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Marchetto, Raquel. "O uso do software GeoGebra no estudo de progressões aritméticas e geométricas, e sua relação com funções afins e exponenciais." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/172105.
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Esta pesquisa teve por objetivo verificar como é que o aluno consegue por si próprio manipular os recursos, tais como gráficos disponibilizados pelo software GeoGebra, para auxiliar nas práticas diárias de sala de aula, mais especificamente no que tange a construir a conexão entre as progressões aritméticas e as funções afins, bem como entre as progressões geométricas e as funções exponenciais. Este software possibilita fazer análises a partir de diferentes registros tais como: gráficos, tabelas e registros algébricos, seguindo a teoria dos registros semióticos de Duval. Como metodologia, desenvolvemos roteiros de atividades com duas turmas do 2º ano do Ensino Médio do Colégio Estadual Visconde de Bom Retiro. Os alunos foram convidados a construir, verificar e interpretar seus próprios resultados, refletindo e analisando estratégias para responder à questão: Quais relações os alunos conseguem evidenciar, através da comparação entre gráficos (obtidos com o GeoGebra) de funções afins e exponenciais, com progressões aritméticas e geométricas, respectivamente? Ao final da pesquisa, os registros coletados possibilitaram a validação qualitativa da proposta, mostrando que os alunos avançaram na compreensão dos conteúdos abordados.The aim of this research was to verify how the student can himself manipulate the resources, such as plots made available by the GeoGebra software, to aid in the daily classroom practices, specifically in the construction of the connection between arithmetic progressions and linear functions, as well as between geometric progressions and exponential functions. This software makes possible to analyze from different registers such as: plots, tables and algebraic records, following the theory of semiotic records of Duval. Our methodology consisted in developing activity scripts with students of two classes of the 2nd year of the High School of Visconde de Bom Retiro State College. More specifically, they were asked to build, verify and interpret their own results, speculating and analyzing strategies to answer the question: What relations are the students able to highlight through comparing plots (obtained with GeoGebra) of linear and exponential functions, with arithmetic progressions and geometric, respectively? At the end of the research, the collected records made possible the qualitative validation of the proposal, showing that the students improved their understanding of the focused contents.
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Cergoli, Daniel. "Ensino de logaritmos por meio de investigações matemáticas em sala de aula." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/45/45135/tde-29112017-171710/.
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Neste trabalho são apresentadas duas propostas de sequências didáticas para ensino de logaritmos. A primeira delas é destinada ao aperfeiçoamento de professores de Matemática e a outra, para alunos de Ensino Médio. Tais sequências foram desenvolvidas com base em pesquisas realizadas pelo Prof. João Pedro da Ponte sobre o processo de investigação matemática. A sequência didática para professores foi aplicada no Centro de Aperfeiçoamento do Ensino de Matemática do Instituto de Matemática e Estatística da Universidade de São Paulo (CAEM IME USP). Já a sequência para alunos foi aplicada em uma escola da rede estadual situada no município de São Paulo. Ambas foram analisadas sob os pontos de vista da eficiência e adequação, bem como da clareza das ideias apresentadas. As sequências didáticas têm como ponto de partida a observação das propriedades comuns a várias tabelas, cada uma contendo uma progressão geométrica ao lado de uma progressão aritmética. Tais propriedades caracterizam o que virá a ser definido como logaritmo. Essa introdução ao conceito de logaritmo é diferente da usual, que se baseia na solução de uma equação exponencial. O processo de investigação matemática visa a um aprendizado eficaz por parte do aluno, proporcionado por atividades que conduzam o aluno, de forma gradual, a fazer descobertas, formular conjecturas e buscar validações. Tais investigações são coordenadas e supervisionadas pelo professor, cujo papel é fundamental no processo de construção do conhecimento.This dissertation presents two didactic sequences for teaching and learning logarithms. One of them aims at Mathematics teachers and is designed for improving their knowledge. The other sequence is meant to be used on high school students. Both didactic sequences were developed based upon research carried out by Professor João Pedro da Ponte on Mathematical Investigations. The didactic sequence for teachers was applied at CAEM IME USP. The one for students was applied at a state school in the city of São Paulo. They were analysed from the points of view of efficiency and of adequacy, as well as of the clarity of the presented ideas. The didactic sequences start with the observation of properties common to multiple tables, each containing a geometric progression side by side with an arithmetic progression. The observed properties characterize what will be later defined as logarithm. Such introduction to the concept of logarithm is different from the usual, which is based on the solution of an exponential equation. The Mathematical Investigation process aims at an effective learning by the students, which is provided by activities that lead the student to gradually make discoveries, formulate conjectures, and search for validations. These investigations are coordinated and supervised by the teacher, whose role in the knowledge construction process is fundamental.
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Biani, Rosana Prado. "A progressão continuada rompeu com mecanismos de exclusão?" [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/252086.
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Orientador : Maria Marcia Sigrist MalavasiDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação
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Resumo: Este trabalho analisa a seletividade, o fracasso escolar e a exclusão após a implantação da Progressão Continuada na rede escolar pública estadual de São Paulo. Situa-se na perspectiva do materialismo histórico dialético, sua abordagem é qualitativa e sua metodologia é o estudo de caso. Além do levantamento bibliográfico e do estudo dos documentos oficiais sobre a Progressão Continuada a fim de caracterizá-la enquanto proposta do governo estadual foi feito o acompanhamento, por um ano letivo, em escola da rede estadual de Campinas, em duas classes de 4ª série com o objetivo de observar como se concretizou a proposta na prática escolar cotidiana. Os dados foram obtidos por meio dos documentos escolares dos alunos-sujeitos da pesquisa ¿ fichas de matrícula, listas ¿piloto¿ (com nomes dos alunos, classes às quais pertenciam, listas das classes de recuperação paralela e de férias), espelhos de classe (com notas bimestrais em cada disciplina), das observações do cotidiano escolar ¿ aulas, reuniões de pais, recreios, reforço, sala das professoras e das entrevistas gravadas com os alunos e as professoras. A análise dos dados permite afirmar que: 1) da forma como se concretizou, a Progressão Continuada não rompeu com mecanismos e processos de seleção, fracasso e exclusão levando a escola a manter o seu caráter seletivo e excludente; 2) a exclusão, antes exterior à escola ¿ pelo não ingresso, repetência e evasão ¿ acontece, agora, com a criança na escola ¿ pela pouca qualidade da aprendizagem; 3) os mecanismos de exclusão estão intimamente ligados aos processos avaliativos e intensificaram, dentro da escola, a produção das desigualdades o que, numa análise, contribui com a manutenção das desigualdades sociais. No entanto, pode-se afirmar que a implementação da proposta criou condições objetivas para que as discussões sobre as finalidades da educação, a função social da escola, a organização e a cultura escolar, as práticas pedagógicas e a qualidade na educação ganhassem novas dimensões de análise o que poderá contribuir historicamente para a superação da escola seletiva e a construção da escola para todas as crianças
Abstract: This project analyses the selectivity, the school failure and the exclusion after the implementation of the continued progression in public schools in the state of São Paulo. To be situated on the perspective of historical dialectical materialism, his approach is qualitative and his methodology is the case study. Beyond the bibliographical research and of the analyses of official document about the continued progression in order the label it as a state government proposal, made the follow up for one school year, of two school groups of fourth grades in a public school in the city of Campinas intending to observe how that proposal has been stabilished in the every day school practices. The data was obtained through school documents of the students-subject of this research ¿ such documents were enrollment forms, ¿pilot¿ lists (list containing the names of the students, classes they belong to, reinforcement parallel classes and of vacation), class reports (lists containing students grades on each of subject each bimester), observation of differents moments of the school routine ¿ classes, parent meetings, break, reinforcement, teacher¿s room and finally interviews recorded with students and teachers. The data analyses permit to assert that: 1) the way the Continued Progression proposal was stabilished it didn¿t stop with the mechanisms and process of selection, failure and exclusion in a way that the school kept their selective and excludent character; 2) the exclusion, which in the past was happening outside the school ¿ for the no access, repetition and desertion ¿ now happens with the child in the school ¿ for the little quality of the apprenticeship; 3) the exclusion mechanisms are deeply connected to the evaluation process and intensified, in the school, the production of inequalyties situations which, in analyses, contributes to keeping the social differences and inequalyties. So, we can affirm that the implementation of proposal has criated objectives conditions for wich the discussions about the purpose of education, the social role of the school, the school organization and culture, the pedagogical practices and the quality in education received new dimensions of analyse which may contribute historical for superation of the selective school and the construction of the school for all childrens
Mestrado
Ensino, Avaliação e Formação de Professores
Mestre em Educação
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Josefsson, Erik. "Progression of ancestral brutalism." Thesis, Högskolan i Borås, Institutionen Textilhögskolan, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-17068.
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Within the fine arts, clean and flat structures functionas a narrator for the clean, modern and hightech society. A society with a hygienic fear of death, illness and chaotic structures. The aim of the work is through the materialand surface inflict the hidden, the other side, the darkness and death, in strict and formal mens archetype garments.Program: Modedesignutbildningen
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Hjeltman, Måsse, and Thomas Ivarsson. "Historieläromedelsböcker, genus & progression." Thesis, Malmö högskola, Lärarutbildningen (LUT), 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-33118.
