The impact of research on policy: a case of qualifications reform

The relationship between research and policymaking has been discussed repeatedly. However, the debate tends to be in general, abstract terms or from a macro-economic perspective with any examples described in a fairly cursory way. Despite the inherent complexity of the research-policy interface, analyses tend to homogenize ‘research’ and ‘policy’ as coherent entities with discussions often focusing on products (research and policies) rather than on the relationships between producers (researchers and policy makers). Here we take one piece of research on qualifications that has influenced policy rhetoric over the last 5 years. We trace the career of the research from its production in the late 1990s in order to understand the conditions of its dormancy, reemergence and use over the ensuing years. The paper serves to document the case, which is important in its own right, but also proposes a typology of ways in which research gets adopted and adapted into policy

Structural mechanism underpinning cross-reactivity of a CD8(+) T-cell clone that recognizes a peptide derived from human telomerase reverse transcriptase

T-cell cross-reactivity is essential for effective immune surveillance but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focused antigen binding involving contact with more peptide residues. To further explore the structural features that allow the clonally expressed TCR to functionally engage with multiple peptide-major histocompatibility complexes (pMHCs), we examined the ILA1 CD8(+) T-cell clone that responds to a peptide sequence derived from human telomerase reverse transcriptase. The ILA1 TCR contacted its pMHC with a broad peptide binding footprint encompassing spatially distant peptide residues. Despite the lack of focused TCR-peptide binding, the ILA1 T-cell clone was still cross-reactive. Overall, the TCR-peptide contacts apparent in the structure correlated well with the level of degeneracy at different peptide positions. Thus, the ILA1 TCR was less tolerant of changes at peptide residues that were at, or adjacent to, key contact sites. This study provides new insights into the molecular mechanisms that control T-cell cross-reactivity with important implications for pathogen surveillance, autoimmunity, and transplant rejection

Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination

Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy to quantify the organization of TCR–CD3 complexes into nanoscale clusters and to distinguish between triggered and nontriggered TCR–CD3 complexes. We found that only TCR–CD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Moreover, both pMHC dose and TCR–pMHC affinity determined the density of TCR–CD3 clusters, which scaled with overall phosphorylation levels. Thus, TCR–CD3 clustering translates antigen recognition by the TCR into signal initiation by the CD3 complex, and the formation of dense signaling-competent clusters is a process of antigen discrimination

Comparison of peptide-major histocompatibility complex tetramers and dextramers for the identification of antigen-specific T cells

Fluorochrome-conjugated peptide–major histocompatibility complex (pMHC) multimers are widely used for flow cytometric visualization of antigen-specific T cells. The most common multimers, streptavidin–biotin-based ‘tetramers’, can be manufactured readily in the laboratory. Unfortunately, there are large differences between the threshold of T cell receptor (TCR) affinity required to capture pMHC tetramers from solution and that which is required for T cell activation. This disparity means that tetramers sometimes fail to stain antigen-specific T cells within a sample, an issue that is particularly problematic when staining tumour-specific, autoimmune or MHC class II-restricted T cells, which often display TCRs of low affinity for pMHC. Here, we compared optimized staining with tetramers and dextramers (dextran-based multimers), with the latter carrying greater numbers of both pMHC and fluorochrome per molecule. Most notably, we find that: (i) dextramers stain more brightly than tetramers; (ii) dextramers outperform tetramers when TCR–pMHC affinity is low; (iii) dextramers outperform tetramers with pMHC class II reagents where there is an absence of co-receptor stabilization; and (iv) dextramer sensitivity is enhanced further by specific protein kinase inhibition. Dextramers are compatible with current state-of-the-art flow cytometry platforms and will probably find particular utility in the fields of autoimmunity and cancer immunology

The emergence of health inequalities in early adulthood: evidence on timing and mechanisms from a West of Scotland cohort

