Marginal and Conditional Confounding Using Logits.

This article presents two ways of quantifying confounding using logistic response models for binary outcomes. Drawing on the distinction between marginal and conditional odds ratios in statistics, we define two corresponding measures of confounding (marginal and conditional) that can be recovered from a simple standardization approach. We investigate when marginal and conditional confounding may differ, outline why the method by Karlson, Holm, and Breen recovers conditional confounding under a "no interaction"-assumption, and suggest that researchers may measure marginal confounding by using inverse probability weighting. We provide two empirical examples that illustrate our standardization approach.

What cultural hierarchy? Cultural tastes, status and inequality.

Research on cultural stratification often draws on Bourdieu's misrecognition model to interpret socioeconomic gradients in cultural tastes and participation. In this model, an assumed cultural hierarchy leads individuals to adopt cultural tastes and behaviours whose status is congruent with that of their socioeconomic position (SEP). Yet, this assumed cultural hierarchy remains opaque. In this paper, we derive and test three empirical implications of the cultural hierarchy: (1) cultural activities have different status (recognition); (2) individuals in high and low SEPs have similar perceptions of the status of cultural activities (necessary condition for misrecognition); and (3) individuals prefer and engage in cultural activities whose status matches that of their SEP (status congruence). We collected survey data in Denmark and find that cultural activities differ in terms of perceived status (e.g., opera has higher perceived status than flea market), status perceptions are similar in high- and low-SEP groups and individuals prefer activities whose status matches that of their SEP. These results are consistent with the idea that a cultural hierarchy exists that sustains SEP gradients in cultural tastes and participation.

The student mental health crisis: Assessing psychiatric and developmental explanatory models.

INTRODUCTION: Student mental health problems are now commonly understood using a psychiatric model in which diagnosed anxiety and mood disorders are viewed to be so widespread as to constitute a crisis. Less attention is given to the role of developmental processes, such as identity formation and purpose, in understanding the types of distress current university students can experience. We fill this void by simultaneously assessing the effectiveness of both psychiatric and developmental variables in predicting how often students feel emotional distress in the form of frequently feeling too anxious, depressed, or overwhelmed to study. METHODS: Binary logit models were fitted to online survey data collected from a cross-sectional, nation-wide sample of 1010 Canadian full-time university students aged 18 to 24 (63% female). RESULTS: Our findings confirm that the psychiatric and developmental models both explain variance in academic distress. We also found that a developmental model operationalized using key measures of identity formation and purpose significantly accounted for academic distress, over and above variance explained by psychiatric diagnoses. In other words, not only do many students with a psychiatric diagnosis experience distress linked to problems with identity/purpose that interferes with studying, but so do a considerable proportion of students without any diagnosis. This impact persists after controlling for a host of variables assessing demographic/family background, academic preparation and performance, and a number of factors believed to aggravate emotional distress. CONCLUSIONS: Universities can respond to the mental health crisis by approaching some forms of distress as developmental problems associated with identity and purpose.

Cumulated and most recent job control and risk of disability pension in the Danish Work Life Course Cohort (DaWCo).

BACKGROUND: Previous studies have found low job control to be associated with a higher risk of disability pension (DP). Most studies have measured job control only at one time-point, and there is a lack of knowledge regarding the role of exposure duration. This study examines the prospective association between job control and DP measuring exposure both cumulated throughout work life and most recent. METHODS: We included 712 519 individuals (about 4.5 million person-years) from The Danish Work Life Course Cohort which follows young employees in Denmark from their entry into the labour market. Job control was assessed with a job exposure matrix and DP with register data on public transfer payments. We adjusted for several potential life course confounders, including physical demands at work and parental socioeconomic position and psychiatric and somatic diagnoses. RESULTS: Employees in occupations with low job control had a higher risk of DP. There were effects of both cumulated and most recent job control when mutually adjusted. Fully adjusted hazard ratios (HRs) were 1.14 [95% confidence intervals (CIs) 1.11-1.17] and 1.15 (95% CI 1.02-1.29) for cumulated and most recent job control, respectively. Without mutual adjustment, estimates were 1.15 (95% CI 1.13-1.18) and 1.55 (95% CI 1.39-1.72) for cumulated and most recent low job control, respectively. CONCLUSIONS: Low job control predicts a higher risk of DP, even after adjustment for physical demands at work. The results indicate both gradual and short-term effects of low job control on DP risk.

