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OBJECTIVES: This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. METHODS: We searched PubMed and Embase for published prospective cohort studies and included available cohorts with unpublished individual-participant data. We used a random-effects meta-analysis to calculate summary estimates across studies. RESULTS: We identified ten published cohort studies and included unpublished individual-participant data from 18 studies. In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1–5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence interval (CI) 1.03–1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I^2=45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13–2.01), a weaker association in Europe (1.11, 95% CI 1.00–1.22), and no association in North America (0.97, 95% CI 0.70–1.34) or Australia (0.95, 95% CI 0.70–1.29). Differences by other characteristics were small. CONCLUSIONS: This observational evidence suggests a moderate association between long working hours and onset of depressive symptoms in Asia and a small association in Europe.

OBJECTIVES: Unhealthy lifestyle (eg, smoking) as well as sleep problems are associated with increased risk of sickness absence, but the financial impact of these associations beyond risk ratios is not well known. We aimed to estimate the additive contribution of lifestyle and sleep problems (risk factors) to direct costs of short-term (7 servings/week for women and >14 servings/week for men); physically inactive [

Background: Exposure to disinfection by-products (DBPs) in drinking water and chlorinated swimming pools are associated with adverse health outcomes, but biological mechanisms remain poorly understood. Objectives: Evaluate short-term changes in metabolic profiles in response to DBP exposure while swimming in a chlorinated pool. Materials and methods: The PISCINA-II study (EXPOsOMICS project) includes 60 volunteers swimming 40min in an indoor pool. Levels of most common DBPs were measured in water and in exhaled breath before and after swimming. Blood samples, collected before and 2h after swimming, were used for metabolic profiling by liquid-chromatography coupled to high-resolution mass-spectrometry. Metabolome-wide association between DBP exposures and each metabolic feature was evaluated using multivariate normal (MVN) models. Sensitivity analyses and compound annotation were conducted. Results: Exposure levels of all DBPs in exhaled breath were higher after the experiment. A total of 6,471 metabolic features were detected and 293 features were associated with at least one DBP in exhaled breath following Bonferroni correction. A total of 333 metabolic features were associated to at least one DBP measured in water or urine. Uptake of DBPs and physical activity were strongly correlated and mutual adjustment reduced the number of statistically significant associations. From the 293 features, 20 could be identified corresponding to 13 metabolites including compounds in the tryptophan metabolism pathway. Conclusion: Our study identified numerous molecular changes following a swim in a chlorinated pool. While we could not explicitly evaluate which experiment-related factors induced these associations, molecular characterization highlighted metabolic features associated with exposure changes during swimming. Keywords: Disinfection by-products, DBPs, Metabolome, LC-MS, Blood, Exposome

Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P =.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2–8.5) hours with tafoxiparin and 7.03 (1.5–14.3) hours with the placebo (P =.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P =.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P =.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P =.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants. [ABSTRACT FROM AUTHOR]

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis; (iii) application of linear mixed models to remove unwanted variability, including samples’ originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.

Transposition of the great arteries (TGA) is one of the most common cyanotic congenital heart diseases requiring neonatal surgical intervention. Parallel circulations that result in impaired cerebral oxygen delivery already in utero may lead to brain damage and long-term neurodevelopmental delay. Balloon atrial septostomy (BAS) is often employed to mix deoxygenated and oxygenated blood at the atrial level. However, BAS causes a sudden increase in arterial blood oxygenation and oxidative stress. We studied changes in oxygen saturation as well as metabolic profiles of plasma samples from nine newborn infants suffering from TGA before and until 48 h after undergoing BAS. The plasma metabolome clearly changed over time and alterations of four metabolic pathways, including the pentose phosphate pathway, were linked to changes in the cerebral tissue oxygen extraction. In contrast, no changes in levels of lipid peroxidation biomarkers over time were observed. These observations suggest that metabolic adaptations buffer the free radical burst triggered by re-oxygenation, thereby avoiding structural damage at the macromolecular level. This study enhances our understanding of the complex response of infants with TGA to changes in oxygenation induced by BAS.

This paper presents a fully integrated, four-stack, single-ended, single stage power amplifier (PA) for millimeter-wave (mmWave) wireless applications that was fabricated and designed using 45 nm complementary metal oxide semiconductor silicon on insulator (CMOS SOI) technology. The frequency of operation is from 20 GHz to 30 GHz, with 13.7 dB of maximum gain. The maximum RF (radio frequency) output power (Pout), power-added efficiency (PAE) and output 1 dB compression point are 20.5 dBm, 29% and 18.8 dBm, respectively, achieved at 24 GHz. The error vector magnitude (EVM) of 12.5% was measured at an average channel power of 14.5 dBm at the center of the the 3GPP/NR (third generation partnership project/new radio) FR2 band n258—i.e., 26 GHz—using a 100 MHz 16-quadrature amplitude modulation (QAM) 3GPP/NR orthogonal frequency division modulation (OFDM) signal.

