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Leach, Sarah Elizabeth, and kimg@deakin edu au. "Nursing Work and Nursing Knowledge: Exploring the Work of Womens' Health Nurses Patterns of Power and Praxis." Deakin University. Nursing, 1998. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20031126.084144.
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The majority of women's health nurses in this study work in generalist community health centres. They have developed their praxis within the philosophy and policies of the broader women's health movement and primary health care principles in Australia. The fundamental assumption underlying this study is that women's health nurses possess a unique body of knowledge and clinical wisdom that has not been previously documented and explored. The epistemological base from which these nurses' operate offers important insights into the substantive issues that create and continually shape the practice world of nurses and their clients. Whether this represents a (re)construction of the dominant forms of health care service delivery for women is examined in this study.
The study specifically aims at exploring the practice issues and experience of women's health service provision by women's health nurses in the context of the provision of cervical cancer screening services. In mapping this particular group of nurses practice, it sets out to examine the professional and theoretical issues in contemporary nursing and women's health care.
In critically analysing the powerful discourses that shape and reshape nursing work, the study raises the concern that previous analyses of pursing work tend to universalise the structural and social subordination of nurses and nursing knowledge. This universalism is most often based on examples of midwifery and nursing work in hospital settings, and subsequently, because of these conceptualisations, all of nursing is too often deemed as a dependent occupation, with little agency, and is analysed as always in relation to medicine, to hospitals, to other knowledge forms.
Denoting certain discourses as dominant proposes a relationship of power and knowledge and the thesis argues that all work relations and practices in health are structured by certain power/knowledge relations. This analysis reveals that there
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are many competing and complimentary power/knowledge relations that structure nursing, but that nursing, and in particular women's health nurses, also challenge the power/knowledge relations around them. Through examining theories of power and knowledge the analysis, argues that theoretical eclecticism is necessary to address the complex and varied nature of nursing work. In particular it identifies that postmodern and radical feminist theorising provide the most appropriate framework to further analyse and interpret the work of women's health nurses.
Fundamental to the position argued in this thesis is a feminist perspective. This position creates important theoretical and methodological links throughout the whole study. Feminist methodology was employed to guide the design, the collection and the analysis. Intrinsic to this process was the use of the 'voices' of women's health nurses as the basis for theorising. The 'voices' of these nurses are highlighted in the chapters as italicised bold script. A constant companion along the way in examining women's health nurses' work, was the reflexivity with feminist research processes, the theoretical discussions and their 'voices'. Capturing and analysing descriptive accounts of nursing praxis is seen in this thesis as providing a way to theorise about nursing work. This methodology is able to demonstrate the knowledge forms embedded in clinical nursing praxis.
Three conceptual threads emerge throughout the discussions: one focuses on nursing praxis as a distinct process, with its own distinct epistemological base rather than in relation to 'other' knowledge forms; another describes the medical restriction and opposition as experienced by this group of nurses, but also of their resistance to medical opposition. The third theme apparent from the interviews, and which was conceptualised as beyond resistance, was the description of the alternative discourses evident in nursing work, and this focused on notions of being a professional and on autonomous nursing praxis.
This study concludes that rather than accepting the totalising discourses about nursing there are examples within nursing of resistanceboth ideologically and
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in practiceto these dominant discourses. Women's health nurses represent an important model of women's health service delivery, an analysis of which can contribute to critically reflecting on the 'paradigm of oppression' cited in nursing and about nursing more generally. Reflecting on women's health service delivery also has relevance in today's policy environment, where structural shifts in Commonwealth/State funding arrangements in community based care, may undermine women's health programs.
In summary this study identifies three important propositions for nursing:
nursing praxis can reconstruct traditional models of health care;
nursing praxis is powerful and able to 'resist' dominant discourses; and
nursing praxis can be transformative.
Joining feminist perspectives and alternative analyses of power provides a pluralistic and emancipatory politics for viewing, describing and analysing 'other' nursing work. At the micro sites of power and knowledge relationsin the everyday practice worlds of nurses, of negotiation and renegotiation, of work on the margins and at the centrewomen's health nurses' praxis operates as a positive, productive and reconstructive force in health care.
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Solari, Tomaso. "Opposition and civilian resistance in the Polish people's republic /." Genève : Institut universitaire de hautes études internationales, 1992. http://catalogue.bnf.fr/ark:/12148/cb371610616.
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Raycraft, Justin. "Restrictions and resistance : an ethnographic study of marine park opposition in southeastern Tanzania." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59027.
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The Mnazi Bay-Ruvuma Estuary Marine Park (MBREMP) in southeastern Tanzania has been touted as a ‘win-win’ project in public discourses, given its potential mutual benefits for marine biodiversity and local resource users. In this thesis, however, I argue that residents of Msimbati, a large fishing village within its catchment area, oppose the marine park, citing its negative impacts on their everyday lives. Drawing on four months of ethnographic fieldwork conducted in Msimbati village, which included participant observation, forty in-depth interviews and four focus group discussions, this thesis examines the village residents’ specific reasons for contesting the MBREMP, and subsequently, the different forms of resistance they employ to mobilize their opposition to the marine park. Using the concept of environmental governance, I maintain that people in Msimbati have been excluded from significant processes of conservation-related decision-making. Consequently, the management priorities of the MBREMP underrepresent their perceived needs and well-being. Furthermore, many study participants perceived the introduction of conservation regulations within the MBREMP as overt assertions of state power intended to control and subjugate the people of Msimbati. I argue that this finding closely resembles Michel Foucault’s notion of governmentality. In response to this perceived top-down flow of power, I discuss the abilities of village residents to exercise their individual and collective agency through explicit acts of resistance against the MBREMP. I argue, however, that the fear of state violence deters most village residents from engaging in acts that convey visible opposition to the MBREMP. Many people in Msimbati instead choose to engage in subtle acts of noncompliance to the conservation regulations. These acts are entangled with material benefits and moral statements about customary rights to resources. They can also facilitate political mobility by undermining the success of the conservation effort, while simultaneously avoiding open confrontation with governing authorities. Ultimately, this thesis brings to the fore the on-the-ground complexities of marine conservation in a resource-dependent coastal fishing village in southeastern Tanzania. I demonstrate the importance of taking an ethnographic approach to understanding the nuanced and context-specific reasons for local opposition to marine protected area formation in coastal communities.Arts, Faculty of
Anthropology, Department of
Graduate
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Sullivan, Kathryn. "RELIGIOUS AND SECULAR RESPONSES TO NAZISM: COORDINATED AND SINGULAR ACTS OF OPPOSITION." Master's thesis, University of Central Florida, 2006. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4322.
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My intention in conducting this research endeavor is to satisfy the requirements of earning a Master of Art degree in the Department of History at the University of Central Florida. My research aim has been to examine literature written from the 1930's through 2006 which chronicles the lives of Jewish and Gentile German men, women, and children living under Nazism during the years 1933-1945. I was particularly interested and hopeful in discovering the various ways in which young German females were affected by the introduction and spread of Nazi ideology. My main goal was to sort through the features of everyday life to extricate the often subtle ways Germans rebuffed conformity to Nazism. And as the research commenced, it became increasingly necessary to acknowledge and distinguish the ongoing historical debate about what aspects of non-conformity are acceptably considered "resistance" among contemporary historians also analyzing this period. The original research questions I hoped to address and discuss were firstly these; Upon the arrival of Nazism on the heels of the Weimar Republic, how was Nazism received by German citizens; secondly, once Nazism gathered a contingent of strong support, what avenues existed for those opposed to Nazism?; and thirdly, in what ways did opposition, resistance, and non-conformance to Nazism manifest itself? This examination focused singly on efforts and motivations of German citizens within Germany, to illuminate reactions and actions of women and children; whether Jewish, Protestant, or Catholic because I feel their stories are often over-looked as being insignificant. This study further recognizes the contributions and great courage which manifest when faced with Hitler's totalitarian regime.M.A.
Department of History
Arts and Humanities
History
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Folwell, Emma Jo. "From massive resistance to new conservatism : opposition to community action programs in Mississippi, 1965-1975." Thesis, University of Leicester, 2014. http://hdl.handle.net/2381/28665.
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This thesis uses the War on Poverty’s Community Action Programs as a prism through which to examine the evolution of post-1965 Massive Resistance and its interconnection with the emerging new conservatism. In examining the white relationship with Mississippi’s antipoverty programs, this thesis traces an ‘evolving resistance’ that utilised some of the methods and mechanisms of the earlier Massive Resistance, but which also drew on ostensibly race natural articulations of opposition to social welfare and saw a return to the paternalism characteristic of earlier Southern race relations. In examining the grassroots development of the colour-blind rhetoric that would become a significant trope of conservative opposition to social welfare, this thesis adds a new dimension to the rural Deep South’s contributions to the emerging national conservatism. Further, this thesis offers new insights into the failings of the War on Poverty at the grassroots by placing racial discrimination and intra-racial class divisions at the heart of its analysis of four Community Action Programs. The Community Action Program Southwest Mississippi Opportunities highlights how OEO failings at the local, regional and national levels perpetuated racial discrimination. The white response to Jackson’s Community Action Program, Community Services Association, reveals how interracial middle-class coalitions developed through the program and perpetuated a destructive racial discrimination. Case studies of two statewide programs, Mississippi Action for Progress and Strategic Training and Redevelopment showcase how intra-racial class divisions aided white supremacists shape antipoverty programs from conduits for community action into mechanisms to suppress black activism, as well as offering new insights into the role of white moderates in Mississippi’s altered racial landscape. Finally, this thesis explores the destructive impact of the nascent Mississippi Republican Party and the Nixon Administration on the War on Poverty at the grassroots.
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Bizer, George Y. "The effects of attitude framing on attitude strength : opposition leads to greater resistance than support /." The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu148639447598052.
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Logan, Michael Farley. "Fighting sprawl and city hall: Resistance to urban growth in the southwest, 1945-1965." Diss., The University of Arizona, 1994. http://hdl.handle.net/10150/186742.
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Serious resistance to urban growth in the Southwest arose at the beginning of the post World War II boom and persisted throughout the 1950s and 1960s. Most historians of the urban West ignore this early resistance. Even New Western historians truncate their studies of urbanization in the Southwest by assuming that serious opposition to development only appeared with the rise of environmentalism in the late 1960s. Urbanization in Tucson and Albuquerque proceeded in the face of constant protest. The expressions of opposition to urban expansion arose in conservative and libertarian political critiques and in ethnic resistance to urban renewal plans that targeted barrio areas. A loosely defined environmentalism appeared in these early forms of resistance as residents fought to preserve their lifestyle and native culture.
