Firefighting and melanoma, epidemiological and toxicological associations: a case report.

The International Agency for Research on Cancer (IARC) classifies firefighting as possibly carcinogenic to humans, and polychlorinated biphenyls (PCBs) as carcinogens with sufficient evidence for development of melanoma in humans. We present a case report of a firefighter with melanoma and history of 33 years of occupational exposure. Based on the available epidemiological and toxicological evidence of association between being a firefighter and developing melanoma, melanoma was recognized by the Norwegian Labour and Welfare Service as an occupational disease in our patient. In 2017, melanoma was acknowledged as an occupational disease in only 8 out of 28 surveyed European countries. Melanoma should be considered as a possible occupational disease among firefighters with a history of relevant exposure. Further recognition of the occupational exposures leading to increased risk of melanoma is still needed for preventive purposes.

Reactive hyperemia and baseline pulse amplitude among smelter workers exposed to fine and ultrafine particles.

OBJECTIVE: Ambient exposure to fine particles is associated with increased cardiovascular morbidity and mortality. Associations between occupational particulate matter (PM) exposure and cardiovascular disease have been studied less. The objective of this study was to examine associations between PM exposure and endothelial function among workers in Norwegian smelters. METHODS: We examined endothelial function with Endo-PAT equipment after a working day (WD) and on a day off (DO) in 59 furnace workers recruited from three metal smelters in Norway. The difference in baseline pulse amplitude (BPA) and reactive hyperemia index (RHI) between the 2 days was analysed in relation to individual exposure to PM < 250 nm (PM250) or the respirable aerosol fraction of particles, and adjusted for relevant covariates. RESULTS: The exposure to PM250 ranged from 0.004 to 5.7 mg/m3. The mean BPA was significantly higher on WD relative to DO (772 vs. 535, p = 0.001). This difference was associated with PM concentrations among participants ≥ 34 years, but not among the younger workers. Reactive hyperemia was significantly lower on workdays relative to days off (1.70 vs. 1.84, p = 0.05). This difference was observed only among participants above the age 34. No associations with PM exposure were observed. CONCLUSIONS: PM exposure was associated with higher BPA among participants older than 34 years. BPA reflects microvessel pulsatility. Our results may indicate an age-dependent cardiovascular susceptibility to PM exposure. Endothelial function measured by RHI was reduced on WD among participants 34 years and older, but we found no associations between PM exposure and RHI.

Multigenic truncation of the semaphorin-plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome.

Moebius syndrome (MBS) is a congenital disorder caused by paralysis of the facial and abducens nerves. Although a number of candidate genes have been suspected, so far only mutations in PLXND1 and REV3L are confirmed to cause MBS. Here, we fine mapped the breakpoints of a complex chromosomal rearrangement (CCR) 46,XY,t(7;8;11;13) in a patient with MBS, which revealed 41 clustered breakpoints with typical hallmarks of chromothripsis. Among 12 truncated protein-coding genes, SEMA3A is known to bind to the MBS-associated PLXND1. Intriguingly, the CCR also truncated PIK3CG, which in silico interacts with REVL3 encoded by the other known MBS-gene REV3L, and with the SEMA3A/PLXND1 complex via FLT1. Additional studies of other complex rearrangements may reveal whether the multiple breakpoints in germline chromothripsis may predispose to complex multigenic disorders.

Narrative review of occupational exposures and noncommunicable diseases.

OBJECTIVE: Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities. METHODS: We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality. RESULTS: We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels. CONCLUSIONS: By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.

Dust exposure is associated with increased lung function loss among workers in the Norwegian silicon carbide industry.