Abstract Background Both smoking and obesity are separately associated with sickness absence. Unhealthy lifestyle habits and health conditions may occur concurrently yet studies focusing on their joint association are few. This study examined the joint associations of smoking and obesity with sickness absence (SA). Methods A mail survey among employees of the City of Helsinki, Finland, during 2000–2002 included data on obesity, smoking and covariates (N = 8960, response rate 67%, 80% women). These data were prospectively linked with register data on self- (1–3 days) and medically certified (4 days or longer) SA among those consenting to the linkage (n = 6986). Pregnant, underweight and those with missing data on key variables were excluded (n = 138). The total number of participants included in the analyses was 6847. The follow-up time was 5 years. Poisson regression was used to calculate rate ratios (RR). Results Among women and men smoking and obesity were associated with self-certified SA. Among women there was a joint association with self-certified SA (obese smokers RR 1.81, 95% CI 1.59–2.07). Among women and men smoking and obesity were jointly associated with medically certified SA (for obese smoking women RR 2.23, 95% CI 1.93–2.57, for obese smoking men RR 2.69, 95% CI 2.03–3.55). Associations remained after adjustments for socioeconomic position, working conditions, health behaviours and self-rated health. Conclusion Both smoking and obesity are jointly associated with all lengths of sickness absence. Support measures for smoking cessation and prevention of obesity could likely to reduce SA.

OBJECTIVES: We aimed to examine the association between changes in psychosocial working conditions and major weight gain among midlife women and men. Furthermore, we examined the associations separately among normal- and overweight participants. METHODS: We used survey data among employees of the City of Helsinki, Finland, from 2000–2002 (phase 1, N=8960), 2007 (phase 2, N=7332), and 2012 (phase 3, N=6814), with a final study sample of 4369 participants. We examined changes in job strain, job demands, and job control from phase 1 to 2. We defined major weight gain as ≥10% weight gain between phases 1 and 3 based on self-reported weight (kg). We performed logistic regression analysis adjusting for baseline age, marital status, and occupational class, stratifying by gender and by baseline body mass index. RESULTS: Job demands among both genders and job strain among women was associated with major weight gain. Furthermore, increased job demands [odds ratio (OR) 1.52, 95% CI 1.05–2.20] or increased job strain (OR 1.53, 95% CI 1.11–2.11) was associated with major weight gain among overweight women. Normal-weight men reporting decreased job demands (OR 4.11, 95% CI 1.48–11.40) and overweight men reporting increasing job demands (OR 2.93, 95% CI 1.26–6.82) exhibited higher odds of major weight gain. CONCLUSIONS: Associations between working conditions and weight gain appeared primarily weak. Our study suggests that overweight individuals might be at a higher risk of weight gain when facing psychosocial strain in the workplace.

Abstract Background Studies suggest an association between weight change and subsequent poor physical health functioning, whereas the association with mental health functioning is inconsistent. We aimed to examine whether obesity and change of body mass index among normal weight, overweight and obese women and men associate with changes in physical and mental health functioning. Methods The Helsinki Health Study cohort includes Finnish municipal employees aged 40 to 60 in 2000–02 (phase 1, response rate 67%). Phase 2 mail survey (response rate 82%) took place in 2007 and phase 3 in 2012 (response rate 76%). This study included 5668 participants (82% women). Seven weight change categories were formed based on body mass index (BMI) (phase 1) and weight change (BMI change ≥5%) (phase 1–2). The Short Form 36 Health Survey (SF-36) measured physical and mental health functioning. The change in health functioning (phase 1–3) score was examined with repeated measures analyses. Covariates were age, sociodemographic factors, health behaviours, and somatic ill-health. Results Weight gain was common among women (34%) and men (25%). Weight-gaining normal weight (−1.3 points), overweight (−1.3 points) and obese (−3.6 points) women showed a greater decline in physical component summary scores than weight-maintaining normal weight women. Among weight-maintainers, only obese (−1.8 points) women showed a greater decline than weight-maintaining normal weight women. The associations were similar, but statistically non-significant for obese men. No statistically significant differences in the change in mental health functioning occurred. Conclusion Preventing weight gain likely helps maintaining good physical health functioning and work ability.