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Limeberry, Veronica A. "Eating In Opposition: Strategies Of Resistance Through Food In The Lives Of Rural Andean And Appalachian Mountain Women." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etd/2466.
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This thesis examines ways in which rural mountain women of Andean Peru and southern Appalachia use their lived histories and food knowledge in ways that counter Cartesian epistemologies regarding national and international food systems. Using women’s fiction and cookbooks, this thesis examines how voice and narrative reclaim women’s spaces within food landscapes. Further, this thesis examines women’s non-profits and grassroots organizations to illustrate the ways in which rural mountain women expand upon their lived histories in ways that contribute to tangible solutions to poverty and hunger in rural mountainous communities. The primary objective of this thesis is to recover rural mountain women’s voices in relation to food culture and examine how their food knowledge contributes to improving local food policy and reducing hunger in frontline communities.
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Sánchez, Montenegro Angélica María. "The colombian indigenous movement´s opposition as a counterweight to power." Politai, 2015. http://repositorio.pucp.edu.pe/index/handle/123456789/92698.
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In order to speak of indigenous resistance and understand it in the Colombian context, wemust take into account not only the conditions of conflict but also how state power is configured. So, we should address the structural failure of the state and understand how it leads to incomplete state intervention in the whole Colombian territory, which in turn, causes unfulfillment of basic needs and lack of legitimacy in peripheral areas. Due to this failure of the state, indigenous communities native to those areas are forced to meet their needs by means of alternative routes, such as the formation of their own government, which is legitimate and legal on constitutional terms. They are able to do so with support from organizations such as the Regional Indigenous Council of the Cauca (CRIC) or the imposed link with illegal armed groups (imposed because it is not legitimate but a reality close to indigenous communities) who use their coercive force to replace public institutions and provide services such as health, safety and the maintenance of order under their particular logics.Indigenous communities have developed self-government with identity and territoriality, which leads to new forms of organization of power. An example of this is the Regional Indigenous Council of Cauca, which represents the interests of all indigenous communities of the Cauca and promotes communication with indigenous people from other areas. This work pays significant attention to the CRIC since it contains characteristics of power such as resistance, discourses of truth and a link with law.Al hablar de resistencia indígena, situándola dentro del contexto colombiano, habremos de tener en cuenta no solo las condiciones de conflicto, sino también cómo se configura el poder dominante materializado en el Estado. De esta forma, debemos adentrarnos en la falla estructural del Estado y cómo, a consecuencia de esto, se evidencia una capacidad incompleta de intervención estatal en todo el territorio colombiano. Como consecuencia, hallamos necesidades básicas insatisfechas y una falta de legitimación del mismo territorio en zonas aledañas. Gracias a esta falla, las comunidades indígenas (propias de estas zonas aledañas) se ven obligadas a satisfacer sus necesidades por ciertas vías alternativas: la formación de un gobierno propio (legítimo y legal en términos constitucionales) con la ayuda de organismos también propios, como el Consejo Regional Indígena del Cauca (CRIC); o la impositiva vinculación (impositiva porque no es legítima, pero es una realidad cercana a las comunidades indígenas) con los grupos armados al margen de la ley, quienes a partir de su fuerza coactiva remplazan en gran medida a las instituciones pública y proveen servicios de salud, seguridad y de mantenimiento del orden bajo sus lógicas.Las comunidades indígenas han desarrollado a partir de sus condiciones un gobierno propio que implica identidad y territorialidad, dando origen a nuevas y ricas formas de organización del poder. Como ejemplo, dado que representa y agrupa los intereses de todas las comunidades indígenas del Cauca y propicia la comunicación con indígenas de otras zonas, está el Consejo Regional Indígena del Cauca, al que prestaremos atención ya que contiene características de mpoder como la resistencia, los discursos de verdad y la vinculación con el derecho.
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Khonsari, Mehrdad. "The National Movement of the Iranian Resistance 1979-1991 : the role of a banned opposition movement in international politics." Thesis, London School of Economics and Political Science (University of London), 1995. http://etheses.lse.ac.uk/2837/.
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Banned opposition movements dedicated to the overthrow of repressive governments have existed for centuries. In the second half of the 20th century, while some terrorist organizations in Western Europe, the United States, and Japan have resorted to violence in pursuit of their goal of world revolution, others, particularly, in the Third World, have engaged in acts of resistance, including violence, for the attainment of their democratic rights. Today, the more serious opposition movements are able to obtain support from outside sources for the pursuit of their aims. This thesis, deals first with the fundamental theoretical questions germane to the study of any opposition movement in current times (Chapter 1). Thereafter, as a researched case study, it focuses on "The National Movement of the Iranian Resistance (NAMIR)", led by Dr. Shapour Bakhtiar which was the first political movement to come out in opposition to the theocratic dictatorship in Iran. The thesis recounts Bakhtiar's political background (Chapter 2) and gives a detailed account of his activities in NAMIR from July 1979 until his brutal assassination in August 1991 (Chapters 3-6). Finally, it is hoped that this researched presentation will facilitate for students of international politics a better understanding of some of the critical concepts and issues relevant to the role of banned opposition movements in contemporary international politics.
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Griffith, James T. "The Influence of Antimicrobial use on Bacterial Resistance." ScholarWorks, 1992. https://scholarworks.waldenu.edu/dissertations/1395.
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Antimicrobial resistance is becoming an increasingly serious problem accompanied by relatively few studies examining the relationship between use and resistance. The present study undertakes a twenty year analysis of antimicrobial production and factors affecting antimicrobial use for a particular microorganism (Stp. faecalis)/antimicrobial agent (Cephalothin) combination. The period is inclusive of the market introduction of the agent and considerate of prescribing practices to the present time. The accumulated data reveal that there is indeed a relationship between total drug availability (medicinal, agricultural) and increased antimicrobial resistance. The data also suggest that national (or global) use changes would likely have a long term beneficial effect on the deteriorating circumstances surrounding microbial resistance to antimicrobial chemotherapeutic agents The methodology utilized includes analysis of primary historical data and graphical representation of indices derived from these data. A literature review examines the impact on antimicrobial resistance by historical duration of use, various mechanisms of resistance, non-medical uses of antimicrobial agents and clinical misuse.
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Thomas, Robin. "Integrons and integron-related antibiotic resistance in acinetobacter." Master's thesis, University of Cape Town, 1999. http://hdl.handle.net/11427/25633.
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Acinetobacter baumannii is responsible for an increasing number of nosocomial infections in patients receiving intensive care and comprehensive antibiotic resistance of these organisms hampers treatment of infections due to A.baumannii. The molecular basis of antibiotic resistance in A.baumannii has not been extensively investigated. A few studies have demonstrated the role of plasmids and transposons in resistance in this organism, but there is little data on the role of integrons and integron-associated antibiotic resistance. This study was undertaken to determine the incidence of integrons in clinical isolates of Acinetobacter from Groote Schuur Hospital (GSH), Cape Town and Universitas Hospital (UH), Bloemfontein, and to characterise the resistance genes carried in the variable regions of these integrons.
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Martin, Aditi Pandya. "Therapeutic drugs in cancer and resistance." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1717.
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We investigated the mechanism of toxicity and resistance development of small molecule tyrosine kinase inhibitor lapatinib in HCT 116 colon cancer cells. Lapatinib mediated cell death in HCT 116 cells was caspase independent and involved cytosolic release of apoptosis inducing factor. Treatment of HCT 116 cells with 10µM Lapatinib lead to the outgrowth of lapatinib resistant HCT 116 cells. Our studies show that alterations in the expression and activation of Bcl-2 family proteins allow lapatinib resistant HCT 116 cells to resist cytotoxic effects of lapatinib as well as of other commonly used chemotherapeutic agents. In hepatoma and pancreatic cancer cells, the effects of combining multi-kinase inhibitor sorafenib with histone deacetylase inhibitors (HDACIs) namely, vorinostat and sodium valproate were investigated. It was found that sorafenib synergizes with HDACIs resulting in enhanced cell death compared to death induced by the drugs individually. The mechanism of action of sorafenib and vorinostat combination treatment as well as sorafenib and sodium valproate combined treatment was shown to involve activation of the CD95 death receptor pathway. Alterations in the CD95 pathway can render cancer cells resistant to chemotherapeutic agents. Hence, we combined sorafenib+sodium valproate with a BH-3 domain mimetic named obatoclax (GX-15-070) which resulted in enhanced toxicity to cancer cells. More importantly, knock-down of CD95 (to mimic non-functional CD95 pathway) reduced cell death induced by sorafenib+sodium valproate combined but failed to protect cells from cell death induced by sorafenib+sodium valproate+obatoclax combined. This suggests that combining sorafenib+HDACI with obatoclax may not only enhance toxicity to cancer cells but may also reduce chances of resistance development via alterations in the CD95 pathway. These studies enhance our knowledge of existing treatment strategies for cancer as well as throw light on how current approaches can be improved in order to better diagnose and treat cancer. Understanding mechanisms of drug action as well as resistance development will allow us to combine existing therapies effectively in order best target cancer cells as well as provide us with information that can help us design new cancer treatment strategies.
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Terzopoulos, Nikolaos. "High output resistance current drive circuits for medical applications." Thesis, Oxford Brookes University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427079.
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Bendall, J. B. "Bacterial resistance to antimicrobial agents in geriatric medical wards." Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381441.
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McCartan-Welch, Kathleen. "Resistance and reflection : the humanities experience for medical students /." free to MU campus, to others for purchase, 1997. http://wwwlib.umi.com/cr/mo/fullcit?p9841346.
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Harness, Oliver. "Change and power in the profession : a study of the lived experiences of teachers' opposition and resistance witin a neoliberal hegemony." Thesis, Northumbria University, 2016. http://nrl.northumbria.ac.uk/31658/.
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Schools in England have undergone huge change since neoliberal ideologies introduced notions of choice and competition. This study seeks to understand how teachers rationalised their roles alongside the demands of performativity associated with managerialisation and marketisation. As such, this research explores the lived experiences of teachers within a neoliberal hegemony. Methodologically, I used a social constructionist paradigm and an interpretative phenomenological analysis after Smith, Flowers and Larkin (2009). I conducted six in-depth semi-structured interviews with teachers in primary, middle and secondary school settings. My interpretative phenomenological analysis used Wenger’s (1989) concept of a community of practice as well as concepts from social theorists such as Habermas (1979, 1996), Giddens (1986, 1991) and Bourdieu (1984, 1994) to frame my thinking. The research found that the changes being experienced by teachers are not aligned with their understandings and beliefs concerning education, either for themselves as a professional body or for the pupils in their care. As such, the teachers express notions such as the suppression of their voice and the oppression of their autonomy. Furthermore, teachers’ descriptions include philosophical and practical resistance to change. The descriptions of change and resistance show alignment towards notions of welfare education not neoliberal managerialisation and marketisation. The nature of the new knowledge concerns changed forms of organisational experiences, from changed forms of organisational communication to changed forms of learning. It is this change, brought about by managerialisation and marketisation, that the teachers describe as resisting, both philosophically and practically. As such the participants describe a clash of lifeworlds and a clash of doxa, such that they experience ontological insecurity. Furthermore the managerialisation and marketisation of schools is at odds with Wenger’s (1989) notion of a community of practice and as such, is degrading organisational learning and practice.
