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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
121

Modelagem hidrológica de uma microbacia florestada da Serra do Mar, SP, com o modelo TOPMODEL : simulação do comportamento hidrológico em função do corte raso / Modelling the hydrology at subtropical forest small catchment in the Serra do Mar, São Paulo, Brazil, using TOPMODEL : simulation of hydrology behavior subject to clear-cutting

Maurício Ranzini 26 June 2002 (has links)
Utilizou-se o modelo hidrológico TOPMODEL, baseado em aspectos físicos e topográficos, em uma das três microbacias do Laboratório de Hidrologia Florestal Eng. Agr. Walter Emmerich, do Instituto Florestal/SP. O laboratório localiza-se na Serra do Mar, junto às cabeceiras do rio Paraibuna, um dos formadores do rio Paraíba do Sul. O modelo usa um índice topográfico que indica as áreas de contribuição para o deflúvio da microbacia e permite simular a vazão e analisar o comportamento hidrológico da microbacia. A primeira parte do trabalho buscou determinar os valores iniciais dos parâmetros de calibração, testar a validade das premissas do modelo, e, principalmente, compreender melhor o funcionamento hidrológico da bacia D. Os resultados indicam uma eficiência maior para as simulações de eventos isolados do que para as de períodos longos. A simulação do comportamento hidrológico em função do corte raso mostrou uma diminuição do tempo de pico e um aumento significativo do volume de vazão simulado: de 17 a 44%, em comparação a bacia D coberta com floresta. Mostram, também, que de 7 a 93% do deflúvio é gerado a partir das áreas variáveis de afluência (A.V.A.). Recomenda-se que o corte raso seja evitado a qualquer custo. Caso seja necessário, as matas ciliares devem ser mantidas; onde elas não existem mais, devem ser recuperadas imediatamente. As áreas com agricultura ou pastagem devem utilizar as melhores técnicas de conservação do solo, de forma que as condições naturais de infiltração não sejam drasticamente alteradas. / A physically based semi-distributed model, TOPMODEL, has been applied to one catchment in Cunha, São Paulo, Brazil. The model uses a topographic index which highlights significant hydrological areas within the catchment. The model simulate streamflow and analyse the behaviour of the catchment. The first part of this paper concerns to the first values of calibration parameters, experiments the validity of the premisses of the model, and, mainly, tries to understand how does the hydrology of D catchment works. The results are more efficient on simulation of isolate events than on events of long period. The simulation of hydrology behaviour subject to clear-cutting has showed a diminution of the time of rise and a significant increase of streamflow simulated: from 17 to 44%, in comparaison to D forest catchment. They also show that from 7 to 93% of the streamflow is generated from saturated contributing areas (sources areas). It\'s advisable to avoid clear-cutting. If necessary, the riparian zone has to be preserved; and where they have been destroyed, they have to be recovered urgently. Agricultural lands or grasslands have to use the best management practices, in order to keep the natural conditions of infiltration.
122

Para entender a participação social em âmbito local: um estudo da ferramenta C.L.E.A.R / To understand citizen participation at the local level: a study of the C.L.E.A.R. tool