Abstract Background Musculoskeletal diseases and mental disorders are major causes of long-term sickness absence in Western countries. Although sickness absence is generally more common in lower occupational classes, little is known about class differences in diagnostic-specific absence over time. Focusing on Finland during 2005–2014, we therefore set out to examine the magnitude of and changes in absolute and relative occupational class differences in long-term sickness absence due to major diagnostic causes. Methods A 70-per-cent random sample of Finns aged 25–64 linked to register data on medically certified sickness absence (of over 10 working days) in 2005–2014 was retrieved from the Social Insurance Institution of Finland. Information on occupational class was obtained from Statistics Finland and linked to the data. The study focused on female (n = 658,148–694,142) and male (n = 604,715–642,922) upper and lower non-manual employees and manual workers. The age-standardised prevalence, the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII) were calculated for each study year to facilitate examination of the class differences. Results The prevalence of each diagnostic cause of sickness absence declined during the study period, the most common causes being musculoskeletal diseases, mental disorders and injuries. The prevalence of other causes under scrutiny was less than 1 % annually. By far the largest absolute and relative differences were in musculoskeletal diseases among both women and men. Moreover, the absolute differences in both genders (p

POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis of polyA+ and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes, long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA+ transcriptome is regulated during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner.

Abstract Background Retirement is a key life event, which is associated with changes in physical activity, however, there is limited evidence with regard to changes in physical activity that take place in post-retirement years. The aim of this study was to examine how leisure-time physical activity changes shortly after the transition to retirement and during the post-retirement years. Methods The phase 1 data were collected in 2000–2002 (n = 8960, response rate 67%) among 40–60-year-old employees of the City of Helsinki, Finland. Phase 2 was carried out in 2007 (n = 7332, response rate 83%) and phase 3 in 2012 (n = 6814, response rate 79%). Disability retirees and those under the age of 50 at baseline were excluded. This yielded 2902 participants. Most of the participants (79%) were women. The mean age of the participants was 54.4 in phase 1. Negative binomial models for repeated measurements with generalized estimating equations (GEE) were used to calculate the incidence rate ratios (IRR) and 95% confidence intervals (CI). These indicated the changes in time spent in self-reported leisure-time physical activity among the retired compared with the continuously employed. Results Of the participants, 851 retired on the grounds of old age during the first period (phases 1–2), and 948 during the second period (phases 2–3). Change in physical activity was positive among those who retired during the first (IRR = 1.10, 95% CI 1.04–1.17) and second (IRR = 1.10, 95% CI 1.04–1.16) periods compared to the continuously employed. During the second period, there was little difference between those who had retired during the first one (IRR = 0.96, 95% CI 0.91–1.02) and the continuously employed. Conclusions The transition to statutory retirement was associated with an immediate increase in leisure-time physical activity, which nevertheless diminished during post-retirement years.

Abstract Background Mental disorders are common diagnostic causes for longer sickness absence and disability retirement in OECD-countries. Short sickness absence spells are also common, and neither trivial for health and work ability. We studied how prior short sickness absence spells and days are associated with subsequent longer sickness absence due to mental disorders in two age-groups of municipal employees during a 2-, 5- and 9-year follow-up. Methods The analyses covered 20–34 and 35–49-year-old employees of the City of Helsinki in 2004. Those with prior ≥14 day sickness absence in 2002, 2003 or 2004 were excluded. Women and men were pooled together. Short, 1–13-day sickness absence spells and days were calculated per the actual time of employment during 2004. Logistic regression analysis was used to calculate odds ratios (OR) and their 95% confidence intervals (CI) for the subsequent long (≥14 days) sickness absence due to mental disorders during three follow-ups. Results The risk for long sickness absence due to mental disorders increased with increasing amount of short sickness absence spells and days. 3 or more short sickness absence spells and 8–14 sickness absence days from short spells in 2004 were strongly associated with subsequent long sickness absence in all three follow-ups. The associations were strongest for the 2-year follow-up; the younger employees tended to have higher risks than the older ones. Conclusions Three spells or 8 days of short sickness absence per year constitutes a high risk for subsequent long sickness absence due to mental disorders and preventive measures should be considered.

