Validity of self-reported exposure to shift work

OBJECTIVE: To evaluate the validity of widely used questionnaire items on work schedule using objective registry data as reference. METHOD: A cohort study of hospital employees who responded to a self-administered questionnaire on work schedule in 2008, 2012 and 2014 and were linked to individual-level pay-roll-based records on work shifts. For predictive validity, leisure-time fatigue was assessed. RESULTS: According to the survey data in 2014 (n=8896), 55% of the day workers had at least 1 year of earlier shift work experience. 8% of the night shift workers changed to day work during the follow-up. Using pay-roll data as reference, questions on ‘shift work with night shifts’ and ‘permanent night work’ showed high sensitivity (96% and 90%) and specificity (92% and 97%). Self-reported ‘regular day work’ showed moderate sensitivity (73%), but high specificity (99%) and ‘shift work without night shifts’ showed low sensitivity (62%) and moderate specificity (87%). In multivariate logistic regression analysis, the age-adjusted, sex-adjusted and baseline fatigue-adjusted association between ‘shift work without night shifts’ and leisure-time fatigue was lower for self-reported compared with objective assessment (1.30, 95% CI 0.94 to 1.82, n=1707 vs 1.89, 95% CI 1.06 to 3.39, n=1627). In contrast, shift work with night shifts, compared with permanent day work, was similarly associated with fatigue in the two assessments (2.04, 95% CI 1.62 to 2.57, n=2311 vs 1.82, 95% CI 1.28 to 2.58, n=1804). CONCLUSIONS: The validity of self-reported assessment of shift work varies between work schedules. Exposure misclassification in self-reported data may contribute to bias towards the null in shift work without night shifts

Tumour inflammatory infiltrate predicts survival following curative resection for node-negative colorectal cancer

<b>Background</b>: A pronounced tumour inflammatory infiltrate is known to confer a good outcome in colorectal cancer. Klintrup and colleagues reported a structured assessment of the inflammatory reaction at the invasive margin scoring low grade or high grade. The aim of the present study was to examine the prognostic value of tumour inflammatory infiltrate in node-negative colorectal cancer. <b>Methods</b>: Two hundred patients had undergone surgery for node-negative colorectal cancer between 1997 and 2004. Specimens were scored with Jass’ and Klintrup’s criteria for peritumoural infiltrate. Pathological data were taken from the reports at that time. <b>Results</b>: Low-grade inflammatory infiltrate assessed using Klintrup’s criteria was an independent prognostic factor in node-negative disease. In patients with a low-risk Petersen Index (n = 179), low-grade infiltrate carried a threefold increased risk of cancer death. Low-grade infiltrate was related to increasing T stage and an infiltrating margin. <b>Conclusion</b>: Assessment of inflammatory infiltrate using Klintrup’s criteria provides independent prognostic information on node-negative colorectal cancer. A high-grade local inflammatory response may represent effective host immune responses impeding tumour growth

Prediction of bullying at work: A data-driven analysis of the Finnish public sector cohort study

AIM: To determine the extent to which change in (i.e., start and end of) workplace bullying can be predicted by employee responses to standard workplace surveys. METHODS: Responses to an 87-item survey from 48,537 Finnish public sector employees at T1 (2017–2018) and T2 (2019–2020) were analyzed with least-absolute-shrinkage-and-selection-operator (LASSO) regression. The predictors were modelled both at the individual- and the work unit level. Outcomes included both the start and the end of bullying. Predictive performance was evaluated with C-indices and density plots. RESULTS: The model with best predictive ability predicted the start of bullying with individual-level predictors, had a C-index of 0.68 and included 25 variables, of which 6 remained in a more parsimonious model: discrimination at work unit, unreasonably high workload, threat that some work tasks will be terminated, working in a work unit where everyone did not feel they are understood and accepted, having a supervisor who was not highly trusted, and a shorter time in current position. Other models performed even worse, either from the point of view of predictive performance, or practical useability. DISCUSSION: While many bivariate associations between socioeconomic characteristics, work characteristics, leadership, team climate, and job satisfaction were observed, reliable individualized detection of individuals at risk of becoming bullied at workplace was not successful. The predictive performance of the developed risk scores was suboptimal, and we do not recommend their use as an individual-level risk prediction tool. However, they might be useful tool to inform decision-making when planning the contents of interventions to prevent bullying at an organizational level

Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

BACKGROUND: Obliterative bronchiolitis after lung transplantation is characterized by chronic airway inflammation leading to the obliteration of small airways. Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular responses to hypoxia and inflammation. The Von Hippel-Lindau protein (pVHL) drives the degradation of oxygen-sensitive subunit HIF-1 alpha that controls the activity of HIF-1. We investigated the effect of myeloid cell targeted gene deletion of HIF-1 alpha or its negative regulator pVHL on the development of obliterative airway disease (OAD) in the recipients of tracheal allografts, a mouse model for obliterative bronchiolitis after lung transplantation. METHODS: Tracheal allografts were heterotopically transplanted from BALB/c donor mice to fully major histocompatibility complex mismatched recipient mice with HIF-1 alpha or VHL gene deletion in myeloid cells. The recipients were left non-immunosuppressed or received tacrolimus daily. Histologic, immunohistochemical, and real-time reverse transcription polymerase chain reaction analyses were performed at 3, 10, and 30 days. RESULTS: In the absence of immunosuppression, myeloid cell-specific VHL deficiency of the recipient mice improved epithelial recovery, decreased inflammatory cell infiltration and expression of pro-inflammatory cytokines, increased regulatory forkhead box P3 messenger RNA expression, and reduced OAD development in tracheal allografts. In the presence of tacrolimus immunosuppression, loss of HIF-1 alpha activity in myeloid cells of the recipient by HIF-1 alpha gene deletion accelerated OAD development in mouse tracheal allografts. CONCLUSIONS: Activity of the HIF-pathway affects the development of allograft rejection, and our results suggest that myeloid cell-specific VHL-deficiency that potentially increases HIF-activity decreases allograft inflammation and the subsequent development of OAD in mouse tracheal allografts. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved.Peer reviewe

Shift work, work time control, and informal caregiving as risk factors for sleep disturbances in an ageing municipal workforce

Objectives This study aimed to examine the contribution of shift work, work time control (WTC) and informal caregiving, separately and in combination, to sleep disturbances in ageing employees. Methods Survey data were obtained from two prospective cohort studies with repeated measurements of working conditions, informal caregiving, and sleep disturbances. We used fixed-effect conditional logistic regression analysis to examine whether within-individual changes in shift work, WTC and informal caregiving were associated with changes in sleep. Secondary analyses included between-individuals comparison using standard logistic regression models. Results from the two cohorts were pooled using meta-analysis. Results Low WTC and informal caregiving were associated with sleep disturbances in within-individual analyses [odds ratios (OR) ranging between 1.13 (95% confidence interval 1.01-1.27) and 1.48 (95% CI 1.29-1.68)] and in between-individuals analyses [OR 1.14 (95% CI 1.03-1.26) to 1.33 (1.19-1.49)]. Shift work alone was not associated with sleep disturbances, but accumulated exposure to shift work, low WTC and informal caregiving was associated with higher risk of sleep disturbances (OR range 1.21-1.76). For some of the sleep outcomes, informal caregiving was related to a higher risk of sleep disturbances when WTC was low and a lower risk when WTC was high. Conclusions Informal caregiving and low WTC are associated with risk of sleep disturbances among ageing employees. The findings also suggest that low WTC in combination with informal caregiving may increase the risk of sleep disturbances whereas high WTC may alleviate the adverse impact of informal caregiving on sleep

Objective working hour characteristics and work-life conflict among hospital employees in the Finnish public sector study

This epidemiological cohort study, based on Finnish public sector data, investigated the associations between objective working hour characteristics and work-life conflict in day and shift work. The comprehensive data of hospital workers (n = 8 931, 92% women, average age 45 years), consisted of survey responses from 2012, linked with the payroll data of working hour characteristics from 91 days preceding the survey. Logistic regression analysis was used to investigate the associations between working hour characteristics and experiencing work-life conflict often/very often. The analyses were adjusted for age (50 years), sex, level of education, marital status, number of small (0-6 years) and school-aged (7-18 years) children, and the overall stressfulness of the life situation. We also conducted stratified analyses of age and sex on the basis of significant interactions. Difficulties in combining work and life were more often associated with shift work without night shifts and shift work with night shifts than with day work (41% and 34 versus 27%; OR for shift work with night shifts 1.78, 95% CI 1.59-2.00, OR for shift work without night shifts 1.42, 95% CI 1.26-1.60). A high proportion (> 25%) of long (> 40h, (OR 1.26, 95% 1.14-1.39) and very long (> 48h, OR 1.31, 95% CI 1.15-1.49) weekly working hours were associated with work-life conflict, and in the stratified analysis, the latter was also true among women (OR 1.54, 95% CI 1.25-1.89). Of the unsocial working hour characteristics, a relatively large amount (> 10% of all shifts) of evening (OR 1.56, 95% CI 1.41-1.72) and night shifts (OR 1.46, 95%CI 1.32-1.61), a high proportion (> 25% of all shifts) of quick returns ( 25% of all days off) was associated with work-life conflict among men (OR 1.90, 95% CI 1.11-3.25), but not in the whole sample. When the two types of shift work were analyzed separately, shift work without night shifts and very long work weeks had higher odds (OR 1.47, 95% CI 1.20-1.80) of work-life conflict than shift work with night shifts. Conversely, weekend work and evening shifts had higher odds of work-life conflict among shift workers with night shifts (OR 1.74, 95% 1.55-1.96; (OR 1.57, 95% CI 1.40-1.77) than among those without night shifts. To conclude, this study shows that shift workers with and without night shifts more often have difficulties combining work and life than day workers. Several unsocial working hour characteristics, including long work weeks, evening and night shifts, weekend work, and quick returns, are associated with work-life conflict