Psychosocial working conditions and depressive disorder: disentangling effects of job control from socioeconomic status using a life-course approach.

PURPOSE: Job control, the combination of skill discretion and decision authority, is considered a central component of the psychosocial working environment. This longitudinal study examines the relation between job control and risk of incident depressive disorder using a life-course approach. METHODS: We analyze data from The Danish Work Life Course Cohort study, including all Danish individuals aged 15-30 who entered the Danish labor market during 1995-2009 and were free from depressive disorder at entry (955,573 individuals). We measured job control using a job exposure matrix. Depressive disorders were measured using information from nationwide registers of psychiatric in- and outpatient admissions. Using Cox regression models we estimated the prospective association between job control and risk of incident depressive disorders. Analyses accounted for a range of potential confounders prior to workforce entry including socioeconomic status in adolescence and parental psychiatric and somatic diagnoses prior to labor market entry, together with potential confounders in adulthood including income, education, and demographics. RESULTS: Lower levels of past year job control were associated with a higher risk of depressive disorder after adjustment for all covariates (HR = 1.27, 95% CI 1.16-1.38). Results stratified by gender showed associations for both men (HR = 1.38, 95% CI 1.19-1.61) and women (HR = 1.19, 95% CI 1.08-1.32). CONCLUSIONS: Our findings suggest that the level of job control at work affects the risk of clinically diagnosed depressive disorder, and that this association is not due to confounding by socioeconomic status.

Education and Cognitive Aging: Accounting for Selection and Confounding in Linkage of Data From the Danish Registry and Survey of Health, Ageing and Retirement in Europe.

Earlier studies report inconsistent associations between education and cognitive aging. We assessed the association, accounting for selective dropout due to death or dementia, and, in a subsample, accounting for confounding by early-life intelligence. Data from the Danish component of the Survey of Health, Ageing and Retirement in Europe (n = 3,400) were linked to registry data (education records, dementia diagnoses, and mortality) and the Danish Conscription Database (youth intelligence measurements for 854 men). Word recall and verbal fluency were assessed up to 4 times over 10 years (2004-2013) and combined by averaging the z scores. We fitted a joint model linking a time-to-event model for dementia or death to a linear mixed-effects model for cognitive change. Rate of cognitive decline was slower among people with high education compared with low education (ß = 0.112, 95% confidence interval (CI): 0.056, 0.170). Adjusting for youth intelligence did not attenuate the association between education and cognitive decline (crude ß = 0.136, 95% CI: 0.028, 0.244 vs. adjusted ß = 0.145, 95% CI: 0.022, 0.269). The results suggest that higher education may slow cognitive decline in later life. In this sample, results changed little when accounting for selective attrition and confounding by intelligence.

Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis.