OBJECTIVES: To investigate the relationship between dust exposure and annual change in lung function among employees in Norwegian silicon carbide (SiC) plants using a quantitative job exposure matrix (JEM) regarding total dust. METHODS: All employees, 20-55 years of age by inclusion (n=456), were examined annually for up to 5 years (1499 examinations). Spirometry was performed at each examination, and a questionnaire encompassing questions of respiratory symptoms, smoking status, job and smoking history, and present job held was completed. A JEM was constructed based on 1970 personal total dust exposure measurements collected during the study period. The association between lung function and total dust exposure was investigated using linear mixed models. RESULTS: The annual change in forced expiratory volume (FEV) in one second per squared height, FEV1/height(2), per mg/m(3) increase in dust exposure was -2.3 (95% CI -3.8 to -0.79) (mL/m(2))×year(-1). In an employee of average height (1.79 m) and exposure (1.4 mg/m(3)) the estimated contribution to the annual change in FEV1 associated with dust was 10.4 mL/year. The annual change in FEV1/height(2) in current, compared with non-smokers was -1.9 (-7.2 to 3.4) (mL/m(2))×year(-1). The estimated overall annual decline in FEV1 among current and non-smokers in the highest exposed group was -91.2 (-124.3 to -58.1) (mL/m(2))×year(-1) and -49.0 (-80.2 to -17.8) (mL/m(2))×year(-1), respectively. CONCLUSIONS: Dust exposure, expressed by a quantitative JEM, was found to be associated with an increased yearly decline in FEV1 in employees of Norwegian SiC plants.

Body stalk anomaly in Denmark during 20 years (1970-1989).

Body stalk anomaly is a severe defect of the abdominal wall with uncovered thoracic and/or abdominal organs. The umbilical cord is absent or very short. Here I present epidemiological and clinical data on 16 infants with body stalk anomaly. The 16 infants represent 3.4% of the 469 infants ascertained in an almost complete nationwide data set of live- and stillborn infants born with abdominal wall defects during the two decades 1970-1989 in Denmark. The prevalence was 0.12 per 10,000 live- and stillborn. Nine of the infants were stillbirths, seven were live births, and they all died shortly after birth. The gestational age at birth varied from 33 to 40 weeks. There was an excess of males M/F ratio: 2.2 (CI: 0.85-10.71). All infants had severe associated malformations. Among the most severe were: severe limb reduction defects (56%), absence of one kidney associated with malformations of genitalia and/or urinary bladder (62%), scoliosis (82%), and anal atresia (57%). A normal karyotype was found in all eight of the infants who were tested. There were two sets of twins; one discordant and one concordant. Mean maternal and paternal ages were 28.5 and 29.5 years, respectively, not significantly different from the mean parental ages of the Danish population during the same period.

Lung cancer incidence among Norwegian silicon carbide industry workers: associations with particulate exposure factors.

OBJECTIVES: An increased lung cancer risk associated with total dust exposure in the silicon carbide (SiC) industry has previously been reported. The aim of the present study was to examine the relative importance of specific exposure factors by using a comprehensive, historic job exposure matrix based on about 8000 measurements. METHODS: Cumulative exposure to total and respirable dust, respirable quartz, cristobalite, and SiC particles and SiC fibres was assessed for 1687 long-term workers employed during 1913-2003 in the Norwegian SiC industry. Standardised incidence ratios for lung cancer, with follow-up during 1953-2008, were calculated stratified by cumulative exposure categories. Poisson regression analyses were performed using both categorised and log-transformed cumulative exposure variables. RESULTS: The lung cancer incidence was about twofold increased at the highest level of exposure to each of the exposure factors (standardised incidence ratios 1.9-2.3 for all agents). Internal analyses showed associations between exposure level and lung cancer incidence for all investigated factors, but a significant trend only for total dust and cristobalite. In multivariate analyses, cristobalite showed the most consistent associations, followed by SiC fibres. CONCLUSIONS: The results indicated that crystalline silica in the form of cristobalite was the most important occupational exposure factor responsible for lung cancer excess in the Norwegian SiC industry. SiC fibres seemed to have an additional effect.

The association between symptoms and exposure is stronger in dropouts than in non-dropouts among employees in Norwegian smelters: a five-year follow-up study.