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I denna undersökning ämnar vi ta reda på hur progressionen ser ut gällande framställningen av kvinnor i historieläromedel från 1960-talet till år 2007. Vi har fokuserat kring dem som oftast marginaliserats i innehållet till fördel för de politiska aktiva så som drottningar och andra politiker. Här är det istället bondhustrur, den hemarbetande kvinnan, sömmerskor, hantverkare och andra yrkesarbetande kvinnor som undersöks för att ta reda på om de har en större plats i dag jämfört med på 1960-talet. Vi vill också ta reda på vilket sätt de framställs och har framställts. Är de aktiva och driver handlingen framåt eller ett bihang till den politiska historien? Vi har sett i vår analys att en positiv förändring skett, men att det finns mycket kvar att göra.In this study, we intend to find out what the progression looks like when it comes to representations of women in childrens history text books from the 1960´s to year 2007. We have focused on the most frequently marginalized working women for the benefit of the political active women as queens and other politicians.Here it is, instead, peasant wives, the woman home workers, seamstresses, burghers, craftsmen and other working women in these groups who´s being studied and whether they have a larger place today compared to the 1960's. We also want to find out how they are constructed and produced. Are they active and operates forward or a appendage of the political history? We have seen in our analyze that the progression is good, but there’s still much work to do.
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Strouthidis, N. G. "Measuring progression in glaucoma." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1446208/.
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Background: Primary open angle glaucoma is characterised by progressive optic neuropathy associated with characteristic visual field loss. The ability to measure disease progression is of vital importance in the management of patients with glaucoma. Conventionally, disease progression has been monitored using static automated perimetry. Recently, devices which image the optic nerve head quantifiably have been introduced. This thesis sets out to compare structural and functional progression in ocular hypertensive subjects followed longitudinally using novel progression algorithms. Plan of research: The investigations may be considered in three parts. Firstly, the factors affecting the test-retest variability of the Heidelberg Retina Tomograph (HRT) are identified and methods to improve repeatability are investigated. Secondly, novel HRT trend and event analyses, based on the findings of the test-retest studies, are compared with established field progression techniques in ocular hypertensive and control subjects. Thirdly, a previously described novel spatial filter is assessed in terms of its impact on the monitoring of visual field progression and in terms of its agreement with a previously described 'structural' map. Results: Rim area was identified as the most repeatable HRT parameter its variability can be improved by using the 320pm reference plane and by using only good quality images. Agreement as regards structural and functional progression was poor, regardless of the estimated specificities of the algorithms used or technique adopted. The novel spatial filter appeared to confer some advantage in terms of specificity, comparable to the effect of confirmatory testing. The functional relationship between test-points, characterised by the filter, correlated well with the expected structural pattern. Clinical significance: The poor agreement suggests that the monitoring of both structure and function is essential to provide the best chance of detecting progression at all stages of the disease. Spatial filtering techniques may provide some additional benefit in the monitoring of progression, particularly once structural data are incorporated.
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Ambring, Erik. "Gameplay Progression : Om skapandet av en jämn progression av spelmoment till dataspelet Testament." Thesis, University of Skövde, School of Humanities and Informatics, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-3162.
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Det här arbetets slutgiltiga uppgift har varit att skapa ett första utkast till enövergripande plan för en jämn fördelning av spelmoment för spelet Testament, ett spel som utvecklas för Svenska Kyrkan med syfte att användas inom konfirmandundervisning. Med spelmoment menas exempelvis story, miljö, utrustning och liknande.
Arbetet ger inledningsvis en kort översikt över hur leveldesignen inom dataspel har utvecklats och går därefter in på det mer specifika området gameplay progression, utvecklat av Mike Lopez, som ger en översyn över vad som krävs för att skapa ett spel med en jämn fördelning av spelmoment.Därefter används denna metod för att analysera det redan befintliga spelet The Legend of Zelda: Twilight Princess, för att testa Lopez metod, innan arbetet med att skapa en egen plan tar vid.
Resultatet av uppsatsen har nått målet med en övergripande plan för en jämnfördelning av spelmoment för spelet Testament, en plan som dock kommer att behöva ses över och omarbetas under det att utvecklingen av det faktiska spelet tar vid, men som ger en bra överblick över vilka delar som fungerar väl och vilka som kan behöva extra arbete i den stundande utvecklingen.
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Costa, Antonio Carlos de Lima. "O estudo de Induções e Recorrências - uma abordagem para o Ensino Médio." Universidade Federal da Paraíba, 2015. http://tede.biblioteca.ufpb.br:8080/handle/tede/8064.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
This work presents a research on the Induction Principles and the Recurrences, its history, mathematical concepts and applications used. Were developed some statements of Induction Principle and the Recurrences using some basic concepts from Number Theory, Combinatorics, Geometry and Set Theory that can be explored in high school. Was submitted a few activities that can be applied in the classroom of the high school in the development of mathematical concepts such as Arithmetic Progression, Geometric Progression, Geometry, Combinatorial Analysis and Numeric Sets among other topics.
Este trabalho apresenta uma pesquisa sobre os Princípios de indução e Recorrências, sua história, conceitos matemáticos utilizados e aplicações. Foram desenvolvidas algumas demonstrações do Princípio de indução e Recorrências, utilizando-se alguns conceitos básicos de Teoria dos Números, Análise Combinatória, Teoria dos Conjuntos e Geometria que podem ser explorados no Ensino Médio. Foram apresentadas algumas atividades que podem ser aplicadas em sala de aula do Ensino Médio no desenvolvimento de conceitos matemáticos como Progressão Aritmética, Progressão Geométrica, Geometria, Combinação e Conjuntos Numéricos entre outros temas.
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Reichart, Sven. "Progression nach kurativer kolorektaler Karzinomchirurgie." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-99172.
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Hung, Tzong Tyng Clinical School Prince of Wales Hospital Faculty of Medicine UNSW. "Studies of bladder cancer progression." Awarded by:University of New South Wales, 2009. http://handle.unsw.edu.au/1959.4/39786.
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Bladder cancer (BlCa) is the second most common genitourinary cancer, affecting both men and women. Most (70%) cases present at the superficial stage; 20% of these recur with muscle-invasive disease. Major genetic alterations associated with BlCa include: loss/gain in expression or mutations in Retinoblastoma (RB) gene, human epidermal growth factor receptors (HERs), H-ras, p53 and FGFR3. Only p53 mutations are well correlated with invasive BlCa; other changes show variable correlations with disease status. To understand the progression of BlCa, a model of nine human BlCa cell sublines derived from a single parent but differing in in vivo characteristics, has been developed previously. These cells represent a heterogenous population from a single tumour and a model of different stages of BlCa progression, from non-tumourigenic to invasive. Two sublines were selected for further investigation: C3 (non-tumourigenic) and B8 (invasive). These were transfected with green (C3-GSP-2) and red fluorescent reporters (B8-RSP-gck) respectively to investigate the effects of their co-injection in vivo, specifically, promotion of C3 tumour growth by B8 cells. Surprisingly, B8 tumour growth was inhibited by C3 cells in vivo at different cell numbers and proportions of cells injected. Microarray analysis of C3 and B8 cells revealed differential expression of 1367 genes with dramatic differences in the transforming growth factor-?? and integrin-mediated pathways. Gene expression of BMP2, INHBB, FST, NOG, ID4 and TGF- ??1, in the TGF- ?? pathway was further analysed with qRT-PCR in all nine sublines. Expression of BMP2 was significantly related to tumourigenic potential (p=0.0238, Mann-Whitney) and INHBB to invasive ability (p=0.0476, Mann-Whitney). The BlCa model did not include a metastatic component. To broaden the model, cell lines were established from an invaded lymph-node (B8-RSP-LN) and a bone-metastasis (B8-RSP-BN) after subcutaneous and intra-cardiac injection of B8-RSP-gck cells. No significant differences were observed in the migratory capability and anchorage-independent colony formation of these metastatic cells compared with B8 cells. Evaluation of expression of the panel of TGF-beta genes (BMP2, INHBB, FST, NOG, ID4 and TGF- ??1) and metastasis-related genes (MMP9, MMP2 and KAI1) indicated that expression of BMP2, FST, ID4 and MMP9 was decreased or lost in the metastatic sublines.
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Hung, Tzong-Tyng Clinical School Prince of Wales Hospital Faculty of Medicine UNSW. "Studies of bladder cancer progression." Awarded by:University of New South Wales. Clinical School - Prince of Wales Hospital, 2007. http://handle.unsw.edu.au/1959.4/40450.
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Bladder cancer (BICa) is the second most common genitourinary cancer, affecting both men and women. Most (70%) cases present at the superficial stage; 20% of these recur with muscle-invasive disease. Major genetic alterations associated with BICa include: loss/gain in expression or mutations in Retinoblastoma (RB) gene, human epidermal growth factor receptors (HERs), H-ras, p53 and FGFR3. Only p53 mutations are well correlated with invasive BICa; other changes show variable correlations with disease status. To understand the progression of BICa, a model of nine human BICa cell sublines derived from a single parent but differing in in vivo characteristics, has been developed previously. These cells represent a heterogenous population from a single tumour and a model of different stages of BICa progression, from non-tumourigenic to invasive. Two sublines were selected for further investigation: C3 (non-tumourigenic) and B8 (invasive). These were transfected with green (C3-GSP-2) and red fluorescent reporters (B8-RSP-gck) respectively to investigate the effects of their co-injection in vivo, specifically, promotion of C3 tumour growth by B8 cells. Surprisingly, B8 tumour growth was inhibited by C3 cells in vivo at different cell numbers and proportions of cells injected. Microarray analysis of C3 and B8 cells revealed differential expression of 1367 genes with dramatic differences in the transforming growth factor- ?? and integrin-mediated pathways. Gene expression of BMP2,INHBB, FST, NOG, ID4 and TGF- ??1, in the TGF- ?? pathway was further analysed with qRT-PCR in all nine sublines. Expression of BMP2 was significantly related to tumourigenic potential (p=0.0238, Mann-Whitney) and INHBB to invasive ability (p=0.0476, Mann-Whitney). The BICa model did not include a metastatic component. To broaden the model, cell lines were established from an invaded lymph-node (B8-RSP-LN) and a bonemetastasis (B8-RSP-BN) after subcutaneous and intra-cardiac injection of B8- RSP-gck cells. No significant differences were observed in the migratory capability and anchorage-independent colony formation of these metastatic cells compared with B8 cells. Evaluation of expression of the panel of TGF-beta genes (BMP2, INHBB, FST, NOG, /04 and TGF- (31) and metastasis-related genes (MMP9, MMP2 and KAI1) indicated that expression of BMP2, FST, /04 and MMP9 was decreased or lost in the metastatic sublines.
