No description available.

Thesis (Ph. D.)--University of Adelaide, Dept. of Paediatrics, Women's and Children's Hospital, 1995. / Includes publications and manuscripts by the author. Includes bibliographical references (leaves 196-215).

No description available.

Proefschrift Universiteit van Amsterdam. / Auteursnaam op omslag: Amâde M'charek. Lit. opg.: p. 205-219. - Met een samenvatting in het Nederlands.

Recent research in human genetics has sparked popular interest in genetic explanations for all human phenomena. In turn, bioethicists have been busy responding to their own call for stringent guidelines for the use of genetic information. But bioethicists in general fail to attend to deeper considerations of the nature of scientific knowledge and its role in the transformation of human subjectivity. For this reason, bioethicists are accessories after the fact to that transformation, and hence in order to study that change we must displace bioethical analyses of the Human Genome Project --that is, displace virtually all of the literature on the HGP. In this thesis, I offer a different and more radical interpretation of the role of scientific knowledge in altering our conception of what it is to be a human being. Physicians, genetic counsellors, and other experts in our gene culture offer fundamentally questionable and yet practically unquestioned genetic explanations of who and what we really are. These genetic experts, by virtue of their prestigious position in our economy of knowledge, impute needs only they can satisfy, impart a vocabulary only they are invited (and certified) to understand, and draw us into new networks of administration and control at the subcellular level. Drawing on the work of Duden, Foucault, Illich, and Poerksen, I argue that our attraction to technoscientific understandings of our "essence" is dangerous and disabling, and I sketch a strategy of resistance. / Thesis / Master of Arts (MA)

Because of the Human Genome Project, enormous quantities of biological data, e.g., microarray data, are generated. Since the amount of biological data is very large, data mining techniques can be used to help biologists efficiently analyze the biological data. For microarray data, biclustering, which performs simulataneous clustering of rows (e.g., genes) and columns (e.g., conditions), has proved of great value for finding interesting patterns. There were several types of biclusters proposed. To mine biclusters with coherent values, most of the previous methods need to compute Maximum Dimension Sets (MDSs) for every two genes in the microarray data. Since the number of genes is far larger than the number of conditions, this step is inefficient. On the other hand, to mine biclusters with coherent evolutions, the Co-gclustering method was proposed which could simultaneously find biclusters with both coregulated and negative-coregulated patterns. However, its time complexity is exponential to the number of conditions, which is not efficient. Therefore, in this dissertation, to efficiently solve the problem of biclustering for microarray databases, first, we propose a Condition Enumeration Tree (CE-Tree) method which mines biclusters with coherent values. Second, we propose an Up-Down Bit Pattern (UDB) method which mines biclusters with coherent evolutions. In the first proposed method, CE-Tree, to mine biclusters, instead of generating MDSs for every two genes, we generate only MDSs for every two conditions. Then, we expand the CE-Tree in a special local breadth-first within global depth-first manner to efficiently find the clustering result. From the experimental results on real data, we have shown that the CE-Tree method could mine biclusters more efficiently than several previous methods. In the second proposed method, UDB, we utilize up-down bit patterns to record the condition pairs where one gene is upregulated or downregulated. Then, we utilize bit operations and apply a heuristic idea on these up-down bit patterns to efficiently find the clustering result. As compared to the Co-gclustering method, the UDB method reduces the time complexity from exponential time to polynomial time. From the experimental results on real data, we have shown that the UDB method is more efficient than the Co-gclustering method.

Includes publications and manuscripts by the author. / Bibliography: leaves 196-215. / 1 v. : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The goal of the human genome project addressed in this thesis, was the construction of a genetric linkage map with a resolution of between 2-5 cM by the year 1995. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, Women's and Children's Hospital, 1995

Thesis (M.S.)--Rochester Institute of Technology, 2008. / Typescript. Includes bibliographical references (leaves 82-83).