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Perras, Stefan. "Electricity transmission line planning: Success factors for transmission system operators to reduce public opposition." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-161770.
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Europe requires significant transmission grid expansions to foster the integration of electricity markets, enhance security of supply and integrate renewable energies. However, next to lengthy authorization processes, transmission system operators (TSOs) in Europe are currently facing extreme public opposition in their transmission line projects leading to significant project delays. These delays imply significant additional costs for TSOs as well as society as a whole and put the transformation of the European energy system at risk. Existing scientific literature currently lacks comprehensive studies that have tried to identify generalizable success factors to overcome public opposition in transmission line projects. The goal of work at hand was to close this research gap. Potential success factors were collected through extensive literature review and interviews throughout Europe with respective stakeholders such as citizen action groups, NGOs or energy experts. Experiences from analogue large infrastructure projects like wind parks, carbon capture and storage facilities, hydro dams, nuclear waste repositories, etc. were also used to form hypotheses. The findings were transformed into a structural equation model and tested through a questionnaire answered by almost all European TSOs.
Results revealed that people’s trust in the TSO is of utmost importance for less public opposition. It can be regarded as the critical success factor per se. TSOs can create trust through stakeholder participation, sufficient communication, proper organizational readiness and liaison with stakeholders. Furthermore, appropriate technical planning can help to reduce public opposition in transmission line projects. In total 18 concrete and actionable success factors were identified for TSO management to facilitate the establishment of these aforementioned aspects. They will help European TSOs to reduce public opposition and thus accelerate the implementation of new transmission lines. Interestingly, economic benefits for people did not turn out to be a Significant success factor in reducing their opposition against new transmission lines.
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JONES, NIKITA M. "COMMUNITY RESISTANCE TO THE SECTION 8 HOUSING CHOICE VOUCHER PROGRAM: A CASE STUDY OF THE MULTI-NEIGHBORHOOD HOUSING TASK FORCE IN CINCINNATI, OHIO." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116257807.
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Evans, Joanna. "Investigation of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis." Doctoral thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/10434.
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The emergence of antibiotic resistant strains of Mycobacterium tuberculosis, coupled with the time it takes to perform phenotypic drug susceptibility testing of this organism, makes the treatment of tuberculosis increasingly difficult. Several genotypic assays for the rapid detection of drug resistance in M. tuberculosis have been developed, but the sensitivity with which these assays identify resistance differs geographically. Additionally, the identification of phenotypically resistant isolates with no identifiable genotypic marker suggests that other factors, such as differential gene expression, may play a role in the development of drug resistance in M. tuberculosis. This investigation aims to both develop and evaluate rapid genotypic assays for the detection of resistance to both first- and second-line drugs in M. tuberculosis, and to investigate the role of alternative sigma factors in the progression to multidrug resistant M. tuberculosis.
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Duncan, Terrence. "An Examination of Physician Resistance Related to Electronic Medical Records Adoption." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1257.
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The 2009 American Recovery and Reinvestment Act, signed under the Obama administration, mandated physicians to complete certification for electronic medical records (EMRs). Despite these mandates and the increased access to information technology, slow adoption rates persist on the use of EMRs. Guided by the theory of planned behavior and the technology acceptance model, the purpose of this quantitative study was to examine the relationship between the independent variables perceived ease of use, perceived usefulness, perceived behavioral control, perceived social influence, attitudes toward EMR, and the dependent variable user acceptance. This study identified physicians in the United States as end-users of EMRs. In this study, 76 randomly selected physicians in the United States, identified as end-users of EMRs, completed an electronic survey requiring responses to a 5-point Likert Scale model. Standard multiple regression analysis served as the means used to analyze the regression model. Despite the regression model being statistically significant, none of the individual independent variables had statistical significance in predicting user acceptance. Interdependence and homoscedasticity likely contributed to this phenomenon. Social change implications include understanding of physician perceptions and beliefs--how physician perceptions and beliefs affect EMR adoption. Because adoption rates did not achieve 100% certification by end-users, another social change implication includes the necessity of examining how end-user acceptance could decrease medical errors, increase efficiencies in physician workload, and improve communication within the health care industry.
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Bonnedahl, Jonas. "Antibiotic Resistance in Enterobacteriaceae Isolated from Wild Birds." Doctoral thesis, Uppsala universitet, Infektionssjukdomar, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-145480.
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The presence and spread of clinically important antibiotic-resistant bacteria in reservoirs from natural environments are not well studied compared to the clinical environments. The overall aim of this project was to study the presence of clinically important antibiotic-resistant bacteria in a reservoir from natural environments. Wild birds were chosen not only as indicators of the level of antibiotic resistance in surrounding natural bacterial populations, but also since birds can act as vectors of several potential pathogens including enteropathogens and because they by migration have an ability to spread these pathogens across geographical regions. The studies in this thesis showed that wild birds carry antibiotic-resistant enterobacteriaceae. The levels and spectrum of antibiotic resistance varies between different bird populations and geographical regions. In bird populations without interaction with human activities throughout the year, antibiotic resistance is lacking. Antibiotic-resistant bacteria could however probably be dispersed to remote regions by bird migration. Extended-spectrum beta-lactamases (ESBLs) and especially CTX-M types are found in comparable high levels in gull populations considering the recent emergence of these resistance genes in clinical settings. The CTX-M types found in wild birds are the same types that are found in clinical settings and in food producing animals from the same regions. ESBL-producing E. coli isolated from Yellow-legged Gulls are genetically heterogenous, reflecting that these resistance genes are present across the full E. coli genetic diversity. In wild birds CTX-M are found both in E. coli strains with previously known “human signature” as well as “novel” strains. This indicates that these genes are indeed very mobile and rapidly dispersing both through horizontal gene transfer and through successful clones. The findings in this thesis indicate that bird colonies could act as melting pots and reservoirs for new resistance types and that wild birds could act as important indicators of the level of antibiotic resistance dispersal in natural environments.
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Eby, Anne Kathryn. "Factors affecting medical-surgical area nurses' compliance with contact precautions." Thesis, Montana State University, 2009. http://etd.lib.montana.edu/etd/2009/eby/EbyA1209.pdf.
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Multidrug-resistant organisms are a significant threat in health care facilities, and are associated with many adverse consequences for infected patients. However, despite these concerns and the evidence that contact precautions are an effective way to address them, compliance with contact precautions guidelines among health care workers remains low (Farr, 2000). The primary goal of this study was to examine factors affecting medical-surgical nurses' compliance with contact precautions guidelines when caring for patients colonized by or infected with multidrug-resistant organisms. A secondary purpose of this study was to describe demographic characteristics of medical-surgical nurses to determine if certain characteristics (e.g. age, time in practice, level of education) had a relationship with their compliance in using contact precautions guidelines. Finally, this study examined barriers to the use of contact precautions and consequences for failure to follow contact precautions guidelines. A survey tool was developed by the researcher for this study to examine these questions, and an exploratory, cross-sectional, correlation descriptive study was conducted. The study group was made up primarily of female nurses with associate or bachelor degrees. Nurses from the orthopedic and neurosurgery unit made up the largest percentage of respondents. All respondents indicated that they were familiar with CP guidelines. Eight primary barriers to the use of contact precautions were listed by participants. Half of the participants listed one of the time management categories ("no time" or "urgency") as the primary barrier to compliance with contact precautions. Participants' age, years experience and level of education were not statistically significant predictors of the participants' level of compliance. There was not a statistically significant difference between the barriers to compliance groups (no time/urgency versus other) on their ability to comply with contact precautions. Lastly, there was not a statistically significant relationship among the primary consequence of non-compliance with CP guidelines (medical versus other) and the participants' level of compliance (low versus high).
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Prenkert, Malin. "On mechanisms of drug resistance in acute myeloid leukemia." Doctoral thesis, Örebro universitet, Hälsoakademin, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-10603.
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In this thesis focus has been to increase the knowledge and understanding of some of the mechanisms responsible for drug resistance in acute myeloid leukemia, as well as identify possibilities to predict drug resistance at diagnosis. We have studied the intracellular behavior of cytostatic drugs and their main metabolites (paper I) and the cellular response to cytostatic drugs (paper III). A new flow cytometry in vitro chemosensitivity assay was developed, to enable identification of viable myeloid cells and determination of drug sensitivity (paper II). Finally, possible new markers involved in drug resistance were investigated (paper IV). In conclusion we found that idarubicin and daunorubicin are equally toxic at the same intracellular concentrations. The contribution of the main metabolites to the cytotoxic effects of idarubicin and daunorubicin, in both drug sensitive and drug resistant human myeloid leukemia cells, is low. It is most likely the pharmacokinetic properties of idarubicin and daunorubicin that confer their main cytotoxic effect. With the new flow cytometry chemosensitivity assay we selectively identified viable CD13/CD33 expressing myeloid cells and found that the cytotoxicity results correlated to clinical parameters, such as secondary AML and resistant disease. Short-term exposure of leukemia cell lines with different levels of drug resistance to ara-C revealed that Pgp mRNA and protein ex-pression levels, as well as GSTπ mRNA levels, were rapidly up-regulated. Clinically, this up-regulation may be of importance for the sequential scheduling of daunorubicin and ara-C during the induction treatment of AML. CRIM1 has never been studied in the context of drug resistance before. We show for the first time that baseline expression of CRIM1 mRNA is much higher in drug resistant leukemia cells compared to drug sensitive cells. We also found a co-variance between CRIM1 and Pgp mRNA expression levels in leukemia cell lines with different levels of drug resistance, suggesting that CRIM1 may be useful as a marker of drug resistance.
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Burman, Richard J. "Investigating excitatory GABAergic signalling & benzodiazepine resistance in an in vitro model of status epilepticus." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/27886.