Yara Maria Garbelotto 21 June 2017 (has links)
Nas últimas décadas, os governos municipais vêm adotando abordagens participativas em diversas políticas públicas setoriais, estimulados pelas esferas governamentais superiores que passaram a vincular a transferência de recursos financeiros ou a habilitação para exercer determinada atividade à criação e pleno funcionamento de instituições participativas. Por indução governamental, financiamento de órgãos internacionais ou pela autonomia jurídica que lhes foi concedida pela Constituição de 1988, os municípios brasileiros criaram ou reproduziram diversas instâncias de participação social: conselhos municipais, conferências temáticas, orçamentos participativos, audiências públicas, etc. Porém, o êxito dessas abordagens - no sentido de incluir os atores que estão à margem dos processos decisórios - não depende unicamente de sua institucionalização. Diversos fatores interferem na decisão de indivíduos e de organizações sociais em participar destas instâncias governamentais. Se há interesse em lograr êxito com essa abordagem, é importante compreender como estes fatores atuam no território, e o que o governo municipal pode fazer para aprimorar suas práticas. Um diagnóstico correto é o primeiro passo para um planejamento adequado, e o uso de uma ferramenta específica pode identificar forças e fraquezas relacionadas ao processo participativo, auxiliando na seleção de melhores estratégias. Na ausência de instrumentos criados no próprio país, a adaptação de instrumentos estrangeiros pode ser uma alternativa. Com esse cenário, o objetivo dessa pesquisa é validar uma ferramenta analítica, elaborada pela União Europeia, voltada ao diagnóstico das iniciativas governamentais de participação. Para tanto, utilizou-se de: i) levantamento bibliográfico e documental para análise do embasamento conceitual; ii) tradução, comparação com outros materiais e oficina com especialistas para a adaptação transcultural e validação do conteúdo; iii) estudo de campo para aplicação teste da ferramenta. O estudo de campo ocorreu em Barueri - SP e a análise centrou-se nas iniciativas participativas da Secretaria de Recursos Naturais e Meio Ambiente. Constatou-se que o processo de diagnóstico exige conhecimentos técnicos qualificados e um tempo médio de seis meses para conclusão. Por outro lado, promove uma reflexão entre seus participantes, fomentando a revisão das práticas em curso. Os resultados gerados pela ferramenta foram condizentes com a realidade percebida. A ferramenta mostrou-se válida para o contexto brasileiro, mas recomendam-se mais experiências para ajustes finos à nossa realidade sociocultural / Since the 1990s, several initiatives to improve citizen participation have been created by local authorities in Brazil. Public policies councils, thematic conferences, participatory budgets and public hearings are the most widespread. However, getting people to participate is not a simple task. Several factors interfere in the decision of individuals and social groups to participate. Local authorities can strengthen citizen participation, but they need better understand the obstacles as well as the possible boosters that exist in their localities. A good assessment is is the first step towards adequate planning, and the use of a specific tool can help to analyse diferente dimensions of engagement, assisting in the selection of better strategies. Adaptation of foreigns instruments can be an alternative when theres no nacional tool developed. The Council of Europe designed an instrument for a self-assessment process, to help local authorities and other organisations or groups at the local level to better understand public participation in their localities. This dissertation aims to use this tool and understand if its adaptable to brazilian circumstances. For such end, was used: i) bibliographical and documental survey; ii) cross-cultural adaptation, made by translation and workshop with experts; iii) road test in Barueri SP. The road test focused on participation initiatives of the local environmental agency: Secretaria de Recursos Naturais e Meio Ambiente. The study demonstrates that self-assessment process requires qualified technical knowledge and an average time of six months. On the other hand, its use provided an occasion to reflect together, policymakers and stakeholders, driving to consider strategies for addressing some gaps detected in citizen participation. The results of the road test were consistent with the perceived reality. The tool proved to be valid for the Brazilian context, but are recommended more experiences for fine adjustments to our sociocultural reality
123

De la ligne claire à la ligne « pas claire » : émancipations esthétiques de la bande dessinée en France et aux États-Unis à l’orée des années 70 / To the Clear Line from the « not clear line » : aesthetic emancipations of comics in France and the United States at the beginning of the 70s