BACKGROUND & AIMS: Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We aimed to identify novel protein biomarkers of disease severity and prognosis in primary sclerosing cholangitis (PSC). METHODS: Using a bead-based array targeting 63 proteins, we profiled a derivation panel of Norwegian endoscopic retrograde cholangiography bile samples (55 PSC, 20 disease controls) and a Finnish validation panel (34 PSC, 10 disease controls). Selected identified proteins were measured in serum from two Norwegian PSC cohorts (n=167 [1992-2006] and n=138 [2008-2012]), inflammatory bowel disease (n=96) and healthy controls (n=100). RESULTS: In the bile derivation panel, the levels of 14 proteins were different between PSC patients and controls (p<0.05); all were confirmed in the validation panel. Twenty-four proteins in the bile derivation panel were significantly (p<0.05) different between PSC patients with mild compared to severe cholangiographic changes (modified Amsterdam criteria); this was replicated for 18 proteins in the validation panel. Interleukin (IL)-8, matrix metallopeptidase (MMP)9/lipocalin (LCN)2-complex, S100A8/9, S100A12 and tryptophan hydroxylase (TPH)2 in the bile were associated with both a PSC diagnosis and grade of cholangiographic changes. Stratifying PSC patients according to tertiles of serum IL-8, but not MMP9/LCN2 and S100A12, provided excellent discrimination for transplant-free survival both in the serum derivation and validation cohort. Furthermore, IL-8 was associated with transplant-free survival in multivariable analyses in both serum panels independently of age and disease duration, indicating an independent influence on PSC progression. However, the Enhanced Liver Fibrosis (ELF®) test and Mayo risk score proved to be stronger predictors of transplant-free survival. CONCLUSIONS: Based on assaying of biliary proteins, we have identified novel biliary and serum biomarkers as indicators of severity and prognosis in PSC. LAY SUMMARY: Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We have identified inflammatory proteins including calprotectin and IL-8 as important indicators of disease severity and prognosis in bile and serum from patients with primary sclerosing cholangitis.

Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs.

This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for Lawsonia intracellularis-induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg). All groups were treated once a day for 5 days. In all groups, treatment caused a rise in the numbers and proportions of tetracycline-resistant coliform bacteria right after treatment, followed by a significant drop by the time that the pigs left the nursery unit. The counts and proportions of tetracycline-resistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated with tiamulin did not show significant changes in the numbers or proportions of tetracycline-resistant coliforms. Selection for tetracycline-resistant coliforms was significantly correlated to selection for ampicillin- and sulfonamide-resistant strains but not to selection for cefotaxime-resistant strains. In conclusion, the difference in the dose of oxytetracycline and the way in which the drug was applied did not cause significantly different levels of selection of tetracycline-resistant coliform bacteria under the conditions tested.IMPORTANCE Antimicrobial resistance is a global threat to human health. Treatment of livestock with antimicrobials has a direct impact on this problem, and there is a need to improve the ways that we use antimicrobials in livestock production. We hypothesized that antibiotic resistance development following treatment of diarrhea in nursery pigs could be reduced either by lowering the dose of oxytetracycline or by replacing the commonly used practice of flock treatment with individual or small-group treatments, since this would reduce the number of pigs treated. However, the study showed no significant difference between treatment groups with respect to the number or proportion of tetracycline-resistant coliforms selected. The most important conclusion is that under practical field conditions, there will be no added value, in terms of lowering resistance development, by exchanging flock treatment for individual or small-group treatment of nursery pigs. The reason for the lack of an effect of single-animal treatment is probably that such animals share the environment with treated animals and take up resistant bacteria from the environment.

Amblyopia treatment of adults with dichoptic training using the virtual reality oculus rift head mounted display: preliminary results.

BACKGROUND: The gold standard treatments in amblyopia are penalizing therapies, such as patching or blurring vision with atropine that are aimed at forcing the use of the amblyopic eye. However, in the last years, new therapies are being developed and validated, such as dichoptic visual training, aimed at stimulating the amblyopic eye and eliminating the interocular supression. PURPOSE: To evaluate the effect of dichoptic visual training using a virtual reality head mounted display in a sample of anisometropic amblyopic adults and to evaluate the potential usefulness of this option of treatment. METHODS: A total of 17 subjects (10 men, 7 women) with a mean age of 31.2 years (range, 17-69 year) and anisometropic amblyopia were enrolled. Best corrected visual acuity (BCVA) and stereoacuity (Stereo Randot graded circle test) changes were evaluated after 8 sessions (40 min per session) of dichoptic training with the computer game Diplopia Game (Vivid Vision) run in the Oculus Rift OC DK2 virtual reality head mounted display (Oculus VR). RESULTS: Mean BCVA in amblyopic eye improved significantly from a logMAR value of 0.58 ± 0.35 before training to a post-training value of 0.43 ± 0.38 (p < 0.01). Forty-seven percent of the participants achieved BCVA of 20/40 or better after the training as compared to 30% before the training. Mean stereoacuity changed from a value of 263.3 ± 135.1 before dichoptic training to a value of 176.7 ± 152.4 s of arc after training (p < 0.01). A total of 8 patients (47.1%) before dichoptic treatment had unmeasurable stereoacuity while this only occurred in 2 patients (11.8%) after training. CONCLUSIONS: Dichoptic training using a virtual reality head mounted display seems to be an effective option of treatment in adults with anisometropic amblyopia. Future clinical trials are needed to confirm this preliminary evidence. TRIAL REGISTRATION: Trial ID: ISRCTN62086471 . Date registered: 13/06/2017. Retrospectively registered.