PURPOSE: We have investigated the association between respiratory symptoms and dust exposure among employees in 18 Norwegian smelters using a longitudinal design. METHODS: All employees (N = 3,084) were examined annually for 5 years (12,996 health examinations). At each examination, the subjects reported if they had respiratory symptoms, coded as 1 (yes) or 0 (no), on a respiratory questionnaire. Symptom score was constructed as the sum of symptoms (0-5). Full-time workers in the production line were classified as line operators; subjects never exposed in the production line were regarded as non-exposed. The remaining individuals were classified as non-line operators. A job-exposure matrix regarding dust exposure was also available. Analyses of repeated measurements were performed using generalised linear mixed model with log-link (Poisson regression). Adjustments were made for overdispersion. RESULTS: The mean age at inclusion was 39.0 years, and 89% were men. The median dust exposure in tertiles 1-3 was 0.19, 1.76 and 3.47 mg/m(3). The longitudinal analyses showed that the association between symptoms-score ratio (SSR) and job category was significantly stronger in dropouts compared with non-dropouts (p = 0.01). Among the dropouts, SSR was 1.61 (95% confidence interval: 1.27-2.05) and 1.39 (1.09-1.77) in line operators and non-line operators compared with non-exposed employees, respectively. The corresponding SSR for subjects who completed the study was 1.13 (1.01-1.27) and 1.12 (1.00-1.26), respectively. Similarly, among the dropouts, the SSR between the second and the first tertile was 1.28 (1.05-1.55) and 1.37 (1.13-1.66) between the third tertile and the first tertile. CONCLUSIONS: Line operators had more respiratory symptoms than non-exposed employees. This effect was significantly stronger in dropouts than in those who continued their jobs, indicating that there is a selection of subjects without respiratory symptoms in this industry.

A novel strategy for retrospective exposure assessment in the Norwegian silicon carbide industry.

The objective was to construct a retrospective job-exposure matrix (JEM) for the Norwegian silicon carbide industry. More than 3300 historical total dust measurements were available (1967-2005); however, there were few measurements of other agents. Total dust measurements were therefore used as the basis for the JEM, and a novel method was developed to estimate exposure to other agents. Multiple linear regression models were developed to describe historical exposure to total dust. Exposure estimates were extrapolated backward to periods without exposure data by adjustments for process and work-hour related changes. An exposure assessment study was performed where total dust was sampled in parallel with fibers or respirable dust. The respirable dust was analyzed for the content of quartz, cristobalite, and silicon carbide. Mixed-effect models were developed to estimate the exposure to these agents from total dust exposure, plant, and job group. Exposure to asbestos and polycyclic aromatic hydrocarbons was assigned qualitatively. Multiple linear regression models of total dust described historical exposure best in the furnace department (R(2) (adj) = 0.49-0.74). Models in the other departments explained less variance (R(2) (adj) = 0.12-0.32). Exposure determinants and total dust explained a substantial proportion of the between- (70-100%) and within-worker (8.0-54%) variance in the mixed-effect models. The relative bias between available historical measurements and the estimated exposure to dust components varied between -39% (fiber) and 40% (quartz). However, corrections were not considered necessary due to limitations in the historical data. The component-specific metrices were sufficiently different from each other (r(Pearson) < 0.7), with the exception of total and respirable dust (r(Pearson) = 0.84) and total dust and cristobalite (r(Pearson) = 0.72), and will enable component-specific epidemiologic analyses in the future. Improved and less correlated estimates of exposure levels for the different components in the dust were obtained with the updated exposure assessment. Due to limitations in the measurement data, assumptions had to be made, especially in the period before 1967. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a file containing tables outlining multiple linear regression models for prediction of total dust exposure in the processing departments of Norwegian SiC producing plants, evaluation of the predictive abilities of the reduced total dust models, and mixed models for pedicting exposure to fibers and respirable quartz, cristobalite, non-fibrous silicon carbide and respirable dust from total dust exposure.].

