Coherently-averaged dual comb spectrometer at 7.7†µm with master and follower quantum cascade lasers.

We demonstrate coherent averaging of the multi-heterodyne beat signal between two quantum cascade laser frequency combs in a master-follower configuration. The two combs are mutually locked by acting on the drive current to control their relative offset frequency and by radio-frequency extraction and injection locking of their intermode beat signal to stabilize their mode spacing difference. By implementing an analog common-noise subtraction scheme, a reduction of the linewidth of all heterodyne beat notes by five orders of magnitude is achieved compared to the free-running lasers. We compare stabilization and post-processing corrections in terms of amplitude noise. While they give similar performances in terms of signal-to-noise ratio, real-time processing of the stabilized signal is less demanding in terms of computational power. Lastly, a proof-of-principle spectroscopic measurement was performed, showing the possibility to reduce the amount of data to be processed by three orders of magnitude, compared to the free-running system.

Frequency comb metrology with an optical parametric oscillator.

We report on the first demonstration of absolute frequency comb metrology with an optical parametric oscillator (OPO) frequency comb. The synchronously-pumped OPO operated in the 1.5-µm spectral region and was referenced to an H-maser atomic clock. Using different techniques, we thoroughly characterized the frequency noise power spectral density (PSD) of the repetition rate frep, of the carrier-envelope offset frequency fCEO, and of an optical comb line νN. The comb mode optical linewidth at 1557 nm was determined to be ~70 kHz for an observation time of 1 s from the measured frequency noise PSD, and was limited by the stability of the microwave frequency standard available for the stabilization of the comb repetition rate. We achieved a tight lock of the carrier envelope offset frequency with only ~300 mrad residual integrated phase noise, which makes its contribution to the optical linewidth negligible. The OPO comb was used to measure the absolute optical frequency of a near-infrared laser whose second-harmonic component was locked to the F = 2→3 transition of the 87Rb D2 line at 780 nm, leading to a measured transition frequency of νRb = 384,228,115,346 ± 16 kHz. We performed the same measurement with a commercial fiber-laser comb operating in the 1.5-µm region. Both the OPO comb and the commercial fiber comb achieved similar performance. The measurement accuracy was limited by interferometric noise in the fibered setup of the Rb-stabilized laser.

Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma.

OBJECTIVES: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. METHODS: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. RESULTS: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. CONCLUSIONS: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

[Compensation of occupational diseases during monitoring of the ARDCO cohort]. / Les reconnaissances en maladie professionnelle lors du suivi de la cohorte ARDCO.

INTRODUCTION: Questions concerning under-reporting of occupational diseases (OD) linked to asbestos exposure are regularly voiced in France. Monitoring of the French multicenter Asbestos-Related Disease Cohort (ARDCO), which ensures post-occupational medical surveillance of subjects having been exposed to asbestos, provides information on (1) the medico-legal steps taken following screening by computed tomography (CT) for benign thoracic diseases, and (2) recognition of OD as a causal factor in malignant diseases. METHODS: OD recognition - and possible compensation - was analyzed in July 2021 among 13,289 volunteers in the cohort recruited between 2003 and 2005. RESULTS: Fifteen percent of the subjects in the cohort were found to have at least one recognized asbestos-related OD (78.2% benign pleural disease, 10.3% asbestosis, 14.2% lung cancer, and 6.0% mesothelioma). Only 58% of pleural plaques reported by the radiologist who performed the CT resulted in their recognition as ODs. On a parallel track, 88.7% of the mesotheliomas identified based on French National health insurance data and 46.9% of lung cancers were recognized as ODs. CONCLUSIONS: This study confirms the feasibility of a system designed to facilitate recognition, leading to possible compensation, of asbestos-related occupational diseases. The system could be improved by better training of the medical actors involved.

[Compensation for occupational diseases after tomodensitometry screening for benign pleuro-pulmonary disease in a multiregional post-occupational medical surveillance program of asbestos-exposed retired workers]. / Déclaration et reconnaissance en maladie professionnelle après dépistage tomodensitométrique de maladies pleuropulmonaires bénignes dans le programme multirégional de surveillance postprofessionnelle de personnes exposées à l'amiante.

