Esôfago de Barrett é definido como a substituição do epitélio escamoso normal por epitélio colunar com metaplasia intestinal especializada (MIE), tendo como causa a persistência do refluxo gastro-esofágico. Seu diagnóstico é baseado na identificação endoscópica e na confirmação histológica da presença de MIE. Esôfago de Barrett é a principal causa do desenvolvimento do adenocarcinoma esofágico. Aos pacientes com esôfago de Barrett é recomendada vigilância endoscópica com biópsias seriadas tentando-se diagnosticar, precocemente, lesões precursoras ou o adenocarcinoma em estágio precoce e factível de resposta à terapia. O aumento da incidência do adenocarcinoma tem contribuído para o estudo de novas técnicas endoscópicas visando melhorar a detecção destas lesões. Este estudo foi realizado objetivando-se avaliar a eficácia da cromoscopia com azul de metileno, associada a magnificação de imagem com ácido acético, na detecção de MIE, displasia e adenocarcinoma. Prospectivamente, 35 pacientes com diagnóstico de esôfago de Barrett em acompanhamento ambulatorial, com extensão superior a 2,0 cm, realizaram dois exames de endoscopia digestiva alta, sendo um convencional com biópsias seriadas e um segundo com aplicação de azul de metileno, seguida do ácido acético, magnificação de imagem e biópsias. Realizaram-se biópsias adicionais de qualquer alteração do relevo mucoso. A freqüência diagnóstica da metaplasia intestinal especializada foi de 71,4% e 77,1% para biópsias orientadas pelo método convencional e pelo método da cromoscopia/magnificação de imagem, respectivamente (p=0,41). Freqüência de displasia ou adenocarcinoma foi de 9% para as biópsias orientadas pelo método convencional e 6% para biópsias orientadas pela cromoscopia/magnifcação de imagem. Tanto os pacientes com displasia de alto grau quanto aqueles com adenocarcinoma apresentaram alterações em sua superfície mucosa visíveis em ambos os métodos endoscópicos. A sensibilidade e a especificidade da cromoscopia, quando avaliamos as áreas coradas em detectar MIE foi de 88% e 50%, respectivamente. A sensibilidade e a especificidade das áreas não coradas em detectar displasia e/ou adenocarcinoma foi de 75% e 100%, respectivamente. A sensibilidade e a especificidade da magnificação de imagem, quando avaliamos as áreas com padrão viliforme em detectar MIE foi 88% e 50%, respectivamente. Tanto a sensibilidade quanto a especificidade das áreas com padrão amorfo em detectar displasia e/ou adenocarcinoma foi de 100%. A sensibilidade e a especificidade da cromoscopia/magnificação de imagem, para padrão corado e viliforme, em detectar MIE foi de 83% e 50%, respectivamente. Já a sensibilidade e a especificidade das áreas não coradas e com padrão amorfo em detectar displasia e/ou adenocarcinoma teve seu cálculo prejudicado pela pequena amostra estudada. Na comparação dos dois métodos empregados, verificaram-se resultados similares na detecção de metaplasia intestinal, displasia e câncer. A realização de cromoscopia/magnificação de imagem proporcionou: alta sensibilidade e baixa especificidade na detecção da metaplasia intestinal especializada e baixa sensibilidade e alta especificidade na detecção de displasia ou adenocarcinoma. Alterações da superfície mucosa corresponderam as áreas neoplásicas. / Barrett\'s esophagus is defined as the replacement of the normal squamous epithelium by columnar lined esophagus. The diagnosis requires endoscopically visible columnar lined esophagus and histologic identification of characteristic specialized intestinal-type metaplasia (SIM). Gastroesophageal reflux has been proposed as a risk factor for Barrett`s esophagus and this disease has been shown to be the main cause of esophageal adenocarcinoma. After the diagnosis of Barrett`s esophagus, endoscopy surveillance is recommended with multiple biopsies of the columnar lined esophagus at quadrants of 2 cm intervals to determine epithelial dysplasia or adenocarcinoma in early and curable stage. Due to the increase in the incidence of esophageal adenocarcinoma new techniques of endoscopic surveillance have been proposed. The aim of this study was to evaluate the