Abstract Background Sickness absence has been shown to be a risk marker for severe future health outcomes, such as disability retirement and premature death. However, it is poorly understood how all-cause and diagnosis-specific sickness absence is reflected in subsequent physical and mental health functioning over time. The aim of this study was to examine the association of all-cause and diagnosis-specific sickness absence with subsequent changes in physical and mental health functioning among ageing municipal employees. Methods Prospective survey and register data from the Finnish Helsinki Health Study and the Social Insurance Institution of Finland were used. Register based records for medically certified all-cause and diagnostic-specific sickness absence spells (>14 consecutive calendar days) in 2004–2007 were examined in relation to subsequent physical and mental health functioning measured by Short-Form 36 questionnaire in 2007 and 2012. In total, 3079 respondents who were continuously employed over the sickness absence follow-up were included in the analyses. Repeated-measures analysis was used to examine the associations. Results During the 3-year follow-up, 30% of the participants had at least one spell of medically certified sickness absence. All-cause sickness absence was associated with lower subsequent physical and mental health functioning in a stepwise manner: the more absence days, the poorer the subsequent physical and mental health functioning. These differences remained but narrowed slightly during the follow-up. Furthermore, the adverse association for physical health functioning was strongest among those with sickness absence due to diseases of musculoskeletal or respiratory systems, and on mental functioning among those with sickness absence due to mental disorders. Conclusions Sickness absence showed a persistent adverse stepwise association with subsequent physical and mental health functioning. Evidence on health-related outcomes after long-term sickness absence may provide useful information for targeted interventions to promote health and workability.

Health inequalities exist across countries and populations, but little is known about their long-term trends and even less about factors shaping the trends. We examined the magnitude of absolute and relative educational inequalities in self-rated health over 36 years among Finnish adults, considering individual covariates and macro-economic fluctuations. Our data were derived from representative annual cross-sectional surveys in 1979–2014 conducted among adult men and women. Participants aged 25–64 were included and nine periods used (n = 8870–14235). Our health outcome was less-than-good self-rated health (SRH) and our socioeconomic indicator was completed years of education as a continuous variable. Educational inequalities in self-rated health were analysed using the relative index of inequality (RII) and the slope index of inequality (SII). Nine time-variant sociodemographic and health-related covariates were included in the analyses. Linear trends suggested stable or slightly curvilinear overall trends in both absolute and relative health equalities over 36 years. Among men, absolute and relative inequalities narrowed immediately after economic recession in Finland in 1993–1994. Among women, inequalities narrowed during financial crisis in 2008–2009. Adjusting for most covariates reduced the magnitude of inequalities throughout the nine periods, but affected little the temporal patterning of health inequalities. Educational inequalities in self-rated health remained during 36 years in Finland. While among men and women health inequalities narrowed during and after recessions, they widened soon back to the pre-recession level. The perseverance of the trends calls for novel and powerful measures to tackle health inequalities. Keywords: Self-rated health, Inequalities, Trends, Determinants

Objectives To identify groups of municipal employees between the ages of 20 and 34 years with distinct utilisation trajectories of primary care services provided by occupational health service (OHS), measured as the annual number of OHS visits, and to identify demographic and socioeconomic risk factors that distinguish employees in the high utilisation trajectory group(s).Methods The present study is a retrospective register-based cohort study. All municipal employees of the City of Helsinki, Finland, aged 20–34 in the Helsinki Health Study, recruited from 2004 to 2013, with follow-up data for 4 years were included in the study (n=9762). The outcome measure was group-based trajectories of OHS utilisation, identified with a group-based trajectory analysis. The demographic and socioeconomic variables used to predict the outcome were age, first language, educational level and occupational class. The analyses were stratified by gender.Results A large proportion of the young employees do not use OHS. Trajectory groups of ‘No visits’ (50%), ‘Low/increasing’ (18%), ‘Low/decreasing’ (22%) and ‘High/recurrent’ (10%) use were identified. We found occupational class differences in OHS utilisation patterns showing that lower occupational classes had a higher propensity for ‘High/recurrent’ OHS utilisation for both genders.Conclusions Preventive measures should be targeted particularly to the trajectory groups of ‘Low/increasing’ and ‘High/recurrent’ in order to intervene early. In addition, OHS utilisation should be closely monitored among the two lowest occupational classes. More research with longitudinal OHS data is needed.