Andrieu de Levis, Jean-Charles 28 November 2019 (has links)
Déployant une esthétique tournée vers la claire lisibilité des images garantissant leur performativité narrative, la ligne claire s’est naturellement constituée comme un style graphique idéel pour la bande dessinée. Mais en bâtissant un univers orienté vers la neutralisation de l’empreinte plastique de l’auteur, elle restreint singulièrement les ressources expressives de la représentation. À l’orée des années 70, de nombreux auteurs américains et français participent à redéfinir de façon radicale les canons du neuvième art et explorent le potentiel figural de l’image et du récit : l’icône et la linéarité narrative se trouvent alors perturbées par de multiples expérimentations. Elles sont placées en déséquilibre et accède à travers cette instabilité à une richesse insoupçonnée. La bande dessinée découvre l’équivoque et s’accorde à l’incertitude d’une pratique expérimentale et non plus normée. Tourmentée, l’image atteint à une puissance poétique qui étend le champ d’expression du neuvième art. Nous souhaitons observer les conditions d’émergence de ces auteurs et de production de ces œuvres qui entrent en dissidence avec l’esthétique « classique », afin d’analyser les procédés stylistiques employés pour détourner la bande dessinée des conventions de la ligne claire. Nous verrons ainsi que les diverses stratégies que nous avons relevées conduisent, selon les degrés d’intensité développés par les auteurs, à une conversion des images et des récits qui les amènent progressivement à s’éloigner de la limpidité figurative et narrative pour aller vers une confusion figurale de plus en plus affirmée. / The Clear Line naturally constituted itself as an ideal graphic style for the comic strip by deploying an aesthetic turned towards the clear legibility of the images, guarantying their narrative performativity. By building a graphic universe oriented towards the neutralization of the author's plastic imprint, it strangely restricts the expressive resources of the representation. At the dawn of the 1970s, many American and French authors tried to radically redefine the canons of the ninth art and explore the figural potential of the image and narrative: the icon and the narrative linearity are then disturbed by multiple experiments. They are placed in imbalance and access through this instability to an unsuspected wealth. Comics discover this ambiguity and the uncertainty of an experimental practice no longer normed. Tormented, the image reaches a poetic power that extends the field of expression of the ninth art.We wish to observe the conditions of emergence of these dissenting authors and works parting with the "classical" aesthetic, and analyze the stylistic processes used to divert the comics from the conventions of the Clear Line. The various strategies we have identified, to the levels of intensity developed by the authors, lead to a conversion of images and narratives, gradually moving away from figurative and narrative limpidity towards a growingly assertive figural confusion.
124

Health Literacy as a Measure to Reduce Cost, Improve Health and Access

Dee, Vivian 01 January 2018 (has links)
The United States dedicates greater than 17% of its gross national product to healthcare. This percentage is expected to go up to 20% by 2018. Despite the high cost of care, the health care system remains inefficient and ineffective. Barriers include reduced access to care related to low health literacy. Complicating low health literacy is the high readability score of patient education materials. The high readability score is in part due to tools that are not standardized and measure different aspects of education materials creating varying readability scores. The purpose of this quality improvement project was to adopt a tool, the Clear Communication Index, which is evidence-based and standardized using the federal Plain Language Guidelines, to assess the reading score of educational materials in a 62-bed acute long-term care facility. The plan, do, study, and act model was used as a translational framework to guide this project, and the theory of goal attainment served as the theoretical support for the project. The Clear Communication Index worksheet was used to assess the readability of documents given to patients at discharge. Any score below 90% was considered difficult to understand and required revision. One month after implementation, patient satisfaction scores on 2 metrics showed improvement. The score for 'When I left the hospital, I clearly understood the purpose for taking each of my medications?' increased from 58.2% to 90.7%. The 2nd patient satisfaction survey metric, 'During this hospital stay, did you get information in writing about what symptoms or health problems to look out for after you left the hospital?,' increased from 73.1% to 83.3%. The results may promote social change by providing equal care access to all through readable educational materials.
125

A quantitative study of the water quality and plankton of Upper Blue Lake, Lower Blue Lake, and the Oaks Arm of Clear Lake in Lake County, California

Hayes, Stephen Patrick 01 January 1974 (has links)
This study was undertaken to examine any possible associations between the measurements of water quality and lake conditions, and the quantity and composition of plankton present in Upper Blue Lake, Lower Blue Lake, and the Oaks Arm of Clear Lake during the sampling period. A secondary objective of this study was to provide a record of these measurements. These measurements, when taken collectively, are important indicators of the trophic state or nutrient condition of the waters of the three lakes from February through October 1972.
126

