Slipping anchor? Testing the vignettes approach to identification and correction of reporting heterogeneity

Anchoring vignettes are increasingly used to identify and correct heterogeneity in the reporting of health, work disability, life satisfaction, political efficacy, etc. with the aim of improving interpersonal comparability of subjective indicators of these constructs. The method relies on two assumptions: vignette equivalence – the vignette description is perceived by all to correspond to the same state; and, response consistency - individuals use the same response scales to rate the vignettes and their own situation. We propose tests of these assumptions. For vignette equivalence, we test a necessary condition of no systematic variation with observed characteristics in the perceived difference in states corresponding to any two vignettes. To test response consistency we rely on the assumption that objective indicators fully capture the covariation between the construct of interest and observed individual characteristics, and so offer an alternative way to identify response scales, which can then be compared with those identified from the vignettes. We also introduce a weaker test that is valid under a less stringent assumption. We apply these tests to cognitive functioning and mobility related health problems using data from the English Longitudinal Survey of Ageing. Response consistency is rejected for both health domains according to the first test, but the weaker test does not reject for cognitive functioning. The necessary condition for vignette equivalence is rejected for both health domains. These results cast some doubt on the validity of the vignettes approach, at least as applied to these health domains

Elimination of TFA-Mediated Cleavage in Distributed Drug Discovery

Distributed Drug Discovery (D3) is a multi-disciplinary approach to the discovery of new drugs, which target neglected diseases or conditions common to developing-world countries. As part of a continuing effort to improve D3 methodology, two approaches for eliminating the final step TFA-mediated resin cleavage are proposed for investigation. Cleavage under basic conditions (saponification) and mild acid conditions (dilute HCl/hexafluoroisopropanol or dilute HCl/trifluoroethanol) represent improvements in safety and convenience to the undergraduate student researcher. Previous studies have shown that saponification provides yields comparable to the traditional TFA cleavage but recovery is not as convenient. Further improvements in the saponification workup will be evaluated by analyzing the effectiveness of simple trituration with acetone compared to use of a strong anion-exchange resin or drying reagents to isolate the free acid from the salt. Different trituration procedural modifications have been made and are being tested. Results have shown that in the presence of methanol, esterification will occur when the acid is liberated from the salt using HCl. To counter this problem, the samples are first evaporated to remove methanol and then the pH is adjusted with HCl. It was shown that using acetic acid did not result in pH levels low enough to guarantee complete protonation of the carboxylate. Through the use of a Bill-Board, an apparatus that holds six reaction vessels, several procedural modifications can be carried out simultaneously. Analysis is conducted by liquid chromatography coupled with a mass spectrometer and with nuclear magnetic resonance spectroscopy. Further studies will be carried out to assess the efficiency and practicality of using mild acidic conditions for cleavage using HCl/hexafluoroisopropanol or dilute HCl/trifluoroethanol. Both saponification and mild acid cleavage would represent improvements in safety and convenience to the undergraduate student researcher

How do we get people into contact? Predictors of intergroup contact and drivers of contact seeking

Compared to the impressive amount of research on consequences of intergroup contact, relatively little work has been devoted to predictors of intergroup contact. Although opportunities for intergroup contact are constantly growing in modern diverse societies, these contact opportunities are not necessarily exploited. In the present review article, we describe current research on predictors of intergroup contact and drivers of contact seeking on a micro‐, meso‐, and macro‐level. We provide an overview of predictors, while focusing on recent research that is especially relevant for designing interventions and planning social policies aiming at increasing contact between different groups in varied societies. On the micro‐level, we discuss relational self‐expansion motives and confidence in contact as predictors of intergroup contact. On the meso‐level, we focus on the role of intragroup processes and historical intergroup conflicts in facilitating contact. On the macro‐level, we reflect on changing societal norms as a potential tool to increase the frequency intergroup contact. By focusing on the applied value of research findings, discussing diverse predictors, and applying a multilevel approach, we also address recent criticisms of the intergroup contact literature and demonstrate the generative nature of contemporary research in this area

Phospholipid signaling in innate immune cells

Phospholipids comprise a large body of lipids that define cells and organelles by forming membrane structures. Importantly, their complex metabolism represents a highly controlled cellular signaling network that is essential for mounting an effective innate immune response. Phospholipids in innate cells are subject to dynamic regulation by enzymes, whose activities are highly responsive to activation status. Along with their metabolic products, they regulate multiple aspects of innate immune cell biology, including shape change, aggregation, blood clotting, and degranulation. Phospholipid hydrolysis provides substrates for cell-cell communication, enables regulation of hemostasis, immunity, thrombosis, and vascular inflammation, and is centrally important in cardiovascular disease and associated co-morbidities. Phospholipids themselves are also recognized by innate-like T cells, which are considered essential for recognition of infection or cancer, as well as self-antigens. This review will describe the major phospholipid metabolic pathways present in innate immune cells and summarize the formation and metabolism of phospholipids as well as their emerging roles in cell biology and disease