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Moroz, Kelly. "Drug use, initiation and progression." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0020/MQ55227.pdf.
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Horsford, Bernard I. "Career progression of black managers." Thesis, Cranfield University, 2003. http://hdl.handle.net/1826/4275.
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This research programme examined the factors that affect the
career progression of Black managers in the United Kingdom.
The research comprised two distinct but related studies. The first
study was a qualitative investigation of the factors affecting the
career progression of Black managers (n = 64).
The main finding from the first study was that for some the
achievement of high salaries and senior positions may be at the
expense of one's positive Black racial identity attitudes and wellbeing.
The second study was a quantitative examination of aspects
revealed as important correlates of career success in study 1.
Two hundred and sixty-one respondents (97 Black and 163 White
respondents) across all major industry sectors participated. The
results of the second study confirmed that Black managers were
more disadvantaged than their White peers. The proposition that
for some Black managers a "sell out" effect occurs was supported.
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Shahrabi, Farahani Hossein. "Computational Modeling of Cancer Progression." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-121597.
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Cancer is a multi-stage process resulting from accumulation of genetic mutations. Data obtained from assaying a tumor only contains the set of mutations in the tumor and lacks information about their temporal order. Learning the chronological order of the genetic mutations is an important step towards understanding the disease. The probability of introduction of a mutation to a tumor increases if certain mutations that promote it, already happened. Such dependencies induce what we call the monotonicity property in cancer progression. A realistic model of cancer progression should take this property into account. In this thesis, we present two models for cancer progression and algorithms for learning them. In the first model, we propose Progression Networks (PNs), which are a special class of Bayesian networks. In learning PNs the issue of monotonicity is taken into consideration. The problem of learning PNs is reduced to Mixed Integer Linear Programming (MILP), which is a NP-hard problem for which very good heuristics exist. We also developed a program, DiProg, for learning PNs. In the second model, the problem of noise in the biological experiments is addressed by introducing hidden variable. We call this model Hidden variable Oncogenetic Network (HON). In a HON, there are two variables assigned to each node, a hidden variable that represents the progression of cancer to the node and an observable random variable that represents the observation of the mutation corresponding to the node. We devised a structural Expectation Maximization (EM) algorithm for learning HONs. In the M-step of the structural EM algorithm, we need to perform a considerable number of inference tasks. Because exact inference is tractable only on Bayesian networks with bounded treewidth, we also developed an algorithm for learning bounded treewidth Bayesian networks by reducing the problem to a MILP. Our algorithms performed well on synthetic data. We also tested them on cytogenetic data from renal cell carcinoma. The learned progression networks from both algorithms are in agreement with the previously published results. MicroRNAs are short non-coding RNAs that are involved in post transcriptional regulation. A-to-I editing of microRNAs converts adenosine to inosine in the double stranded RNA. We developed a method for determining editing levels in mature microRNAs from the high-throughput RNA sequencing data from the mouse brain. Here, for the first time, we showed that the level of editing increases with development.QC 20130503
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Li, Weiling. "Genetic changes in melanoma progression." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5595.
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Melanoma is a highly aggressive tumour with a poor prognosis for patients with advanced disease because it is resistant to current therapies. Therefore, the development of novel strategies for melanoma treatment is important. The characterization of the molecular mechanisms underlying melanoma proliferation, progression, and survival could help the development of novel targeted melanoma treatments. The MAPK and PI3K pathways both play important roles in melanoma progression. In the MAPK pathway, DUSP6, which acts as a phosphatase to negatively control the activation of ERK1/2, is involved in the development of human cancers. The MAPK pathway also regulates expression of the DNA repair gene ERCC1 following EGF treatment. ERCC1 is essential for nucleotide excision repair, which is one of the major systems for removal of cisplatin induced DNA lesions. The aims of this project were: 1, to investigate the molecular changes in our immortal mouse melanocyte cell lines that were needed for them to form tumours in a xenograft model; 2, to investigate whether the MAPK pathway regulates ERCC1 following cisplatin treatment and protects melanoma cells from death. Through comparison of the RAS/RAF/MEK/ERK (MAPK) and the PI3K/AKT (AKT) signalling pathways between our immortal mouse melanocyte cell lines and their tumour derivatives in our xenograft model, we identified a molecularly distinct subtype of mouse melanoma characterized by reduced ERK and AKT activity and increased expression of DUSP6. Functional analyses employing ectopic overexpression indicated that increased expression of DUSP6 enhanced anchorage independent growth ability and invasive ability in our mouse melanocytes, suggesting that increased DUSP6 expression may contribute to melanoma formation in the xenograft assay. We also demonstrated that higher expression of p-ERK suppressed invasion, but not anchorage independent growth, in our subtype of mouse melanoma by enforced expression of constitutively active MEK1 and MEK2. In addition, the role of DUSP6 in classical human melanoma was investigated in this Genetic changes in melanoma progression study. Inhibition of anchorage independent growth and invasion were observed after exogenous expression of DUSP6 in human melanoma cells. This suggested that DUSP6 played different roles in classic human melanoma than in our distinct subtype of mouse melanoma. Our study also investigated the phosphorylation level of ERK1/2 and the mRNA and protein level of ERCC1 and its partner XPF in the human melanoma cell line following cisplatin treatment. Significant increases in expression of p-ERK, ERCC1 and XPF were found in cisplatin treated cells. Moreover, a MEK inhibitor inhibited ERCC1 induction by cisplatin, but did not significantly affect XPF induction. This suggested that the MAPK pathway was involved in regulation of ERCC1 but not XPF. Furthermore, the DUSP6 level decreased after cisplatin treatment and overexpression of DUSP6 inhibited ERCC1 and XPF induction and reduced resistance to cisplatin. DUSP6 seems to play a crucial role in resistance of melanoma to cisplatin. In addition, a novel larger ERCC1 transcript was identified in human cell lines and was found to be upregulated by cisplatin. The ratio of larger ERCC1 transcript relative to the normal ERCC1 transcript increased following cisplatin treatment. The functions of this larger ERCC1 transcript in cisplatin resistance deserve further study.
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Johnson, Timothy Scott. "Transglutaminase apoptosis and tumour progression." Thesis, Nottingham Trent University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283035.
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Chan, Yin-Ping Rita. "Thematic progression in educational text." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252733.
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Chuprovska, Yu Ya. "Characteristics of breast cancer progression." Thesis, БДМУ, 2020. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18208.
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Jansson, Alexander. "Strategic conditions for negotiation progression." Thesis, Uppsala universitet, Institutionen för freds- och konfliktforskning, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-413153.
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This thesis investigates conditions for formal negotiation onset. The cases that are investigated are found in the overarching conflict between the Government of Colombia and the guerilla group, Ejército de Liberación Nacional (ELN). The thesis argues that ideology and ecological rationality set the framework for disputant negotiation strategies and that disputants decide whether to progress negotiations to an elevated stage based on their perceived relative strategic position. It is hypostasized, firstly, that the disputants go to formal negotiations when the guerilla perceives itself in a favorable entrapment position, and the government perceives that the guerilla is not in a favorable entrapment position. Secondly, it is hypothesized that disputants go to formal negotiations when there are no perceptions of opponent devious objectives. The findings show weak support for the hypotheses.
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Russell, Michael L. "The Phenomenology of Harmonic Progression." Thesis, University of North Texas, 2020. https://digital.library.unt.edu/ark:/67531/metadc1703408/.
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This dissertation explores a method of music analysis that is designed to reflect the phenomenology of the listening experience, specifically in regards to harmony. It is primarily inspired by the theoretical approaches of the music theorist Moritz Hauptmann and by the writings of philosopher Edmund Husserl.
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Hutchings, Natalie. "Identification of visual field progression." Thesis, Aston University, 1996. http://publications.aston.ac.uk/14548/.