Enhanced liver fibrosis score predicts transplant-free survival in primary sclerosing cholangitis.

UNLABELLED: There is a need to determine biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC). We evaluated the prognostic utility of the enhanced liver fibrosis (ELF) score in Norwegian PSC patients. Serum samples were available from 305 well-characterized large-duct PSC patients, 96 ulcerative colitis patients, and 100 healthy controls. The PSC patients constituted a derivation panel (recruited 1992-2006 [n = 167]; median age 41 years, 74% male) and a validation panel (recruited 2008-2012 [n = 138]; median age 40 years, 78% male). We used commercial kits to analyze serum levels of hyaluronic acid, tissue inhibitor of metalloproteinases-1, and propeptide of type III procollagen and calculated ELF scores by the previously published algorithm. Results were also validated by analysis of ELF tests using the ADVIA Centaur XP system and its commercially available reagents. We found that PSC patients stratified by ELF score tertiles exhibited significantly different transplant-free survival in both panels (P < 0.001), with higher scores associated with shorter survival, which was confirmed in the validation panel stratified by ELF test tertiles (P = 0.003). The ELF test distinguished between mild and severe disease defined by clinical outcome (transplantation or death) with an area under the curve of 0.81 (95% confidence interval [CI] 0.73-0.87) and optimal cutoff of 10.6 (sensitivity 70.2%, specificity 79.1%). In multivariate Cox regression analysis in both panels, ELF score (hazard ratio = 1.9, 95% CI 1.4-2.5, and 1.5, 95% CI 1.1-2.1, respectively) was associated with transplant-free survival independently of the Mayo risk score (hazard ratio = 1.3, 95% CI 1.1-1.6, and 1.6, 95% CI 1.2-2.1, respectively). The ELF test correlated with ultrasound elastography in separate assessments. CONCLUSION: The ELF score is a potent prognostic marker in PSC, independent of the Mayo risk score.

The G protein-coupled estrogen receptor 1 (GPER1/GPR30) agonist G-1 regulates vascular smooth muscle cell Ca²âº handling.

The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood pressure regulation but the mechanisms are not identified. Here, we hypothesize that GPER1 controls blood pressure by regulating vascular smooth muscle cell Ca(2+) handling. Treatment with the GPER1 agonist G-1 (in the µM concentration range) acutely reduced spontaneous and synchronous Ca(2+) spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 µM) attenuated the thromboxane A2 analogue U46619-stimulated Ca(2+) spike activity but had no effect on the U46619-induced increase in the basal level of Ca(2+). The voltage-sensitive L-type Ca(2+) channel blocker nifedipine (100 nM) reduced Ca(2+) spike activity similar to G-1. Pharmacological, but not physiological, concentrations of the estrogen 17ß-estradiol reduced Ca(2+) spike activity. The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca(2+) spike activity, supporting a GPER1-dependent mechanism. G-1 (1 µM) and nifedipine (100 nM) attenuated the 30-mM KCl-evoked rise in intracellular Ca(2+) concentration, suggesting that G-1 blocks inflow of Ca(2+) via voltage-sensitive Ca(2+) channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates vascular smooth muscle cell Ca(2+) handling by lowering Ca(2+) spike activity, suggesting a role for this mechanism in GPER1-mediated control of blood pressure. © 2013 S. Karger AG, Basel.