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Status epilepticus (SE) describes a state of persistent seizures which are unrelenting. First- line treatment for status epilepticus uses a group of drugs, the benzodiazepines, that promote the action of the major inhibitory neurotransmitter within the brain, gamma (γ)-aminobutyric acid (GABA). In a subset of patients however, benzodiazepines prove to be ineffective in terminating SE. Previous data from in vitro models has demonstrated that during single seizures, instead of being inhibitory, activation of the GABAA receptor can have an excitatory effect on neurons. To date, it is unknown whether this shift in GABAergic function contributes to SE, nor how it may modulate the anticonvulsant properties of benzodiazepines. In this thesis I explore the role of excitatory GABAergic signaling in an in vitro model of SE and how this may affect the anticonvulsant efficacy of the benzodiazepine, diazepam. Firstly, I confirm that benzodiazepine-resistant SE is prevalent in a South African paediatric population. Secondly, consistent with its established mechanism of action, I show that diazepam enhances GABAAR synaptic currents. Thirdly, using the in vitro 0 Mg²⁺ model of status epilepticus I show that whilst early application of diazepam has anticonvulsant properties, this is lost when the drug is applied during prolonged epileptiform activity. Fourthly, to investigate this phenomenon I use optogenetic activation of GABAergic interneurons to show that interneurons can drive epileptiform discharges during SE-like activity in vitro. Finally, I confirm that during seizure-like events there is a transient shift in GABAergic signaling that is caused by activity driven changes in the transmembrane Cl⁻ gradient. This thesis provides insight into how excitatory GABAergic signaling during prolonged seizures may contribute towards benzodiazepine resistance in SE. I believe that these results are relevant for understanding of the pathophysiology of SE and may help inform optimal treatment protocols for this condition.
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Smit, Odette. "Early infant HIV diagnosis and characterization of HIV drug resistance in Gauteng, South Africa." Diss., University of Pretoria, 2021. http://hdl.handle.net/2263/79141.
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Despite the high prevalence of the human immunodeficiency virus (HIV) in South African women of reproductive age, the South African (SA) Prevention of Mother-to-Child Transmission (PMTCT) programme has significantly reduced the incidence of new HIV infections in infants from >20% in 2004 to <2% and overall MTCT approximately >5%. The PMTCT programme, however, faces challenges in terms of early infant diagnosis (EID) because of HIV polymerase chain reaction (PCR) indeterminate results as well as HIV drug resistance (HIVDR) secondary to antiretroviral therapy (ART) exposure of mothers and infants. The National Health and Laboratory Services (NHLS) uses the Roche COBAS®AmpliPrep (CAP)/COBAS®TaqMan® (CTM) HIV-1 Qualitative Test (Roche Molecular Systems, Pleasanton, CA) (CAP/CTM) platform as part of EID. Recently, the Roche cobas® 6800/8800 System has been introduced to test HIV viral load and HIV DNA PCR for EID. The platform is already processing samples for HIV viral load; however, verification for HIV DNA PCR for EID with dried blood samples (DBS) is needed, especially for CAP/CTM HIV PCR indeterminate results (Cycle threshold [Ct]>33 with any relative fluorescent intensity [RFI] value or Ct≤33 and RFI <5 on the CAP/CTM, Ct>38 on the Roche cobas® 6800/8800 System). In addition, HIVDR in newly diagnosed infants significantly limits treatment options. Therefore, the current study verified the Roche cobas® 6800/8800 System against the CAP/CTM system for the detection of HIV in EID and determined the HIVDR prevalence and profiles in infants <6 months, and how this affects current SA PMTCT and EID guidelines.
The study comprised 642 DBS samples (235 HIV PCR positive, 193 HIV PCR negative and 214 HIV PCR indeterminate) previously tested on the CAP/CTM assay. Overall, 99.6% (234/235) CAP/CTM HIV PCR positive samples remained positive, while 99.5% (192/193) HIV PCR negative samples remained negative with the Roche cobas® 6800/8800 System. The HIV PCR indeterminate results as detected by the CAP/CTM decreased from 100% (214/214) to 8.4% (18/214) with the Roche cobas® 6800/8800 System. The Roche cobas® 6800/8800 System had a specificity of 99.5% and a sensitivity of 99.6%, but this decreased to 96.3% and 90.8% when HIV PCR indeterminate results were included. The kappa value increased from 0.5, which signifies moderate agreement, to 0.9, which is excellent agreement, when RFI from the CAP/CTM was excluded for result determination. The overall agreement between the two assays, taking only cycle threshold values into account, was 93.8%.
As for HIVDR, mutations were detected in 42.9% (24/56) of infants <6 months. The most common non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation causing high-level resistance was K103N (21.4% [12/56]), followed by Y181C and the NRTI mutation, M184V, both in 8.9% (5/56) of infants. Also, major protease inhibitor (PI) mutations, M46L and V82A were detected in one case each (1.8%).
In conclusion, the performance of the Roche cobas®6800/8800 System was comparable to the CAP/CTM; however, it detected fewer HIV PCR indeterminate results, thus potentially offering conclusive results in a larger proportion of infants. The detection of high levels of the NNRTI mutation, K103N, emphasises the need for constant surveillance since nevirapine is included as part of the SA PMTCT guidelines and the World Health Organization recommends that NNRTIs should be phased-out of as part of PMTCT once the resistance prevalence exceeds 10%.Dissertation (MSc (Medical Virology))--University of Pretoria, 2021.
National Health Laboratory Services Trust and RDP UP
Medical Virology
MSc (Medical Virology)
Restricted
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Bell, Carol Jane. "Variability, oxidation resistance and wear of 'medical grade' ultra-high molecular weight polyethylene." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394335.
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Manenzhe, Rendani Innocent. "Nasopharyngeal colonization dynamics with Streptococcus pneumoniae and associated antimicrobial resistance in a South African birth cohort." Doctoral thesis, Faculty of Health Sciences, 2019. https://hdl.handle.net/11427/31664.
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Introduction: Nasopharyngeal (NP) colonization by Streptococcus pneumoniae (the pneumococcus) precedes the development of respiratory tract infection. Colonization by antimicrobial-resistant pneumococci, especially in infants, is a major public health concern as pneumococcus is a frequent cause of bacterial acute respiratory tract infections among children. This study longitudinally investigated antimicrobial resistance amongst pneumococci colonizing the nasopharynx of South African infants immunized with the 13- valent pneumococcal conjugate vaccine (PCV13). Furthermore, the study explored strainlevel pneumococcal colonization patterns and associated antimicrobial resistance determinants as well as the composition of the NP antibiotic resistome using shotgun metagenomic sequencing. Methods: NP swabs were collected every second week from birth through the first year of life from 137 infants who were immunized with 2+1 doses of PCV13. These were the first 137 infants enrolled in the cohort who had the most complete fortnightly NP sampling (defined as at least 23-26 fortnightly collected NP swabs). Pneumococci were identified and serotyped using conventional techniques, and their antibiotic susceptibility profiles determined by disc diffusion and E-test. A subset of 196 NP samples from 23 infants were selected based on changes in serotype or antimicrobial resistance. These were subjected to broth enrichment, total nucleic acid extraction and subsequent shotgun metagenomic sequencing. Sequence reads were assembled and aligned to reference pneumococcal genomes. In-silico pneumococcal capsular, multilocus sequence typing, and antimicrobial resistance determinants were described. Finally, antibiotic resistance genes were identified from all bacterial contigs, to determine the NP resistome. Results: 1520 pneumococcal (760 non-duplicate) isolates were recovered from 137 infants; including non-typeable (n = 99), PCV13 (n = 133), and non-PCV13 serotypes (n = 528). The prevalence of penicillin, erythromycin, and cotrimoxazole non-susceptibility was 19% (147/760; 95% CI 17-22%) (3% resistant), 18% (136/760; 95% CI 15-21%) (14% resistant) and 45% (344/760; 95% CI 42-49%) (36% resistant), respectively. The predominant penicillin-non-susceptible serotypes included 15B/15C (n = 20), 19A (n = 13), 15A (n = 10), 19F (n = 8), and 21 (n = 8). Multi-drug resistance (MDR) was observed in 9% (68/760; 95% CI 7-11%) of the isolates. PCV13 serotypes were more likely to be non-susceptible, compared to non-PCV13 serotypes, to penicillin (26% vs. 16%, p = 0.007), erythromycin (23% vs. 15%, p = 0.027) and cotrimoxazole (62% vs. 41%, p < 0.001). Non-susceptibility to penicillin, erythromycin, and cotrimoxazole remained relatively constant through the first year of life (X 2 test for trend: p = 0.184, range 0 – 25%; p = 0.171, range 0 – 27%; and p = 0.572, range 0 – 55%, respectively). Overall, penicillin or erythromycin-non-susceptible pneumococci were carried for a shorter duration than susceptible pneumococci (penicillin [mean days, 18 vs. 21, p = 0.013] and erythromycin [mean days, 18 vs. 21, p = 0.035]). Forty-five percentage (61/137) of infants carried the same serotype which acquired or lost resistance over time, and these changes were predominantly for penicillin (76%, 79/104). Of the 196 NP samples sequenced, 174 had corresponding positive cultures for pneumococci and, of these, 152 were assigned an in-silico serotype. Metagenomic sequencing detected a single pneumococcal serotype in 85% (129/152), and co-colonization in 15% (23/152) of NP samples, respectively. In total, 22 different pneumococcal serotypes were identified, with 15B/15C (n = 49) and 16F (n = 21) being the most common non-PCV13 serotypes, while 23F (n = 9) and 19A (n = 8) were the most common PCV13 serotypes. Twenty-six different sequence types (STs), including 4 novel STs were identified. Mutations in the folA and folP genes, associated with cotrimoxazole resistance, were detected in 89% (87/98) of cotrimoxazole-non-susceptible pneumococci and mutations in the pbp1a and pbp2x genes, known to confer beta-lactam resistance, were identified in penicillin nonsusceptible ST705215B/15C isolates. A total of 329 antimicrobial resistance (AMR) genes were detected in 64% (125/196) of the sequenced samples, including 36 non-redundant genes ranging from 1 to 14 genes per sample. The predominant AMR genes detected were those conferring resistance to beta-lactams (52%, 172/329), macrolide-lincosamide-streptogramin (17%, 56/329), and tetracycline (12%, 38/329). The msrD, ermB, and mefA genes were only detected from pneumococcal reads. The predominant resistance genes detected from nonpneumococcal reads included blaOXA-60, blaOXA-22, and blaBRO-1. Conclusion: NP carriage of antibiotic-non-susceptible pneumococci was relatively constant throughout the first year of life. Despite high vaccine coverage levels, PCV13 serotypes were identified and were more commonly non-susceptible to penicillin, erythromycin, and cotrimoxazole. Overall, penicillin or erythromycin-non-susceptible pneumococci were carried for a shorter duration than susceptible pneumococci, however, non-susceptible PCV13 serotypes were carried for a longer duration than non-susceptible non-PCV13 serotypes. Direct shotgun sequencing from enriched NP samples was shown to be a powerful technique for a detailed description of the pneumococcal component of the NP microbiome and resistome, and its use should be explored similarly for other bacteria in this niche.