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The study developed statistical techniques to evaluate visual field progression for use with the Humphrey Field Analyzer (HFA). The long-term fluctuation (LF) was evaluated in stable glaucoma. The magnitude of both LF components showed little relationship with MD, CPSD and SF. An algorithm was proposed for determining the clinical necessity for a confirmatory follow-up examination. The between-examination variability was determined for the HFA Standard and FASTPAC algorithms in glaucoma. FASTPAC exhibited greater between-examination variability than the Standard algorithm across the range of sensitivities and with increasing eccentricity. The difference in variability between the algorithms had minimal clinical significance. The effect of repositioning the baseline in the Glaucoma Change Probability Analysis (GCPA) was evaluated. The global baseline of the GCPA limited the detection of progressive change at a single stimulus location. A new technique, pointwise univariate linear regressions (ULR), of absolute sensitivity and, of pattern deviation, against time to follow-up was developed. In each case, pointwise ULR was more sensitive to localised progressive changes in sensitivity than ULR of MD, alone. Small changes in sensitivity were more readily determined by the pointwise ULR than by the GCPA. A comparison between the outcome of pointwise ULR for all fields and for the last six fields manifested linear and curvilinear declines in the absolute sensitivity and the pattern deviation. A method for delineating progressive loss in glaucoma, based upon the error in the forecasted sensitivity of a multivariate model, was developed. Multivariate forecasting exhibited little agreement with GCPA in glaucoma but showed promise for monitoring visual field progression in OHT patients. The recovery of sensitivity in optic neuritis over time was modelled with a Cumulative Gaussian function. The rate and level of recovery was greater in the peripheral than the central field. Probability models to forecast the field of recovery were proposed.
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Cahlin, Christian. "Cyclooxygenase activity and tumor progression /." Göteborg : Departments of Surgery and Transplantation, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, 2008. http://hdl.handle.net/2077/18198.
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Riordan, Edward A. "Imaging markers for osteoarthritis progression." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/20347.
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Joint damage in osteoarthritis (OA) involves characteristic changes in multiple joint tissue types, with alterations in the shape of subchondral bone and composition of synovial fluid occurring concomitantly with cartilage damage. Systemic risk factors such as obesity and local biomechanical processes that determine joint loading have long been shown to predispose to the disease, and more recent evidence suggests that specific genetic loci and inflammatory processes may make contributions, but the exact mechanisms driving the initiation and progression of the disease are yet to be elucidated. Advances in imaging that allow visualisation of minute changes in structures such as cartilage composition and subchondral bone shape have enabled longitudinal tracking of early disease development. It is hoped that the identification of early imaging biomarkers for later disease will not only assist in clarifying disease pathogenesis, but facilitate the development of disease-modifying interventions by shortening the lead time for assessing their effectiveness. This thesis aimed to clarify the current information on the utility of imaging biomarkers in research into the pathogenesis and treatment of osteoarthritis, and investigate potential imaging markers in the two regions that contribute the most to the disease burden of osteoarthritis; the knee and the hand. It utilises data from three clinical studies; a cross-sectional survey on quality of life indices in patients with arthritis, and the ongoing KANON (Knee Anterior Cruciate Ligament Non-operative vs. Operative Treatment) and COMBO (Combined Conservative Therapies on Clinical Outcomes in Thumb Base Osteoarthritis) trials. The chapters are presented in mixed manuscript form and journal format owing to differing stages of publication, and are designed to be read independently. Chapter one presents an introduction to the current understanding of the pathogenesis of OA and the role of imaging in clinical research. Chapter two presents published data from a cross-sectional survey that included 1039 participants via an online platform and utilised the validated ICOAP (Measure of Intermittent and Constant Osteoarthritis Pain) and EQ5D scores. The data identified the knees and hands as the regions in which pain was the most common, and in which arthropathy was the most detrimental to activities of daily living. This regional distribution differed slightly from studies in which participants were drawn from clinician referral, rather than from a convenience sample, raising points on the potential advantages of online platforms, and framing the subsequent focus on research into imaging biomarkers for OA of the knees and hands. Chapter three provides a further introduction to magnetic resonance imaging (MRI) to provide a background for the subsequent two chapters, and consists of a published book chapter that focuses on MRI as an imaging modality that enables direct visualisation of changes in both structure and composition in different joint tissues through the modification of contrast and sequences. In chapter four, post-traumatic osteoarthritis is discussed in two published manuscripts in terms of its value in investigating disease pathogenesis through imaging. Traumatic joint injury, and anterior cruciate ligament (ACL) rupture in particular, is strongly linked to the subsequent development of osteoarthritis, so provides an opportunity to track pathological changes from a defined starting point, and therefore potentially identify early imaging markers for subsequent disease. Chapter five presents data from serial MRIs in the KANON trial, which included 121 individuals who had sustained an acute anterior cruciate ligament (ACL) rupture to a previously uninjured knee. In the trial, 62 participants were randomised to undergo early ACL reconstruction and structured rehabilitation, and 59 were allocated to undergo structured rehabilitation alone, with an optional delayed ACL reconstruction. MRIs of the knee were obtained for all participants at baseline, two years, and five years, and for a subgroup of 63 participants, additional MRIs were performed at 3, 6, and 12 months. The serial MR imaging has enabled the effects of concomitant injuries such as osteochondral fractures and meniscal tears to be tracked, as well as providing longitudinal measurements of changes in cartilage and subchondral bone that can then be correlated with clinical outcomes. Data on the regional changes in the area of bone covered by cartilage (cAB) as a potential biomarker for disease, and the effects of baseline injuries to other joint structures, are presented. In chapter six, data on radiographic markers in trapeziometacarpal (base of thumb) osteoarthritis are presented from the COMBO trial. It includes two manuscripts – one published and one in the process of review – that present data from the first 100 participants included in the COMBO trial. Radiographic markers have traditionally had a poor correlation with symptomatic and functional outcomes, so generalised estimating equations are used for bilateral data to minimize the influence of interpersonal confounding factors and account for the fact that within-person measurements are not independent. The radial subluxation ratio is investigated in the manuscripts as a marker for structural and functional osteoarthritis progression, and radiographic markers of disease severity are analysed in relation to pain and functional outcomes in symptomatic disease. In summary, magnetic resonance imaging and radiographic markers are investigated in relation to their utility as indicators of osteoarthritis progression, and in acting as outcomes for the assessment of potential interventions in clinical trials.
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CERESA, DAVIDE. "Clonal tracking of Glioma progression." Doctoral thesis, Università degli studi di Genova, 2019. http://hdl.handle.net/11567/977087.
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Khaleeli, Z. "Understanding progression in primary progressive multiple sclerosis : a longitudinal clinical and magnetic resonance imaging study." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19213/.
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The work in this thesis applies magnetization transfer imaging (MTI) and conventional MRI measures (brain volume, T2 lesion load and enhancing lesions) to investigate the mechanisms underlying progression in primary progressive multiple sclerosis (PPMS), and identifies MR markers to predict and monitor progression. First, we demonstrated that MTI was sensitive to change in the normal appearing brain tissues over one year, and that clinical progression over this period was predicted by baseline normal appearing white matter (NAWM) MT ratio (MTR). However, our second study showed that over three years, grey matter MTR became a better predictor of progression than any other MRI measure. Grey matter MTR and T2 lesion load changes reflected concurrent progression during this study. To localize the baseline grey matter injury more precisely, we developed a voxelbased technique to identify areas of grey matter MTR reduction and volume loss in patients compared with controls. The regions of grey matter MTR reduction identified correlated with clinical function in anatomically related systems. Finally, because our studies showed that lesion load influenced progression, we used contrast enhanced T1-weighted imaging to examine active focal inflammation. We found that while lesion activity declined over five years, levels of activity at the start of the study could influence mobility five years later. The work presented in this thesis suggests that grey matter damage has a predilection for certain brain regions and is an important determinant of progression in early PPMS. In the white matter, changes in lesion volume and activity continue to influence progression, but NAWM injury may have a declining role. MTR is a sensitive and responsive tool for predicting, monitoring, and localizing clinically relevant brain injury in early PPMS.
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Verma, Kuldeep Kumar. "Different ladders for police progression? : reviewing black and minority officers' progression in the police service." Thesis, University of Portsmouth, 2015. https://researchportal.port.ac.uk/portal/en/theses/different-ladders-for-police-progression(f30809ef-d3dd-419c-b7a5-1c83c9c812cc).html.
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The Police Service has a strategic priority to improve approaches to progression forunder-represented groups; however, it is facing continued challenges for this priority, as there is a lack of progression for Black and Minority Ethnic (BME) officers. There are implicit suggestions in policy that increasing BME officers in the police would improve police culture in the form of attenuating the racism that may be creating barriers to recruitment and progression. Reform efforts have taken place in the UK Police Services in the last decade to have a more diverse workforce, especially with regard to race, sex and sexual orientation. However, contemporary research has repeatedly demonstrated that there are inherent problems in assimilation of officers that are not white males (Holdaway and O’Neill,2004; Bolton and Feagin, 2004; Cashmore, 2001). The common themes from previous research are that BME officers face barriers of stereotyping, police culture and racism that affects their working environment and prospects of progression. This thesis examined BME senior officers perceptions of progression in the British Police Service. The research was conducted within a qualitative paradigm to examine barriers to career progression that affected BME officers so that professional knowledge is improved for police leaders to consider alternative employment practices. This thesis focused on BME and white Superintendents working in the United Kingdom. BME Superintendents were excluded from the sub-culture of progression, which contained informal practices that were rooted to covert institutional racism. The predominant informal practice found was networks that operated covertly and were linked to chief officer sponsors who could provide mobility. Within the networks there was axiomatic knowledge providing vital dissemination of information for progression. BME Superintendents were negatively impacted by exclusion from these informal practices and exhibited physical and psychological behaviours such as working hard,anxiety and having a lack of confidence. A model describing the cause and effect of BME progression in the British Police Service was developed through this research and is presented as new professional knowledge.