The role of vowel hyperarticulation in clear speech to foreigners and infants

Kangatharan, Jayanthiny January 2015 (has links)
Research on clear speech has shown that the type of clear speech produced can vary depending on the speaker, the listener and the medium. Although prior research has suggested that clear speech is more intelligible than conversational speech for normal-hearing listeners in noisy environments, it is not known which acoustic features of clear speech are the most responsible for enhanced intelligibility and comprehension. This thesis focused on investigating the acoustic characteristics that are produced in clear speech to foreigners and infants. Its aim was to assess the utility of these features in enhancing speech intelligibility and comprehension. The results of Experiment 1 showed that native speakers produced exaggerated vowel space in natural interactions with foreign-accented listeners compared to native-accented listeners. Results of Experiment 2 indicated that native speakers exaggerated vowel space and pitch to infants compared to clear read speech. Experiments 3 and 4 focused on speech perception and used transcription and clarity rating tasks. Experiment 3 contained speech directed at foreigners and showed that speech to foreign-accented speakers was rated clearer than speech to native-accented speakers. Experiment 4 contained speech directed at infants and showed that native speakers rated infant-directed speech as clearer than clear read speech. In the fifth and final experiment, naturally elicited clear speech towards foreign-accented interlocutors was used in speech comprehension tasks for native and non-native listeners with varying proficiency of English. It was revealed that speech with expanded vowel space improved listeners’ comprehension of speech in quiet and noise conditions. Results are discussed in terms of the Lindblom’s (1990) theory of Hyper and Hypoarticulation, an influential framework of speech production and perception.
127

Individual game design elements in to-do lists – How the addition of feedback and clear goals is experienced

Lindholm, Oscar January 2017 (has links)
Gamification research has for a long time been interested in determining its definition and in which fields it works. By combining several game design elements and applying them in different non-game contexts it has been proven to successfully enhance certain activities, partly depending on the users and the contexts. Modern gamification research has started looking into how it works and in doing so, examining the individual effects of the game design elements. In this study, feedback and clear goals have been chosen as the game design elements to be examined when implemented individually in to-do lists. Feedback was represented as emoticons that changed from neutral to happy as tasks were checked off the list. Clear goals were implemented in the lists as an explicit goal. Together with a plain to-do list, nine participants used the three lists for nine days while keeping a visual diary. Afterward, they were subjected to interviews regarding their experiences. The framework of the self-determination theory was used in analyzing the results. The results showed that when using the list with feedback the participants were slightly better at clearing tasks but that the motivation, sometimes, seemed to come from trying to avoid negative feelings that the neutral emoticons seemed to invoke. The list with clear goals showed that in many cases the participants were actively trying to reach the given goal, seemingly, even when the participants mentioned not doing so. It was also, more often than not, experienced as controlling.
128

Carcinome à cellules claires du rein : phénotype métastatique et résistance aux thérapies ciblées / Clear cell renal cell carcinoma : metastatic phenotype and resistance to anti-angiogenic therapy