Specific biotinylation and sensitive enrichment of citrullinated peptides.

Protein citrullination is a posttranslational modification where peptidylarginine is enzymatically deiminated to form peptidylcitrulline. Although the role of protein citrullination in both health and disease is being increasingly recognised, techniques available to identify citrullinated proteins and to map their citrullination site(s) are rare and often show poor sensitivity. Here, we present a sensitive technique for specific modification and selective enrichment of citrullinated peptides from complex biological samples. The technique is based on highly specific in-solution biotinylation of citrulline residues followed by selective enrichment of modified peptides using streptavidin beads. We demonstrate that a synthetic citrulline-containing peptide can be selectively enriched when less than 0.5 pmol is spiked into a highly heterogeneous peptide mixture. After enrichment, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of an aliquot of the streptavidin eluate corresponding to theoretically 50 fmol of the spiked-in peptide showed a prominent signal. We further demonstrate the sensitivity of our technique by enrichment of citrullinated peptides from enzymatically deiminated myelin basic protein (MBP), when 10 pmol was spiked into a heterogeneous biological digest. In MALDI-TOF MS analysis, six MBP-derived citrullinated peptides were observed, showing the efficiency of this enrichment strategy. The high sensitivity combined with the remarkable specificity of the described technique makes it a valuable tool for elucidating citrullination in various biological processes.

Differential effects of LPS from Escherichia coli and Porphyromonas gingivalis on IL-6 production in human periodontal ligament cells.

OBJECTIVE: Periodontal ligament (PDL) cells produce IL-6 upon stimulation with inflammation promoters, but the signaling pathways involved have not been characterized. This study investigates underlying mechanisms behind regulation of PDL cell IL-6 production by E. coli and P. gingivalis LPS. MATERIALS AND METHODS: Human PDL cells, endothelial cells and monocytes were stimulated with E. coli or P. gingivalis LPS in the presence or absence of pharmacological agents in order to disclose pathways involved in LPS signaling. Gene expression and cellular protein levels were assessed by quantitative real-time PCR and ELISA, respectively. RESULTS: Stimulation with LPS from E. coli (1 µg/ml) for 24 h enhanced PDL cell IL-6 expression several fold, demonstrated both on transcript and protein levels, but P. gingivalis LPS (1-5 µg/ml) had no effect. TLR2 mRNA was more highly expressed than TLR4 transcript in PDL cells. Treatment with the non-selective nitric oxide synthase inhibitor L-NAME (100 µM) reduced E. coli LPS-induced PDL cell IL-6 by 30%, while neither aminoguanidine (10 µM), an inhibitor of inducible nitric oxide synthase, nor estrogen (17ß-estradiol, 100 nM) influenced IL-6. Treatment with the glucocorticoid dexamethasone (1 µM) totally prevented the E. coli LPS-induced PDL cell IL-6. In endothelial cells, neither E. coli LPS nor P. gingivalis LPS promoted IL-6 production. In monocytes, serving as positive control, both E. coli and P. gingivalis LPS stimulated IL-6. CONCLUSIONS: E. coli LPS but not P. gingivalis LPS stimulates PDL cell IL-6 production through a glucocorticoid-sensitive mechanism involving nitric oxide formation, probably via endothelial nitric oxide synthase.

Employment success of social assistance recipients: A provincial analysis by industry.

