A capture-recapture approach for screening using two diagnostic tests with availability of disease status for the test positives only

The article considers screening human populations with two screening tests. If any of the two tests is positive, then full evaluation of the disease status is undertaken; however, if both diagnostic tests are negative, then disease status remains unknown. This procedure leads to a data constellation in which, for each disease status, the 2 x 2 table associated with the two diagnostic tests used in screening has exactly one empty, unknown cell. To estimate the unobserved cell counts, previous approaches assume independence of the two diagnostic tests and use specific models, including the special mixture model of Walter or unconstrained capture-recapture estimates. Often, as is also demonstrated in this article by means of a simple test, the independence of the two screening tests is not supported by the data. Two new estimators are suggested that allow associations of the screening test, although the form of association must be assumed to be homogeneous over disease status. These estimators are modifications of the simple capture-recapture estimator and easy to construct. The estimators are investigated for several screening studies with fully evaluated disease status in which the superior behavior of the new estimators compared to the previous conventional ones can be shown. Finally, the performance of the new estimators is compared with maximum likelihood estimators, which are more difficult to obtain in these models. The results indicate the loss of efficiency as minor.

Contribution of redox status to hepatitis C virus E2 envelope protein function and antigenicity

Disulfide bonding contributes to the function and antigenicity of many viral envelope glycoproteins. We assessed here its significance for the hepatitis C virus E2 envelope protein and a counterpart deleted for hypervariable region-1 (HVR1). All 18 cysteine residues of the antigens were involved in disulfides. Chemical reduction of up to half of these disulfides was compatible with anti-E2 monoclonal antibody reaction, CD81 receptor binding, and viral entry, whereas complete reduction abrogated these properties. The addition of 5,5'-dithiobis-2-nitrobenzoic acid had no effect on viral entry. Thus, E2 function is only weakly dependent on its redox status, and cell entry does not require redox catalysts, in contrast to a number of enveloped viruses. Because E2 is a major neutralizing antibody target, we examined the effect of disulfide bonding on E2 antigenicity. We show that reduction of three disulfides, as well as deletion of HVR1, improved antibody binding for half of the patient sera tested, whereas it had no effect on the remainder. Small scale immunization of mice with reduced E2 antigens greatly improved serum reactivity with reduced forms of E2 when compared with immunization using native E2, whereas deletion of HVR1 only marginally affected the ability of the serum to bind the redox intermediates. Immunization with reduced E2 also showed an improved neutralizing antibody response, suggesting that potential epitopes are masked on the disulfide-bonded antigen and that mild reduction may increase the breadth of the antibody response. Although E2 function is surprisingly independent of its redox status, its disulfide bonds mask antigenic domains. E2 redox manipulation may contribute to improved vaccine design.

Amplified fragment length polymorphism genetic fingerprinting challenges the taxonomic status of the near-endemic species Chara curta Nolte ex Kutz. (Characeae)

Amplified fragment length polymorphism (AFLP) genetic fingerprinting of 14 accessions of Chara curta and Chara aspera Willd., sampled across a range of habitats and morphologies in Britain, suggests that these taxa are part of the variation within a single species complex. Two primer combinations generating 397 fragments (97% of which were polymorphic), analysed by Jaccard's similarity coefficient and principal co-ordinate analysis, did not recover groups which reflect the current taxonomy. By contrast with the genetic study, a Gower general similarity coefficient and principal co-ordinate analysis of 52 morphological characters recovered the currently recognized species groups. A Mantel test showed no significant correlation between the genetic data and the morphological data, supporting the hypothesis that phenotypic variability in Chara L. is either to some extent environmentally induced or represents developmental stages. Implications for the conservation status of C. curta in Britain are discussed. (c) 2007 The Linnean Society of London, Botanical Journal of the Linnean Society, 2007, 155, 467-476.