Kammerer-Jacquet, Solène-Florence 03 October 2016 (has links)
Le carcinome rénal à cellules claires (ccRCC) est la tumeur du rein la plus fréquente. Il se caractérise par une inactivation fréquente du gène suppresseur de tumeur VHL retrouvée dans 70% des tumeurs conduisant à une transcription des gènes cibles du facteur de transcription HIF dont le VEGF. Il s’agit d’une tumeur agressive métastatique chez 50% des patients. Le sunitinib, un inhibiteur des récepteurs tyrosine kinase anti-angiogénique, est actuellement le plus utilisé en 1ère ligne malgré 30% des patients qui progressent rapidement. L’avènement d’un nouvel anti-angiogénique ciblant MET (cabozantinib) et d’immunomodulateurs (anticorps anti-PD-1, nivolumab) rend cruciale la découverte de facteurs prédictifs de réponse au traitement. Dans une 1ére partie, nous avons étudié une série rétrospective de 98 ccRCC consécutifs pour lesquels nous souhaitions étudiés le statut VHL complet et le corréler à l’expression de PD-L1. De plus, alors que le pronostic est différent entre ccRCC métastatiques synchrones (d’emblée) et métachrones (à distance), leur phénotype n’avait jamais été comparé. Pour cela, nous avons effectué une analyse histologique des principaux facteurs pronostiques, immunohistochimique (CAIX, VEGF, PAR3, PD-1 et PD-L1) et moléculaire (statut complet VHL : délétion, mutation et méthylation du promoteur) corrélée à la survie spécifique. Nous avons démontré que le statut VHL non-inactivé (niVHL) était associé à la présence de métastases synchrones, une composante sarcomatoïde, un infiltrat lymphocytaire dense, une surexpression de VEGF, une expression de PD-L1 et à un mauvais pronostic. Nous avons aussi comparé les phénotypes des ccRCC métastatiques métachrones et synchrones. Ces derniers étaient associés à une  composante sarcomatoïde, une expression cytoplasmique de PAR-3, une surexpression de VEGFA, un statut niVHL et à un mauvais pronostic depuis le diagnostic des métastases. Dans une 2ème partie, nous avons étudié une série rétrospective de 90 ccRCC métastatiques consécutifs traités par sunitinib en première ligne afin d’identifier des facteurs prédictifs de réponse ou de résistance. Nous avons utilisé les mêmes techniques que précédemment avec en plus le statut MET (mutation en NGS et expression en IHC). Les patients ont été classés en résistants primaires, intermédiaires et longs répondeurs en fonction de la durée de leur réponse évaluée par des critères radiologiques (RECIST). Nous avons aussi caractérisé le profil génétique de 73 ccRCC de cette série par CGH array pour lesquels nous disposions de congélation. Les patients résistants primaires avaient plus souvent un mauvais pronostic (score de Heng), des métastases hépatiques, une infiltration de la graisse hilaire. Sur le plan cytogénétique, leurs tumeurs présentaient des altérations génétiques plus nombreuses tant au niveau des gains que des pertes. Parmi ces altérations récurrentes, étaient décrites les gains du 5p, 7p, 8q22.1-qter et la perte de la région 6q21-q25.3. Le modèle de Cox multivarié mettait en évidence 4 facteurs indépendants : le score de Heng, des métastases hépatiques, une infiltration de la graisse hilaire et le gain du 8q qui intégrés dans un nomogramme pronostique avaient un c-index de 0.74 et 0.77 pour la survie sans progression et la survie globale. En conclusion, notre étude a permis d’identifier un sous-type de ccRCC avec un statut niVHL de mauvais pronostic qu’il conviendrait d’étudier de manière plus approfondie sur le plan génomique. De plus, nous avons montré une différence de phénotype entre les ccRCC des patients métastatiques synchrones et métachrones alors que leur prise en charge est actuellement équivalente. Enfin nous avons mis