Search for the active ingredients from a 2-aminothiazole DMSO stock solution with antimalarial activity

Chemical decomposition of DMSO stock solutions is a common incident that can mislead biological screening campaigns. Here, we share our case study of 2-aminothiazole 1, originating from an antimalarial class that undergoes chemical decomposition in DMSO at room temperature. As previously measured biological activities observed against Plasmodium falciparum NF54 and for the target enzyme Pf IspE were not reproducible for a fresh batch, we tackled the challenge to understand where the activity originated from. Solvent- and temperature-dependent studies using HRMS and NMR spectroscopy to monitor the decomposition led to the isolation and in vitro evaluation of several fractions against Pf IspE. After four days of decomposition, we successfully isolated the oxygenated and dimerised compounds using SFC purification and correlated the observed activities to them. Due to the unstable nature of the two isolates, it is likely that they undergo further decomposition contributing to the overall instability of the compound

Predicting long-term sickness absence with employee questionnaires and administrative records: a prospective cohort study of hospital employees

Objective: This study aimed to compare the utility of risk estimation derived from questionnaires and administrative records in predicting long-term sickness absence among shift workers. Methods This prospective cohort study comprised 3197 shift-working hospital employees (mean age 44.5 years, 88.0% women) who responded to a brief 8-item questionnaire on work disability risk factors and were linked to 28 variables on their working hour and workplace characteristics obtained from administrative registries at study baseline. The primary outcome was the first sickness absence lasting ≥90 days during a 4-year follow-up. Results The C-index of 0.73 [95% confidence interval (CI) 0.70–0.77] for a questionnaire-only based prediction model, 0.71 (95% CI 0.67–0.75) for an administrative records-only model, and 0.79 (95% CI 0.76–0.82) for a model combining variables from both data sources indicated good discriminatory ability. For a 5%-estimated risk as a threshold for positive test results, the detection rates were 76%, 74%, and 75% and the false positive rates were 40%, 45% and 34% for the three models. For a 20%-risk threshold, the corresponding detection rates were 14%, 8%, and 27% and the false positive rates were 2%, 2%, and 4%. To detect one true positive case with these models, the number of false positive cases accompanied varied between 7 and 10 using the 5%-estimated risk, and between 2 and 3 using the 20%-estimated risk cut-off. The pattern of results was similar using 30-day sickness absence as the outcome. Conclusions The best predictive performance was reached with a model including both questionnaire responses and administrative records. Prediction was almost as accurate with models using only variables from one of these data sources. Further research is needed to examine the generalizability of these findings

High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions

Pharmaceutical nanosuspensions are formed when drug crystals are suspended in aqueous media in the presence of stabilizers. This technology offers a convenient way to enhance the dissolution of poorly water-soluble drug compounds. The stabilizers exert their action through electrostatic or steric interactions, however, the molecular requirements of stabilizing agents have not been studied extensively. Here, four structurally related amphiphilic Janus-dendrimers were synthesized and screened to determine the roles of different macromolecular domains on the stabilization of drug crystals. Physical interaction and nanomilling experiments have substantiated that Janus-dendrimers with fourth generation hydro- philic dendrons were superior to third generation analogues and Poloxamer 188 in stabilizing indomethacin suspensions. Contact angle and surface plasmon resonance measurements support the hypothesis that Janus-dendrimers bind to indomethacin surfaces via hydrophobic interactions and that the number of hydrophobic alkyl tails determines the adsorption kinetics of the Janus-dendrimers. The results showed that amphiphilic Janus-dendrimers adsorb onto drug particles and thus can be used to provide steric stabilization against aggregation and recrystallization. The modular synthetic route for new amphiphilic Janus-dendrimers offers, thus, for the first time a versatile platform for stable general-use stabilizing agents of drug suspensions.Peer reviewe