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Moodley, Vineshree Mischka. "Acinetobacter baumannii : an evaluation of five susceptibility test methods to detect tobramycin resistance in an epidemiologically related cluster." Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/11686.
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Acinetobacter baumannii is a major pathogen causing nosocomial infections, particularly in critically ill patients. This organism has acquired the propensity to rapidly develop resistance to most antibiotics. At several hospitals within Cape Town, tobramycin and colistin remain frequently the only therapeutic options. The Vitek2 automated susceptibility testing (AST) is used in the clinical laboratory to determine selected susceptibility profiles. The suspicion of a possible AST-related technical error when testing for susceptibility to tobramycin in A. baumannii precipitated this study.
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Garny, Seike. "Distribution, frequency and contribution to the expression of antibiotic resistance gene of an IS element in Acinetobacter baumannii." Master's thesis, University of Cape Town, 2006. http://hdl.handle.net/11427/2708.
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Mahal, Dawn. "Resistance to change in primary care : an exploration of the role of professional identity." Thesis, University of Stirling, 2017. http://hdl.handle.net/1893/27608.
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This thesis contributes to the academic knowledge in the field of professional identity and organisational change. This thesis also has a practical implication as the findings helped to shape an organisational change within the co-funders organisation. The research was guided by the wish to explore the extent to which professional identity affects the willingness of those within Primary healthcare Units to accept fundamental changes in their working practices. Specifically, the aim was to establish the relationship of professional identity to processes of change. As the owners of small businesses who contract their services to the Health Board, the opinions of General Practitioners (GPs) were deemed to be of particular interest. The study was undertaken using a mixed method design, based upon a Constructivist grounded theory methodology. This was chosen as the ideal vehicle to examine the complex nature of identity within healthcare professionals and how they viewed organisational changes. Research started with unstructured interviews (n-14) and the analysis of the data obtained was fed into a questionnaire (n-97). The questionnaire offered validation of the initial findings. The findings of the research showed that professional identity has a bearing on the willingness of professionals to accept changes to their working environment. The resistance demonstrated by Healthcare staff, and specifically, GPs, to organisational change could be linked to feeling a perceived threat to their professional identity. Therefore, to undertake a successful organisational change, change managers must recognise that identity is vitally important and can affect the success or failure of an organisational change. Consideration of how any change may be perceived by professionals, within an identity context, must be built into the organisational change programme and revisited regularly during the change programme.
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Sundström, Johan. "Left ventricular hypertrophy and the insulin resistance syndrome." Doctoral thesis, Uppsala University, Department of Public Health and Caring Sciences, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-580.
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Left ventricular hypertrophy (LVH) and the insulin resistance syndrome are common conditions associated with a markedly increased cardiovascular risk. In a fairly large prospective longitudinal study of men from the general population, we found that an unfavorable serum fatty acid profile and components of the insulin resistance syndrome such as dyslipidemia, obesity and hypertension at age 50 predicted the prevalence of LVH at age 70. In cross-sectional analyses at age 70, several components of the insulin resistance syndrome were significantly related to left ventricular relative wall thickness and concentric remodeling, but less to LVH. Left ventricular relative wall thickness was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in a healthy, normotensive sample of the cohort investigated with positron emission tomography, whereas left ventricular mass index was not related to myocardial or skeletal muscle insulin sensitivity. At age 70, echocardiographic LVH was related to a variety of common electrocardiographic diagnoses. In a prospective mortality analysis with baseline at age 70 and a median follow-up time of five years, echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of other cardiovascular risk factors, implying that echocardiographic and electrocardiographic LVH in part carry different prognostic information.
In summary, components of the insulin resistance syndrome predicted LVH twenty years later, but were cross-sectionally more related to increased left ventricular relative wall thickness and concentric remodeling. Echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of components of the insulin resistance syndrome.
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Mlamla, Zandile Cleopatra. "Improving methods for genotypic drug resistance testing in Mycobacterium tuberculosis." Thesis, Stellenbosch : University of Stellenbosch, 2011. http://hdl.handle.net/10019.1/6756.
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Thesis (MScMedSc)--University of Stellenbosch, 2011.ENGLISH ABSTRACT: An important next step to Tuberculosis control relies on the translation of basic science and modern diagnostic techniques into primary health care clinics. These assays must be rapid, inexpensive, interpretation of results must be easy and they must be simple so that a healthcare worker with limited training can perform the tests under safe conditions. This study consists of four aims. The first aim was to develop a methodology to sterilize sputum specimens for rapid TB diagnosis and drug resistance testing. Candidate bactericides were identified from the literature, and tested for their bactericidal activity in Mycobacterium tuberculosis. We identified ultraseptin®aktiv as a powerful bactericidal agent which sterilizes sputum specimens for subsequent safe handling prior to light emitting diode microscopy and it also provides a DNA template for PCR-based tests. An algorithm has been proposed for the processing of specimens and rapid diagnosis of TB and drug resistant TB while patients wait for results. Recently, the World Health Organization has endorsed the MTBDRplus test for diagnosis of TB and drug resistant TB. However genotypic tests may have more problems than anticipated. With the HIV pandemic, an increase of non-tuberculous mycobacteria has been reported. The sensitivity of genotypic tests in specimens with underlying non-tuberculous mycobacterial species therefore requires further evaluation. This study therefore also aimed at determining the reliability of the MTBDRplus assay for detection of drug resistant TB where non-tuberculous bacterial load is high. Clinically relevant non-tuberculous mycobacterium DNA and DNA from a multi-drug resistant TB isolate were obtained. Ratios of the different NTM with the MDR-TB DNA were made and subjected to the MTBDRplus assay. Known mix NTM and TB infected clinical isolates and sputum sediments were also evaluated for TB and drug resistance detection on the MTBDRplus assay. Under these conditions, this study provides evidence that the MTBDRplus test cannot reliably detect TB and drug resistance TB in specimens with underlying non-tuberculous mycobacteria. Thirdly, to evaluate the sensitivity of the MTBDRplus assay for detecting drug resistance in hetero-resistant isolates, ratios were made using purified DNA from an MDR and pan-susceptible TB isolate. The MTBDRplus assay was then performed on the different ratios. We report that the MTBDRplus assay can efficiently detect wild type DNA in genes associated with resistance during the early evolution of drug resistance. However, in the later stage during treatment when both the wild type and mutants are present, the detection limit for the mutant DNA was 1:55. Due to these results, the MTBDRplus assay should still be further improved or other tests should be developed to address these limitations. And finally to combat cross amplicon contamination during the final steps of genotypic detection with the MTBDRplus assay, a proof of concept for a patentable closed tube line probe device was proposed on the 4th aim. This device can be improved to enable automated drug resistance genotyping of multiple specimens. The results of this study highlight the need for a sensitive inexpensive point of care drug resistance test that does not require intensive training.
AFRIKAANSE OPSOMMING: 'n Belangrike volgende stap om Tuberkulose te beheer is om basiese wetenskap resultate te gebruik sodat moderne diagnose tegnieke ontwikkel kan word wat in primêre gesondheidsorg klinieke toegepas kan word. Hierdie toetse moet vinnig, goedkoop, en die interpretasie van resultate moet maklik wees. Die toetse moet eenvoudig wees sodat 'n gesondheidswerker met beperkte opleiding die toetse onder veilige omstandighede kan uitvoer. Hierdie studie bestaan uit vier doelwitte, waarvan die eerste was om 'n metode te ontwikkel vir die sterilisasie van sputum monsters vir vinnige TB diagnose en die toesting van middelweerstandigheid. Kandidaat kiemdodende middels was geïdentifiseer vanaf die literatuur en die middels se kiekdodende aktiviteit was getoets op Mycobacterium tuberculosis. Ons het ultraseptin®aktiv geïdentifiseer as 'n kragtige kiemdodende middel wat bakteria in sputum monsters steriliseer vir veilige hantering voordat diagnose met 'n lig uitstralende diode mikroskopie gedoen kan word. Hierdie behandeling met ultraseptin®aktiv bied ook 'n DNA templaat vir PCR-gebaseerde toetse. 'n Algoritme is voorgestel vir die hantering van monsters en die vinnige diagnose van sensitiewe- en middel weerstandige Tuberkulose terwyl die pasiënte by die kliniek wag vir die resultate. Onlangs het die Wêreld Gesondheid Organisasie die genotipiese MTBDRplus toets vir die diagnose van Tuberkulose en middel-weerstandige Tuberkulose onderskryf. Hierdie toets word tans op groot skaal in Suid Afrika gebruik. Dit kan egter wees dat genotipiese toetse baie meer probleme kan he as wat aanvanklik verwag is. Die HIV pandemie gaan toenemend gepaard met n toename van nie-tuberkulose mycobacteria. Die sensitiwiteit van genotipiese toetse op monsters met onderliggende nie-tuberkulose mikobakteriese spesies vereis dus verdere evaluasie. Die doel van hierdie studie was ook om die betroubaarheid van die MTBDRplus-toets te bepaal vir die opsporing van middelweerstandige TB waar die nie-tuberkulose bakteriële lading hoog is. DNA van kliniese relevante nie-tuberkulose mikobakteria en multi-middelweerstige TB isolate was bekom. Verskillende verdunnigs van die spesifieke NTM DNA te same met die van MDR-TB DNA is gemaak en onderwerp aan die MTBDRplus toets. Bekende gemengde NTM- en TB geïnfekteerde kliniese isolate en sputum sedimente was ook geevalueer vir die opsporing van TB en middel weerstandigheid met die MTBDRplus toets. Hierdie studie verskaf bewyse dat die MTBDRplus toets nie betroubaar is met die diagnose van sensitiewe- en middel weerstandige Tuberkulose in monsters met onderliggende nie-tuberkulose mycobacteria nie. Verskillende verdunnings van gesuiwerde DNA van MDR en pan-sensitiewe TB isolate is gemaak om die sensitiwiteit van die MTBDRplus toets vir die opsporing van middelweerstandigheid te bepaal. Die MDRDRplus toets is gebruik met hierdie verdunnings. Resultate in hierdie studie toon dat die MTBDRplus toets effektief is met die identifisering van wilde-tipe DNA (dit beteken middel sensitief) in gene wat geassosieer word met middel weerstandigheid gedurende die vroeë ontwikkeling van weerstandigheid. Hier teenoor toon die resultate dat in die later stadium tydens behandeling, wanneer beide die wilde-tipe (sensitief) en mutante DNA (weerstandig) teenwoordig is, is die opsporingslimiet vir die mutante DNA maar 1:55. As gevolg van hierdie resultate raai ons aan dat die MTBDRplus toets nog verder verbeter moet word of dat ander toetse ontwikkel moet word om hierdie beperkinge aan te spreek. Amplikon kruiskontaminasie kan n groot impak hê op die betroubaarheid van enige genotipiese diagnostiese toets. Die finale stappe van MTBDRplus toets behels die gebruik van 'n oop sisteem sodat kontaminasie maklik kan plaasvind. In die 4de doewit 'n konsep vir 'n patenteerbare geslotebuis toestel ontwikkel en die resultate het getoon dat kontaminasie suksesvol uitgeskakel kan word. Hierdie toestel kan verbeter na 'n outomatiese apparaat verbeter word sodat die module genotipering van verskeie monsters moontlik kan maak. Die resultate van hierdie studie beklemtoon die noodsaaklikheid van 'n sensitiewe goedkoop “point of care” diagnostiese toets wat nie intensiewe opleiding benodig nie.