en évidence un nomogramme pronostique dans les ccRCC métastatiques traités par sunitinib en 1ère line. Ce nomogramme s’il est confirmé par une étude prospective plus large pourrait avoir un impact clinique important dans la sélection des patients les plus à même de bénéficier des anti-angiogéniques. / Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. It is characterized by frequent inactivation of the tumor suppressor gene VHL found in 70% of tumors leading to the transcription of HIF transcription factor target genes such as VEGF. This is an aggressive tumor with 50% of metastatic patients. Sunitinib, an inhibitor of receptor tyrosine kinase antiangiogenic, is currently the most used in 1st line despite 30% of patients who progress quickly. The advent of a new anti-angiogenic targeting MET (cabozantinib) and immunomodulators (anti-PD-1 antibody, nivolumab) makes crucial discovery of predictors of response to treatment. In the first part, we studied a retrospective study of 98 consecutive ccRCC. We assessed complete VHL status and correlated it with the expression of PD-L1. Moreover, while the prognosis is different between ccRCC synchronous metastatic and metachronous, their phenotype have never been compared. In this purpose, we performed an analysis of the main pathological prognostic factors, immunohistochemical markers (CAIX, VEGF, PAR3, PD-1 and PD-L1) and molecular (VHL status: deletion, mutation and promoter methylation) correlated with specific survival. We demonstrated that non-inactivated VHL tumors (niVHL) were associated with the presence of synchronous metastases, sarcomatoid component, a dense lymphocytic infiltrate, an overexpression of VEGF, an expression of PD-L1 and a poor prognosis. We also compared the phenotypes of metachronous and synchronous metastatic ccRCC. The first ones were associated with sarcomatoid component, cytoplasmic expression of PAR-3 overexpression VEGFA and niVHL status and a poor prognosis even from the diagnosis of metastases. In the second part, we studied a retrospective study of 90 consecutive metastatic ccRCC treated with first line sunitinib to identify predictors of response or resistance. We used the same techniques as above plus the MET status (mutation in Next-Generation sequencing and expression by IHC). Patients were classified as primary-refractory, intermediate and long-term responders depending on the duration of their response as assessed by radiological criteria (RECIST). We also characterized the genetic profile of 73 ccRCC of this series by CGH array for which we had frozen tumor. Primary refractory patients often had poor prognosis (Heng criteria), liver metastases, infiltration of the hilar fat. Cytogenetically, their tumors had many more genetic alterations, both gains as losses. These recurrent alterations were gains of 5p, 7p, 8q22.1-qter and loss of 6q21-q25.3 region. The multivariate Cox model highlighted four independent factors: the score of Heng, liver metastases, infiltration of the hilar fat and gain of 8q which integrated into a prognostic nomogram had a c-index of 0.74 for survival progression-free survival and 0.77 for overall survival. In conclusion, our study identified a subtype of ccRCC with a poor prognosis with niVHL status that should be explored at the genomic level. Furthermore, we showed a phenotype difference between ccRCC synchronous and metachronous metastatic patients whereas their care is currently the same. Finally we have identified a prognostic nomogram in metastatic ccRCC treated with sunitinib in the first line. This nomogram if confirmed by a larger prospective study could have a significant clinical impact in the selection of patients most likely to benefit from anti-angiogenic therapy.
129