BackgroundThere is increasing evidence that childhood socioeconomic position and childhood adversities influence adult health. However, the potential contribution of these factors to disability retirement is poorly understood. This study aimed to examine the associations between childhood adversities, parental education and disability retirement.MethodsData on parental education and childhood adversities were derived from the Helsinki Health Study baseline survey, conducted in 2000-02 among 40- to 60-year old employees of the City of Helsinki, Finland. Data on disability retirement and their diagnoses were obtained from the Finnish Centre of Pensions and followed until the end of 2016. The analyses included 5992 employees. The associations of parental education and childhood adversities with disability retirement due to any cause, musculoskeletal diseases and mental disorders were analysed using Cox regression analysis.ResultsLow parental education was associated with an increased risk of disability retirement due to any cause (maternal education: HR 1.74, 95% CI 1.16-2.62; paternal education: 1.86, 1.38-2.51) and due to musculoskeletal diseases (maternal education: 4.44, 1.66-11.92; paternal education: 3.81, 2.02-7.17). However, adjustment for own education mainly abolished the associations. Economic difficulties in the childhood family, parental alcohol problems and having been bullied at school or by peers increased the risk of disability retirement due to all studied diagnostic groups, whereas parental death or divorce had no effect. Childhood illness (1.53, 1.20-1.95) and parental mental illness (1.68, 1.28-2.20) were associated with disability retirement due to any cause and due to mental disorders (1.65, 1.05-2.59; 3.60, 2.46-5.26). The associations between childhood adversities and disability retirement remained after adjustment for own education, whereas working conditions, and weight and health behaviours somewhat attenuated the associations.ConclusionsParental education and childhood adversities contributed to disability retirement even in midlife. Policy actions investing in children's well-being might promote work ability in midlife.

This study investigates cross-cultural differences in the interrelation between school performance, school segregation, and stress-related health among 9th-grade students in the greater Stockholm and Helsinki areas. Contrary to the Swedish case, it has been proposed that school performance in Finland is largely independent of the specific school attended and of socioeconomic background. Finland also stands out as a contrast to Sweden considering their better performance in the Programme for International Student Assessment (PISA) surveys. Our first 2 hypotheses explore whether there is a greater degree of school segregation in Stockholm than in Helsinki, and our second pair of hypotheses test whether Finland's school success has come at a price in terms of increased student stress. Our results largely confirm that Stockholm schools are less "equal" and more segregated than those in Helsinki. We also find that school performance is more strongly linked to stress-related complaints among students in Helsinki than in Stockholm, especially among Finnish girls.

Drill ships and offshore rigs use azimuth thrusters for propulsion, maneuvering and steering, attitude control and dynamic positioning activities. The versatile operating modes and the challenging marine environment create demand for flexible and practical condition monitoring solutions onboard. This study introduces a condition monitoring algorithm using acceleration and shaft speed data to detect anomalies that give information on the defects in the driveline components of the thrusters. Statistical features of vibration are predicted with linear regression models and the residuals are then monitored relative to multivariate normal distributions. The method includes an automated shaft speed selection approach that identifies the normal distributed operational areas from the training data based on the residuals. During monitoring, the squared Mahalanobis distance to the identified distributions is calculated in the defined shaft speed ranges, providing information on the thruster condition. The performance of the method was validated based on data from two operating thrusters and compared with reference classifiers. The results suggest that the method could detect changes in the condition of the thrusters during online monitoring. Moreover, it had high accuracy in the bearing condition related binary classification tests. In conclusion, the algorithm has practical properties that exhibit suitability for online application.

Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely understood. Within the “Metabolomic profiles throughout the continuum of colorectal cancer” (MetaboCCC) consortium we analyzed data generated by untargeted, mass spectrometry-based metabolomics using plasma from 88 colorectal cancer patients, 200 patients with high-risk adenomas and 200 patients with low-risk adenomas recruited within the “Colorectal Cancer Study of Austria” (CORSA). Univariate logistic regression models comparing colorectal cancer to adenomas resulted in 442 statistically significant molecular features. Metabolites discriminating colorectal cancer patients from those with adenomas in our dataset included acylcarnitines, caffeine, amino acids, glycerophospholipids, fatty acids, bilirubin, bile acids and bacterial metabolites of tryptophan. The data obtained discovers metabolite profiles reflecting metabolic differences between colorectal cancer and colorectal adenomas and delineates a potentially underlying biological interpretation.

The identification of patients at high-risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre-surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort; false discovery rate (FDR) was used to account for multiple testing. Sixty-nine patients (15%) had a recurrence after a median follow-up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism p = 0.04; pFDR = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well-established metabolomics assay. The observed results require follow-up in larger studies.