BACKGROUND: Underreporting of occupational diseases related to asbestos exposure remains a matter of concern in France. The aim of this study was to evaluate the number of claims for compensation for asbestos-related non-malignant pulmonary or pleural occupational disease in subjects having undergone a chest CT-scan in a multiregional screening programme. METHODS: Among the 5444 voluntary retired asbestos-exposed subjects recruited in four regions between 2003 and 2005 who had undergone a chest CT-scan, the number of claims for compensation for an asbestos-related pulmonary or pleural benign disease was analysed in 2006 and 2010. RESULTS: Following CT-scan screening, 17.2% of participants were acknowledged as presenting with an asbestos-related non-malignant occupational disease, essentially pleural plaques, by the French National Health Insurance fund. Underreporting decreased as duration of follow-up after CT-scan increased. Nevertheless, 4 years after CT-scan, underreporting was still as high as 36% for subjects identified as presenting with pleural plaques. Mean duration between the date of CT-scan and the date of recognition as occupational disease was 7.4 months, shorter in cases where screening was coordinated by specialized centres. CONCLUSION: A plan of action for an easier claiming process for compensation of asbestos-related diseases is desired. This could probably be obtained through improved sensitization of physicians engaged in the follow-up of asbestos-exposed subjects, and by standardization of the interpretation and reporting of asbestos-related abnormalities observed on chest CT-scans.

RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay.

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0-1 Gy), moderately (1-2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.

RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.

[Chronic central nervous system effects of pesticides: state-of-the-art]. / Effets chroniques des pesticides sur le système nerveux central : état des connaissances épidémiologiques.

BACKGROUND: Given the neurotoxic properties of pesticides, suggested by experimental results and clinical observations, many epidemiological studies have investigated neurological effects following acute or chronic exposure to pesticides. This review provides an overview of current knowledge about pesticide effects on the central nervous system: neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis), cognitive disorders, and psychiatric disorders (mood disorders, anxiety, depression and suicide). RESULTS: Parkinson's disease, the most widely studied in relation with pesticide exposure, particularly with insecticides and herbicides, was observed to be a risk factor of the disease. Evidence is scarce for Alzheimer's disease and amyotrophic lateral sclerosis, but quite consistent. Cognitive and psychiatric disorders were often observed in relation with organophosphate insecticide exposure. Cognitive disorders were found associated with acute and chronic exposures, and psychiatric disorders mostly with poisonings. These epidemiologic studies were limited by a lack of detailed and reliable exposure assessment. The role of genetic susceptibilities has been recently observed, but must be further investigated.

Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005.

The evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980-2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (-3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998-2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980-1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.

Pleural plaques and asbestosis: dose- and time-response relationships based on HRCT data.

Most studies on asbestos-related diseases are based on chest radiographs, and dose-response relationships are still controversial. The aim of this study was to describe the most relevant parameters of asbestos exposure linked to pleural plaques and asbestosis diagnosed by high-resolution computed tomography (HRCT). A large screening programme including systematic HRCT examinations was organised from 2003 to 2005 in France for formerly asbestos-exposed workers. The time since first exposure (TSFE), level, duration and cumulative exposure to asbestos were used in adjusted unconditional logistic regression to model the relationships of the two diseases. Analysis of a population of 5,545 subjects demonstrated that TSFE (p<0.0001) and cumulative exposure (p = 0.02) (or level, depending on the models used), were independently associated with the frequency of pleural plaques. Only cumulative exposure (p<0.0001) or level of exposure (p = 0.02) were significantly associated with asbestosis. All trend tests were significant for these parameters. To date and to our knowledge, this study is the largest programme based on HRCT for the screening of asbestos-exposed subjects. Both time-response and dose-response relationships were demonstrated for pleural plaques, while only dose-response relationships were demonstrated for asbestosis. These parameters must be included in the definition of high-risk populations for HRCT-based screening programmes.

[Respiratory effects of manufactured nanoparticles]. / Effets respiratoires des nanoparticules manufacturées.

