The Irish paradigm on the natural progression of hepatitis C virus infection: an investigation in a homogeneous patient population infected with HCV 1b (Review)

The aetiological agent of chronic hepatitis C is the hepatitis C virus. The hepatitis C virus is spread by parenteral transmission of body fluids, primarily blood or blood products. In 1989, after more than a decade of research, HCV was isolated and characterised. The hepatitis C viral genome is a positive-sense, single-stranded RNA molecule approximately 9.4 kb in length, which encodes a polyprotein of about 3100 amino acids. There are 6 main genotypes of HCV, each further stratified by subtype. In 1994, a cohort of women was identified in Ireland as having been iatrogenically exposed to the hepatitis C virus. The women were all young and exposed as a consequence of the receipt of HCV 1b contaminated anti-D immunoglobulin. The source of the infection was identified as an acutely infected female. As part of a voluntary serological screening programme involving 62,667 people, 704 individuals were identified as seropositive for exposure to the hepatitis C virus; 55.4% were found to be positive for the viral genome 17 years after exposure. Of these women 98% had evidence of inflammation, but suprisingly, a remarkable 49% showed no evidence of fibrosis. Clinicopathology and virological analysis has identified associations between viral load and the histological activity index for inflammation, and, between inflammation and levels of the liver enzyme alanine aminotransferase. Infection at a younger age appears to protect individuals from progression to advanced liver disease. Molecular analyses of host immunogenetic elements shows that particular class II human leukocyte associated antigen alleles are associated with clearance of the hepatitis C virus. Additional class II alleles have been identified that are associated with stable viraemia over an extended period of patient follow-up. Although, investigation of large untreated homogeneous cohorts is likely to become more difficult, as the efficacy of anti-viral therapy improves, further investigation of host and viral factors that influence disease progression will help provide an evidence based approach were realistic expectations regarding patient prognosis can be ascertained.

The object binary interface: C++ objects for evolvable shared class libraries

Object-oriented design and object-oriented languages support the development of independent software components such as class libraries. When using such components, versioning becomes a key issue. While various ad-hoc techniques and coding idioms have been used to provide versioning, all of these techniques have deficiencies - ambiguity, the necessity of recompilation or re-coding, or the loss of binary compatibility of programs. Components from different software vendors are versioned at different times. Maintaining compatibility between versions must be consciously engineered. New technologies such as distributed objects further complicate libraries by requiring multiple implementations of a type simultaneously in a program. This paper describes a new C++ object model called the Shared Object Model for C++ users and a new implementation model called the Object Binary Interface for C++ implementors. These techniques provide a mechanism for allowing multiple implementations of an object in a program. Early analysis of this approach has shown it to have performance broadly comparable to conventional implementations.

Building an index of well-being for children living in Ireland: conceptual, measurement and policy considerations

This study conceptualised and measured children’s well-being in Ireland and considered how such conceptualisations and approaches to the measurement of well-being might inform social policy for children and families living in Ireland. This research explored what is meant by children’s well-being and how it can be conceptualised and measured so as to reflect the multi-dimensionality of the concept. The study developed an index of well-being that was both theoretically and methodologically robust and could be meaningfully used to inform social policy developments for children and their families. For the first time, an index of well-being for children was developed using an explicitly articulated unifying theory of children’s well-being. Moreover, for the first time an index of wellbeing was developed for 13-year old children living in Ireland using data from Wave 2 of the national longitudinal study of children. The Structural Model of Child Well-being (SMCW), the theoretical framework that underpins the development of this study’s index, offers a comprehensive understanding of well-being. The SMCW builds on, and integrates, a range of already-established theories concerning children’s development, their agency, rights and capabilities into a unifying theory that explains well-being in its entirety. This conceptualisation of well-being moves beyond the narrow focus on child development adopted in some recent studies of children’s well-being and which perpetuate individualised and self-responsibilising conceptualisations of well-being. This study found that the SMCW can be meaningfully applied, both theoretically and operationally, to the construction of an index of well-being for children. While it was not the purpose of this study to validate the SMCW, in the process of developing the index, I concluded that there was a theoretical ‘fit’ between the conceptual orientation of the SMCW and the wider children’s well-being literature. The ‘nested’ structure of the SMCW facilitated the identification of domains, sub-domains and indicators of well-being reflecting typical conventions of index construction. The findings from the resulting index, in both its categorical and continuous forms, demonstrated how a comprehensive theory of well-being can be used to illustrate how children are faring and which children are experiencing poorer or better well-being. Furthermore, this study demonstrated how the SMCW and the resultant index can be meaningfully used to support the implementation and review of the national policy framework for children and young people in Ireland.