Saponification of N-Acylated L-Phenylalanine Wang and Merrifield Resins. Assessment of Cleavage Efficiency and Epimerization

poster abstractAs part of a continuing effort to modify Distributed Drug Discovery (D3) synthetic procedures to enhance safety and accommodate the limited resources available to students in developing-world countries, we have recently begun to examine alternatives to trifluoroacetic acid (TFA)-cleavage of amino acid derivatives from polystyrene-based resins. Cleavage of a representative example, N-(4-chlorobenzoyl)-L-phenylalanine, from both Wang and Merrifield resins was accomplished in thirty minutes at room temperature using 0.5M sodium hydroxide in methanol/tetrahydrofuran. In a side-by-side comparison with cleavage using TFA, results indicated that saponification from Wang resin was incomplete after thirty minutes. Experiments designed to examine separately the effect of reaction time, temperature, and concentration were performed and results will be presented. Additionally, investigations were performed to assess the degree of epimerization which had occurred during cleavage of Merrifield-bound L-phenylalanine acylated with both (R)- and (S)-mandelic acid. Results revealed a small but significant amount of epimerization (15:1 to 31:1 diastereomeric ratios) after a thirty-minute cleavage time at room temperature

Entering out-of-home care during childhood: Cumulative incidence study in Canada and Australia

Cumulative incidence provides a more accurate indicator than annual incidence rates of the number of children who experience out-of-home care during childhood. The study utilises a cohort of all children born in Western Australia (WA) 1994–2005 and Manitoba 1998–2008 using de-identified linked data. Life tables were used to calculate the age-specific cumulative incidence over time and for at-risk groups. Cox regression was used to compare risk factors for entry to care. Manitoba had a larger proportion of children entering care compared to WA (9.4% vs 1.5% by age 12). Over time children entered care at a younger age in both WA (HR = 1.5, CI:1.4–1.5) and Manitoba (HR = 1.5, CI:1.5–1.6). Similar factors were associated with earlier age care entries in both countries including: socioeconomic disadvantage, young maternal age, maternal hospital admissions for mental health issues, substance misuse and assault. Supplementary analysis for WA showed a time trend with young children (<3 years of age) who entered care spending an increasing proportion of their early years in care. Whilst Manitoba had a larger proportion of children entering care, over time in Western Australia children have been entering care at a younger age and spending more time in care. These latter factors contribute to an increased burden on the out-of-home care system. Manitoba had over five times greater cumulative incidence than WA, however risk factors for entry to out-of-home care were consistent in both countries. Knowledge of the risk factors for entry to out-of-home care can inform targeted support and prevention programs

dtorsin, the Drosophila Ortholog of the Early-Onset Dystonia TOR1A (DYT1), Plays a Novel Role in Dopamine Metabolism

Dystonia represents the third most common movement disorder in humans. At least 15 genetic loci (DYT1-15) have been identified and some of these genes have been cloned. TOR1A (formally DYT1), the gene responsible for the most common primary hereditary dystonia, encodes torsinA, an AAA ATPase family protein. However, the function of torsinA has yet to be fully understood. Here, we have generated and characterized a complete loss-of-function mutant for dtorsin, the only Drosophila ortholog of TOR1A. Null mutation of the X-linked dtorsin was semi-lethal with most male flies dying by the pre-pupal stage and the few surviving adults being sterile and slow moving, with reduced cuticle pigmentation and thin, short bristles. Third instar male larvae exhibited locomotion defects that were rescued by feeding dopamine. Moreover, biochemical analysis revealed that the brains of third instar larvae and adults heterozygous for the loss-of-function dtorsin mutation had significantly reduced dopamine levels. The dtorsin mutant showed a very strong genetic interaction with Pu (Punch: GTP cyclohydrolase), the ortholog of the human gene underlying DYT14 dystonia. Biochemical analyses revealed a severe reduction of GTP cyclohydrolase protein and activity, suggesting that dtorsin plays a novel role in dopamine metabolism as a positive-regulator of GTP cyclohydrolase protein. This dtorsin mutant line will be valuable for understanding this relationship and potentially other novel torsin functions that could play a role in human dystonia