Nanotechnology, defined as techniques aimed to design, characterize and produce materials on a nanometer scale, is a fast-growing field today. Nanomaterials are made of nanoobjects (nanoparticles, nanofibers, nanotubes...). The nanoscale confers on these materials their novel, hitherto unknown, chemical and physical properties by the laws of quantum physics which are essentially expressed on this scale. Nanotechnology applications are numerous (e.g., cosmetics, industry and medicine) and they keep growing. We can safely predict that the production and utilization of nanomaterials will increase greatly in the years to come. Nonetheless, the same properties that make these nanomaterials very attractive are a source of concern: there are questions about their potential toxicity, their long-term side effects, and their biodegradability. These questions are based on knowledge of the toxic effects of micrometric particles in air pollution and the fear that these effects will be amplified because of the nanometric size of the new materials. We present in this article a global but not exhaustive summary of current knowledge. We begin by defining lung penetration, deposition, translocation and elimination of nanoparticles. Finally, we consider the respiratory effects of metallic nanoparticles, titanium dioxide nanoparticles in particular, and carbon nanotubes. In vivo and in vitro experimental studies currently available highlight the existence of biological effects of nanoparticles on the respiratory system with generation of oxidative stress, pro-inflammatory and pro-thrombotic effects and the possible development of fibrosis and pulmonary emphysema or DNA damage. A better understanding of the potential biological effects of nanoparticles is required to implement appropriate preventive measures in the workplace and/or in the general population, if this should be necessary.

[Asbestos-related cancer risk in the presence of asbestosis or pleural plaques]. / Risque de cancer lié à l'amiante en présence d'asbestose ou de plaques pleurales.

INTRODUCTION: The relationships between benign asbestos-related diseases (asbestosis and pleural plaques) and thoracic cancers are still debated. The aim of this paper is to analyse epidemiological data which investigate this topic. STATE OF THE ART: Published studies show that there is a significant relationship between occupational exposure to asbestos and lung cancer risk, even in the absence of abnormalities consistent with asbestos exposure on postero-anterior chest x-ray. In subjects with occupational exposure to asbestos, an increased risk of lung cancer and pleural mesothelioma is observed in subjects with pleural plaques on chest x-ray, in comparison with the general population. In exposed subjects with similar cumulative exposure to asbestos, it is not demonstrated that pleural plaques are associated with an increased risk of lung cancer or pleural mesothelioma. PERSPECTIVES: All the analysed studies are only based on radiographic data. Their results must be confirmed by additional studies including a rigorous evaluation of the cumulative exposure to asbestos and chest CT-scans. CONCLUSION: In the present state of knowledge, isolated pleural plaques do not justify specific medical surveillance, as compared to that required by the mere estimated cumulative exposure to asbestos.

Maternal occupational exposures to nanoscale particles and small for gestational age outcome in the French Longitudinal Study of Children.

OBJECTIVES: To investigate the association between maternal occupational exposures to nanoscale particles (NPs) during pregnancy and small for gestational age (SGA). METHODS: This study included 11,224 mothers and singleton birth pairs from the French Longitudinal Study of Children (ELFE cohort), which included infants born after 33 weeks of gestation or more in continental France in 2011. Mothers who did not work during pregnancy were excluded from the analyses. Maternal occupational exposures to NPs was estimated using a job-exposure matrix for the probability (>50%: occupationally exposed group, n = 569; 0%: occupationally non-exposed group, n = 9113; between these two thresholds: uncertain group, n = 1542) and frequency of exposure. Associations were estimated from multivariate logistic regression models for occupationally exposed vs occupationally unexposed groups in a first analysis, and with the frequency-weighted duration of work for the occupationally exposed group only in a second analysis. RESULTS: Among working mothers, 5.1% were occupationally exposed to NPs. Maternal occupational exposures to NPs was associated with SGA (ORa = 1.63, 95% CI: 1.22, 2.18). The frequency-weighted duration of work for the occupationally exposed group (n = 569) was not associated with SGA (ORa = 1.02, 95% CI: 0.97, 1.08) in adjusted analyses. CONCLUSIONS: These results, showing a significant association between occupational exposures to NPs and SGA, should encourage further studies to examine the adverse effect of NPs exposure on fetal development.