Abstract Background Mental symptoms are prevalent among populations, but their associations with premature mortality are inadequately understood. We examined whether mental symptoms contribute to cause-specific mortality among midlife employees, while considering key covariates. Methods Baseline mail survey data from 2000–02 included employees, aged 40–60, of the City of Helsinki, Finland (n = 8960, 80 % women, response rate 67 %). Mental symptoms were measured by the General Health Questionnaire 12-item version (GHQ-12) and the Short Form 36 mental component summary (MCS). Covariates included sex, marital status, social support, health behaviours, occupational social class and limiting long-standing illness. Causes of death by the end of 2013 were obtained from Statistics Finland (n = 242) and linked individually to survey data pending consent (n = 6605). Hazard ratios (HR) and 95 % confidence intervals (95 % CI) were calculated using Cox regression analysis. Results For all-cause mortality, only MCS showed a weak association before adjustments. For natural mortality, no associations were found. For unnatural mortality (n = 21), there was a sex adjusted association with GHQ (HR = 1.96, 95 % CI = 1.45–2.64) and MCS (2.30, 95 % CI = 1.72–3.08). Among unnatural causes of death suicidal mortality (n = 11) was associated with both GHQ (2.20, 95 % CI = 1.47–3.29) and MCS (2.68, 95 % CI = 1.80–3.99). Of the covariates limiting long-standing illness modestly attenuated the associations. Conclusions Two established measures of mental symptoms, i.e. GHQ-12 and SF-36 MCS, were both associated with subsequent unnatural, i.e. accidental and violent, as well as suicidal mortality. No associations were found for natural mortality due to diseases. These findings need to be corroborated in further populations. Supporting mental health through workplace measures may help counteract subsequent suicidal and other unnatural mortality among midlife employees.

OBJECTIVES: The aim of this study was to examine the association between pre-retirement physical working conditions and changes in physical health functioning during the retirement transition process. METHODS: Follow-up survey data were collected among ageing employees of the City of Helsinki, Finland, at three time points: wave 1 (2000–2002), wave 2 (2007) and wave 3 (2012). We focused on those who retired full time due to old age between waves 1 and 3 (N=1658). Exposure to physical workload, occupational environmental hazards, and computer work were divided into quartiles and used as measures of pre-retirement physical working conditions. Physical health functioning was measured by the physical component summary (PCS) of the Short-Form 36 questionnaire. Repeated-measures analysis was used to study the associations. RESULTS: Higher pre-retirement exposure to physical workload and environmental hazards was associated with lower physical health functioning before and after retirement. The differences in functioning narrowed somewhat during the retirement transition process, as physical health functioning in the higher exposure groups improved significantly compared to lower exposure groups. In addition, both high and low exposure to computer work were associated with lower functioning before retirement. However, functioning among those in the lowest exposure group improved during the follow-up whereas in all other exposure groups it declined slightly. This resulted into significantly lower post-retirement functioning among those in the highest as compared to the lower exposure groups. CONCLUSIONS: Retirees with higher exposure to adverse physical working conditions before retirement had lower pre- and post-retirement physical health functioning despite improvements in their functioning during the retirement transition process.

The present study is based on the onomastics of the Land of Canaan during the second millennium BC. The results from onomastics are compared with the corresponding archaeological data and with parallel literary sources. The aim of the research has been to distinguish the different linguistic groups, especially the Canaanites and the Amorites, and to determine their principal areas of settlement. In accordance with the basic archaeological results, the toponyms show a dramatic change that took place in the Land of Canaan in the beginning of the Middle Bronze Age II (approximately 2000 BC). In the Land of Canaan there appeared toponymic types originating from the area of Phoenicia and spreading to the coastal area of modern Israel. Slightly later another kind of toponymic types appeared in the Galilee, the Judean Hill Country and in the Middle Zone of the Transjordan, the origin of which is to be found in Syro-Mesopotamia. It is remarkable that none of these particular types are found in the Hill Country of Ephraim.

The intake of processed meat has been associated with several adverse health outcomes such as type II diabetes and cancer; however, the mechanisms are not fully understood. A better knowledge of the metabolite profiles of different processed and non-processed meat products from this heterogeneous food group could help in elucidating the mechanisms associated with these health effects. Thirty-three different commercial samples of ten processed and non-processed meat products were digested in triplicate with a standardized static in vitro digestion method in order to mimic profiles of small molecules formed in the gut upon digestion. A metabolomics approach based on high-resolution mass spectrometry was used to identify metabolite profiles specific to the various meat products. Processed meat products showed metabolite profiles clearly distinct from those of non-processed meat. Several discriminant features related to either specific ingredients or processing methods were identified. Those were, in particular, syringol compounds deposited in meat during smoking, biogenic amines formed during meat fermentation and piperine and related compounds characteristic of pepper used as an ingredient. These metabolites, characteristic of specific processed meat products, might be used as potential biomarkers of intake for these foods. They may also help in understanding the mechanisms linking processed meat intake and adverse health outcomes such as cancer.

