaliados. Inicialmente todos os pacientes foram submetidos a um pré-teste que avaliava: 1) a intensidade da dor; 2) a qualidade do sono; 3) a capacidade de realização de atividades diárias. Aleatoriamente 2 grupos foram formados, o primeiro submetido ao bloqueio intra-articular e o segundo ao bloqueio dos nervos geniculados. A solução formada por: lidocaína 1% sem vasoconstrictor - 9 mL - 90 mg adicionada de Dexametasona - 1mL - 10 mg era padrão e utilizada nos dois grupos de intervenção. Após um seguimento semanal por 12 semanas consecutivas, os paciente foram reconvocados e submetidos ao outro procedimento proposto, dessa forma todos os pacientes atuaram como o seu próprio controle (desenho de estudo \"crossover\"). Nos seguimentos semanais, assim como no pré-teste, eram avaliados a intensidade da dor, a qualidade do sono e a capacidade de realização de atividades diárias. Os resultados mostraram que o bloqueio intra-articular e o bloqueio dos nervos geniculados apresentam redução importante da dor (p < 0,01), melhora na capacidade de realização de atividades diárias (p < 0,01) e melhora na qualidade do sono (p < 0,01), no entanto não houve diferença significativa no resultado entre os grupos estudados (p > 0,05). Conclui-se que o bloqueio dos nervos geniculados surge como uma alternativa segura, minimamente invasiva e de alta eficácia, apresentando resultados semelhantes ao bloqueio intra-articular. / Chronic pain of the knee secondary to osteoarthritis is a common pathology, progressive with age and which increases its prevalence as life expectancy is raised together with obesity and overweight. A consequence of these symptoms is reflected directly on the capacity of undertaking daily activities, the quality of sleep and the work capacity of each individual. The psychological, social and economic impact of chronic knee pain represents a challenge to public health, demanding efficient treatment at a worthwhile cost. Pharmaceutical therapies frequently present a limited benefit associated with various side effects. Non-surgical invasive procedures such as an injection intra-articular of hyaluronic acid, represents an alternative in refractory cases to clinical treatment, being used as a complementary therapy, however, presenting limited and insufficient benefit for the control of pain in severe cases. Surgical procedures such as complete arthroplasty of the knee, usually presents satisfactory results in patients with an advanced osteoarthritis, but are limited by their high cost, inherent surgical risk and small resolving capability facing a high prevalence. Blocking the genicular nerves is a recently described technique, easily applied by clinical management. Patients were selected in this study with moderate and severe osteoarthritis, with refractory pain in optimized clinical treatment. 16 patients were selected and a total of 22 knees were evaluated. Initially all the patients were submitted to a pre-test which evaluated: 1) the intensity of pain; 2) the quality of sleep; 3) the capacity to undertake daily activities. Two groups were formed randomly, the first submitted to intra-articular blocking and the second to blocking the genicular nerves. A solution of lidocaine 1% without a vasoconstrictor - 9 mL - 90 mg and Dexametasona - 1 mL - 10 mg was standard and used for intervention in both groups. After a weekly appraisal for 12 consecutive weeks, the patients were recalled and submitted to another proposed procedure and in this way all the patients acted as their own control (a \"crossover\" study design). In the following weeks, as also in the pretest, the intensity of pain, the quality of sleep and the capacity of undertaking daily activities were evaluated. The results showed that the intra-articular block and the blocking of the genicular nerves presented an important reduction of pain (p<0,01) but there was no significant difference in the result between the groups studied (p>0,05). It is therefore concluded that the blocking of the genicular nerves appears as a safe alternative, minimally invasive and highly efficient, presenting results similar to the intra-articular blocking.