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Rosa, Marcella Suelma de Torrecillas. "Expressão tecidual e sérica de microRNAs associados a receptores de estrógeno e progesterona em meningiomas grau I, II e III." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-09112018-110503/.
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Os meningiomas são os tumores primários do Sistema Nervoso Central (SNC) mais frequentes e representam 35,5% dos casos considerando-se todas as faixas etárias. Apesar dos progressos ocorridos nas últimas décadas, a tumorigênese dos meningiomas ainda permanece como um desafio. Há um consenso da necessidade de ferramentas moleculares para ajudar tanto no diagnóstico quanto no prognóstico dos meningiomas. Neste contexto, alguns trabalhos demonstram a importância do papel dos receptores de estrógeno e progesterona, assim como o entendimento das alterações nos níveis de expressão dos microRNAs (miRNAs) na tumorigênese dos meningiomas. Alguns estudos demonstram que o perfil de expressão sérico dos miRNAs tem correlação com a classificação e evolução clínica, sendo de grande interesse o uso desse material por se tratar de um procedimento não-invasivo, ou seja, como biomarcadores. Objetivos: avaliar o perfil de expressão tecidual e sérica de microRNAs associados as vias dos receptores de estrógeno e progesterona em meningiomas grau I, II e III. Pacientes e métodos: foram utilizadas amostras de tecido e plasma de 40 pacientes com meningiomas grau I, II e III. Para a análise da expressão dos miRNAs miR-34a, miR-143, miR-145 e miR-335 foi utillizada a técnica de PCR em tempo real. Resultados: os miRNAs: miR-34a e miR-145 apresentaram diferença estatística significativa nas amostras de tecido tumoral entre os grupos estudados com menor expressão nas amostras de meningiomas grau II quando comparadas as amostras grau I e III. Não observamos diferença estatística estatística significativa na expressão dos miRNAs nas amostras de plasma. Conclusão: os miRNAs selecionados não apresentaram correlação com a progressão tumoral em meningiomas.Meningiomas are the most common primary Central Nervous System (CNS) tumors, accounting for 35.5% of the cases, considering all age groups. Despite the progress made in recent decades, the tumorigenesis of meningiomas still remains a challenge. There is a consensus of the need for molecular tools to assist both diagnosis and prognosis of meningiomas. In this context, some studies demonstrate the importance of the role of estrogen and progesterone receptors, as well as the understanding of alterations in microRNA (miRNAs) expression levels in the tumorigenesis of meningiomas. Some studies have shown that the serum expression profile of the miRNAs correlates with the classification and clinical evolution, being of great interest the use of this material because it is a non-invasive procedure, i.e., as biomarkers. Objectives: To evaluate the tissue and serum expression profile of microRNAs associated with the estrogen and progesterone receptor pathways in meningiomas grade I, II and III. Patients and methods: tissue and blood samples from 40 patients with grade I, II and III meningiomas were used. For analysis of miRNA expression miR-34a, miR-143, miR-145 and miR-335 was used the real-time PCR technique. Results: miRNAs: miR-34a and miR-145 presented a significant statistical difference in the tumor tissue samples between the groups with lower expression in the samples of grade II meningiomas when compared to samples I and III. We did not observe statistically significant statistical difference in miRNA expression in blood samples. Conclusion: the selected miRNAs showed no correlation with tumor progression in meningiomas.
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Carneiro, Vinicius Marques. "Perfil de expressão tecidual e plasmática dos microRNAs miR-130a, miR-181c e miR-181d em meningiomas grau I, II e III." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-01022016-155451/.
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Introdução: Os meningiomas são neoplasias intracranianas de crescimento lento que se originam das células meningoteliais da aracnoide e representam os tumores intracranianos mais comuns, contabilizando 13-26% deste total, sendo um dos primeiros tumores sólidos a terem alterações genéticas identificadas. Inúmeros tem sido os avanços para a melhor compreensão das vias moleculares correlacionadas com a tumorigênese e progressão tumoral dos meningiomas, neste contexto tem se destacado o papel dos microRNAs que são RNAs não-codificantes (ncRNAs) constituídos por 19 a 25 nucleotídeos, cuja função é o silenciamento do RNAm em nível póstranscricional. Portanto, o objetivo do nosso estudo foi avaliar a expressão tecidual e plasmática dos miRNAs miR-181d, miR-181c e miR-130a. Pacientes e métodos: Os miRNAs miR-181d, miR-181c e miR-130a foram selecionados a partir de estudo prévio do nosso grupo pela técnica de análise em larga escala de microarrays, onde foram comparados meningiomas grau I com amostras controles de aracnóides. Neste trabalho foi avaliada expressão destes miRNAs no tecido tumoral e plasma de meningiomas grau I, II e III. Resultados: O miR-181d apresentou-se hiperexpresso nos grupos estudados, no tecido tumoral quanto no plasma. O nível de expressão foi maior de acordo com a progressão do grau do tumor. Os miR-181c e miR-130a não apresentaram diferença estatística nos grupos estudados em ambos tecido tumoral e plasma. Conclusões: O miR-181d tem potencial para ser utilizado como biomarcador para meningiomas e está associado com sua progressão tumoral.Introduction: Meningiomas are intracranial tumors of slow growth that originate from meningothelial arachnoid cells and represents the most common intracranial tumors, accounting for 13-26% of this total, beeing one of the first solid tumors to have identified genetic alterations There are technological advances available to a better understanding of the molecular pathways correlated with tumorigenesis and tumor progression of meningiomas. The role of microRNAs in this process is very importante. MicroRNAs are non-coding RNAs (ncRNAs) consisting of 19 to 25 nucleotides, with function of mRNA silencing post-transcriptional level. The aim of our study was to evaluate the tissue expression and plasma of miRNAs miR-181d, miR-181c and miR-130a. Patients and methods: The miRNAs miR-181d, miR-181c and miR-130a were selected from a previous study of our group by analysis technique on large scale called microarrays, which were compared meningiomas grade I with arachnoid controls samples. In this study, we evaluated expression of these miRNAs in tumor tissue and plasma meningiomas grade I, II and III. Results: The miR-181d was presented upregulated in the all groups in both tumor tissue and in plasma. The level of expression was increased according to the progression of tumor grade. The miR-181c and miR-130a showed no statistical difference in the groups studied in both tumor tissue and plasma. Conclusions: The miR-181d has potential as a biomarker for meningiomas and is associated with tumor progression.
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Andrade, Afonso Martins. "Avaliação, ciclo e progressão no ensino de matemática: uma consequência refletida ou uma saída aleatória?" Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/48/48134/tde-12062008-132214/.
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Esta pesquisa é resultado da minha inquietação e do desconforto produzido ao longo dos últimos anos de atuação no magistério público, levando-me a questionar as hipóteses elaboradas e as finalidades identificadas na construção dos caminhos que culminaram na adoção do sistema de ciclos com progressão continuada implantado no Ensino Fundamental na Rede Pública de Ensino do Estado de São Paulo. Tendo como base tal inquietação, o objetivo deste trabalho é compreender melhor tal elaboração assim como de que maneira a ausência de novos métodos, estratégias e instrumentos de avaliação pode ser vista como possível fator presente na manutenção do baixo desempenho e na iminente possibilidade de fracasso na disciplina de Matemática ou de que forma estes assuntos se inter-relacionam. Considerando que os processos de construção (métodos) e de utilização dos instrumentos de avaliação sempre foram vistos como capazes de efetuar a mediação entre a \"medição do desempenho escolar\" (atribuição de conceitos ou notas) e a \"capacidade de apropriação de conhecimento\" por parte do aluno (sucesso ou fracasso na disciplina); sinto-me confiante em propor que os processos de construção e utilização dos instrumentos de avaliação podem ser postos como o foco principal de uma pesquisa.This research results from my discomfort and uneasiness grown, during the last years, by my experience as a Math teacher in a public school. Such preoccupation led me to question the hypotheses elaborated and finalities in the construction of the paths that culminated in the adoption of the system of continued progression cycles nowadays implanted in the 1st. to 8th. grades of Elementary School (Ensino Fundamental) in the Public School System of the State of São Paulo and how the lack of new methods, strategies and instruments of evaluation can be faced as a possible factor of the maintenance of the low performance and of the imminent possibility of failure in the discipline of Mathematics or how such subjects interrelate. The construction and usage processes (methods) of the evaluation instruments have always been seen as capable of mediating the \"measurement of school accomplishment\" (attribution of letter or number grades) and \"the capacity of appropriation of knowledge\" by the student (success or failure in the discipline). Therefore, the construction and usage processes of the evaluation instruments can be placed as the main focus of a research.
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Gallégo, Hélène. "Progression de l'athérosclérose après angioplastie des coronaires : une analyse multivariée des relations entre progression et resténose." Bordeaux 2, 1989. http://www.theses.fr/1989BOR23024.
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Ibrahimi, Merita, and Flurije Bajrami. "Svenska som andraspråk : Arbetssätt för progression." Thesis, Linnéuniversitetet, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-18577.
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Hörkkö, T. (Tuomo). "Growth and progression in colorectal cancer." Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:9514282809.
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Abstract
Colorectal cancer is the second most common malignancy in the Western World. The overall 5-year survival is still only 50–60%. Thus, better prognostic markers are needed to improve survival of the disease.