Demographic, lifestyle and biospecimen-related factors at the time of blood collection can influence metabolite levels in epidemiological studies. Identifying the major influences on metabolite concentrations is critical to designing appropriate sample collection protocols and considering covariate adjustment in metabolomics analyses. We examined the association of age, sex, and other short-term pre-blood collection factors (time of day, season, fasting duration, physical activity, NSAID use, smoking and alcohol consumption in the days prior to collection) with 133 targeted plasma metabolites (acylcarnitines, amino acids, biogenic amines, sphingolipids, glycerophospholipids, and hexoses) among 108 individuals that reported exposures within 48 h before collection. The differences in mean metabolite concentrations were assessed between groups based on pre-collection factors using two-sided t-tests and ANOVA with FDR correction. Percent differences in metabolite concentrations were negligible across season, time of day of collection, fasting status or lifestyle behaviors at the time of collection, including physical activity or the use of tobacco, alcohol or NSAIDs. The metabolites differed in concentration between the age and sex categories for 21.8% and 14.3% metabolites, respectively. In conclusion, extrinsic factors in the short period prior to collection were not meaningfully associated with concentrations of selected endogenous metabolites in a cross-sectional sample, though metabolite concentrations differed by age and sex. Larger studies with more coverage of the human metabolome are warranted.

Summary: Background: Obesity increases the risk of several chronic diseases, but the extent to which the obesity-related loss of disease-free years varies by lifestyle category and across socioeconomic groups is unclear. We estimated the number of years free from major non-communicable diseases in adults who are overweight and obese, compared with those who are normal weight. Methods: We pooled individual-level data on body-mass index (BMI) and non-communicable diseases from men and women with no initial evidence of these diseases in European cohort studies from the Individual-Participant-Data Meta-Analysis in Working Populations consortium. BMI was assessed at baseline (1991–2008) and non-communicable diseases (incident type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease) were ascertained via linkage to records from national health registries, repeated medical examinations, or self-report. Disease-free years from age 40 years to 75 years associated with underweight (BMI

Most equine lower respiratory diseases present as increased airway neutrophilia, which can be detected in tracheal wash (TW) or bronchoalveolar lavage fluid (BALF) cytology samples. The aim was to compare the TW and BALF results in a population of client-owned horses with and without clinical respiratory disease signs. A secondary aim was to determine the sensitivity (Se) and specificity (Sp) of TW and BALF neutrophilia in detecting respiratory disease. The cutoff values for neutrophils were also evaluated. Retrospective data from 154 horses of various breeds that had been subject to both TW and bronchoalveolar lavage (BAL) sampling at rest during 2009−2015 were used. The horses were divided into three groups based on the presenting signs, physical examination, and endoscopy mucus score. Neutrophil counts of >20% in TW and >5% in BAL were considered abnormal. Cytology results between groups, correlations between TW and BALF cell types, and tracheal mucus score were analyzed. Two graph receiving operating characteristic (ROC) curves of the neutrophil percentage values of TW and BALF were created to determine the optimal cutoff values and to calculate the diagnostic Se and Sp for diagnosing airway inflammation in horses with and without clinical respiratory signs. The Se and Sp of TW and BALF neutrophil percentages were further estimated using a two-test one-population Bayesian latent class model. The two tests showed substantial agreement, and only 17.5% of the horses were classified differently (healthy vs. diseased). The neutrophil percentage was found to correlate between TW and BALF. The Se and Sp of TW were generally higher than for BAL when estimated with area under the curve or Bayesian model. Cutoff values of 17.7% for TW and 7% for BALF were indicated by the ROCs. We conclude that TW is a more sensitive and specific method in our patient population. We suggest that the current neutrophil cutoff values of 20% for TW and 5% for BALF would still be appropriate to use in clinical diagnosis of airway inflammation. However, further studies with other cell types and in other populations are warranted to determine the best sampling method for individual horses.

Background Smoking is declining, but in most countries lower educated smoke more than higher educated. Our aim was to examine development with these differences in a country with strict tobacco control policies, Finland. Methods We used annual population-based random sample data of 25-64 year-olds from 1978-2016 (N=104,317). Response rate varied between 84% and 40% during the study period. We used relative education as a measure for socioeconomic position. For each year education was stratified into tertiles, and low and high educated were included in further analysis. The outcome variable was daily smoking. Weights were used in order to enhance the population representation. Prevalence figures and logistic regression analysis were used. Results At the start of the study period, 40% of lower educated men and 33% of higher educated men smoked. For women, the corresponding proportions were 18% and 13%, respectively. Smoking decreased in each educational group except lower educated women. Preliminary analyses suggest that, compared with the time period before 2009, all population groups except lower educated women were less likely to smoke after 2009. In the 2010s, educational differences in smoking slightly declined both among women and men due to a more prevalent decline in smoking among lower educated. In 2016 among men, 26% of lower educated smoked, while 6% of higher educated smoked. Among women corresponding proportions were 19% and 9%. Conclusions Smoking has declined both among lower and higher educated and socioeconomic differences diminished in the 2010s in Finland. However, educational differences in smoking are still marked, which underlines the need for further actions reducing the overall public impact of these differences. Further analyses will test relative differences in smoking among socioeconomic groups and careful sensitivity analyses will be conducted to validate the results.