Medical Research Council of South Africa
University of Stellenbosch, Dept. of Molecular Biology and Human Genetics
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Bard, Amanda E. "The Effectiveness of Resistance Exercises in the Management of Medial Tibial Stress Syndrome." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/scripps_theses/279.
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Medial tibial stress syndrome (MTSS) is a stress and overuse injury that presents as pain on the medial aspect of the lower two-thirds of the tibia. It is most often caused by repetitive actions on hard surfaces such as running, marching, and dancing. Individuals most affected by MTSS are runners, members of the military, dancers, and athletes that play soccer, volleyball and basketball. While MTSS has a relatively standard presentation of pain on the medial aspect of the tibia, it can occasionally be mistaken for other injuries such as stress fractures or compartment syndrome. If a diagnosis is unsure, methods such as x-ray, bone-scan, and MRI can be utilized to better obtain the correct diagnosis. A variety of treatments exist for MTSS including, ice, massage, muscle strengthening, and rest. A combination of these various techniques is most often what is employed. In this study, the effectiveness of a set of resistance ankle exercises in combination with ice and massage was tested and compared to that of ice and massage alone. The hypothesis was that athletes receiving the exercises as part of their treatment, in addition to the icing and massaging, would have a greater decrease in pain from MTSS than athletes just receiving ice and massage as treatment. The exercises would strengthen the muscles of the lower leg that, when weak, can contribute to the development of MTSS. Results indicated that the exercises yielded a more significant decrease in pain from MTSS than ice and massage alone.
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Claassen, Mathilda. "In-house genotypic antiretroviral resistance test : optimisation and validation for use in research and diagnostics." Thesis, Stellenbosch : University of Stellenbosch, 2011. http://hdl.handle.net/10019.1/6520.
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Thesis (MScMedSc)--University of Stellenbosch, 2011.It is estimated that 32.8 million people are living with Human Immunodeficiency Virus (HIV) globally with the number of people receiving antiretroviral therapy in low- and middle- income counties increasing to more than 5 million people in 2009. These successes are threatened by treatment failure and the development of resistance to treatment. With an estimated 3.7% patients failing first line treatment after 2 years and 17.9% after 4 years on treatment there is a need for a practical and cheap in-house drug resistance assay that can be used to provide drug resistance data to clinicians and to use as a research tool to investigate drug resistance. In this study we attempted to optimize and validate an in-house drug resistance assay, adapted from Jacobs et al, 2008, to be used as a diagnostic tool and to study the presence of antiretroviral resistance in patients on the Western Cape Mother-To-Child-Transmission (MTCT) regimen. Quality control samples were received from The National Institute of Communicable Diseases AIDS Virus Research Unit, The Round Robin HIV-1 genotyping assessment system from the University of Würzburg and the QCMD assessment system were used for the optimization and validation of an in-house drug resistance assay. The ViroSeq™ HIV-1 Genotyping System was used for comparison of sample and mutation detection. It was possible to optimise and validate a genotyping assay for diagnostic testing and research use by comparison with the ViroSeq™ HIV-1 Genotyping System and evaluation with external quality assessment systems. This assay could subsequently be used to determine the development of genotypic-antiretroviral resistance in patients treated according to the provincial prevention of mother-to-child-transmission (PMTCT) protocol in the Western Cape (single dose nevirapine (sd-NVP), combined with a short course Zidovudine (AZT)). Patient samples were collected from pregnant women who took part in the Western Cape PMTCT program and visited the Tygerberg Obstetrics Clinic and Delft Community Hospital. EDTA blood was obtained to measure CD4-cell count, viral load, and to do genotyping for viral subtype and the presence of resistance mutations. Information on prior exposure to antiretroviral therapy was also collected. A detected resistance rate of 17.1% in this predominantly HIV-1 subtype C population is lower than previously recorded when sd-NVP was administered to HIV-1 subtype C positive patients in PMTCT programs. This could indicate that a dual PMTCT regimen including AZT and NVP reduces the risk of resistance to NVP relative to a regimen that uses sd-NVP. The genotyping assay uses four primers to amplify the PR and the RT gene separately to obtain PCR products, of 487 and 804 base pairs respectively for sequencing. The two PCR products were sequenced with three and five primers respectively to sequence the complete PR and approximately 250 amino acids of the RT gene. The sequences generated, thus, are analysed and aligned with the Sequencer V4.7 software to obtain a consensus sequence of approximately 1200 base pairs for analysis of resistance mutations in the protease and reverse transcriptase genes. The developed assay was hence further simplified and improved, by combining the PR and RT assay into one, which was optimised and validated for use in the routine diagnostic setting. The final genotyping assay uses 8 primers for sequencing to obtain a 1200 bp sequence for genotyping that contains the protease and the 5’ of the reverse transcriptase genes in which antiretroviral resistance associated mutations are found. The assay was accredited by SANAS in 2008.
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Thulin, Elisabeth. "Mechanisms and Dynamics of Mecillinam Resistance in Escherichia coli." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-330856.
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The introduction of antibiotics in healthcare is one of the most important medical achievements with regard to reducing human morbidity and mortality. However, bacterial pathogens have acquired antibiotic resistance at an increasing rate, and due to a high prevalence of resistance to some antibiotics they can no longer be used therapeutically. The antibiotic mecillinam, which inhibits the penicillin-binding protein PBP2, however, is an exception since mecillinam resistance (MecR) prevalence has remained low. This is particularly interesting since laboratory experiments have shown that bacteria can rapidly acquire MecR mutations by a multitude of different types of mutations. In this thesis, I examined mechanisms and dynamics of mecillinam resistance in clinical and laboratory isolates of Escherichia coli. Only one type of MecR mutations (cysB) was found in the clinical strains, even though laboratory experiments demonstrate that more than 100 genes can confer resistance Fitness assays showed that cysB mutants have higher fitness than most other MecR mutants, which is likely to contribute to their dominance in clinical settings. To determine if the mecillinam resistant strains could compensate for their fitness cost, six different MecR mutants (cysB, mrdA, spoT, ppa, aspS and ubiE) were evolved for 200-400 generations. All evolved mutants showed increased fitness, but the compensation was associated with loss of resistance in the majority of cases. This will also contribute to the rarity of clinical MecR isolates with chromosomal resistance mutations. How MecR is mediated by cysB mutations was previously unclear, but in this thesis I propose and test a model for the mechanism of resistance. Thus, inactivation of CysB results in cellular depletion of cysteine that triggers an oxidative stress response. The response alters the intracellular levels of 450 proteins, and MecR is achieved by the increase of two of these, the LpoB and PBP1B proteins, which rescue the cells with a mecillinam-inhibited PBP2. Mecillinam is used for UTI treatments and to investigate mecillinam resistance in a more host-like milieu, MecR strains were grown in urine and resistance was examined. Interestingly, this study showed that neither laboratory, nor clinical cysB mutants are resistant in urine, most likely because the cysteine present in the urine phenotypically reverts the bacteria to susceptibility. These findings suggest that mecillinam can be used to treat also those clinical strains that are identified as MecR in standard laboratory tests, and that testing of mecillinam susceptibility in the laboratory ought to be performed in media that mimics urine to obtain clinically relevant results. In summary, the work described in this thesis has increased ourgeneral knowledge of mecillinam resistance and its evolution. Hopefully this knowledge can be put to good use in clinical settings to reduce the negative impact of antibiotic resistance.
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Tsai, Hung-Yin. "Cultural Encounters in Medicine: (Re)Constituting Traditional Medicine in Taiwan under Colonization, Modernity, and Exchange." Diss., Virginia Tech, 2021. http://hdl.handle.net/10919/104579.
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Today we have many alternative medicines, not a few of which connect back to aboriginal cultures. Some of these alternative medicines were born under the influence of European imperialism, as they were not "alternative" until modern empires and modern medicine came to these distant regions. The present study begins with a broad question: how did conceptions of the relationship between modern Western medicine and traditional local non-Western medicine come to be? To explore the historical origins of these two conceptions, I focus herein on Japanese colonial Taiwan (1895–1945), where modern medicine became dominant while traditional medicine also flourished. My research finds that the historical realities of colonial Taiwan were not reflected in the progressive narrative of medicine. According to this narrative, modern medicine became dominant around the world while traditional medicines were swept into the ash heap of history because only modern medicine was the true, effective science of preventing, diagnosing, and treating physical ailments. The history of colonial Taiwan teaches us a much different lesson: practitioners of traditional medicine there were a significant part of the public health system during the colonial period. For example, they rallied against the plague in the late 19th century, diagnosing and treating patients when antibiotics had yet to be developed. Even so, the island witnessed an institutional medical shift, in which licensed practitioners of modern medicine deified modern medicine and denigrated traditional medicine, labeling the latter "primitive" and "non-medicine." In response, practitioners of traditional medicine produced new narratives aiming to challenge this colonial boundary between medicine and non-medicine. These practitioners' fundamental argument was that traditional medicine, though epistemologically different from modern medicine, was still legitimate medicine. From this effort, we now have the widely held belief today that both modern medicine and traditional medicine are legitimate, but distinct, medicines. This historical outcome of colonial resistance occurred worldwide. In my study, I identify the social, political, and colonial contexts of medical resistance in Japanese Taiwan, revealing their roots in issues related to inequality, distrust, economic affordability, and conceptions of body and health care.Doctor of Philosophy
In this study, I explore conceptions of modern and traditional medicine through a historical lens, and break down two related myths: the first myth is the progressive narrative of modern medicine, which holds that modern medicine became dominant because of its medical superiority; and the second myth is the narrative held by extremist supporters of traditional medicine, who insist that only millennia-old traditional medicine can resolve human ailments without giving rise to untoward side effects and exorbitant costs. I show that, in the case of Japanese colonial Taiwan (1895–1945), both modern and traditional medicine flourished. The history of colonial Taiwan shows us that modern medicine on the island became dominant for two main reasons: first, the public health system successfully dealt with epidemics, which were the most significant threat to life at that time; and second, the colonial government recognized only modern medicine and labeled traditional medicine a non-medicine despite relying on its practitioners in the pre-antibiotic age. The history of colonial Taiwan also shows us that traditional medicine is not "old wisdom" unchanged for thousands of years. Beginning in the 19th century, practitioners of Taiwanese traditional medicine re-constituted it for colonial consumption, arguing that traditional medicine was also true medicine, though epistemologically distinct from modern medicine. This conception of traditional medicine has since informed many current views of traditional medicine. In 2018, the World Health Organization (WHO) published the eleventh revision of the International Classification of Diseases (ICD-11), which, for the first time, featured a chapter on traditional Chinese medicine covering such topics as diagnostic techniques for Qi, blood, and fluid disorders. This inclusion of traditional medicine into the ICD-11 is a major step forward in this process of medical integration and may help resolve the historical confrontation between modern and traditional medicine. However, the WHO decision limits recognition of traditional medicine to Chinese medicine, excluding all other kinds of traditional medicine. Thus, the historical question of whether or not traditional medicine is a true medicine remains ultimately unanswered.