Most colorectal cancers develop from pre-existing adenomas including conventional, flat and serrated adenomas. The most important prognostic factors include tumour stage, histologic subtype and poor differentiation. The prognosis of colorectal cancer depends mainly on tumour stage. The growth of colorectal cancer is determined by cell proliferation, differentation and apoptosis. The progression of colorectal cancer is associated with the growth pattern of colorectal cancer and its invasive margin. Cancer cell budding means the presence of cells scattered in the stroma at the invasive margin, and is associated with β-catenin, an adhesion protein involved in the nuclear Wnt/β-catenin pathway. Hormones may be directly involved in the growth of a cancer, for example sex hormones play an important role in the development of most gynaecological cancers. The knowledge about the dependency of cancers on other hormones, such as thyroid hormones, is limited. This thesis focuses on factors affecting growth and prognosis in colorectal cancer.
Antibodies for Ki-67, caspase cleavage site for keratin 18, β-catenin and TRβ1 were used to determine their possible associations with colorectal cancer growth patterns and the characteristics of the invasive margin. Apoptosis and proliferation were decreased at the invasive margin, particularly in serrated adenocarcinomas. The invasive margin showed a presence of budding cell clusters in 24.0% of the cases and this predicted a very poor 5-year-survival (15.4%, P < 0.00001), but nuclear β-catenin accumulation did not predict budding. Thyroid hormone receptor TRβ1 was associated with polypoid growth, presence of KRAS mutations and also with a higher WHO histological grade and advanced Dukes' stage, and in in vitro analysis, thyroid hormone T3 had a modulatory effect on colorectal cancer cell protein synthesis and apoptosis.
In conclusion, the growth type of colorectal cancer, i.e. conventional polypoid, flat or serrated, has an association with the characteristics of the invasive margin. Budding margin is associated with poor prognosis in colorectal cancer, and could be utilised in diagnostic pathology. Association of TRβ1 expression with polypoid growth pattern and the presence of KRAS mutations suggest that abnormalities in thyroid hormone signalling involving TRβ1 play a role in the development of some types of colorectal adenocarcinomas.
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Quaglia, Alberto. "Mechanisms of progression in hepatocellular carcinoma." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271505.
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Rowan, Mark Stephen. "Information-selectivity of Alzheimer's disease progression." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4328/.
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Homeostatic synaptic scaling mechanisms, which normally balance potentiation during learning, may direct the progression of the disease throughout the brain as cells scale up their sensitivity to compensate for lost activation. Such a mechanism would be likely to target those cells with the lowest contribution of information to the network in early stages of the disease, resulting in delayed onset of cognitive symptoms and making timely intervention and treatment of the disease more difficult. These predictions were investigated in a Hopfield-type neural network. Lesioning according to the scaling-driven progression hypothesis of AD showed that the pathology is capable of targeting neurons with lowest information contribution to the network at early stages of the disease. Additional experiments revealed a positive-feedback loop by which noisy compensatory synaptic scaling mechanisms caused the accelerated degradation of recent memories, which were themselves preferentially used as drivers of the compensatory mechanism. The hypothesis was then tested in a biologically-realistic spiking model of neocortex. Cell death, modelled as an abstract excitotoxicity mechanism based on scaling factor values, confirmed the earlier results and showed that low-information neurons (and neurons from cortical layers with the lowest information contribution) were again the first to die in scaling-driven AD pathology.
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Ng, Grace. "Genomic investigations of cervical cancer progression." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613036.
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Vedhara, Kavita. "A psychoneuroimmunological investigation into HIV progression." Thesis, University of Newcastle upon Tyne, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260956.
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Bengtsson, Filip, and Philip Undin. "Moderna progression system, en kooperativ regress." Thesis, Blekinge Tekniska Högskola, Institutionen för teknik och estetik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-12935.
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Digitala spel är ett av dagens största digitala medier där det dagligen släpps nya spel. En av de största spel-genrerna är multiplayer First-Person Shooter (FPS) spel. Inom multiplayer FPS-spel, där kooperativt lagsamarbete spelar stor roll, har det på senare år uppkommit en trend där de flesta av dessa spel innehåller progression system som kan vara direkt skadande för spelets kooperativa upplevelse. Genom att undersöka frågeställningen “Hur kan vi med hjälp av progression system göra moderna FPS-spel mer kooperativa?” har vi försökt ta fram hur spelutvecklare istället kan öka den kooperativa upplevelsen i sina spel. Genom att ha undersökt och diskuterat områden som system, mänsklig motivation samt kooperativ spelteori har vi fått fram belöningspåverkan av en spelares beteende. Med hjälp av vår tidigare forskning har vi grundligt analyserat och brutit ner två av marknadens största titlar inom multiplayer FPS-spel, vi kom fram till att med hjälp av ett genomtänkt progression system kan bidra med ökad fokus på den kooperativa aspekten av dessa spel.
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Laranjeira, Simão. "Modelling the progression of neurodegenerative diseases." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:ebb621d0-e4e6-405e-9e54-ba385c3ebd0a.
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Neurodegenerative disease is an umbrella term for pathologies that primarily damage neurons. As their incidence increases with age it is becoming of a greater concern for the west, due to its aging population. Due to their chronic nature and the difficulty to create reliable and reproducible animal models of these diseases their pathophysiologies are still poorly understood. For all these reasons, a mathematical modelling approach is suggested. The methodology of the work here consisted of identifying the state of the art models that describe the healthy behaviour of cells (e.g. metabolism and ionic regulation) and adapting them for pathological environments. With these models hypotheses provided by clinicians and pathologists were tested. The work focuses on developing models of mechanisms common to neurodegenerative diseases, which include: glutamate excitotoxicity, aquaporin water kinetics, inflammatory complement lysis and acute inflammation. Glutamate excitotoxicity was modelled by creating a compartmental model of glutamate exchange between neurons and astrocytes. This model was the first model of glutamate kinetics validated in an ischaemic stroke context. The aquaporin water kinetics and complement lysis models were developed in the context of the autoimmune disease Neuromyelitis Optica. Through this project a hypothesised trigger for the pathology was confirmed. Additionally, the first model of astrocytic cytotoxic oedema due to complement lysis was developed. Finally, a preventative drug for complement lysis was simulated. Acute inflammation was explored in the context of understanding the potential of chemerin as a pro-resolving cytokine. To that effect, a model of acute inflammation was developed where pro-resolving mechanisms were included. This model was the first to attempt model the effects of an intervention in inflammation. The results indicated that there is a maximum inhibitory effect of chemerin on inflammation. Additionally, two preventive avenues for chronic inflammation were found. With this work, the first attempts of capturing relevant mechanisms of neurodegenerative diseases were presented. These models can now be further developed and adapted to other pathological environments.
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Santos, Carlo Steven. "Circadian Control of Cell Cycle Progression." Thesis, Virginia Tech, 2009. http://hdl.handle.net/10919/76987.
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Tumorigenesis is the result of uncontrolled cell growth due to the deregulation of cell cycle checkpoints 1. Period 2 (Per2) is a tumor suppressor that oscillate in expression in a 24-hour cycle 2, 3. Here, we show that Per2 interacts with the tumor suppressor protein p53. Both G1 and G2 checkpoint pathways involve a p53 dependent pathway which can trigger the cell to go through cell arrest or programmed cell death4. Understanding all the mitigating factors involved in regulating cell cycle progression under DNA damage can offer a better idea in how cells become immortal.
Initially discovered through screening of a human liver cDNA library, the novel interaction between p53-Per2 was further documented using co-precipitation. Interestingly, under genotoxic stress conditions, p53 and Per2 were not found to bind which leads us to suspect that Per2 does not affect active p53 which may possibly be due to post translational modifications of its active state. Furthermore we investigated p53's ability to act as a transcription factor in the presence of Per2, showing that the Per2-p53 complex prevents p53 from binding to DNA. This implies that the tetramerization of p53 may also be another factor in Per2's ability to bind to p53. A truncated p53 lacking the last 30 amino acids that theoretically increase p53's ability to form a tetramer showed a drastic reduction in binding to Per2 5, 6. On the other hand, p53 lacking the tetramerization domain showed binding similar to wildtype. Consequently we speculate that the ability of Per2 to modulate p53 and act as a tumor suppressor protein may be dependent on either the post translational modifications of p53 or its oligomeric state.Master of Science
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Wilson, William. "Kant on the Progression of Representation." Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/77888.
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Recently, the key point of contention in Kant scholarship has revolved around a question concerning whether, for Kant, intuitions can play their role of presenting objects to the mind without the discursive activity of the intellect. According to 'conceptualist' interpretations, intuitions depend for their generation on the activity of the understanding. According to 'nonconceptualist' interpretations, at least some intuitions do not depend for their generation on the activity of the understanding. I argue that although the conceptualism/nonconceptualism debate has brought greater clarity to a number of issues within Kant's critical philosophy, the debate partially rests on a conflation of two importantly distinct representational states, namely 'intuition' [Anschaaung] and 'perception' [Wahrnehmung]. I argue that once this distinction is noted, many of the passages that would appear to threaten a nonconceptualist interpretation lose their force. In addition, I argue that if we understand the conceptualist claim in terms of the kind of structure a particular representational state possesses, then we have good reason to reject the idea that, for Kant, sensory experience is fundamentally conceptual in character.Master of Arts
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Flaten, Kayla. "The Progression of Agile Software Development." Scholarship @ Claremont, 2017. http://scholarship.claremont.edu/cmc_theses/1717.