Occupational Exposure Assessment Tools in Europe: A Comprehensive Inventory Overview.

OBJECTIVES: The Network on the Coordination and Harmonisation of European Occupational Cohorts (OMEGA-NET) was set up to enable optimization of the use of industrial and general population cohorts across Europe to advance aetiological research. High-quality harmonized exposure assessment is crucial to derive comparable results and to enable pooled analyses. To facilitate a harmonized research strategy, a concerted effort is needed to catalogue available occupational exposure information. We here aim to provide a first comprehensive overview of exposure assessment tools that could be used for occupational epidemiological studies. METHODS: An online inventory was set up to collect meta-data on exposure assessment tools. Occupational health researchers were invited via newsletters, editorials, and individual e-mails to provide details of job-exposure matrices (JEMs), exposure databases, and occupational coding systems and their associated crosswalks to translate codes between different systems, with a focus on Europe. RESULTS: Meta-data on 36 general population JEMs, 11 exposure databases, and 29 occupational coding systems from more than 10 countries have been collected up to August 2021. A wide variety of exposures were covered in the JEMs on which data were entered, with dusts and fibres (in 14 JEMs) being the most common types. Fewer JEMs covered organization of work (5) and biological factors (4). Dusts and fibres were also the most common exposures included in the databases (7 out of 11), followed by solvents and pesticides (both in 6 databases). CONCLUSIONS: This inventory forms the basis for a searchable web-based database of meta-data on existing occupational exposure information, to support researchers in finding the available tools for assessing occupational exposures in their cohorts, and future efforts for harmonization of exposure assessment. This inventory remains open for further additions, to enlarge its coverage and include newly developed tools.

Determinants of Burnout among Teachers: A Systematic Review of Longitudinal Studies.

We aimed to review the determinants of burnout onset in teachers. The study was conducted according to the PROSPERO protocol CRD42018105901, with a focus on teachers. We performed a literature search from 1990 to 2021 in three databases: MEDLINE, PsycINFO, and Embase. We included longitudinal studies assessing burnout as a dependent variable, with a sample of at least 50 teachers. We summarized studies by the types of determinant and used the MEVORECH tool for a risk of bias assessment (RBA). The quantitative synthesis focused on emotional exhaustion. We standardized the reported regression coefficients and their standard errors and plotted them using R software to distinguish between detrimental and protective determinants. A qualitative analysis of the included studies (n = 33) identified 61 burnout determinants. The RBA showed that most studies had external and internal validity issues. Most studies implemented two waves (W) of data collection with 6-12 months between W1 and W2. Four types of determinants were summarized quantitatively, namely support, conflict, organizational context, and individual characteristics, based on six studies. This systematic review identified detrimental determinants of teacher exhaustion, including job satisfaction, work climate or pressure, teacher self-efficacy, neuroticism, perceived collective exhaustion, and classroom disruption. We recommend that authors consider using harmonized methods and protocols such as those developed in OMEGA-NET and other research consortia.

Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes.

Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements.

Prevalence of airflow limitation among employees in Norwegian smelters: a longitudinal study.

AIMS: To investigate the association between airflow limitation and occupational exposure and to compare a fixed limit with an age adjusted limit for airflow limitation. METHODS: 3924 employees in 24 Norwegian smelters and related workplaces were investigated annually over 5 years (n=16, 570) using spirometry and a respiratory questionnaire on smoking habits and job category. Employees working full time on the production line were classified as line operators; subjects who never worked on the production line were regarded as non-exposed. A job exposure matrix (JEM) was available in most smelters. Airflow limitation was expressed as (i) forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC ratio) <0.7 and (ii) FEV(1)/FVC ratio less than the lower limit of normal (LLN). Longitudinal analyses on the prevalence of airflow limitation were performed using a generalised linear mixed model. RESULTS: The prevalence of airflow limitation was stable during follow-up. The OR of airflow limitation during follow-up was 1.24 (95% CI 1.03 to 1.50) in line operators compared with unexposed subjects for FEV(1)/FVC ratio <0.7 and 1.44 (1.14 to 1.81) for FEV(1)/FVC ratio

Mortality from non-malignant respiratory diseases among workers in the Norwegian silicon carbide industry: associations with dust exposure.