Etablir le diagnostic d'une réaction d'hypersensibilité aiguë (RHA) peropératoire est difficile du fait de l'incidence supérieure des diagnostiques différentiels. Les facteurs de risques en sont mal établis. Il n'existe pas de signe clinique fiable aidant à un diagnostic rapide. Alors que 25% des explorations immunologiques classiques ne mettent pas en évidence un mécanisme IgE-médié, des études animales et humaines suggèrent un rôle des IgG dans ces RHA non caractérisées. Ce travail s'est basé sur deux cohortes de patients : la première pour étudier des phénotypes en lien avec l'apparition d'un bronchospasme, la seconde pour analyser des marqueurs diagnostiques au bloc opératoire et explorer un mécanisme alternatif impliquant les IgG. La survenue d'un bronchospasme au cours d'une RHA peropératoire n'est pas associée à un antécédent d'asthme mais au curare comme agent étiologique. La mise en évidence de la valeur diagnostique d'une hypocapnie inférieure à 20 mmHg dans le caractère sévère de la RHA devrait aider les cliniciens à l'établissement rapide du diagnostic. La présence d'IgG spécifiques anti-curares était associée à la survenue d'une RHA sévère suggérant une participation des IgG à la gravité de la RHA en association avec les IgE. En fonction du curare administré, le mécanisme de la RHA semble différent : implication d'anticorps (IgE et/ou IgG) dans 90% pour succinylcholine et rocuronium mais uniquement 50% pour atracurium suggérant une importante contribution de l'histamino-libération dans ces réactions. L'ensemble de ces travaux devraient permettre d'améliorer les performances diagnostiques en temps réel et à distance lors de la survenue d'une RHA peropératoire. / Diagnosis of intra-anesthetic acute hypersensitivity reactions (AHR) is challenging because of elevated incidences of differential diagnoses. Risk factors remain mostly unknown and there is no reliable clinical sign to help physicians in establishing a rapid diagnosis. In 25% of cases, immunologic exploration cannot identify the culprit agent through the exploration of the IgE-mediated pathway. Several animal and human studies suggest a role of IgG in the physiopathology of anaphylaxis, which could explain these uncharacterized AHR. This PhD has focused on two cohorts of patients: the first cohort allowed the exploration of phenotypic links in relation to bronchospasm occurrence; the second cohort analyzed clinical markers of severe AHR and the alternative pathway involving IgG against neuromuscular blocking agents (NMBA). Analysis of risk factors identified a NMBA as the culprit agent of the intra-anesthetic AHR to be the only factor statistically associated with bronchospasm. We propose that a hypocapnia below 20 mmHg may be a novel and useful tool for physicians for the rapid diagnosis of severe intra-anesthetic AHR. Among the second cohort of patients, NMBA-specific IgG were identified and associated with clinical severity, suggesting that they may participate in the severity of NMBA-AHR in association with IgE. The chemical structure of a given NMBA may dictate the mechanism of anaphylaxis to this particular NMBA: an IgE/IgG-pathway for succinylcholine and rocuronium, whereas atracurium may be rather linked to spontaneous histamine release mechanisms. Altogether, our results might improve diagnosis efficacy at the time of the AHR and during immunologic explorations.

Mathematical models displaying travelling waves appear in a variety of domains. These waves are often faced with different kinds of perturbations. In some cases, these perturbations result in propagation failure, also known as wave-blocking. Wave-blocking has been studied in the case of several specific models, often with the help of numerical tools. In this thesis, we will display a technique that uses symmetry and a center manifold reduction to find a criterion which defines regions in parameter space where a wave will be blocked. We focus on waves with low velocity and small symmetry-breaking perturbations, which is where the blocking initiates; the organising center. The range of the tools used makes the technique easily generalizable to higher dimensions. In order to demonstrate this technique, we apply it to the bistable equation. This allows us to do calculations explicitly. As a result, we show that wave-blocking occurs inside a wedge originating from the organising center and derive an expression for this wedge to leading order. We verify our results with some numerical simulations.