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This paper examines the use of Agile Software Development in the technology industry and how it came to be one of the leading models used in project management. By investigating the software development methods used in the late 1900s, it becomes clear where the system needed improvement in order to improve the efficiency in developing products. In investigating the Agile Manifesto, new and essential components are introduced that become vital in successfully producing a product. From this, it is easier to understand why Agile is so commonly used in the software development industry and how it became so effective.
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Khoynezhad, Shirin. "Halofuginone Prevents the Progression of Osteoarthritis." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17331948.
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Background: Halofuginone (HF) is a natural product that has been shown to have therapeutic benefits in a variety of pathologic conditions, from cancer to autoimmune diseases. These beneficial effects are mainly through inhibition of pro-inflammatory cytokines. Inflammatory cytokines have been recently shown to exert a crucial role in development of osteoarthritis and one of their most important targets is Matrix metallopeptidase-13 (MMP-13). In this preclinical study, we investigated the effect of HF on the progression of Osteoarthritis.
Methods: The effect of adding HF ± IL-1β/TNF-α on mRNA expression of MMP-13 on the C28/I2 Chondrocytes was evaluated with qPCR in vitro. To study the effect of HF in vivo, a mice destabilization of the medial meniscus (DMM) osteoarthritis model was employed and untreated control group were compared with early treatment with HF (starting 48 hours post-surgery for 12 weeks) and late treatment (4 weeks post-surgery for 8 weeks). After sacrificing the animal, joint destruction in the knee tissue was assessed with Safranine O/Fast Green staining and MMP13 expression was evaluated by immunohistochemical staining.
Results: In chondrocytes, MMP-13 expression was significantly increased with IL-1β or TNF-α (13.77-fold, p-value<0.05 and 5.8-fold, p-value<0.05, respectively). Addition of HF Significantly reduced MMP13 expression close to baseline levels (1.73-fold, p-value<0.05 when co-incubated with IL-1β and 1.6-fold p-value<0.05 when co-incubated with TNF-α). Injection of HF in the mice osteoarthritis model in vivo, significantly reduced Osteoarthritis progression according to OARSI scoring (3.8 vs. 1.16 vs. 1.07, p-value<0.05) and there was no difference between early vs. late administration of HF. While MMP-13 was overexpressed in the control (DMM surgery without HF treatment) groups in IHC staining, expression of MMP13 was suppressed by injection of HF in both groups.
Conclusion: Halofuginone inhibits MMP-13 expression and diminishes joint destruction. These preclinical findings provide supporting data for clinical investigation of HF as a therapeutic target for osteoarthritis.
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Sou, Paul Wing. "Cell‐cell interactions in tumour progression." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/13961.
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Background: When EMT arises in carcinomas, it is often localised, the tumours being composed of both cells that have undergone an EMT, and cells that have retained epithelial characteristics. We hypothesised that these two cancer cell populations can cooperate to increase malignancy. Aim: To test Snail2 and the G12V mutant form of Hras for the ability to cooperate to increase malignancy when they are present in different clones. Methods: Snail2 and Hras were expressed in head and neck squamous cell carcinoma (HNSCC) cells as fluorescent protein fusions, enabling us to follow the behaviour of individual populations of cells when they were present as mixtures. Live-cell and end-point assays were used to study cell proliferation, migration and invasion in vitro and tumour growth and dissemination in vivo, following subcutaneous injection into nude mice. Results: HNSCC cells that expressed Snail2 exhibited decreased cell-cell adhesion and increased migration and invasion of extracellular matrix in vitro. In vivo, they were unable to form tumours, but disseminated to draining lymph nodes from the site of injection. Hras increased cell proliferation, but did not cause an EMT. Hras enabled the formation of tumours in vivo that failed to disseminate. In mixed populations, Hras cells imparted their enhanced growth property onto neighbouring cells and Snail2 enhanced the invasiveness of neighbouring cells. In vivo, Hras-expressing cells enabled Snail2-expressing cells to form part of the tumour. Furthermore, tumours that grew from mixtures of Snail2-expressing and Hras-expressing cells grew faster than those formed from cells that express both genes. Conclusion: In carcinomas that have genetically diverse cell populations, the cells that undergo an EMT can interact with cells that do not undergo an EMT, leading to a collective population that is more malignant than the subpopulations that comprise it.
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Algotar, Amit Mohan. "RISK FACTORS FOR PROSTATE CANCER PROGRESSION." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/195437.
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Introduction: This dissertation seeks to identify novel, potentially modifiable risk factors that could be used to reduce the risk of prostate cancer (PCa) progression. Aim 1 investigates the effects of obesity and smoking on PCa progression, aim 2 studies the effects of specific medication use on PCa progression, and aim 3 identifies factors associated with faster PCa progression.Methods: Data from 140 subjects from the Watchful Waiting study followed every 3 months for up to 5 years were used. Multiple linear regressions were used to determine associations with baseline PSA. PSA velocity (rate of change of PSA over time) was used as a surrogate marker for PCa progression. Mixed effect models were used to assess the effect of obesity, smoking and medication use on PSA velocity(aim1 and 2). For aim 3, subjects were categorized as slow, intermediate and fast progressors based on tertiles of PSA velocity. In addition to the above variables, age, Gleason score, chromogranin-A, family history, selenium and free PSA were investigated as determinants of faster PCa progression using multiple logistic regressions. Analyses were run using two models, comparing slow progressors to fast progressors (model1) and slow progressors to a combination of fast and intermediate progressors (model2).Results: Aspirin use was negatively associated with baseline PSA (coefficient = -0.39 and 95% confidence interval (CI):-0.612, -0.158). Aspirin effect was statistically significant in never smokers (coefficient = -0.54, 95% CI: -0.916, -0.170) but not in ever smokers (coefficient = -0.22, 95% CI: -0.505, 0.065). Ever smoking was statistically significantly associated with higher PSA velocity compared to never smoking (coefficient = -0.001, 95% CI: 0.0002, 0.002). In aim 3, pack-years of smoking were positively associated whereas aspirin use was negatively associated with high PSA velocity in both models. Odds Ratio and 95% CI for smoking and aspirin use for model1 and 2 respectively; 1.03 (0.92, 1.13), 1.02 (1.00, 1.03), 0.24(0.06, 0.94) and 0.26(0.10, 0.68).Conclusions: Although more studies are needed before recommendations can be made, if these results are borne to be true in other studies these modifiable risk factors can be potentially be used in prevention of PCa progression.
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Romano, Elena. "Role of TFF1 in tumor progression." Doctoral thesis, Universita degli studi di Salerno, 2017. http://hdl.handle.net/10556/2573.
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2015 - 2016Trefoil Factor 1 (TFF1) is a small secreted protein, belonging to the trefoil factor family, characterized by a conserved “trefoil domain” containing six cysteine residues that form a three loop disulphide structure. It is expressed in the gastrointestinal tract, where plays an essential role in mucosal protection through mucous-barrier formation, and also in mucosal repair through promotion of restitution after injury. In recent years clinical and experimental studies have shown an active function of the trefoil peptides in the genesis of neoplastic processes. TFF1 is mainly associated with breast cancer and gastric cancer (GC), but have been described changes in expression levels also in pancreatic cancer, lung, prostate and colorectal. TFF1 had been described as a tumor suppressor gene in gastric cancer, but it is markedly elevated in gastric mucosa with atypical hyperplasia, diffuse-type gastric cancer and with lymph node metastasis. However, the distinct signalling pathways have not been fully elucidated, nor have definitive functional receptors for trefoil proteins been identified. In this PhD project, experiments were performed to understand the role of TFF1 in human GC development with particular attention to invasion and epithelial-mesenchymal transition (EMT) processes. Previously it has been demonstrated that TFF1 selectively binds copper ions, which influence homodimer formation and its biological activity. Here, by using TFF1 recombinant protein on AGS cell line and a TFF1 over-expressing clone (AGS-AC1), we demonstrated that TFF1 stimulated invasion of GC cell lines. The pro-invasive activity of TFF1 was strictly regulated by copper and was associated with a greater MMP-2 activity. We also reported that TFF1 was implicated in the occurrence of EMT, not only in the GC models but also in a prostate cancer cell line, in a same manner with a reduction of epithelial markers such as E-cadherin and cytokeratins 8 and 18 and an increase of mesenchymal ones such as vimentin. Additionally, in hypoxic condition, a significant increase of TFF1 expression was associated with hypoxia-related mesenchymal/metastatic process. Furthermore, we demonstrated a TFF1 auto-induction mechanism with the identification of a specific responsive element located between -583 bp and -212 bp region of its promoter. This region is responsive to the presence of TFF1 and able to positively regulate its expression also during hypoxia and synergistically with HIF1-α induction. Additionally, we observed that TFF1 can regulate the methylation status of its promoter. We hypothesized that it can auto-activate its own expression regulating the density of methylated CpGs. Finally, we investigated the relationship between TFF1 and the N-formyl peptide receptors (FPR1, FPR2 and FPR3), involved in innate immunity, inflammation and cancer, including GC. For the first time we reported a functional relationship between TFF1 and FPRs. In particular, we found that recombinant TFF1 protein in AGS cells induced FPR expression and FPRs influenced pro-invasive activity of TFF1. [edited by author]
XV n.s. (XXIX )
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SOKOLOVA, VIKTORIJA. "MICRORNA INVOLVEMENT IN COLON CANCER PROGRESSION." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/214611.
