published_or_final_version / abstract / toc / Chinese Historical Studies / Master / Master of Arts

Infection with hepatitis C virus (HCV) is cleared spontaneously in only 20% of cases with the majority of individuals developing a chronic infection. This discrepancy in disease outcome is incompletely understood but current understanding of the immune response to HCV suggests that rapid induction of a broadly neutralising antibody (nAb) response leads to resolution of acute infection. The majority of nAb identified target the envelope glycoproteins, particularly E2, and most appear to inhibit binding of E2 to the cellular receptor CD81. Antibodies targeting other interactions, such as those with the receptor CLDN or the fusion determinant, are underrepresented in the repertoire of anti-HCV antibodies. However, the antibody discovery process may have been biased by the nature of the assays used. Therefore new assays are needed to enable the discovery and characterisation of antibodies in an unbiased manner. To facilitate this, a novel insect cell display library was developed for mapping antibody-binding epitopes. Cells expressing specific E2 mutants provided the necessary proof-of-principle that loss of antibody binding could be detected in this system before a library expressing randomly mutated E2 was developed. Sorting experiments demonstrated that single cells could be isolated and enriched based on loss of antibody binding. Secondly, a method for characterising the immunoglobulin (Ig) genes of HCV infected patients was developed; Ig genes were isolated from small numbers of B cells and the sequences analysed. Finally, a patient cohort was studied with a view to investigating the evolution of the antibody response during early infection. The unreliable nature of the samples prevented such analysis; however a DNA fingerprinting method of testing the origin and relatedness of serum samples was developed. This will improve the reliability of future studies. Together these methods provide a work model for the assessment of samples and the isolation and characterisation of antibodies.

This thesis is a study-of the contribution of public health administration to the control of Infectious diseases in Fife during the period c. 1855-1950. It is a local study in the social history of medicine which attempts to test the conflicting theories of Thomas McKeown and Simon Szreter about the role of social intervention in mortality decline during the period. It covers the period from the earliest date when civil registration data on mortality from specified causes are available for Fife. During this period mortality from the main infectious diseases in the county declined almost continuously and by 88% from a rate of 608 deaths per 100 000 inhabitants during the years 1855-60. Public health administration is here defined as measures for disease prevention and control administered by local government. Such measures include the provision of adequate water supplies and drainage, improvement of housing, port sanitation, immunisation and the provision of infectious diseases hospitals and child welfare services. The first three chapters of this study include an introduction, a description of the geographical, demographic and economic conditions in Fife during the period and a description of the development of a system of public health administration in the county. This is followed by studies of the main infectious diseases, including smallpox, typhus and typhoid, diarrhoeal disease, diphtheria, scarlet fever, measles and whooping cough, influenza and all forms of tuberculosis. The pattern of mortality from each disease in Fife is described. Then from the records of local authorities in the county, the role of public health administration in the attempted control of each disease is described and evaluated. The conclusion assesses the overall contribution of public health administration to the decline in mortality from the main infectious diseases in Fife and suggests the relative importance of different measures in the process of disease control.

Thesis (Ph. D.)--University of New South Wales, 1999. / Also available online.

Thesis (Ph.D.) -- McMaster University, 2006. / Supervisor: David J. D. Earn. Includes bibliographical references.

Thesis (Ph.D.)--University of Wollongong, 2005. / Typescript. Includes bibliographical references: leaf 140-179.

Thesis (Ph.D.)--Michigan State University. Dept. of Epidemiology, 2008. / Title from PDF t.p. (viewed on Apr. 2, 2009) Includes bibliographical references (p.145-152). Also issued in print.

Thesis (Ph. D.)--University of Texas at El Paso, 2008. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf viii-xiii, 3rd gp.) Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf viii-xiii, 3rd gp.) Also available online.