Service Level Management for Service Value Networks

The ongoing trend towards a global services economy creates considerable market opportunities for various stakeholders. A service intermediary who offers complex services to customers and consumes services from suppliers and thus creates a service value network, faces the challenge of adhering to agreed service levels while minimizing associated costs, risks and potential penalties. Starting from a lifecycle model for service value networks, this paper identifies the service level management tasks to be performed by a service intermediary. For each of these tasks, supporting software tools have been developed. Together, they form an integrated tool chain which provides effective support for service level management of service intermediaries. The tools have been evaluated in case studies and industrial settings. The paper contributes the first study of an end-to-end service level management for service value networks

The transforming growth factor-β high-producer genotype is associated with response to hepatitis C virus-specific therapy in HIV-positive patients with acute hepatitis C

Background: Coinfection with the hepatitis C virus (HCV) in HIV-positive patients is an emerging health problem. The factors affecting response to HCV-specific therapy are poorly understood but may involve host genetic factors. HCV NS5A-induced inhibition of transforming growth factor-[beta] signaling has been suggested as a potential mechanism involved in HCV pathogenesis. Transforming growth factor-[beta], a multifunctional cytokine, displays gene polymorphisms (transforming growth factor-[beta] codon 10T/C and codon 25G/C) associated with differential cytokine secretion. Here, we studied whether transforming growth factor-[beta] gene polymorphisms affect treatment response in HCV/HIV coinfection. Methods: Transforming growth factor-[beta] genotypes were determined in 60 HIV-positive patients with acute hepatitis C treated with pegylated interferon-[alpha]. Patients were classified into those with a high-producer genotype and others with non-high-producer genotypes. Rates of sustained virological responses were compared between high-producer and non-high-producer patients. As a control, 100 healthy, 201 HIV(+)/HCV(-), and 148 HCV(+)/HIV(-) subjects were studied. Results: Transforming growth factor-[beta] genotype distribution did not differ significantly between the groups. In HIV/HCV coinfection carriers of the transforming growth factor-[beta] high-producer genotype had significantly higher sustained virological response rates than patients with a transforming growth factor-[beta] non-high-producer genotype (75 vs. 41.7%; P = 0.039). In a forward-conditional stepwise regression model, transforming growth factor-[beta] high-producer genotype was confirmed as an independent positive predictor for sustained virological response in interferon-[alpha] therapy (odds ratio, 4.4; 95% confidence interval, 1.5–13.4; P = 0.009). Conclusion: Response rates to interferon-[alpha] therapy are enhanced in acute HCV-infected HIV-positive patients carrying the transforming growth factor-[beta] ‘high-producer’ genotype. This finding may indicate that a transforming growth factor-[beta] ‘high-producer’ state can partially compensate HCV NS5A-induced inhibition of transforming growth factor-[beta] signaling

The TGF-β high producer genotype is associated with response to HCV-specific therapy in HIV-positive patients with acute hepatitis C

Background: Co-infection with the Hepatitis C virus (HCV) in HIVpositive patients is an emerging health problem. The factors affecting response to HCV-specific therapy are poorly understood but may involve host genetic factors. HCV NS5A-induced inhibition of TGF-b signaling has been suggested as a potential mechanism involved in HCV pathogenesis. TGF-b, a multifunctional cytokine, displays gene polymorphisms (TGF-b codon 10 T/C and codon 25G/C) associated with differential cytokine secretion. Here, we studied whether TGF-b gene polymorphisms affect the treatment response in HCV/HIV co-infection

HLA class I allele associations with HCV genetic variants in patients with chronic HCV genotypes 1a or 1b infection

BACKGROUND & AIMS: The adaptive immune response against hepatitis C virus (HCV) is significantly shaped by the host's composition of HLA-alleles with the consequence that the HLA phenotype is a critical determinant of viral evolution during adaptive immune pressure. In the present study, we aimed to identify associations of HLA class I alleles with HCV subtypes 1a and 1b genetic variants. METHODS: The association between HCV genetic variants and specific HLA-alleles was investigated in a cohort of 159 patients with chronic HCV genotypes 1a- and 1b-infection who were treated with pegylated interferon-alfa 2b and ribavirin in a prospective controlled trial for 48 weeks by direct sequencing of the genes encoding the HCV proteins E2, NS3, and NS5B and by HLA class I-genotyping of patients. HCV genetic variants were associated with specific HLA-alleles and the binding strength of accordant amino acid sequences to the corresponding HLA-allele was assessed by using the SYFPEITHI-algorithm. RESULTS: Overall, associations between HLA class I alleles and HCV sequence variation were rare. Five unknown HLA class I-associated viral genetic variations were identified, which in part affected the binding of predicted HCV CD8+ T cell epitopes to the respective HLA-allele. In addition, different patterns of HLA class I-allele/HCV sequence associations between the two subtypes were observed. CONCLUSIONS: We identified several unknown HLA class I-restricted HCV variants which in part impair binding to predicted HCV CD8+ T cell epitopes with remarkable differences between HCV subtypes 1a and 1b quasispecies