Poverty continues to burden millions of Canadians each year, and social assistance (SA) is one program that provides last-resort financial assistance, conditional upon looking for and accepting work. Using tax panel data of SA recipients from across seven Canadian regions between 2000 and 2018, we model the probabilities of employment success (ES) across industry of employment, SA benefit amounts, unionization, and individual-level characteristics. We adopt an economic stance to explain reliance upon SA, examining the broader macroeconomic indicators of ES, and to demonstrate the factors associated with exiting SA. We find that many SA recipients do not present evidence of recent employment, indicating a disconnect between stated SA program aims and their outcomes. We provide evidence for increased SA benefits and unionization as significant predictors of ES of SA recipients.

La pauvreté continue de peser sur des millions de Canadiens chaque année, et l'aide sociale (AS) est un programme qui fournit une aide financière de dernier recours, à condition de chercher et d'accepter un emploi. À l'aide de données fiscales de panel sur les bénéficiaires de l'aide sociale de sept régions canadiennes entre 2000 et 2018, nous modélisons les probabilités de réussite professionnelle en fonction du secteur d'emploi, du montant des prestations d'aide sociale, de la syndicalisation et des caractéristiques individuelles. Nous adoptons une position économique pour expliquer le recours à l'AS, en examinant les indicateurs macroéconomiques plus larges de la réussite professionnelle, et pour démontrer les facteurs associés à la sortie de l'AS. Nous constatons que de nombreux bénéficiaires de l'AS ne présentent pas de preuve d'emploi récent, ce qui indique un décalage entre les objectifs déclarés du programme d'AS et leurs résultats. Nous fournissons des preuves que l'augmentation des prestations d'AS et la syndicalisation sont des prédicteurs importants de la réussite de l'emploi des bénéficiaires de l'AS.

Sources of mathematics self-efficacy: The interactive role of parental education and perceptions of teachers.

Using US National Education Longitudinal Study (NELS) data, we explore how parental education and primary students' perceptions of their teachers interact to impact students' self-efficacy in mathematics. Our results demonstrate that students tend to have higher self-efficacy if they perceive that their teacher promotes the importance of mathematics. This relationship holds regardless of parental education, though it is strongest for children of parents without a university education. Children of less educated parents also tend to have lower self-efficacy if they attend private schools, which typically have high average parental socio-economic status (SES). School type has no discernable impact on children of university-educated parents. These findings are highly relevant to the Canadian context, which is characterized by schools being stratified by SES and the high importance of STEM education for occupational outcomes.

En utilisant les données de l'étude longitudinale de l'éducation nationale américaine, nous explorons comment l'éducation parentale et les perceptions qu'ont les élèves du primaire de leurs enseignants interagissent pour influencer l'auto-efficacité des élèves en mathématiques. Nos résultats démontrent que les élèves ont tendance à avoir une plus grande efficacité personnelle s'ils perçoivent que leur enseignant promeut l'importance des mathématiques. Cette relation est valable quel que soit le niveau d'éducation des parents, bien qu'elle soit plus forte pour les enfants dont les parents n'ont pas fait d'études universitaires. Les enfants de parents moins éduqués ont également tendance à avoir une moins bonne auto-efficacité s'ils fréquentent des écoles privées, où le statut socio-économique moyen des parents est généralement élevé. Le type d'école n'a pas d'impact perceptible sur les enfants dont les parents ont fait des études universitaires. Ces résultats sont très pertinents dans le contexte canadien, qui se caractérise par une stratification des écoles en fonction du statut socio-économique et une grande importance de l'enseignement des STIM pour les résultats professionnels.

Psychosocial working conditions and sickness absence among younger employees in Denmark: a register-based cohort study using job exposure matrices.