Electronic data has become the standard method of storing information in our modern age. Evolving from paper-based data to electronic data creates opportunities to share information between organizations in record speeds, especially when handling large data sets. However, sharing sensitive information creates requirements for electronic data exchange: privacy requires that the original data will not be revealed to unauthorized parties. In the healthcare sector in particular, there are two important use cases that require exchanging information in a privacy-preserving way. 1. Contract research organizations (CROs) need to verify the eligibility of a participant in a phase 1 clinical trial. One criterion is checking that an individual is not concurrently enrolled in a trial at another CRO. However, privacy laws and the maintenance of a private list of participants for competitive purposes prevent CROs from checking against that criterion. 2. A patient’s medical record is usually distributed amongst several healthcare organizations. To improve healthcare services, it is important to have a patient’s complete medical history: either to help diagnose an illness or to gather statistics for better disease control. However, patient medical files need to be confidential. Two healthcare organizations cannot link their large patient databases by disclosing identity revealing details (e.g., names or health card numbers). This thesis presents the development and evaluation of protocols capable of querying and linking datasets in a privacy-preserving manner: TRACK for checking concurrent enrolment in phase 1 clinical trials, and SHARE for linking two large datasets in terms of millions of (patient medical) records. These protocols are better than existing approaches in terms of the privacy protection level they offer (e.g., against dictionary and frequency attacks), of the reliance on trusted third parties, and of performance when performing blocking. These protocols were extensively validated in simulated scenarios similar to their real-world counterparts. The thesis presents novel identity representation schemes that offer strong privacy measures while being efficient for very large databases. These schemes may be used by other researchers to represent identity in different use cases. CROs may implement the protocols (and especially TRACK) in systems to check if an individual exists in another CRO’s dataset without revealing the identity of that individual. Two healthcare organizations may use a system based on this research (and especially the SHARE protocol) to discover their common patients while protecting the identities of the other patients.

The growing flow of people and goods around the globe has allowed new, non-native species to establish and spread in already fragile ecosystems. The introduction of invasive species can have a detrimental impact on the already established species. Thus, it is important that we understand the mechanisms that facilitate or prevent invasion. Since reaction-diffusion invasion models produce travelling waves we can study invasion by looking at the mechanisms that allow for wave propagation failure, or wave-blocking. In this thesis we consider a perturbed reaction-diffusion model in which the perturbation resides in either the reaction or diffusion term. In doing so we exploit the underlying symmetry of our problem to define a region in the appropriate parameter space that leads to wave blocking. As a demonstrative example we apply our theory to the bistable equation and consider the effects of various perturbations.