Avaliação da contaminação do sequenciamento do genoma mitocondrial por inserções nucleares de origem mitocondrial (NUMTs) no carcinoma renal de células claras / Evaluation of the mitochondrial genome sequencing contamination by nuclear inserts of mitochondrial origin (NUMTs) in clear cell renal carcinoma

Sares, Cláudia Tarcila Gomes 09 March 2018 (has links)
O carcinoma renal de células claras é o tumor renal maligno mais frequentemente diagnosticado nos adultos. Uma série de defeitos genéticos tem sido observada no tecido tumoral renal e tais achados podem estar envolvidos na gênese ou progressão desses tumores. Alterações metabólicas e genéticas da mitocôndria são fatores que contribuem para muitas doenças humanas, incluindo o câncer. Objetivo: Estabelecer método para extração mitocondrial sem contaminação pelo DNA nuclear; verificar se existe contaminação por inserções nucleares de origem mitocondrial (NUMTs) no sequenciamento do genoma mitocondrial no carcinoma renal de células claras. Métodos: Para o estudo foram selecionados quatro pacientes portadores de carcinoma renal de células claras. Após a cirurgia obtivemos de cada paciente um fragmento de tumor e um fragmento de parênquima renal sem comprometimento neoplásico, as amostras de cada paciente foram extraídas de forma que ao final pudéssemos obter quatro amostras de DNA, sendo duas com isolamento da mitocôndria e duas sem o isolamento da mitocôndria. As amostras obtidas foram submetidas às seguintes análises genéticas: Sequenciamento completo do mtDNA; Reação em cadeia da polimerase para avaliação da contaminação do mtDNA obtido com isolamento da organela por DNA nuclear; avaliação do número de cópias do mtDNA (depleção) e patogenicidade das mutações. Resultados: Com os resultados obtidos neste estudo podemos afirmar que é possível a realização da extração do DNA mitocondrial sem a contaminação do genoma nuclear; e que o DNA mitocondrial extraído de maneira clássica do DNA total não apresentou contaminação por inserções nucleares de origem mitocondrial (NUMTs). / Clear cell renal carcinoma is the most frequently diagnosed malignant renal tumor in adults. A number of genetic defects have been observed in renal tumor tissue and such findings may be involved in the genesis or progression of these tumors. Metabolic and genetic changes in mitochondria are contributing factors to many human diseases, including cancer. Objective: To establish a method for mitochondrial extraction without nuclear DNA contamination; check for contamination by nuclear inserts of mitochondrial origin (NUMTs) in the sequencing of the mitochondrial genome in clear cell renal carcinoma. Methods: Four patients with clear cell renal carcinoma were selected for the study. After surgery, we obtained from each patient a tumor fragment and a renal parenchyma fragment without neoplastic involvement, the samples from each patient were extracted so that in the end we could obtain four DNA samples, two with mitochondrial isolation and two without the mitochondria isolation of mitochondria. The obtained samples were submitted to the following genetic analyzes: Complete sequencing of mtDNA; Polymerase chain reaction to evaluate the contamination of mtDNA obtained with organelle isolation by nuclear DNA; evaluation of mtDNA copy number (depletion) and pathogenicity of mutations. Results: With the results obtained in this study we can affirm that it is possible to perform mitochondrial DNA extraction without contamination of the nuclear genome; and that the mitochondrial DNA extracted from the classical DNA of the total DNA was not contaminated by nuclear inserts of mitochondrial origin (NUMTs).
130

Expressão de Ciclina D1 em Carcinoma de Células Renais / Expression of Cyclin D1 in Renal Cell Carcinoma