OBJECTIVE: Previous literature has established associations between psychosocial working conditions and sickness absence (SA), but only few studies have examined associations among younger employees. This study aimed to investigate associations between psychosocial working conditions and SA among employees, aged 15-30 years, who entered the labor market in Denmark between 2010 and 2018. METHOD: We followed 301 185 younger employees in registers for on average 2.6 years. Using job exposure matrices, we assessed job insecurity, quantitative demands, decision authority, job strain, emotional demands, and work-related physical violence. Adjusted rate ratios of SA spells of any length were estimated for women and men separately with Poisson models. RESULTS: Among women, employment in occupations with high quantitative demands, low decision authority, high job strain, high emotional demands, or high work-related physical violence was associated with higher rates of SA. Being employed in occupations with high versus low emotional demands showed the strongest association with SA, with a rate ratio of 1.44 [95% confidence interval (CI) 1.41-1.47]. Among men, being employed in occupations with low decision authority showed the strongest association with SA (1.34, 95% CI 1.31-1.37), whereas occupations with high quantitative demands, high job strain, and high emotional demands were associated with lower rates of SA. CONCLUSION: We found that several psychosocial working conditions were associated with SA spells of any length. Associations with SA spells of any length resemble associations with long-term SA, suggesting that results from previous studies on long-term SA may be generalizable to all lengths of SA among younger employees.

An automated analysis of highly complex flow cytometry-based proteomic data.

The combination of color-coded microspheres as carriers and flow cytometry as a detection platform provides new opportunities for multiplexed measurement of biomolecules. Here, we developed a software tool capable of automated gating of color-coded microspheres, automatic extraction of statistics from all subsets and validation, normalization, and cross-sample analysis. The approach presented in this article enabled us to harness the power of high-content cellular proteomics. In size exclusion chromatography-resolved microsphere-based affinity proteomics (Size-MAP), antibody-coupled microspheres are used to measure biotinylated proteins that have been separated by size exclusion chromatography. The captured proteins are labeled with streptavidin phycoerythrin and detected by multicolor flow cytometry. When the results from multiple size exclusion chromatography fractions are combined, binding is detected as discrete reactivity peaks (entities). The information obtained might be approximated to a multiplexed western blot. We used a microsphere set with >1,000 subsets, presenting an approach to extract biologically relevant information. The R-project environment was used to sequentially recognize subsets in two-dimensional space and gate them. The aim was to extract the median streptavidin phycoerythrin fluorescence intensity for all 1,000+ microsphere subsets from a series of 96 measured samples. The resulting text files were subjected to algorithms that identified entities across the 24 fractions. Thus, the original 24 data points for each antibody were compressed to 1-4 integrated values representing the areas of individual antibody reactivity peaks. Finally, we provide experimental data on cellular protein changes induced by treatment of leukemia cells with imatinib mesylate. The approach presented here exemplifies how large-scale flow cytometry data analysis can be efficiently processed to employ flow cytometry as a high-content proteomics method.

The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner.

The G protein-coupled oestrogen receptor GPER1, also known as GPR30, has been implicated in oestrogen signalling, but the physiological importance of GPER1 is not fully understood. The GPER1 agonist G-1 has become an important tool to assess GPER1-mediated cellular effects. Here, we report that this substance, besides acting via GPER1, affects the microtubule network in endothelial cells. Treatment with G-1 (3 µM) for 24 h reduced DNA synthesis by about 60 % in mouse microvascular endothelial bEnd.3 cells. Treatment with 3 µM G-1 prevented outgrowth of primary endothelial cells from mouse aortic explants embedded in Matrigel. Treatment with G-1 (0.3-3 µM) for 24 h disrupted bEnd.3 cell and HUVEC microtubule structure in a concentration-dependent manner as assessed by laser-scanning confocal immunofluorescence microscopy. G-1-induced (3 µM) disruption of microtubule was observed also after acute (3 and 6 h) treatment and in the presence of the protein synthesis inhibitor cycloheximide. Disruption of microtubules by 3 µM G-1 was observed in aortic smooth muscle cells obtained from both GPER1 knockout and wild-type mice, suggesting that G-1 influences microtubules through a mechanism independent of GPER1. G-1 dose dependently (10-50 µM) stimulated microtubule assembly in vitro. On the other hand, microtubules appeared normal in the presence of 10-50 µM G-1 as determined by electron microscopy. We suggest that G-1-promoted endothelial cell anti-proliferation is due in part to alteration of microtubule organization through a mechanism independent of GPER1. This G-1-promoted mechanism may be used to block unwanted endothelial cell proliferation and angiogenesis such as that observed in, e.g. cancer.