Orientador: Angélica de Fátima de Assunção Braga / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T07:44:34Z (GMT). No. of bitstreams: 1 Carvalho_VanessaHenriques_D.pdf: 2552683 bytes, checksum: d3aa5b35758ce570c520c2ba8cc486fc (MD5) Previous issue date: 2013 / Resumo: Os anestésicos locais (AL) podem interagir com os bloqueadores neuromusculares (BNM) e modificar as suas propriedades farmacocinéticas e farmacodinâmicas, no entanto o mecanismo dessa interação é controverso. Este estudo experimental, realizado em preparações nervo frênico - hemidiafragma de rato e músculo biventer cervicis de pintainho, teve por objetivo avaliar o efeito de diferentes AL na transmissão neuromuscular e sua influência no bloqueio produzido pelo pancurônio. Foram avaliados os seguintes parâmetros: efeito na transmissão neuromuscular dos AL (ropivacaína, levobupivacaína, mistura em excesso enantiomérico de bupivacaína) e do pancurônio empregados isoladamente; o bloqueio produzido pelo pancurônio em preparações previamente expostas aos AL; a eficácia da neostigmina e da 4-aminopiridina na reversão do bloqueio neuromuscular produzido pelo pancurônio isoladamente e em preparações previamente expostas aos AL; a ação dos AL na resposta contraturante à acetilcolina; seus efeitos nos potenciais de membrana e nos potenciais de placa terminal em miniatura. Os resultados foram expressos em médias e desvios padrão e analisados através dos testes t de Student, Wilcoxon, Anova, Kruskall-Wallis e Mann-Whitney. Adotou-se um nível de significância de 5% (p<0,05). Na preparação nervo frênico - hemidiafragma de rato, os AL nas concentrações empregadas, não alteraram a amplitude das respostas musculares mas, potencializaram o efeito do pancurônio. O bloqueio neuromuscular foi parcial e totalmente revertido com a neostigmina e com a 4-aminopiridina, respectivamente. Não causaram alteração significativa nos potenciais de membrana e produziram diminuição progressiva na amplitude e na frequência dos potenciais de placa terminal em miniatura. Na preparação biventer cervicis de pintainho os AL, com exceção da ropivacaína, promoveram diminuição na resposta contraturante da acetilcolina. Os resultados obtidos neste estudo demonstram um sinergismo entre os fármacos estudados, resultante das ações pré e pós-juncionais dos anestésicos locais / Abstract: Local anaesthetics (LA) may interact with neuromuscular blockers and modify their pharmacokinetic and pharmacodynamic properties. However, the mechanism of this interaction is controversial. This experimental study, conducted in rat phrenic nerve diaphragm preparations and chick biventer cervicis, aimed to evaluate the effect of different LA in neuromuscular transmission and its influence on pancuronium induced blockade. The following parameters were evaluated: the effect on neuromuscular transmission of LA (ropivacaine , levobupivacaine mixture enantiomeric excess bupivacaine) and pancuronium used in isolation; the blockade produced by pancuronium in preparations previously exposed to LA; the effectiveness of neostigmine and 4 - aminopyridine in the reversal of neuromuscular blockade produced by pancuronium alone and in preparations previously exposed to AL; the action of LA in the contractile response to acetylcholine; its effects on membrane potentials and miniature endplate potentials. The results were expressed as means and standard deviations and analyzed using Student's t, Wilcoxon, ANOVA, Kruskal-Wallis and Mann-Whitney tests. A significance level of 5 % (p < 0,05) was adopted . In the rat phrenic nerve diaphragm preparation the LA, in the concentrations used, did not alter the amplitude of muscle response but potentiated the effect of pancuronium. Neuromuscular blockade was partially and fully reversed with neostigmine and 4- aminopyridine, respectively. There was no significant change in membrane potential and a progressive decrease in the amplitude and frequency of miniature endplate potentials was produced. In the chick biventer cervicis preparation the LA, with the exception of ropivacaine, led to a decrease in the contractile response to acetylcholine. The results of this study demonstrate a synergistic effect between the drugs studied, resulting from prejunctional and postjunctional actions of LAs / Doutorado / Farmacologia / Doutora em Farmacologia

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22730号 / 医博第4648号 / 新制||医||1046(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 遊佐 宏介, 教授 溝脇 尚志, 教授 篠原 隆司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The Course Timetabling Problem is a widely studied optimization problem where a number of sections are scheduled in concert with the assignment of students to sections in order to maximize the desirability of the resulting schedule for all stakeholders. This problem is commonly solved as a linear program with variables for each student or group of students with identical schedules. In this paper we explore an alternative formulation that aggregates binary student variables into integer variables denoting the number of students enrolled in a course. Our solution method assumes decomposition of the general schedule into time blocks, and applies a unique set theory based, integer linear programming formulation that seeks to maximize the total number of students enrolled in their desired sections across the time blocks. Once the problem has been solved, the simpler problem of disaggregating the solution is resolved. This approach can be used to find exact solutions, given sufficient computing power, or simplified to quickly find solutions within calculable bounds of optimality. Case studies with a local elementary school and a local high school show that the new formulation is significantly faster and can be made to be reasonably accurate.

{This Diploma thesis deals with Internet censorship. Various technical solutions for Internet censorship are presented together with censorship analysis options. Several possibilities for blocked content access and censorship circumvention in general are discussed. The topic is analyzed from the global point of view and is related to the People's Republic of China.

Imposition of my diploma thesis is replace current fluid motor that the derive benefit from to indexing turret head behind electrically driven motor in the sliding headstock machine with indication KMX 326 C. Suggested system must be the most toughest and have to correspond with all the dated up parameters for cutting. Integral part of structural design is also becomingly select accurate blocking a turret head. Fluid motor substitutes behind electrical drive from next reasons: - high transmission loss on energy - sensitivity to cleanness liquid - characteristics mechanism depend upon features liquid ( thermal expansivity, fadeaway)