Submitted to the faculty of the Informatics Graduate Program in partial fulfillment of the requirements for the degree Master of Science in Bioinformatics in the School of Informatics Indiana University May 2006 / A plethora of genomic and proteomic information was uncovered by the U.S Human Genome Project (HGP) – mostly by means of bioinformatics tools and techniques. Despite the impact that bioinformatics and pharmacogenomics were projected to have in the drug discovery and development process, the challenges facing the pharmaceutical industry, such as the high cost and the slow pace of drug development, appear to persist. Socio-economic barriers exist that mitigate the full integration of bioinformatics and pharmacogenomics into the drug discovery and development process, hence limiting the desired and expected effects.

As pesquisas envolvendo seres humanos geram preocupações éticas, pois os voluntários aceitam riscos e inconveniências com o objetivo de contribuir para o avanço do conhecimento científico e beneficiar outrem. A disposição para participar de pesquisas clínicas se mostra quando o paciente adere ao Termo de Consentimento Livre e Esclarecido (TCLE), compreendendo-o, assinando-o e comprometendo-se a cumprir todas as normas estabelecidas nesse documento, embora consciente de que, a qualquer momento, poderá suspender sua adesão. O TCLE aborda informações que precisam estar descritas de forma clara e de fácil compreensão, destacando riscos, possíveis benefícios e procedimentos. Além disso, garantir a participação voluntária e sua desistência em qualquer momento da pesquisa. Atualmente discute-se a possibilidade de sujeitos de pesquisa não entenderem totalmente o texto do TCLE nem seus direitos como participantes, mesmo tendo assinado o TCLE e aderido à pesquisa. A presente casuística analisa os dados de 793 pacientes, que foram convidados a participar de diferentes protocolos de pesquisa clínica, como especifica a seguir: 380 pacientes, que foram convidados a participar do grupo controle do projeto Genoma Clínico do Câncer; 365 pacientes, que foram convidados a participar do projeto Genoma Clínico do Câncer do Aparelho do Digestivo por apresentarem tumor em uma das seguintes localizações: câncer colorretal, câncer esofágico, câncer de cárdia ou câncer gástrico.; 48 pacientes que foram convidados a participar do Estudo Multicêntrico, Internacional, Randomizado, de Grupos Paralelos, Controlado por Placebo, Duplo-Cego, com subsidiária cega, para determinar o efeito de 156 semanas de tratamento com MK-966(antiinflamatório Anti-COX 2) na recorrência de pólipo adenomatoso de intestino grosso, em pacientes com histórico de adenoma colorretal ressecado por colonoscopia. Coletaram-se dados dos fichários de pesquisa científica para avaliar a aderência do sujeito de pesquisa ao protocolo, correlacionando-a com fatores demográficos (raça, sexo e idade), sociais (local de nascimento, morada atual e instituição de tratamento), relação risco/beneficio envolvida e nível de escolaridade. O grau de dificuldade dos textos que compõem os TCLE foi avaliado, aplicando-se os Índices de Legibilidade Flesch Reading Ease e Flesch- Kincaid. Aplicou-se questionário aos entrevistadores para avaliar, a posteriori, a postura do sujeito de pesquisa à adesão ao TCLE no momento de sua assinatura ou discordância. A adesão dos sujeitos de pesquisa aos protocolos propostos não teve influência dos fatores demográficos e sociais, no entanto, verificou-se maior adesão entre os pacientes de instituição de tratamento público (99,7%) em comparação com instituição de tratamento privada (93,7%). A adesão foi maior entre os pacientes que participaram de protocolos com menor risco (99,73%) em comparação com os pacientes que participaram de protocolos com maior risco (81,3%). Apesar de a adesão não ter tido influência do nível de escolaridade, este foi menor ou igual a 8 anos de estudo para 462 pacientes (58,26%), entre os quais 444 (96,1%) pacientes eram de instituição de tratamento público. Os índices de legibilidade obtidos variaram de 9.9 12 para o teste de Flesch-Kincaid e 33,1 51,3 para o teste de Flesch Reading Ease. Os resultados encontrados na aplicação dos testes de legibilidade classificaram todos os textos avaliados em nível de difícil compreensão, exigindo maior nível de escolaridade para o seu entendimento Os entrevistadores estimaram, através do questionário aplicado a eles, que 90% dos pacientes do hospital público preferem ouvir a explicação do TCLE a ler o texto. Na instituição privada esta