OBJECTIVES: Increased mortality from asthma, chronic bronchitis and emphysema has previously been reported among workers in the silicon carbide (SiC) industry. The objective of the present study was to evaluate the influence of specific exposure factors on mortality from obstructive lung diseases (OLD), using a newly revised job-exposure matrix. MATERIALS AND METHODS: 1687 long-term workers employed in 1913-2003 in the Norwegian SiC industry were characterised with respect to cumulative exposure to quartz, cristobalite, SiC particles and SiC fibres. Standardised mortality ratios (SMRs) for underlying causes of death, 1951-2007, were calculated stratified by category of cumulative exposure, and Poisson regression analyses of OLD were performed using cumulative exposure variables. RESULTS: An increased total mortality (SMR 1.1, 95% CI 1.0 to 1.2) and increased mortality from cancer, non-malignant respiratory diseases and external factors, were observed. The SMR of OLD was increased at the highest level of cumulative exposure to all investigated exposure factors. In the internal analyses, a twofold increased risk of OLD was observed with increasing levels of cumulative exposure to SiC particles. In a multivariate model, SiC particles showed the most stable increased risk estimate when controlled for other exposure factors, among workers with less than 15 years of employment. Among workers with more than 15 years of employment, crystalline silica, primarily cristobalite, seemed to be the most important exposure factor. CONCLUSION: Exposure to SiC and crystalline silica may contribute to OLD development among SiC industry workers in different time windows, and possibly through different mechanisms.

Incidence of airflow limitation among employees in Norwegian smelters.

We have investigated the association between the incidence of airflow limitation and occupational exposure. The employees (n = 3,924) were investigated annually during five years (n = 16,570) using spirometry. Exposure was classified using job category and a job exposure matrix. Airflow limitation was expressed using two indices: (i) as forced expiratory volume in one second/force vital capacity (FEV(1) /FVC) <0.7 and (ii) lower limit of normal (LLN). The incidence of airflow limitation was 21.2/1000 years(-1) and 15.1/1000 years(-1) using the fixed limit (0.7) and the LLN criterion, respectively. We found a dose-response relationship between the incidence of airflow limitation and tobacco consumption and with job-category in non-smokers. The associations between airflow limitation and covariates were independent of how airflow limitation was defined. The incidence of airflow limitation defined as FEV(l) /FVC <0.7 yielded higher incidence rates of airflow limitation than LLN. We found a significant association between the incidence of airflow limitation and occupational exposure in non-smokers.

Predictors of Occupational Burnout: A Systematic Review.

We aimed to review occupational burnout predictors, considering their type, effect size and role (protective versus harmful), and the overall evidence of their importance. MEDLINE, PsycINFO, and Embase were searched from January 1990 to August 2018 for longitudinal studies examining any predictor of occupational burnout among workers. We arranged predictors in four families and 13 subfamilies of homogenous constructs. The plots of z-scores per predictor type enabled graphical discrimination of the effects. The vote-counting and binomial test enabled discrimination of the effect direction. The size of the effect was estimated using Cohen's formula. The risk of bias and the overall evidence were assessed using the MEVORECH and GRADE methods, respectively. Eighty-five studies examining 261 predictors were included. We found a moderate quality of evidence for the harmful effects of the job demands subfamily (six predictors), and negative job attitudes, with effect sizes from small to medium. We also found a moderate quality of evidence for the protective effect of adaptive coping (small effect sizes) and leisure (small to medium effect sizes). Preventive interventions for occupational burnout might benefit from intervening on the established predictors regarding reducing job demands and negative job attitudes and promoting adaptive coping and leisure.