Lima, Marcela Sampaio 12 June 2013 (has links)
Carcinoma de Células Renais (CCR) representa uma família de tumores distintos com evolução clínica imprevisível. Uma variedade de moléculas tem sido avaliada como marcadores prognósticos para CCR. Ciclina D1, uma proteína reguladora do ciclo celular, encontra-se superexpressa em vários tumores primários. Nosso objetivo é avaliar sua expressão como marcador prognóstico em CCR. Antes disso, traçamos um perfil clínico e histopatológico da amostra e verificamos sua relação com os fatores prognósticos considerados clássicos pela literatura. 109 espécimes de pacientes diagnosticados com CCR foram obtidos entre 2005 e 2010 no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto USP e submetidos à análise imunoistoquímica juntamente com 07 amostras de tecido renal normal. A maior parte das características epidemiológicas e clínicas de nossa amostra foi similar àquelas descritas na literatura mundial. Houve predomínio do gênero masculino, da raça branca, com idade próxima a 60 anos, frequência de pacientes assintomáticos em torno de 36% e grande prevalência do CCR de células claras (71,55%). A mortalidade específica da doença foi de 13,76%, sendo o CCR de células claras o tipo mais frequente entre os óbitos e casos metastáticos. Os casos que exibiram má evolução clínica, definida pela ocorrência de metástase e/ou óbito por CCR (22,01%), estiveram associados à presença de sintomas ao diagnóstico, maior tamanho tumoral, grupo de estágio alto (III ou IV), grau nuclear de Fuhrman alto (3 ou 4), presença de necrose e de diferenciação sarcomatóide no tumor, além de outros fatores histológicos desfavoráveis (p < 0,01). Isso indica que as variáveis utilizadas na avaliação de prognóstico em países desenvolvidos podem ser aplicadas aos nossos pacientes. Não houve expressão imunoistoquímica de Ciclina D1 nos casos de tecido renal normal. Observou-se heterogeneidade de marcação nuclear intratumoral no total de casos e menor expressão proteica entre os CCR papilífero e cromófobo. Pacientes com tumores com Ciclina D1baixa (até 30% de células positivas) apresentaram má evolução clínica (p = 0,03), maior tamanho tumoral (p = 0,01), presença de sintomas ao diagnóstico (p = 0,04), grau nuclear alto (p = 0,001), presença de necrose (p = 0,004) e de diferenciação sarcomatóide (p = 0,04) no tumor, além de menor sobrevida sem metástase e/ou óbito por CCR (p = 0,03). Após análise multivariada, a expressão de Ciclina D1 não apresentou valor prognóstico independente para má evolução clínica, embora tenha aumentado levemente a acurácia prognóstica do modelo adotado. Em todas as análises realizadas para o CCR de células claras isoladamente, observamos significância estatística semelhante à do total de casos (CCR). Nosso estudo demonstrou que: a proteína Ciclina D1 encontra-se superexpressa em CCR; os tipos de CCR parecem exibir diferentes padrões de marcação imunoistoquímica da Ciclina D1; alta marcação da proteína (acima de 30% de células positivas) esteve associada à boa evolução clínica e à maioria dos fatores prognósticos favoráveis bem estabelecidos na literatura. Novas investigações são necessárias para descobrir que mecanismos levam a seu acúmulo nas células neoplásicas e quais outros eventos podem estar contribuindo para a progressão da doença. / Renal Cell Carcinoma (RCC) is a family of distinct tumors with unpredictable clinical outcome. A variety of molecules have been evaluated as prognostic markers for RCC. Cyclin D1, a cell cycle regulatory protein, is overexpressed in several primary tumors. Our purpose is to evaluate its expression as a prognostic marker in RCC. Before that, we drew a clinical and histopathological profile of the sample and verified its relationship with prognostic factors regarded as classics in literature. 109 specimens from patients diagnosed with RCC were obtained between 2005 and 2010 at Hospital das Clínicas - Ribeirão Preto School of Medicine USP and submitted to immunohistochemical analysis, along with 07 normal kidney tissue samples. Most epidemiological and clinical characteristics of our sample were similar to those described in the literature. There was a predominance of male, Caucasian, aged about 60 years, the frequency of asymptomatic patients around 36%, and high prevalence of clear cell RCC (71.55%). The disease-specific mortality was 13.76%, being the clear cell RCC the most frequent type among deaths and metastatic cases. Cases that exhibited poor clinical outcome, defined by the occurrence of metastasis and/or death by RCC (22.01%), were related to the presence of symptoms at diagnosis, larger tumor size, high stage group (III or IV), high Fuhrman nuclear grade (3 or 4), presence of necrosis and sarcomatoid differentiation in the tumor and other unfavorable histological factors (p < 0.01). This indicates that the variables used in the assessment of prognosis in developed countries can be applied to our patients. There was no immunohistochemical expression of Cyclin D1 in cases of normal kidney tissue. There was intratumoral heterogeneity in nuclear staining in all cases and lower protein expression among papillary and chromophobe RCC. Patients with Cyclin D1low tumors (up to 30% positive cells) showed poor clinical outcome (p = 0.03), larger tumor size (p = 0.01), presence of symptoms at diagnosis (p = 0.04), high nuclear grade (p = 0.001), presence of necrosis (p = 0.004) and sarcomatoid differentiation (p = 0.04) in the tumor and lower survival without metastasis and/or death by RCC (p = 0.03). After multivariate analysis, the expression of Cyclin D1 showed no independent prognostic value for poor clinical outcome, although it has slightly increased the prognostic accuracy of the model adopted. In all analyzes performed for clear cell RCC alone, we observed statistical significance similar to that of the total cases (RCC). Our study showed that: Cyclin D1 protein is overexpressed in RCC; RCC types seem to exhibit different patterns of immunohistochemical staining for Cyclin D1; high protein expression (over 30% positive cells) was related to good clinical outcome and to most favorable prognostic factors well established in the literature. Further investigations are necessary to reveal which mechanisms lead to its accumulation in neoplastic cells and what other events might be contributing to the progression of the disease.

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