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Loss of response to TGF-β occurs in many cancers and disruption of its regulatory circuitry appears as a central event in the genesis of colorectal cancer (CRC) malignancy. Lack of an inhibitory response to TGF-β is common to most colon cancer cell lines. Recently, abrogation of the TGF-β growth inhibitory response mediated by different miRNAs has been reported. By searching for miRNAs in regions showing copy number changes and concordant gene expression in 36 sporadic CRCs compared to their normal counterpart, we identified the miR-17-92 cluster localized on the 13q31 locus, gained and highly expressed at early stages of CRC. We selected the TGF-β sensitive FET colon carcinoma and investigated the relationship between enhanced expression of miR-20a and TGF-β mediated growth inhibition. We found that miR-20a affects p21 levels and has a negative and significant effect on the cytostatic response mediated by TGF-β. We confirmed that p21 down-modulation is addressed by direct binding of its 3’-UTR by miR-20a. Moreover, we observed also that miR-20a is able to block the transactivation of the 2.3-kb CDKN1A promoter upon TGF-β stimulation, but not the activation of the Smad3/4-reponsive reporter. We also found that two of the c-MYC repressor genes, E2F5 and KLF11, are directly targeted by miR-20a, thus resulting in abrogation of the TGF-β mediated repression of c-MYC. Our experiments suggest for miR-20a an interference with the TGF-β homeostasis in colon cancer addressing the up-regulation of p21 expression, through mechanisms involving more effectors of the TGF-β cascade.
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Sauty, Benoît. "Multimodal modelling of Alzheimer's Disease progression." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS348.
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La maladie d'Alzheimer (MA) est une pathologie multi-facette qui peut être surveillée grâce à une grande variété de modalités de données. Cette thèse vise à exploiter des données longitudinales multimodales, principalement des données d'imagerie et des tests cognitifs, pour fournir une description statistique de la progression de la MA et permettre une prévision individuelle de la dégradation future. Les modèles de progression à effet-mixtes de la maladie (DPMs) sont couramment utilisés pour ces tâches. Dans ce contexte, notre première contribution remet en question l'hypothèse fréquente selon laquelle les biomarqueurs suivent des fonctions linéaires ou logistiques au fil du temps, et nous proposons un cadre géométrique qui suppose que les données se trouvent sur une variété et suivent des géodésiques au fil du temps. Nous apprenons la métrique riemannienne de l'espace d'observation et sommes capables de modéliser une plus grande variété de biomarqueurs, sans hypothèses préalables sur la forme de la trajectoire au fil du temps. En utilisant des auto-encodeurs variationnels, nous étendons ensuite ce cadre aux données de neuroimagerie (IRM ou TEP), afin de fournir des modèles de progression en grande dimension qui décrivent les motifs d'altérations structurelles et fonctionnelles du cerveau au cours de la MA. Nous appliquons ensuite cette famille de DPMs à des données réelles afin d'étudier l'hétérogénéité de la progression de la MA, en décrivant l'influence du génotype APOE-e4 et du sexe sur les motifs d'altérations cérébrales. Enfin, nous utilisons ces DPMs avec un ensemble de biomarqueurs d'imagerie et extrait du fluide cérébrospinal pour identifier les combinaisons spécifiques de paramètres qui permettent de prévoir les déclins cognitifs chez les patients à différents stades de la maladie. La thèse démontre que les DPMs peuvent modéliser efficacement la progression de la MA en utilisant une grande variété de données longitudinales multimodales et fournir des informations précieuses sur les manifestations cliniques et la progression de la maladie. Ces résultats peuvent informer la conception d'essais cliniques et faciliter des stratégies de traitement individualisées et plus précises pour les patients atteints de la MAAlzheimer's disease (AD) is a multi-facet pathology, that can be monitored through a variety of data types. This thesis aims to leverage multimodal longitudinal data, especially imaging scans and cognitive tests, to provide a statistical description of the progression of AD and to enable individual forecasting of future decline. Mixed-effect disease progression models (DPMs) are commonly used for these tasks. In this context, our first contribution questions the frequent assumption that biomarkers follow linear or logistic functions over time, and we propose a geometric framework that assumes the data lie on a manifold and follow geodesics over time. We learn the Riemannian metric of the observation space and are able to model a wider variety of biomarkers, without priors on the shape of the trajectory over time. Using variational auto-encoders, we then extend this framework to neuroimaging data (MRI or PET scans), in order to provide high-dimensional progression models that describe the patterns of structural and functional alterations of the brain over the course of AD. We then apply this family of DPMs to clinical studies data in order to investigate the heterogeneity of AD progression, due to APOE-e4 genotype and sex on patterns of brain alterations. Lastly, we use said DPMs with a set of imaging and fluid biomarkers to identify the specific combinations of input features that best forecast cognitive declines in patients at different stages of the disease. The thesis demonstrates that DPMs can effectively model the progression of AD using a great variety of multimodal longitudinal data and provide valuable insights into the disease's clinical manifestations and progression. These findings can inform clinical trial design and facilitate more accurate prognosis and individualized treatment strategies for patients with AD
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M'Hammed, Oubella Abdelkrim. "Progression narrative et progression thématique dans "l'enfant de sable" et "la nuit sacrée" de Tahar Ben Jelloun." Paris 3, 1992. http://www.theses.fr/1993PA030085.
Full textAbstract:
Nous avons essaye d'aborder, premierement, dans notre travail de these, la naissance et l'evolution de la litterature marocaine d'expression francaise. D'autre part, nous avons examine les fonctions et les fonctionnements de la couverture, du titre, et de l'incipit. Par ailleurs, la presence de plusieurs voix differentes dans "l'enfant de sable" nous a pousse a s'attarder sur les instances enonciatives dans ce roman. Le traitement de la narration dans "la nuit sacree" est plus chronologique a cause du respect relatif des successions des evenements romanesques. Nous avons tente, a la fin de notre travail, de voir comment le theme de la mort fonctionne et progresse dans l'oeuvre de tahar ben jellounWe have tried in this present research to tackle beforehand the birth and the development of moroccan literature expressed in french. On the other hand, we've we've examined the functions and the functionings of the cover, the title, and the starting of the novel. Besides, the presence of several voices in "l'enfant de sable" has urged us on lingering over the asserting processes in this novel. The treatment of the narration in the "la nui sacree" is more chronological because of the relatively respected succession of the romanesque events. We have attempted at the end of this study, to see how the theme of death functions and develops in the work of tahar ben jelloun
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Maero, Athanasius Lutta. "Assessing treatment outcomes of people living with HIV on antiretroviral therapy at Kakamega County General Hospital in Kenya." University of the Western Cape, 2019. http://hdl.handle.net/11394/6891.
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Magister Public Health - MPHBackground: The goal of ART therapy is sustained viral load suppression with good immunological and clinical response. This optimal response to therapy results in the prevention of emergent ART drug-resistant mutations, decrease morbidity, and AIDS-related mortality and sustained retention on ART. Kenya, like most countries in Sub-Saharan Africa, has scaled-up the use of ART and is currently implementing a “Test and Treat” strategy in which any client identified and confirmed with an HIV diagnosis is initiated ART. Few studies have been carried out to ascertain the response of HIV patients initiating treatment in resource-limited settings. Moreover, it has been demonstrated that a certain proportion of patients fail to adequately respond to therapy and therefore require therapy modification. Aim: To assess treatment outcomes and calculate retention of HIV infected adult patients’ (15 years and above) initiating ART at Kakamega County General Hospital. The primary study outcome was the treatment outcome of patients-initiated ART two to three years prior to the study; while, the role of WHO criteria for screening treatment failure was assessed as a secondary outcome. Methods: This was a retrospective cohort study in which patients initiating ART between June 2014 and March 2015 were followed up until they were censored or study closed in August 2017. 284 patients were enrolled in the study after accurately matching information in their clinic files and the electronic medical record. Data were collected from patient records using a chart abstraction tool and transferred to an Access database from where the cleaning and validation of entries were done. Data from Access was transferred to STATA 15.1 for analysis. Descriptive statistics and inferential statistics were then performed to answer the research questions.
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Raghavan, Kesav. "Progression Rates and Sample Size Estimates for Primary Progressive Multiple Sclerosis Based on the CLIMB Study Population." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295863.
Full textAbstract:
Background: The clinical trial design for primary progressive multiple sclerosis (PPMS) requires understanding of disability progression in modern patient cohorts.
Objective: To characterize demographic and clinical characteristics of the CLIMB study
(Boston, MA) PPMS patient cohort and assess rate of disability progression.
Methods: We studied PPMS (n = 73) and relapsing-onset MS (ROMS) patients (n =1541) enrolled in CLIMB, a longitudinal study of MS patients at the Brigham and Women’s Hospital (Boston, MA). Disability progression for each group was compared using interval-censored survival analysis and time to six-month sustained progression.
Results: The PP group had 1.09:1 male:female ratio compared to 1:2.89 for the RO group and greater mean age of onset (PP: 44.4+/-9.6; RO: 32.7+/-9.9; p<0.0001). Motor symptoms at onset and first symptoms localized to spinal cord were each strongly associated with PPMS (p<0.001). Median time from onset to EDSS 6.0 was faster in PPMS (p<0.001). PPMS patients progressed faster to EDSS 3 (p<0.001) and from EDSS 3 to 6 (p<0.001). Median time to sustained progression in the PP group was 4.85
years (95% CI 2.83-8.35), significantly faster than the RO group (p<0.001).
Conclusions: Our modern PPMS cohort is demographically similar to previously studied cohorts. PPMS is associated with faster disability accrual than ROMS. Current real-world observations of time to sustained progression will inform design of new
clinical trials for PPMS.