Harmonized definition of occupational burnout: A systematic review, semantic analysis, and Delphi consensus in 29 countries.

Objective A consensual definition of occupational burnout is currently lacking. We aimed to harmonize the definition of occupational burnout as a health outcome in medical research and reach a consensus on this definition within the Network on the Coordination and Harmonisation of European Occupational Cohorts (OMEGA-NET). Methods First, we performed a systematic review in MEDLINE, PsycINFO and Embase (January 1990 to August 2018) and a semantic analysis of the available definitions. We used the definitions of burnout and burnout-related concepts from the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) to formulate a consistent harmonized definition of the concept. Second, we sought to obtain the Delphi consensus on the proposed definition. Results We identified 88 unique definitions of burnout and assigned each of them to 1 of the 11 original definitions. The semantic analysis yielded a first proposal, further reformulated according to SNOMED-CT and the panelists` comments as follows: "In a worker, occupational burnout or occupational physical AND emotional exhaustion state is an exhaustion due to prolonged exposure to work-related problems". A panel of 50 experts (researchers and healthcare professionals with an interest for occupational burnout) reached consensus on this proposal at the second round of the Delphi, with 82% of experts agreeing on it. Conclusion This study resulted in a harmonized definition of occupational burnout approved by experts from 29 countries within OMEGA-NET. Future research should address the reproducibility of the Delphi consensus in a larger panel of experts, representing more countries, and examine the practicability of the definition.

Twins with omphalocele in Denmark (1970-1989).

Seven pairs of twins, two monozygotic (MZ), two dizygotic (DZ), and three like-sex pairs of unknown zygosity are described. The twin pairs were all discordant for omphalocele except for one pair of conjoined twins. The 8 infants with omphalocele represent 3.1% of the 253 infants with omphalocele, ascertained in an almost complete nationwide data set of live- and stillborn infants with abdominal wall defects in two decades in Denmark (1970-1989). The occurrence of twins with omphalocele was not significantly different from the occurrence of twins in the Danish population in the same period. To our knowledge this is the first report of the occurrence of twins with omphalocele in a systematic nationwide epidemiological study.

Burnout syndrome in Europe: towards a harmonized approach in occupational health practice and research.

Health practitioners and decision makers in the medical and insurance systems need knowledge on the work-relatedness of burnout. To gather the most reliable information regarding burnout diagnosis and recognition in Europe, we used an 8-item standard questionnaire sent by e-mail to occupational health specialists identified via the Network on the Coordination and Harmonization of European Occupational Cohorts (OMEGA-NET) within the European Cooperation in Science and Technology (COST) Action. Participation rate was 100%, and the questionnaire was completed for 37 countries. In 14 (38%) countries burnout syndrome can be acknowledged as an occupational disease. However, only one country included burnout on the list of occupational diseases. The results showed a high variability in burnout diagnosis, in assessment of its work-relatedness, and in conditions allowing compensation of patients. These results reflect a lack of graded evidence on burnout and its determinants. The ongoing research on burnout conducted in the frame of the OMEGA-NET COST Action should be helpful through facilitating standardization of both existing and new data on burnout, a priority outcome requiring harmonization.

Balanced translocation in a patient with severe myoclonic epilepsy of infancy disrupts the sodium channel gene SCN1A.

In a patient with severe myoclonic epilepsy of infancy (SMEI), we identified a de novo balanced translocation, t(2;5)(q24.3,q34). The breakpoint on chromosome 2q24.3 truncated the SCN1A gene and the 5q34 breakpoint was within a highly conserved genomic region. Point mutations or microdeletions of SCN1A have previously been identified in SMEI patients, but this is the first report of a balanced translocation disrupting the SCN1A gene in an epilepsy patient. We therefore recommend that SMEI patients without SCN1A microdeletions or point mutations should be investigated for chromosomal rearrangements.