2 resultados para HLA-DRB1 Chains

em Glasgow Theses Service


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What does this thesis do? This thesis uses Actor-Network Theory (ANT) to examine how a UK retailer’s organization and strategy, and, in turn, its form of management accounting was shaped by its supply chain. The thesis does this by reporting on four related themes in the form of four inter-connected essays. The first essay undertakes a state-of-the-art review of the literature. It examines how accounting issues within supply chains permeate ‘matters of concern’. In accordance with this idea of ANT, the essay illustrates how issues emerged, controversies developed, and matters evolved through an actor-network of accounting researchers within the supply chain domain. This leads on to the second essay, which exemplifies the nature of the UK’s retailing industry within which the supply chain case organization emerged and developed. The purposes of the essay are twofold: to introduce the contextual ramifications of the case organization; and to illustrate the emergence of a new market logic, which led to the creation of a global supply chain and a new form of management accounting therein. The third essay reports on a qualitative case study. It analyses the dualistic relation between ostensive and performative aspects of supply chain strategy, reveals how accounting numbers act as an obligatory passage point within this dualism, and makes a contribution to the ANT debate around the issue of whether and how a dualism between ostensive and performative aspects exists. The final essay reports on another case analysis of institutionalizing a heterarchical form of management accounting: a distributed form of intelligence that penetrates through lateral accountable relations. The analysis reveals a new form of management accounting characterised by ambiguity; it emphasizes the possibilities of compromises and negotiations, and it thus contributes to knowledge by combining an aspect of ANT with heterarchical tendencies in the world of contemporary organizations. Finally, the thesis concludes that it is the supply chain that organises today’s neoliberal capitalism; and it is management accounting that unites both human and non-human actors within such supply chains, despite that form of management accounting being ambiguous. The thesis comprises the introduction, these four essays, and the conclusion.

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In mono-infected individuals, the HLA-B27 allele is strongly associated with spontaneous clearance of HCV in association with a strong CD8+ response targeted against a single epitope within the HCV RNA-dependent RNA polymerase (NS5B). We studied variation across the whole HCV genome and T cell responses over time in a rare cohort of HLA-B27+ patients with acute HCV and HIV co-infection, the majority of whom progressed to chronicity. We used next generation sequencing to detect changes within and outwith the immuno-dominant HLA-B27 restricted HCV-specific CD8+ T cell epitope NS5B2841-2849 (ARMILMTHF) during evolving progression of early HCV infection. Within the Acute HCV UK cohort, 10 patients carried the HLA B27 allele. Of these, 3/8 patients (37.5%) with HIV infection and 2/2 (100%) without HIV spontaneously cleared HCV (p=0.44). Sequential samples from nine HLA-B27+ patients (2 with monoinfection and 7 with HIV co-infection) were available for analysis (four spontaneous clearers and five evolving progressors). Mutations identified using NGS were assessed using a replicon genotype 1a system to evaluate viral fitness. Multiple mutations within the HLA-B27 restricted NS5B2841-2849 epitope were associated with progression to chroncity whereas patients who cleared the HCV infection spontaneously had no or only one mutation at this site (p=0.03). A triple NS5B2841-2849 mutant observed during progression to chronicity was associated with restored replication when compared to wild-type virus while single or double mutants were significantly associated with impaired replication (p=0.0495). T cell responses measured in these patients using ELISpot and flow cytometry. HLA-B27+ patients had significantly higher IFN-γ responses than patients who were HLA-B27- (p=0.0014). Those who progressed to chronicity had lower IFN-γ responses than those who cleared HCV (p=0.0011). Mono-infected patients had higher IFN-γ responses compared to co-infected patients (p=0.0015). HIV co-infection is associated with a lower likelihood of spontaneous clearance of HCV in HLA B27+ patients and this is associated with impaired T cell function in this group.