OBJECTIVES: The aim this study was to examine the effect of changes in physical and psychosocial working conditions on physical health functioning among ageing municipal employees. METHODS: Follow-up survey data were collected from midlife employees of the City of Helsinki, Finland, at three time points: wave 1 (2000–2002), wave 2 (2007), and wave 3 (2012). Changes in physical and psychosocial working conditions were assessed between waves 1 and 2. Physical health functioning was measured by the physical component summary (PCS) of the Short-Form 36 questionnaire at each of the three waves. In total, 2784 respondents (83% women) who remained employed over the follow-up were available for the analyses. Linear mixed-effect models were used to assess the associations and adjust for key covariates (age, gender, obesity, chronic diseases, and health behaviors). RESULTS: Repeated and increased exposure to adverse physical working conditions was associated with greater decline in physical health functioning over time. In contrast, decrease in exposures reduced the decline. Of the psychosocial working conditions, changes in job demands had no effects on physical health functioning. However, decreased job control was associated with greater decline and repeated high or increased job control reduced the decline in physical health functioning over time. CONCLUSIONS: Adverse changes in physical working conditions and job control were associated with greater decline in physical health functioning over time, whereas favorable changes in these exposures reduced the decline. Preventing deterioration and promoting improvement of working conditions are likely to help maintain better physical health functioning among ageing employees.

Objects There is a marked socioeconomic gradient in sickness absences, but the causes of this gradient are poorly understood. This study examined the role of health and work-related factors as determinants of educational differences in long-term sickness absence in an 8-year follow-up. METHODS: The study comprised a population-based sample of 5835 Finns aged 30–64 years (participation 89%, N=3946) in a register-based 8-year follow-up. This is a novel method to predict the population average of sickness absence days per working year (DWY) based on the expected outcome values using Poisson and gamma regression models. RESULTS: The difference in the DWY between the lowest and highest educational level was clear among both men (3.2 days/year versus 8.0 days/year) and women (women 4.4 days/year versus 10.1 days/year). Adjusting for physical working conditions, health status and health behavior, and obesity attenuated the differences. Psychosocial working conditions had only a minor effect on the association. After adjusting for health and work-related factors, the difference attenuated by 1.8 days and 2.6 days among men and women, respectively. CONCLUSIONS: Our results suggest that improvements in physical working conditions and reducing smoking, particularly among employees with a low level of education, may markedly reduce educational differences in sickness absence.

The RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs) and provide insights into the interactome network constructed in human pluripotent cells. Our data reveal that L1TD1 has an important role in RNA splicing, translation, protein traffic, and degradation. L1TD1 interacts with multiple stem-cell-specific proteins, many of which are still uncharacterized in the context of development. Further, we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency.

Poor childhood family conditions have a long-term effect on adult mental health, but the mechanisms behind this association are unclear. Our aim was to study the pathways from problematic family relationships in adolescence to midlife psychological distress via disadvantages in early adulthood. Participants of a Finnish cohort study at the age of 16 years old in 1983 were followed up at ages 22, 32 and 42 years old (N = 1334). Problems in family relationships were measured with poor relationship with mother and father, lack of parental support in adolescent's individuation process and poor home atmosphere, and mental health was assessed using Kessler's Psychological Distress Scale (K10). We analyzed the indirect effects of adolescent family relations on mental health at age 42 years old via various disadvantages (somatic and psychological symptoms, relationship/marital status, low education/unemployment and heavy drinking) at ages 22 and 32 years old. Problematic adolescent family relationships were associated with midlife psychological distress in women (0.19; 95% CI 0.11, 0.26) and men (0.13; 95% CI 0.04, 0.21). However, after adjustment for adolescent psychological symptoms, the association was only significant for women (0.12; 95% CI 0.04, 0.20). Poor family relationships were associated with various disadvantages in early adulthood. The association from poor family relationships (16 years old) to psychological distress (42 years old) was in part mediated via psychological symptoms in women (0.03; 95% CI 0.01, 0.04) and men (0.02; 95% CI 0.00, 0.04) and in women also via heavy drinking in early adulthood (0.02; 95% CI 0.00, 0.03). Adolescent family relationships have a role in determining adult mental health. Targeted support addressing psychological well-being and hazardous drinking for adolescents with problematic family relationships might prevent disadvantages in early adulthood, and further prevent poor midlife mental health.