Background Evidence is inconsistent as to whether or not there are health inequalities in adolescence according to socio-economic position (SEP) and whether or when they emerge in early adulthood. Despite the large health inequalities literature, few studies have simultaneously compared the relative importance of ?health selection? versus ?social causation? at this life-stage. This study followed a cohort through the youth-adult transition to: (1) determine whether, and if so, when, health inequalities became evident according to both class of origin and current SEP; (2) compare the importance of health selection and social causation mechanisms; and (3) investigate whether these phenomena vary by gender. Methods Data are from a West-of-Scotland cohort, surveyed five times between age 15 (in 1987, N=1,515, response=85%) and 36. Self-reported physical and mental health were obtained at each survey. SEP was based on parental occupational class at 15, a combination of own education or occupational status at 18 and own occupational class (with an additional non-employment category) at older ages. In respect of when inequalities emerged, we used the relative index of inequality to examine associations between both parental and own current SEP and health at each age. In respect of mechanisms, path models, including SEP and health at each age, investigated both inter and intra-generational paths from SEP to health (?causation?) and from health to SEP (?selection?). Analyses were conducted separately for physical and mental health, and stratified by gender. Results Associations between both physical and mental health and parental SEP were non-significant at every age. Inequalities according to own SEP emerged for physical health at 24 and for mental health at 30. There was no evidence of selection based on physical health, but some evidence of associations between mental health in early adulthood and later SEP (intra-generational selection). Paths indicated intra-generational (males) and inter-generational (females) social causation of physical health inequalities, and intra-generational (males and females) and inter-generational (females) social causation of mental health inequalities. Conclusions The results suggest complex and reciprocal relationships between SEP and health and highlight adolescence and early adulthood as a sensitive period for this process, impacting on future life-chances and health

Mourning Dove, White-winged Dove, and Band-tailed Pigeon: 2009 Population Status

Mourning Dove Population Status, 2009 This report summarizes information on the abundance and harvest of mourning doves collected annually in the United States. The focus is on results from the Mourning Dove Call-count Survey, but also includes results from the Breeding Bird Survey and the Migratory Bird Harvest Information Program. According to the Call-count survey, the mean number of doves heard per route over the recent 2 years (2008–2009) increased significantly in the Central Management Unit, but did not change significantly in either the Eastern or Western Units. Over the most recent 10 years (2000–2009), there was no significant trend in doves heard for either the Eastern or Western Management Units while the Central Unit declined significantly. Over the 44-year period (1966–2009), there was no significant change in doves heard for the Eastern Unit while the Central and Western Units declined significantly. Based on the mean number of doves seen per route, however, there was no significant change for any of the three Management Units during the recent 10-year period. Over 44 years, there was no change in doves seen for the Eastern and Central Units while the Western Unit declined significantly. White-winged Dove Status in Arizona, 2009 The Arizona Game and Fish Department (AGFD) has monitored white-winged dove populations by means of a call-count survey to provide an annual index to population size. It runs concurrently with the U.S. Fish and Wildlife Service’s Mourning Dove Call-count Survey. The index peaked at 52.3 mean number doves heard per route in 1968, but fell precipitously in the late 1970s. The index has stabilized to around 25 doves per route in the last few years; in 2009, the mean number of doves heard per route was 27.9. AGFD also monitors harvest. Harvest during the 15-day season (September 1-15) peaked in the late 1960’s at ~740,000 birds (1968 AGFD estimate) and has since stabilized at around 100,000 birds; the preliminary 2008 Migratory Bird Harvest Information Program (HIP) estimate of harvest was 95,300 birds. In 2007, AGFD redesigned their dove harvest survey to sample only from hunters registered under HIP so that results from the AGFD survey would be comparable to those from HIP. The preliminary 2008 Arizona harvest estimate was 79,488. Band-tailed Pigeon Population Status, 2009 This report summarizes information on the abundance and harvest of band-tailed pigeons collected annually in the western United States and British Columbia. Annual counts of Interior band-tailed pigeons seen and heard per route have not changed significantly since implementation of the Breeding Bird Survey (BBS) in 1966; however, they decreased (

Job changes, occupational mobility and human capital acquisition : an empirical analysis

Most individuals have more than one job or occupation in their working lives. Most employees are repeatedly faced with the choice of whether to remain in their present job (with the possibility of promotion), or quit to another job in the same occupation with a different firm, or - more radically change occupation. At each stage in an individual's career, the scope for future job or occupational mobility is largely conditioned by the type and quantity of their human capital. This paper presents an empirical study of the factors which link occupational mobility and the acquisition of either firm-based, occupation-specific or general human capital. The data employed are from a cohort of 1980 UK graduates drawn from the Department of Employment Survey 1987. The econometric work presents estimates of the role of firm-based training and occupation-specific training in the career mobility of qualified manpower in the first seven years in the labour marke

Occupational Access and Wage Discrimination

This article presents a study on the quantification of the level of occupational access and wage discrimination in Great Britain. The traditional approach to quantifying the level of sex discrimination is to distinguish gender differences in productive characteristics from the unequal treatment of characteristics according to gender. The role of inter- versus intra-occupational effects in determining the magnitude of wage differences between men and women was examined. The econometric results provided estimates of the wage differential in six broad occupational classifications together with an aggregate picture of how important the occupational distribution of females is in explaining their lower average wage. In summary, the results of the study suggest that the vast majority of the male and female wage differential arises from intra-occupation effects. The results provide evidence to suggest that occupational segregation is not a major contributor to the observed male/female wage differential