The effect of part-time sick leave for employees with mental disorders.

BACKGROUND: Part-time sick leave (PTSL) allows employees on full-time sick leave (FTSL) to resume work at reduced hours. When the partly absent employee's health improves, working hours are increased until the employee is able to work regular hours. Studies have found that PTSL is an effective instrument for reducing sick leave durations for employees with musculoskeletal disorders and for employees on sick leave in general. This is the first published article to document how PTSL affects sick leave durations for employees with mental disorders. AIM: The aim is to estimate the effect of PTSL on the duration until returning to regular working hours for employees with mental disorders. We compare this effect to that of PTSL for employees with non-mental disorders ('other disorders'). METHODS: We use combined survey and register data about 226 employees on long-term sick leave with mental disorders and 638 employees with other disorders. These data contain information about type of disorder, PTSL and FTSL (full-time sick leave) durations, and various background characteristics. We use a mixed proportional hazard regression model that allows us to control for unobserved differences between employees on PTSL and those on FTSL. RESULTS: Our analyses show that PTSL has no effect on the duration until returning to regular working hours for employees with mental disorders. Furthermore, looking at specific disorders such as depression and stress-related conditions, we find no significant effects of PTSL. In contrast, in line with previous research, we find that PTSL significantly reduces the duration until returning to regular working hours for employees with other disorders. The analyses also illustrate the importance of controlling for unobserved differences between employees on PTSL and those on FTSL. Without this control, PTSL significantly reduces the duration until returning to regular working hours. When we control for unobserved characteristics, this effect decreases, and for employees with mental disorders the effect vanishes entirely. DISCUSSION AND LIMITATIONS: The lack of an effect of PTSL for employees with mental disorders needs replication in other studies. If subsequent studies confirm our findings, one should not necessarily conclude that PTSL is an ineffective intervention: PTSL may play a role in combination with other workplace interventions and in combination with person-centred interventions. The study is limited by self-reported data about disorders and a relatively small number of employees with mental disorders. CONCLUSION AND IMPLICATIONS: Our findings suggest that while PTSL reduces sick leave durations for employees with other disorders, it does not affect sick leave durations for employees with mental disorders. These results may indicate that PTSL by itself is insufficient for promoting the return to work of employees with mental disorders. FUTURE RESEARCH: Future studies could benefit from larger data sets with disorder information based on medical assessments. In addition to quantitative effect studies, future studies could focus on qualitative workplace mechanisms that may counteract the potential positive effects of PTSL for employees on sick leave with mental disorders.

Multiplexed immuno-precipitation with 1725 commercially available antibodies to cellular proteins.

Antibody array analysis of complex samples requires capture reagents with exceptional specificity. The frequency of antibodies with label-based detection may be as low as 5%. Here, however, we show that as many as 25% of commercially available antibodies are useful when biotinylated cellular proteins are fractionated by size exclusion chromatography (SEC) first. A microsphere multiplex with 1725 antibodies to cellular proteins was added to 24 SEC fractions, labelled with streptavidin and analyzed by flow cytometry (microsphere-based affinity proteomics, MAP) The SEC-MAP approach resolved different targets captured by each antibody as reactivity peaks across the separation range of the SEC column (10-670kDa). Complex reactivity profiles demonstrated that most antibodies bound more than one target. However, specific binding was readily detected as reactivity peaks common for different antibodies to the same protein. We optimized sample preparation and found that amine-reactive biotin rarely inhibited antibody binding when the biotin to lysine ratio was kept below 1:1 during labelling. Moreover, several epitopes that were inaccessible to antibodies in native proteins were unmasked after heat denaturation with 0.1% of SDS. The SEC-MAP format should allow researchers to build multiplexed assays with antibodies purchased for use in e.g. Western blotting.