Time reclaimed: temporality and the experience of meaningful work

The importance of meaningful work has been identified in scholarly writings across a range of disciplines. However, empirical studies remain sparse and the potential relevance of the concept of temporality, hitherto somewhat neglected even in wider sociological studies of organizations, has not been considered in terms of the light that it can shed on the experience of work as meaningful. These two disparate bodies of thought are brought together to generate new accounts of work meaningfulness through the lens of temporality. Findings from a qualitative study of workers in three occupations with ostensibly distinct temporal landscapes are reported. All jobs had the potential to be both meaningful and meaningless; meaningfulness arose episodically through work experiences that were shared, autonomous and temporally complex. Schutz’s notion of the ‘vivid present’ emerged as relevant to understanding how work is rendered meaningful within an individual’s personal and social system of relevances

Extended Follow-Up Following a Phase 2b Randomized Trial of the Candidate Malaria Vaccines FP9 ME-TRAP and MVA ME-TRAP among Children in Kenya

Background. "FFM ME-TRAP'' is sequential immunisation with two attenuated poxvirus vectors (FP9 and modified vaccinia virus Ankara) delivering the pre-erythrocytic malaria antigen ME-TRAP. Over nine months follow-up in our original study, there was no evidence that FFM ME-TRAP provided protection against malaria. The incidence of malaria was slightly higher in children who received FFM ME-TRAP, but this was not statistically significant (hazard ratio 1.5, 95% CI 1.0-2.3). Although the study was unblinded, another nine months follow-up was planned to monitor the incidence of malaria and other serious adverse events. Methods and Findings. 405 children aged 1-6 yrs were initially randomized to vaccination with either FFM ME-TRAP or control (rabies vaccine). 380 children were still available for follow-up after the first nine months. Children were seen weekly and whenever they were unwell for nine months monitoring. The axillary temperature was measured, and blood films taken when febrile. The primary analysis was time to parasitaemia >2,500/mu l. During the second nine months monitoring, 49 events met the primary endpoint (febrile malaria with parasites >2,500/mu l) in the Intention To Treat (ITT) group. 23 events occurred among the 189 children in the FFM ME-TRAP group, and 26 among the 194 children in the control group. In the full 18 months of monitoring, there were 63 events in the FFM ME-TRAP group and 60 in the control group (HR = 1.2, CI 0.84-1.73, p = 0.35). There was no evidence that the HR changed over the 18 months (test for interaction between time and vaccination p = 0.11). Conclusions. Vaccination with FFM ME-TRAP was not protective against malaria in this study. Malaria incidence during 18 months of surveillance was similar in both vaccine groups. Trial Registration. Controlled-Trials. com ISRCTN88335123

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Prediction of cardiovascular risk using Framingham, ASSIGN and QRISK2: how well do they predict individual rather than population risk?

BACKGROUND: The objective of this study was to evaluate the performance of risk scores (Framingham, Assign and QRISK2) in predicting high cardiovascular disease (CVD) risk in individuals rather than populations. METHODS AND FINDINGS: This study included 1.8 million persons without CVD and prior statin prescribing using the Clinical Practice Research Datalink. This contains electronic medical records of the general population registered with a UK general practice. Individual CVD risks were estimated using competing risk regression models. Individual differences in the 10-year CVD risks as predicted by risk scores and competing risk models were estimated; the population was divided into 20 subgroups based on predicted risk. CVD outcomes occurred in 69,870 persons. In the subgroup with lowest risks, risk predictions by QRISK2 were similar to individual risks predicted using our competing risk model (99.9% of people had differences of less than 2%); in the subgroup with highest risks, risk predictions varied greatly (only 13.3% of people had differences of less than 2%). Larger deviations between QRISK2 and our individual predicted risks occurred with calendar year, different ethnicities, diabetes mellitus and number of records for medical events in the electronic health records in the year before the index date. A QRISK2 estimate of low 10-year CVD risk (<15%) was confirmed by Framingham, ASSIGN and our individual predicted risks in 89.8% while an estimate of high 10-year CVD risk (≥ 20%) was confirmed in only 48.6% of people. The majority of cases occurred in people who had predicted 10-year CVD risk of less than 20%. CONCLUSIONS: Application of existing CVD risk scores may result in considerable misclassification of high risk status. Current practice to use a constant threshold level for intervention for all patients, together with the use of different scoring methods, may inadvertently create an arbitrary classification of high CVD risk