estimativa foi de 40%. Apenas onze sujeitos de pesquisa não aderiram ao TCLE. A adesão não recebeu influência de fatores demográficos e sociais. O risco inerente aos protocolos apresentados influenciou a adesão dos sujeitos de pesquisa. Os textos avaliados não se constituíram em linguagem escrita de fácil entendimento, necessitando mais de 9 anos de estudo para sua compreensão. Esta pesquisa sugere que, apesar da alta incidência de adesão, a avaliação de novos métodos de aplicação do TCLE é necessária para que o sujeito de pesquisa menos instruído tenha condições de compreender adequadamente todo o conteúdo do texto proposto no TCLE. / Researches engaging human beings pose ethical concerns since volunteers take on risks and inconveniences aiming to contribute to advanced scientific knowledge and to benefit others. The moment patients sign the term of voluntary and informed consent TCLE (Termo de Consentimento Livre e Esclarecido) they show they are willing to participate in clinical trials and that they understand the term and commit to complying with all rules in the document, aware that they can, at any moment, withdraw acceptance. The TCLE addresses all issues in the research process and are therefore important to the study participants. The information given at the TCLE must be clearly stated and easily understood, highlighting risks, possible benefits and procedures in addition to guaranteeing volunteer participation and consent withdrawal at any time during the trial. Lately, it has been speculated that the study participants do not totally understand the TCLEs text content and their participants rights before accepting the TCLE and joining the trial. This study analyzes the data from 793 patients, invited to take part in different protocols of clinical trials, as follows: 380 patients, invited to join the Clinic Cancer Genome Project Control Group; 365 patients, invited to join the Genome Clinic Cancer Genome of the Digestive System since they had one of the four tumors: colorectal cancer, cancer of the esophagus, cardia adenocarcinoma and gastric cancer; 48 patients were invited to join the International Multicenter double-blind, randomized, parallel-group, placebocontrolled study, with undisclosed sponsor, to determine the outcome of a 156-week treatment with MK-966(anti-inflammatory Anti-COX 2) in recurrent adenomatous polyp of the large bowel, in patients with a history of colorectal resection for adenoma at colonoscopy. Data were collected from previous scientific studies to assess study participants acceptance, correlating it to demographic factors (ethnic group, gender and age), social (birthplace, home place, health institution), cost/benefit and schooling. The level of difficulty in the TCLE texts was assessed with Flesch Reading Ease and Flesch-Kincaid readability measures. Interviewers answered a questionnaire a posteriori, to evaluate the study participants attitude toward the TCLE acceptance at the moment they signed it or did not accept it. The study participants acceptance of the suggested protocols was not influenced by demographic and social factors. However, patients from public health institutions (99,7%) outnumbered those from private health institutions (93,7%). Acceptance was higher among patients taking part in low-risk protocols (99,73%) than in high-risk protocols (81,3%). Although schooling did not influence acceptance, it was 8 years or less in 462 patients (58,26%), among who 444 (96,1%) were patients from public health institutions. The indices of legibility had varied of 9.9 - 12 for the test of Flesch-Kincaid and 33.1 - 51,3 for the test of Flesch Reading Ease. The results found in the application of the legibility tests had classified all the texts evaluated in level of difficult understanding, demanding higher school level for its agreement. Interviewers reported in questionnaires that 90% of the patients from public hospitals would rather listen to an explanation of the TCLE than read the text whereas in patients from private institution the percentage dropped to 40%. Only eleven study participants did not join the TCLE. Acceptance was not influenced by social and demographic factors, but the protocols risk levels influenced the study participants decisions. The evaluated texts proved to be difficult to understand, demanding over 9 years of schooling to be understood. This study suggests that, in spite of being highly accepted, the TCLE requires new application methods so that less educated people can properly understand its text contents.