Longitudinal selenium status in healthy British adults: assessment using biochemical and molecular biomarkers

Human selenium (Se) requirements are currently based on biochemical markers of Se status. In rats, tissue glutathione peroxidase-1 (Gpx1) mRNA levels can be used effectively to determine Se requirements; blood Gpx1 mRNA levels decrease in Se-deficient rats, so molecular biology-based markers have potential for human nutrition assessment. To study the efficacy of molecular biology markers for assessing Se status in humans, we conducted a longitudinal study on 39 subjects (age 45 +/- 11) in Reading, UK. Diet diaries (5 day) and blood were obtained from each subject at 2, 8, 17 and 23 weeks, and plasma Se, glutathione peroxidase (Gpx3) enzyme activity, and selenoprotein mRNA levels were determined. There were no significant longitudinal effects on Se biomarkers. Se intake averaged 48 +/- 14 mu g/d. Plasma Se concentrations averaged 1.13 +/- 0.16 mu mol/l. Plasma Se v. energy-corrected Se intake (ng Se/kJ/d) was significantly correlated, but neither Gpx3 activity v. Se intake (ng Se/kJ/d) nor Gpx3 activity v. plasma Se was significantly correlated. Collectively, this indicates that subjects were on the plateaus of the response curves. Selenoprotein mRNAs were quantitated in total RNA isolated from whole blood, but mRNA levels for Gpx1, selenoprotein H, and selenoprotein W (all highly regulated by Se in rodents), as well selenoprotein P, Gpx3, and phospholipid hydroperoxide glutathione peroxidase were also not significantly correlated with plasma Se. Thus selenoprotein molecular biomarkers, as well as traditional biochemical markers, are unable to further distinguish differences in Se status in these Se replete subjects. The efficacy of molecular biomarkers to detect Se deficiency needs to be tested in Se-deficient populations.

Sustainable refurbishment: quantifying the impact of façade changes in multi-storey, multi-occupancy buildings

Building refurbishment is key to reducing the carbon footprint and improving comfort in the built environment. However, quantifying the real benefit of a facade change, which can bring advantages to owners (value), occupants (comfort) and the society (sustainability), is not a simple task. At a building physics level, the changes in kWh per m2 of heating / cooling load can be readily quantified. However, there are many subtle layers of operation and mainte-nance below these headline figures which determine how sustainable a building is in reality, such as for example quality of life factors. This paper considers the range of approached taken by a fa/e refurbishment consortium to assess refurbishment solutions for multi-storey, multi-occupancy buildings and how to critically evaluate them. Each of the applued tools spans one or more of the three building parameters of people, product and process. 'De-cision making' analytical network process and parametric building analysis tools are described and their potential impact on the building refurbishment process evaluated.

Post occupancy evaluation of a building employing windcatchers for summer ventilation

A combined windcatcher and light pipe (SunCatcher) was installed in the seminar room at the University of Reading, UK. Monitoring of indoor environment in real weather conditions was conducted to evaluate the application of windcatchers for natural ventilation. In addition, a subjective occupancy survey was undertaken. External weather conditions and internal indoor air quality indicators were recorded. The “tracer-gas decay” method using SF6 was used to establish air change rate for various conditions. The results indicated that the ventilation rate achieved through the windcatcher depends on the difference between internal and external air temperatures, and on wind speed and direction, in agreement with other published work in the area. The indoor air quality parameters were found to be within acceptable levels when the windcatcher was in operation. The measured air change rate was between 1.5ac/h and 6.8ac/h. Occupants’ questionnaires showed 75 per cent satisfaction with the internal conditions and welcomed the installation of the systems in UK buildings.

Occupational choice, socio-economic status and educational attainment: a study of the occupational choices and destinations of young people in the British household panel survey

The article considers young people's occupational choices at the age of 15 in relation to their educational attainment, the occupations of their parents and their actual occupations when they are in their early 20s. It uses data from the British Household Panel Survey over periods of between five and ten years. The young people in the survey are occupationally ambitious: many more aspire to professional, managerial and technical jobs than the likely availability of these occupations. In general ambitions and educational attainment and intentions are well aligned but there are also many instances of misalignment; either people wanting jobs which their educational attainments and intentions will not prepare them for, or people with less ambitious aspirations than their educational performance would justify. Children from more occupationally advantaged families are more ambitious, achieve better educationally and have better occupational outcomes than other children. However, where young people are both ambitious and educationally successful the occupational outcomes are as good for those from disadvantaged as advantaged families. In contrast, where young people are neither ambitious nor educationally successful, the outcomes for those from disadvantaged homes are very much poorer than for other young people. The article suggests that while choice is real it is also heavily constrained for many people. A possible educational implication of the study is that career interventions could be directed at under-ambitious but academically capable young people from disadvantaged backgrounds.