efficacy of magnification chromoendoscopy with methylene blue and acetic acid for the detection of intestinal metaplasia, dysplasia and cancer. Prospectively, 35 patients with Barrett\'s esophagus extending for more than 2,0 cm, underwent two upper digestive endoscopy procedures, including one with conventional biopsies and other with chromoendoscopy using methylene blue and acetic acid instillation, magnification and biopsies. Biopsies were also taken from any suspicious mucosal area. The incidence of MIE were 71,4% e 77,1% from conventional biopsies and chromoendoscopy/magnification, respectively. Dysplasia and adenocarcinoma were diagnosed in 9% and 6% throught conventional biopsies and chromoendoscopy/magnification, respectively. Patients with high grade dysplasia or adenocarcinoma revealed mucosal alterations. The sensitivity and specificity rates for chromoendoscopy for stained areas for MIE were 88% and 50%, respectively. The sensitivity and specificity rates for non stained areas for dysplasia and cancer were 75% and 100%, respectively. The sensitivity and specificity rates for magnification for villous areas for MIE were 88% and 50%, respectively. The sensitivity and specificity rates for distorted areas for dysplasia and cancer were 100%. The sensitivity and specificity rates for chromoendoscopy/magnification (for stained and villous areas) for MIE were 83% and 50%, respectively. The sensitivity and specificity rates for non stained and distorted areas couldn?t be evaluated due to the small number of patients. In conclusion, results of the two methods were similar in detecting intestinal metaplasia, dysplasia and cancer. The chromoendoscopy/magnification method procedure provides high sensitivity and low specificity rates in detecting MIE and low sensitivity and high specificity rates in detecting dysplasia and adenocarcinoma. Alterations in the mucosa corresponded to cancer and dysplasia.

This thesis is a transatlantic examination of self-representational strategies in factory women's poetry from circa 1848-1882, highlighting in particular how the medium of the working-class periodical enabled these socially marginal poets to subjectively engage with and reconfigure dominant typologies of class and gender within nineteenth-century poetics. The first chapter explores how working-class women were depicted in middle-class social-reform literature and working-class men's poetry. It argues that factory women were circumscribed into roles of social villainy or victimage in popular bourgeois reform texts by authors such as Elizabeth Barrett Browning and Caroline Norton, and were cast as idealized domestic figures in working-class men's poetry in the mid-nineteenth century. The remaining three chapters examine the poetry of Manchester dye-worker Fanny Forrester, Scottish weaver Ellen Johnston, and Lowell mill-girl Lucy Larcom as case-studies of factory women's poetics in mid-nineteenth century writing. Chapter Two discusses the life and work of Fanny Forrester in Ben Brierley's Journal, and considers how Forrester's invocation of the pastoral genre opens new opportunities for urban, factory women to engage with ideologies of domestic femininity within a destabilized urban cityscape. Chapter Three considers the work of Ellen Johnston, “The Factory Girl” whose numerous poems in The People's Journal and the Penny Post cross genres, dialects, and themes. This chapter claims that Johnston's poetry divides class and gender identity depending on her intended audience—a division exemplified, respectively, by her nationalistic poetry and her sentimental correspondence poetry. Chapter Four explores the work of Lucy Larcom, whose contributions to The Lowell Offering and her novel-poem An Idyl of Work harness the language and philosophy of Evangelical Christianity to validate women's wage-labor as socially and religiously appropriate. Ultimately, this thesis contends that nineteenth-century factory women's poetry from Britain and America embodies the tensions surrounding the “factory girl” identity, and offers unique aesthetic and representational strategies of negotiating women's factory labor.