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Robberts, Frans Jacob Lourens. "Genetic investigations of pneumocystis jirovecii : detection, cotrimoxazole resistance and population structure." Thesis, Link to the online version, 2005. http://hdl.handle.net/10019.1/1304.
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Raposo, Kelly. "The Effects of Pre-Exercise Carbohydrate Supplementation on Resistance Training Performance During an Acute Resistance Training Session." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3304.
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Abstract
It appears that "carbohydrate loading" may enhance the performance of resistance training, but studies on CHO supplementation prior to a resistance-training bout are limited and have resulted in conflicting findings. PURPOSE: To investigate the effects of pre-exercise CHO supplementation on high-intensity (>75% 1RM) resistance training performance for resistance-trained women during an acute bout of resistance exercise. METHODS: Thirteen resistance trained female participants (21.9 ± 4.8 yrs; 64.5 ± 3.0 in; 137.0 ± 14.8 lbs) came to the Exercise and Performance Nutrition Laboratory on three separate occasions; the day of the Familiarization Trial (FT) and the two Exercise Testing sessions (ET1 and ET2, respectively) all separated by seven days. Familiarization testing determined each participant's 1RM of the bench press and leg press and then 75% of the bench press 1RM and 85% of the leg press 1RM was determined. The participants were then randomly assigned to either the CHO or P treatment session using a double blind, counterbalanced technique in a cross-over design with each participant consuming 1.0 g CHO/kg body weight or a non-caloric P beverage 60 minutes before beginning the exercise bout for each ET. The total volume of weight lifted during five sets of the bench press, the total volume of the weight lifted during five sets of the leg press, and whole body total lifting volume was analyzed by a two-way repeated measures within subjects ANOVA with significance set at P <.05. RESULTS: There was no statistically significant difference between the CHO and P treatments in the three variables analyzed. Specifically total volume of weight lifted in pounds during five sets of the bench press was 3,200 (± 912) and 3,152 (± 852) (p = 0.655), total volume of weight lifted during five sets of the leg press was 44,004 (± 29,711) and 37,705 (± 19,681) (p = 0.136), and total lifting volume was 47,204 (± 30,399) and 40,857 (± 20,434) for the CHO and P treatment, respectively (p = 0.138). CONCLUSIONS: Pre-exercise CHO supplementation does not improve high-intensity resistance training performance for resistance-trained women during an acute resistance training session. PRACTICAL APPLICATIONS: It is evident that consuming CHO 60 minutes prior to performing resistance training exercises will not increase the number of sets, repetitions, or total work volume completed during acute high-intensity (>75% 1RM) resistance training sessions for women. During lower-intensity resistance training sessions, however, pre-exercise CHO supplementation may provide ergogenic effects and enhance resistance-training performance.
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Ahlund, Veronica. "Development of Clostridium difficile resistance to Piperacillin/Tazobactam over a period of ten years." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-57501.
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Kareemaghay, Sedigeh. "Investigating the role of ADAM10 and ADAM17 in cetuximab resistance in head and neck squamous cell carcinoma." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:dd59b38e-ac07-4a6b-b458-74397b76d883.
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Epithermal Growth Factor Receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC). Cetuximab is the first and the only anti-EGFR monoclonal antibody which received approval from FDA for the treatment of HNSCC. However, most patients either do not respond to cetuximab or develop acquired resistance. The aim of my D.Phil. study was to investigate the role of ADAM10 and 17 in resistance mechanisms of cetuximab in HNSCC. Chronic exposure to cetuximab led to an activation of HER receptors and downstream signalling pathways in HNSCC cell lines. Higher levels of ADAM10 and 17 and their substrates, BTC and NRG-1 were found in cetuximab resistant cells compared to their parental cells, suggesting the involvement of ADAM-mediated ligands’ release in reactivation of HER receptors. Inhibition or knockdown of ADAM10 and 17 enhanced cetuximab response and reversed cetuximab resistance in HNSCC cells. In addition, results from this study showed that the combination of cetuximab with EGFR-TKIs had greater effect in parental cells and reversed cetuximab resistance in HNSCC cells. Upregulation of ADAM10 and 17 also was observed in HNSCC TMAs compared to normal head and neck TMAs. High nuclear ADAM10 and cytoplasmic ADAM17 expression levels were associated with shorter DFS. By evaluating tumour excision samples from HNSCC patients who underwent a cetuximab window study high ADAM10 and 17 expression levels were found to be associated with poor response to cetuximab. In conclusion cetuximab-induced ADAM-mediated ligands’ release is a potential mechanism of resistance to cetuximab in HNSCC. Thus, targeting ADAM10/17 or subsequent HER activations may represent an important strategy in overcoming resistance to cetuximab in HNSCC. Results from this study also suggest the implication of ADAM10 and 17 as potential prognostic and predictive biomarkers in HNSCC although further validation is required.
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Struthers, Kyle Remington. "ISCHEMIA IMPAIRS VASODILATION IN SKELETAL MUSCLE RESISTANCE ARTERY." DigitalCommons@CalPoly, 2011. https://digitalcommons.calpoly.edu/theses/546.
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Functional vasodilation in arterioles is impaired with chronic ischemia. We sought to examine the impact of chronic ischemia and age on skeletal muscle resistance artery function. To examine the impact of chronic ischemia, the femoral artery was resected from young (2-3mo) and adult (6-7mo) mice and the profunda femoris artery diameter was measured at rest and following gracilis muscle contraction 14 days later using intravital microscopy. Functional vasodilation was significantly impaired in ischemic mice (14.4±4.6% vs. 137.8±14.3%, p<0.0001 n=8) and non-ischemic adult mice (103.0±9.4% vs. 137.8±14.3%, p=0.05 n=10). In order to analyze the cellular mechanisms of the impairment, a protocol was developed to apply pharmacological agents to the experimental preparation while maintaining tissue homeostasis. Endothelial and smooth muscle dependent vasodilation were impaired with ischemia, 39.6 ± 13.6% vs. 80.5 ± 11.4% and 43.0 ± 11.7% vs. 85.1 ± 10.5%, respectively. From this data, it can be supported that smooth muscle dysfunction is the reason for the observed impairment in arterial vasodilation.
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Maglio, Milena. "Éthique de la sacralité de la vie, éthique de la qualité de la vie : généalogie d'une opposition théorique." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAP005.
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Le débat entre éthique de la sacralité de la vie et éthique de la qualité de la vie se trouve au centre des discours bioéthiques (en particulier ceux en langue anglaise) depuis une quarantaine d'années. La sacralité de la vie est généralement considérée comme une éthique ancienne dont les origines remonteraient aux traditions judéo-chrétienne et hippocratique. L'éthique de la qualité de la vie, quant à elle, est souvent présentée comme une éthique moderne, née consécutivement au développement scientifique et technique qui a marqué le domaine médical depuis soixante ans. La différence entre les deux éthiques consisterait alors dans le fait que chacune d'entre elles attribuerait une valeur distincte à la vie humaine. De là découleraient des considérations morales divergentes sur certaines pratiques : euthanasie, avortement, interruption des traitements, etc. L'abondance de la littérature sur le sujet et la récurrence de l'usage des deux expressions n'empêchent pas que la portée et la signification de ces éthiques restent confuses. Cela est particulièrement évident dans les débats publics, et notamment à l’occasion de cas fortement médiatisés. Qu'entend-on par vie (humaine) ? Par sacralité ? Et par qualité ? Même au sein des « camps » apparemment bien définis, ces questions ne reçoivent pas toujours la même réponse.La présente thèse s'interroge sur la pertinence de l'opposition plus haut présentée au moyen d'une approche généalogique et d'une méthode archéologique. Elle se questionne d'abord sur l'idée commune de la sacralité de la vie et en repère les provenances multiples et hétérogènes. Celles-ci sont ensuite relues en contexte, en s'intéressant aux conditions dans lesquelles l'expression a été mobilisée, ainsi qu'aux discours qui s'y sont opposés. Ce cadre permet de porter un regard neuf sur l'apparition du débat entre éthique de la sacralité de la vie et éthique de la qualité de la vie, ainsi que sur son émergence et sa reconfiguration au sein de la bioéthique. L'enjeu est ici de fournir de nouvelles clés pour penser autrement le débat contemporainThe debate between the sanctity of life ethic and the quality of life ethic has been at the core of bioethical discussions (especially those in English) for forty years. It is generally considered that the sanctity of life is an ancient ethic which belongs to the Judeo-Christian and to the Hippocratic traditions. The quality of life, for its part, is commonly understood as a modern ethic which was born with the scientific and technological development of the medical field started sixty years ago. It is then stated that the difference between the sanctity of life ethic and the quality of life ethic depends on the value that each ethic assigns to human life. A moral judgment about subjects as abortion, euthanasia, the withholding and withdrawal of life support, and so on, is supposed to result from this value. The literature on the subject is abundant, and the expressions “sanctity of life” and quality of life” are often used, but the meaning and the scope of these ethics remain sometimes unclear. This fact becomes more evident in the public debates, especially in the well-known cases. What (human) life, sanctity (of life), and quality (of life) mean? These questions rarely receive the same answer.The purpose of this thesis is to investigate the validity of the opposition between the sanctity of life ethic and the quality of life ethic with a genealogical approach and an archaeological method. The common idea of the sanctity of life is, first, analyzed to find its multiple and heterogeneous “descents” [provenances]. These “descends”, then, are put into context, focusing on the conditions in which the expression “sanctity of life” was mobilized, and on the discourses that opposed to it. This framework, finally, allows to bring a fresh look at the advent of the debate between sanctity of life ethic and quality of life ethic, as well as at its emergence and reconfiguration in bioethics. The challenge is to provide new keys for thinking differently the contemporary debate
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Wu, Simon. "Mathematical Modelling of Insulin Resistance Development Caused by Chronic Inflammation." Thesis, Linköpings universitet, Institutionen för medicinsk teknik, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-158671.
