Quasispecies dynamics and treatment outcome during early hepatitis C infection in a cohort of HIV-infected men

Hepatitis C virus (HCV) is emerging as one of the leading causes of morbidity and mortality in individuals infected with HIV and has overtaken AIDS-defining illnesses as a cause of death in HIV patient populations who have access to highly active antiretroviral therapy. For many years, the clonal analysis was the reference method for investigating viral diversity. In this thesis, a next generation sequencing (NGS) approach was developed using 454 pyrosequencing and Illumina-based technology. A sequencing pipeline was developed using two different NGS approaches, nested PCR, and metagenomics. The pipeline was used to study the viral populations in the sera of HCV-infected patients from a unique cohort of 160 HIV-positive patients with early HCV infection. These pipelines resulted in an improved understanding of HCV quasispecies dynamics, especially regarding studying response to treatment. Low viral diversity at baseline correlated with sustained virological response (SVR) while high viral diversity at baseline was associated with treatment failure. The emergence of new viral strains following treatment failure was most commonly associated with emerging dominance of pre-existing minority variants rather than re-infection. In the new era of direct-acting antivirals, next generation sequencing technologies are the most promising tool for identifying minority variants present in the HCV quasispecies populations at baseline. In this cohort, several mutations conferring resistance were detected in genotype 1a treatment-naïve patients. Further research into the impact of baseline HCV variants on SVR rates should be carried out in this population. A clearer understanding of the properties of viral quasispecies would enable clinicians to make improved treatment choices for their patients.

Essays on cultural and institutional dynamics in economic development using spatial analysis

This thesis seeks to research patterns of economic growth and development from a number of perspectives often resonated in the growth literature. By addressing themes about history, geography, institutions and culture the thesis is able to bring to bear a wide range of inter-related literatures and methodologies within a single content. Additionally, by targeting different administrative levels in its research design and approach, this thesis is also able to provide a comprehensive treatment of the economic growth dilemma from both cross-national and sub-national perspectives. The three chapters herein discuss economic development from two broad dimensions. The first of these chapters takes on the economic growth inquiry by attempting to incorporate cultural geography within a cross-country formal spatial econometric growth framework. By introducing the global cultural dynamics of languages and ethnic groups as spatial network mechanisms, this chapter is able to distinguish economic growth effects accruing from own-country productive efforts from those accruing from interconnections within a global productive network chain. From this, discussions and deductions about the implications for both developed and developing countries are made as regards potentials for gains and losses from such types and levels of productive integration. The second and third chapters take a different spin to the economic development inquiry. They both focus on economic activity in Africa, tackling the relevant issues from a geo-intersected dimension involving historic regional tribal homelands and modern national and subnational administrative territories. The second chapter specifically focuses on attempting to adopt historical channels to investigate the connection between national institutional quality and economic development in demarcated tribal homelands at the fringes of national African borders. The third chapter on the other hand focuses on looking closer at the effects of demarcations on economic activity. It particularly probes how different kinds of demarcation warranted by two different but very relevant classes of politico-economic players have affected economic activity quite distinguishably within the resulting subnational regions in Africa.