L'œsophage et la trachée proviennent du diverticule endodermique du tube de l'intestin antérieur au cours de l'embryogenèse. Des événements cellulaires et moléculaires bien régulés et organisés entraînent la séparation du tube de l'intestin antérieur en œsophage et trachée. Cette séparation est encore mal connue et la perturbation de ce processus se traduit par une anomalie congénitale sévère telle qu'une l’atrésie de l'œsophage avec ou sans fistule trachéo-œsophagienne (AO/FTO). L'AO/FTO est l'une des malformations congénitales gastro-intestinales les plus courantes affectant 1 naissance sur 3000. Cette malformation nécessite une intervention chirurgicale urgente à la naissance et est fréquemment associée à une morbidité à long terme. Les mécanismes sous-jacents au développement embryonnaire de l'AO/FTO sont mal compris. Les modèles animaux ont été largement utilisés pour comprendre les maladies humaines depuis des décennies et ont considérablement contribué à la compréhension du développement de l'œsophage. Cependant, des différences structurelles et morphologiques clés existent entre l'œsophage humain et animal, ce qui nécessite un modèle plus fiable pour comprendre le développement trachée-œsophagien. Les cellules souches pluripotentes induites par l'homme ont été un outil précieux pour comprendre l'organogenèse en imitant le développement et en déchiffrant les mécanismes qui conduisent à des maladies congénitales et acquises. Cette thèse se concentre donc sur l'utilisation de cellules souches pluripotentes induites (IPS) par des patients pour déchiffrer les mécanismes de signalisation impliqués dans le développement de l'œsophage et les maladies congénitales telles que l’OA/FTO. Il étudie également l'une des maladies œsophagiennes acquises possibles, comme l'œsophage de Barrett. Nous avons orienté la différenciation des IPS saines et dérivées de patients vers différents stades de développement, tels que l'endoderme définitif, l'intestin antérieur, l'épithélium œsophagien et trachéal. De plus, l'épithélium œsophagien a été développé davantage dans un environnement tridimensionnel sans matrice pour générer des organoïdes œsophagiens matures. À chaque étape de la progression du développement, des analyses d'immunofluorescence, de qPCR et de séquençage d'ARN ont été effectuées. Nos résultats suggèrent que l'expression des marqueurs endodermiques CXCR4, SOX17, et GATA4 était similaire dans les cellules différenciées des patients et des cellules saines. Cependant, au stade de l'intestin antérieur, nous avons observé une diminution significative de l'expression des gènes et des protéines du facteur transcriptionnel clé SOX2 dans les cellules dérivées du patient. De plus, en utilisant le séquençage d'ARN à molécule unique, nous avons observé que les gènes critiques GSTM1, et RAB37 impliqués dans la morphogenèse cellulaire et associés à l’OA/FTO étaient dérégulés au stade de l'intestin antérieur dans les cellules dérivées du patient. Nous avons également observé une augmentation significative de l'expression du facteur de transcription NKX2.1 habituellement exprimé uniquement dans les cellules trachéales, dans l'épithélium oesophagien dérivé du patient. NKX2.1 est maintenue dans les organoïdes oesophagiens matures même après 2 mois. Ensuite, nous voulions valider l'utilisation potentielle de nos organoïdes dérivés des IPS pour modéliser les maladies acquises de l'œsophage telles que l'œsophage de Barrett. Nous avons induit une métaplasie ou transformation épithéliale avec surexpression de BMP4 dans des organoïdes de l'œsophage sains et dérivés du patient sur une période d'un mois. Nos résultats préliminaires montrent que les organoïdes de l'œsophage dérivés des patients exprimaient des niveaux d'ARNm plus élevés de MUC5AC, un marqueur épithélial cylindrique par rapport au groupe sain. Cela suggère une plus grande sensibilité de l'organoïde de l'œsophage dérivé du patient aux changements epitheliales métaplasiques. En conclusion, nous avons développé les premiers organoïdes œsophagiens tridimensionnels matures sans matrice différenciés des patients OA/FTO et identifié une signature moléculaire unique dans les cellules dérivées du patient au cours de la différenciation dirigée de l'œsophage. De plus, sur la base des résultats préliminaires, nous avons pu confirmer l'incidence plus élevée de l'œsophage de Barrett chez les patients OA/FTO par rapport au groupe sain. Notre travail met donc en évidence l'importance de l'utilisation des IPS dérivées des patients pour modéliser les maladies œsophagiennes congénitales et acquises afin de fournir de nouvelles informations sur le développement des organes au cours de l'embryogenèse. / The esophagus and trachea originate from the endodermal diverticulum of the anterior foregut tube during embryogenesis. Well-regulated and organized cellular and molecular events result in the compartmentalization of the anterior foregut tube into the esophagus and trachea. This compartmentalization is still poorly understood and disruption in this process results in a severe congenital anomaly such as esophageal atresia with or without tracheoesophageal fistula (EA/TEF). EA/TEF is one of the most common gastrointestinal congenital defects affecting 1 in 3,000 births. This malformation requires urgent surgery at birth and is frequently associated with long-term morbidity. The mechanisms underlying the embryonic development of EA/TEF are poorly understood. Animal models have been widely used to understand human diseases for decades and have significantly contributed to the understanding of esophageal development. However, key structural and morphological differences exist between human and animal esophagus, thus necessitating a more reliable model to understand trachea-esophageal development. Human induced pluripotent stem cells (iPSC) have been a valuable tool to understand organogenesis by mimicking development and deciphering mechanisms that lead to congenital and acquired diseases. This thesis therefore focuses on the use of patient-derived