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Obesity has in recent times become a more serious health issue and was estimated to affect over 650 million people world-wide in 2016. Furthermore, the list of obesity-associated diseases is countless, many of which have severe consequences. Type 2 diabetes (T2D) is such a disease, and it was estimated to be over 1.5 million new cases in America alone in 2015. It is thought that insulin resistance development which causes T2D is associated with a low-level chronic inflammation in the adipose tissue. The inflammatory state is caused by the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) which is secreted by macrophages. To further understand the complexity of the underlying mechanisms of both the adipocytes as well as the macrophages, mathematical models are being developed in the fields of systems biology. However, as of now, no mathematical model has been developed which can explain the association between chronic inflammation and the development of insulin resistance. Because of this, a first model will be presented which is able to describe the mechanisms of insulin resistance development caused by chronic inflammation. The model was fitted to data from intraperitoneal glucose tolerance test in mice and yielded a cost below the threshold of chi-square test, which suggests that the model cannot be rejected. Furthermore, the model was expanded, introducing more complexity in the intracellular cascade reaction of an activated macrophage. Once again, the model was fitted to the same data and yielded a cost below the threshold of chi-square test. Uncertainty tests were made to further validate the models and showed a low uncertainty for both models. These results increase the understanding regarding the association between adipocytes and macrophages, in the role of insulin resistance caused by chronic inflammation. This increased knowledge can help, for instance, in the development of new drugs which are able to prevent the development of insulin resistance and T2D.
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Oliveira, Carlos Roberto de. "Breaking down resistance to the gospel through holistic medical missions a strategy for reaching resistant rural towns in Mexico /." Online full text .pdf document, available to Fuller patrons only, 1999. http://www.tren.com.
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Thulin, Hedberg Sara. "Antibiotic susceptibility and resistance in Neisseria meningitidis : phenotypic and genotypic characteristics." Doctoral thesis, Örebro universitet, Hälsoakademin, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-8652.
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Neisseria meningitidis, also known as the meningococcus, is a globally spread obligate human bacterium causing meningitis and/or septicaemia. It is responsible for epidemics in both developed and developing countries. Untreated invasive meningococcal disease is often fatal, and despite modern intensive care units, the mortality is still remarkably high (approximately 10%). The continuously increasing antibiotic resistance in many bacterial pathogens is a serious public health threat worldwide and there have been numerous reports of emerging resistance in meningococci during the past decades. In paper I, the gene linked to reduced susceptibility to penicillins, the penA gene, was examined. The totally reported variation in all published penA genes was described. The penA gene was highly variable (in total 130 variants were identified). By examination of clinical meningococcal isolates, the association between penA gene sequences and penicillin susceptibility could be determined. Isolates with reduced susceptibility displayed mosaic structures in the penA gene. Two closely positioned nucleotide polymorphisms were identified in all isolates with reduced penicillin susceptibility and mosaic structured penA genes. These alterations were absent in all susceptible isolates and were successfully used to detect reduced penicillin susceptibility by real-time PCR and pyrosequencing in paper II. In papers III and IV, antibiotic susceptibility and characteristics of Swedish and African meningitis belt meningococcal isolates were comprehensively described. Although both populations were mainly susceptible to the antibiotics used for treatment and prophylaxis, the proportion of meningococci with reduced penicillin susceptibility was slightly higher in Sweden. A large proportion of the African isolates was resistant to tetracycline and erythromycin. In paper V, the gene linked to rifampicin resistance, the rpoB gene, was examined in meningococci from 12 mainly European countries. Alterations of three amino acids in the RpoB protein were found to always and directly lead to rifampicin resistance. A new breakpoint for rifampicin resistance in meningococci was suggested. The biological cost of the RpoB alterations was investigated in mice. The pathogenicity/virulence was significantly lower in rifampicin resistant mutants as compared with susceptible wild-type bacteria.
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Sorensen, Daniel David. "Dissimilar Metal Joining in the Medical Device Industry." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1494157928729494.
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Sherman, Adam 1965. "Measuring rapid ionic current with a single electrode : a new method for series resistance compensation." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21639.
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This thesis relates to the study of rapid ionic currents in single cells using a single electrode voltage clamp amplifier (SEVC). The practical limitations inherent with the SEW, primarily the effects of series resistance (R s) which dominate when attempting to record rapid ionic currents, are outlined. The various methods in use to compensate for Rs are explored. A novel method of Rs compensation is described which overcomes the stability limitations of conventional designs.To illustrate the advantages of this new Rs compensation, a voltage clamp amplifier implementing this Rs compensation is used to record rapid Na+ current in rat Superior Cervical Ganglia (SCG) neurons and human ventricular myocytes which could not be resolved with conventional equipment. Data obtained using partial Rs compensation is compared to that obtained with full Rs compensation using the new voltage clamp amplifier. Criteria for adequate voltage control of voltage clamped Na+ currents are developed and illustrated.
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Zhang, Wei. "LOSS OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 1 (MRP1/ABCC1) POTENTIATES DOXORUBICIN-INDUCED CARDIOTOXICITY IN MICE." UKnowledge, 2015. http://uknowledge.uky.edu/toxicology_etds/12.
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Doxorubicin (DOX) is a broad-spectrum and effective chemotherapeutic agent, but its use in oncologic practice is limited by dose-dependent cumulative cardiotoxicity. DOX-induced cardiotoxicity is in large part due to its ability to cause oxidative stress. Multidrug resistance associated protein 1 (MRP1/ABCC1) is a member of the ATP-binding cassette (ABC) transporter superfamily. By effluxing a wide variety of endogenous and exogenous substrates, Mrp1 plays important physiological roles in multiple tissues and also protects normal tissues against toxicants. However, the role of MRP1 in heart is largely unknown.
The role of Mrp1 in DOX-induced cardiotoxicity was investigated in Mrp1 null (Mrp1-/-) and their C57BL (WT) littermates. Chronic DOX caused body weight loss and hemotoxicity, and these adverse effects were significantly exacerbated in Mrp1-/- vs WT mice. Importantly, loss of Mrp1 potentiated DOX-induced cardiotoxicity, presenting as worsened cardiac function and more cellular apoptosis in DOX treated Mrp1-/- mice. Mrp1 also protected neonatal mouse cardiomyocytes (CM) and cardiac fibroblasts (CF) culture against DOX cytotoxicity in vitro. This was demonstrated by the decreased cell survival, more apoptosis and more DNA damage in DOX treated Mrp1-/- vs WT cells.
In addition, the effects of deletion of Mrp1 was studied on glutathione (GSH)/glutathione disulfide (GSSG) homeostasis, glutathione conjugate of 4-hydroxy-2-nonenal (GS-HNE) accumulation, protein oxidative damage and expression of antioxidant enzymes. Loss of Mrp1 led to significantly higher GSH and GSSG basal levels in heart. Following DOX treatment, Mrp1-/- CM and CF showed increased GSH and GSSG levels vs WT cells. Meanwhile, DOX increased expression of the GSH synthesis enzymes in Mrp1-/- but not WT cells. Thus, increased GSH synthesis may contribute to the further increase in the GSH pool in DOX-treated Mrp1-/- cells. DOX induced comparable increases of GS-HNE concentration in WT and Mrp1-/- mice hearts. Finally, expression of extracellular superoxide dismutase (ECSOD/SOD3) was significantly lower in Mrp1-/- vs. WT CM treated with either saline or DOX.
In summary, this study is the first to document a protective role of Mrp1 in DOX-induced cardiotoxicity. It gives critical information regarding the potential adverse sequelae of introduction of MRP1 inhibitors as adjuncts to clinical chemotherapy of multidrug resistant tumors.
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Fry, Andrew E. "Genome mapping of malaria resistance genes : the host ligands of PfEMP1." Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:df1ffe4b-ba67-4fc6-9024-b278b887d4f9.
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Erythrocytes infected by mature forms of the Plasmodium falciparum parasite adhere to other components of the vascular space, a behavior considered critical to the pathogenesis of severe malaria. Adhesion is mediated by the P. falciparum erythrocyte membrane protein 1 (PfEMP1), a highly variant antigen expressed by the parasite and subject to switching during the course of an infection. The host ligands of PfEMP1 include CD36, ICAM-1 and the ABO antigens. By employing a series of population- and family-based association studies from multiple African populations, we examined whether variation in the genes underlying these molecules affects susceptibility to severe malaria. Our results suggest that a common frameshift mutation in the ABO glycosyltransferase, responsible for blood group O, is associated with protection from severe malarial phenotypes (P=2x10⁻⁷), particularly severe malarial anaemia. However, we found no significant disease associations with variation in either the ICAM1 or CD36 genes. We focused on two particular functional polymorphisms, the missense ICAM-1Kilifi and the CD36 nonsense mutation T1264G. We genotyped both markers in around 10,000 individuals, but neither demonstrated an association with severe malarial phenotypes. Malaria has been a profound selection pressure shaping human genetic diversity. The last decade has seen the development of several haplotype-based methods to detect signatures of recent positive evolutionary selection. These techniques are potentially invaluable tools in our hunt for genetic variants that protect from life threatening malaria. We used simulations and empirical data from the International HapMap Project to demonstrate the validity of searching for long regions of haplotype homozygosity, as an approach to finding alleles undergoing selective sweeps. We analysed genetic data from a range of populations, particularly those utilized by HapMap, to investigate whether our candidate genes were associated with signals of recent positive selection. We characterized the distribution of a selection event associated with the CD36 1264G allele, focused in Central-West Africa, and demonstrated a novel signal of low population differentiation at the ABO gene, suggestive of longstanding balancing selection. Our work confirms that variation in the host ligands of PfEMP1 modulates severe malaria susceptibility, and highlights the value of using signals of selection, along with functional experiments and genetic association studies, to dissect the biology of severe malaria.