An agent based decentralized matching macroeconomic model

In this paper we present a macroeconomic microfounded framework with heterogeneous agents-individuals, firms, banks-which interact through a decentralized matching process presenting common features across four markets-goods, labor, credit and deposit. We study the dynamics of the model by means of computer simulation. Some macroeconomic properties emerge such as endogenous business cycles, nominal GDP growth, unemployment rate fluctuations, the Phillips curve, leverage cycles and credit constraints, bank defaults and financial instability, and the importance of government as an acyclical sector which stabilize the economy. The model highlights that even extended crises can endogenously emerge. In these cases, the system may remain trapped in a large unemployment status, without the possibility to quickly recover unless an exogenous intervention takes place

Glucocorticoid Effects on the Programming of AT1b Angiotensin Receptor Gene Methylation and Expression in the Rat

Adverse events in pregnancy may ‘programme’ offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11β-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence

Validity of self-reported weight, height, and body mass index among university students in Thailand: Implications for population studies of obesity in developing countries

<p>Abstract</p> <p>Background</p> <p>Large-scale epidemiological studies commonly use self-reported weights and heights to determine weight status. Validity of such self-reported data has been assessed primarily in Western populations in developed countries, although its use is widespread in developing countries. We examine the validity of obesity based on self-reported data in an Asian developing country, and derive improved obesity prevalence estimates using the "reduced BMI threshold" method.</p> <p>Methods</p> <p>Self-reported and measured heights and weights were obtained from 741 students attending an open university in Thailand (mean age 34 years). Receiver operator characteristic techniques were applied to derive "reduced BMI thresholds."</p> <p>Results</p> <p>Height was over-reported by a mean of 1.54 cm (SD 2.23) in men and 1.33 cm (1.84) in women. Weight was under-reported by 0.93 kg (3.47) in men and 0.62 kg (2.14) in women. Sensitivity and specificity for determining obesity (Thai BMI threshold 25 kg/m²) using self-reported data were 74.2% and 97.3%, respectively, for men and 71.9% and 100% for women. For men, reducing the BMI threshold to 24.5 kg/m²increased the estimated obesity prevalence based on self-reports from 29.1% to 33.8% (true prevalence was 36.9%). For women, using a BMI threshold of 24.4 kg/m², the improvement was from 12.0% to 15.9% (true prevalence 16.7%).</p> <p>Conclusion</p> <p>Young educated Thais under-report weight and over-report height in ways similar to their counterparts in developed countries. Simple adjustments to BMI thresholds will overcome these reporting biases for estimation of obesity prevalence. Our study suggests that self-reported weights and heights can provide economical and valid measures of weight status in high school-educated populations in developing countries.</p

Meta-Analysis of TNF 308 G/A Polymorphism and Type 2 Diabetes Mellitus

BACKGROUND AND OBJECTIVES: Many investigations have focused the association between TNF 308 G/A polymorphism and risk for type 2 diabetes mellitus (T2DM). However, the sample sizes of most of the studies were small. The aim of this study is to evaluate the precise association between this variant and risk for T2DM in a large-scale meta-analysis. METHODS: All publications were searched on the association between TNF 308 G/A polymorphism and T2DM. The key words were as follows: diabetes, tumor necrosis factor and polymorphism/variant/genotype. This meta-analysis was assessed by Review manager 5.0. RESULTS: There were 18 studies identified. The odds ratios (ORs) and 95% confidence intervals (CI) for GA+AA versus GG genotype of TNF 308 G/A polymorphism were 1.03 (0.95-1.12), 1.03 (0.94-1.13) and 1.03 (0.78-1.36) in overall, Caucasian and Asian populations, respectively. The sensitivity analysis further strengthened the validity of this association. No publication bias or heterogeneity was observed in this study. CONCLUSION: In summary, there was no significant association detected between the TNF 308 G/A polymorphism and risk for T2DM