induced pluripotent stem cells to decipher signaling mechanisms involved in esophageal development and congenital diseases such as EA/TEF. It also focuses on one of the possible acquired esophageal diseases, namely, Barrett’s esophagus. We directed the differentiation of healthy and patient-derived iPSCs toward different developmental stages, such as definitive endoderm, anterior foregut, esophageal and tracheal epithelium. Furthermore, the esophageal epithelium was matured further in a matrix free 3-dimensional environment to generate mature esophageal organoids. At each stage of development progression, immunofluorescence, qPCR, and RNA sequencing analysis were performed. Our findings suggest that the expression of endodermal markers CXCR4, SOX17, and GATA4, were similar in both patient and healthy differentiated cells. However, at the anterior foregut stage, we observed a significant decrease in the gene and protein expression of key transcription factor SOX2 in patient-derived cells. Furthermore, using nanopore RNA sequencing, we observed that critical genes GSTM1, and RAB7 involved in cellular morphogenesis and associated with EA/TEF to be dysregulated at the anterior foregut stage in patient-derived cells. We also observed a significant increase in the expression of transcription factor NKX2.1, usually expressed only in tracheal cells, in the patient-derived esophageal epithelium. NKX2.1 expression was maintained in matured esophageal organoids even after 2 months. Next, we wanted to validate the potential use of our PSC-derived organoids to model acquired esophagus diseases such as Barrett’s esophagus (BE). We induced epithelial metaplasia with BMP4 overexpression in healthy and patient-derived esophagus organoids over a 1-month period. Our preliminary results show that patient-derived esophagus organoids expressed higher mRNA levels of MUC5AC, an epithelial columnar marker compared with the healthy group. This suggests a higher susceptibility of patient-derived esophagus organoid to metaplastic changes. In conclusion, we developed the first matrix free mature 3-dimensional esophageal organoids differentiated from EA/TEF patient-derived and identified a unique molecular signature in patient derived cells during directed esophagus differentiation. Furthermore, based on the preliminary results, we could confirm the higher incidence of Barrett’s esophagus in EA/TEF patients compared with the healthy group. Our work therefore highlights the significance of using patient-derived iPSCs to model congenital and acquired esophageal diseases to yield new insights on organ development during embryogenesis. It lays the foundation for a personalized medical approach to other diseases and the ones affecting the whole gastrointestinal system in both children and adults.

In 1976, the Southern Baptist Convention adopted its Bold New Thrusts in Foreign Missions with the overarching goal of sharing the gospel with every person in the world by the year 2000. The formation of Cooperative Services International (CSI) in 1985 and the assigning of the first nonresidential missionary (NRM) in 1987 demonstrated the Foreign Mission Board's commitment to take the gospel message to countries that restricted traditional missionary presence and to people groups identified as having little or no access to the gospel. This thesis traces the historical development of the NRM paradigm along with an analysis of the key components of the paradigm and its impact on the Board's missiology. Chapter 1 presents on overview of the thesis, outlining the primary research question addressed by this thesis and the rationale for this research. Chapter 2 focuses on the key events, persons and concepts that directly and indirectly influenced the leadership of the FMB in the development of this new missiological paradigm. Chapter 3 outlines the events leading up to the launching of CSI and the NRM program, the unique contributions of key Board leaders, and the initial growth of the NRM paradigm. Chapter 4 examines the years of growth and maturity of the NRM paradigm under the leadership of Mike Stroope. During this time, the nomenclature changed from NRM to Strategy Coordinator (SC). Chapter 5 seeks to demonstrate the impact of the NRM/SC paradigm on the Board's reorganization in 1997 called New Directions. Chapter 6 explores the CPM phenomenon and its impact on the SC paradigm, giving special attention to the reductionism that occurred as the Board sought to define and describe these movements. Chapter 7 revisits the major objective of this research as expressed in the introductory chapter and offers suggestions for further research. / Christian Spirituality, Church History and Missiology / D.Th.

The basic objective of the theoretical part of this diploma thesis is to present Rogers' Person- centred Approach (PCA) in terms of its development, theory, basic principles and potential applications out of therapeutical context, with emphasis on leadership. The first chapter is devoted to general knowledge of the PCA and in the second chapter there is a more detailed description of possible applications of the PCA in management. The basic objective of the empirical part is to verify the relationship between main necessary conditions of PCA in people management (respectively in person-centered leadership) and employees' organizational commitment. The quantitative research in the form of correlation study has been carried out on a sample of 63 respondents, employees of various organizations in various fields. Barrett-Lennard Relationship Inventory (BLRI) and Organizational Commitment Questionnaire (OCQ) were used as research methods. The results show the significant correlation between organizational commitment and measures of empathic understanding, congruence, and level of regard expressed by managers towards employees. The significant relationship between organizational commitment and unconditionality has not been confirmed. Besides the hypotheses linked to the basic goal there are some other...

In 1976, the Southern Baptist Convention adopted its Bold New Thrusts in Foreign Missions with the overarching goal of sharing the gospel with every person in the world by the year 2000. The formation of Cooperative Services International (CSI) in 1985 and the assigning of the first nonresidential missionary (NRM) in 1987 demonstrated the Foreign Mission Board's commitment to take the gospel message to countries that restricted traditional missionary presence and to people groups identified as having little or no access to the gospel. This thesis traces the historical development of the NRM paradigm along with an analysis of the key components of the paradigm and its impact on the Board's missiology. Chapter 1 presents on overview of the thesis, outlining the primary research question addressed by this thesis and the rationale for this research. Chapter 2 focuses on the key events, persons and concepts that directly and indirectly influenced the leadership of the FMB in the development of this new missiological paradigm. Chapter 3 outlines the events leading up to the launching of CSI and the NRM program, the unique contributions of key Board leaders, and the initial growth of the NRM paradigm. Chapter 4 examines the years of growth and maturity of the NRM paradigm under the leadership of Mike Stroope. During this time, the nomenclature changed from NRM to Strategy Coordinator (SC). Chapter 5 seeks to demonstrate the impact of the NRM/SC paradigm on the Board's reorganization in 1997 called New Directions. Chapter 6 explores the CPM phenomenon and its impact on the SC paradigm, giving special attention to the reductionism that occurred as the Board sought to define and describe these movements. Chapter 7 revisits the major objective of this research as expressed in the introductory chapter and offers suggestions for further research. / Christian Spirituality, Church History and Missiology / D.Th.

The Barrett (1972-1975) and Harcourt-Clark (1991-2001) New Democratic Party (NDP) governments attempted to redefine their relationship with the mining industry by changing the regulatory structures that governed mining in British Columbia. In both cases the mining industry publicly resisted these attempts, and was successful in having the reforms dismantled by subsequent free-enterprise oriented governments. These instances of conflict were centred on a foundational debate over government’s role in, and/or duty to, the mining industry. Intense industry-led resistance occurred when the traditional industry-government compact, which required government to serve as a promoter of the industry, and a liquidator of Crown owned mineral resources, was perceived to have been violated. The Barrett government more stringently asserted its ownership of public mineral resources through the enactment of a mineral royalty, and by assuming greater regulatory authority over mining operations. These actions instigated a substantial public relations campaign against the Barrett government over taxation laws. The Harcourt-Clark government pursued the development of strategic land-use plans and rejected the historic consensus that mining was innately the highest and best use of the land. This led to substantial anti-government rhetoric and an industry withdrawal from all public engagement and land-use planning processes. In both cases the mining industry was able to revive the traditional relationship when free-enterprise oriented governments replaced the NDP administrations. / Graduate / 2018-12-15

A cathedral of the Church of England is the seat of the bishop and a centre of worship and mission. The history of this institution is followed from the English Reformation, which it survived, through to the Commonwealth, which it did not. Restored on the return of the monarchy, it then survived with little further trouble until the nineteenth century, when a lot of its income was diverted to the provision of churches and ministers for the populous urban and industrialised areas, which the Church could not fund in any other way. It was the subject of investigation by two Royal Commissions in the nineteenth century and three church-inspired commissions in the twentieth. These commissions stressed the links that should exist between cathedral, bishop and diocese, which the nineteenth century diocesan revival also encouraged, and suggested changes in instruments of governance to achieve this. Some proposals came to nothing, but others were brought into law. Unlike the Roman Catholic cathedral, the Anglican one never lost its autonomy. The religious situation in Britain today is considered in the light of some contemporary sociology and psychology, and it is recognised that the continued decline in the fortunes of the Church is tied up with the massive subjective turn which characterises contemporary culture. The cathedral has not shared the mistrust which faces the Church, and its various roles are discussed in the light of its continued hold on public affection. The conclusions reached are that, although the cathedral now has strong links with bishop and diocese, it should retain its independence within relationships of interdependence with them, to enable it to harness the popularity which it enjoys to remain a centre of worship, but primarily to concentrate on being a centre of mission. Appropriate ways of achieving that are discussed.