Health consequences of the first Persian Gulf War on French troops.

Since 1993, many studies on the health of Persian Gulf War Veterans (PGWV) have been undertaken. These studies have concluded that there has been an increased mortality due to external causes, no excess of recognized diseases, and no effect on PGWV children. When compared with the non-deployed, PGWV have reported a higher frequency of infertility as well as different symptoms, but a specific Gulf War syndrome was not identified. In October 2000, the French government asked an independent working group to analyse the scientific literature on PGWV health. The group concluded that an exhaustive study of French PGWV was to be undertaken. The objectives of this study were to describe the exposures of PGWV in the operations theatre, to report on the symptoms and diseases that occurred in PGWV and their children during and after the military campaign, and to explore the possibility of a Gulf War syndrome. This exhaustive cross-sectional study, which included all civilians and troops who served in the Gulf from August 1990 to July 1991, began in January 2002. Data were collected by postal self-administered questionnaires. A standardized clinical evaluation was performed by 27 clinics of occupational diseases and nine military hospitals. Symptoms and diseases which appeared after the campaign are described. To date, among 20,261 PGWV, 5,666 participated in the study (28%). The most frequent symptoms described since the return from the Gulf were headaches (83%), neurological or psychological symptoms, and back pain. Apart from well-known symptoms associations (respiratory, neurocognitive, psychological and musculo-skeletal syndromes), no other cluster was highlighted by our analysis.

The French National Mesothelioma Surveillance Program.

OBJECTIVES: The French National Mesothelioma Surveillance Program (NMSP) was established in 1998 by the National Institute for Health Surveillance (InVS). Its objectives are to estimate the trends in mesothelioma incidence and the proportion attributable to occupational asbestos exposure, to help improve its pathology diagnosis, to assess its compensation as an occupational disease, and to contribute to research. METHODS: The NMSP records incident pleural tumours in 21 French districts that cover a population of approximately 16 million people (a quarter of the French population). A standardised procedure of pathological and clinical diagnosis ascertainment is used. Lifetime exposure to asbestos and to other factors (man made mineral fibres, ionising radiation, SV40 virus) is reconstructed, and a case-control study was also conducted. The proportion of mesothelioma compensated as an occupational disease was assessed. RESULTS: Depending on the hypothesis, the estimated number of incident cases in 1998 ranged from 660 to 761 (women: 127 to 146; men: 533 to 615). Among men, the industries with the highest risks of mesothelioma are construction and ship repair, asbestos industry, and manufacture of metal construction materials; the occupations at highest risk are plumbers, pipe-fitters, and sheet-metal workers. The attributable risk fraction for occupational asbestos exposure in men was 83.2% (95% CI 76.8 to 89.6). The initial pathologist's diagnosis was confirmed in 67% of cases, ruled out in 13%, and left uncertain in the others; for half of the latter, the clinical findings supported a mesothelioma diagnosis. In all, 62% applied for designation of an occupational disease, and 91% of these were receiving workers' compensation. CONCLUSIONS: The NMSP is a large scale epidemiological surveillance system with several original aspects, providing important information to improve the knowledge of malignant pleural mesothelioma, such as monitoring the evolution of its incidence, of high risk occupations and economic sectors, and improving pathology techniques.

[Poisons for reproduction in work environment]. / Toxiques pour la reproduction et travail.

This article describes the lawful bases of the reprotoxic risk management in work environment, and sets out the recommendations of the French Société de Médecine du Travail (occupational medicine) for the medical supervision of pregnant wage-earners exposed to toxic substances as far as foetal development is concerned. We start with the description of the lawful bases, clarifying the various types of classification of toxic substances for reproduction, the particular regulation applying to reprotoxic categories 1 and 2, particularly with regard to the labelling of these products, the prohibition of availability to the general public, the principles of prevention and the guarantees of remuneration of the pregnant women exposed to this risk. Then, we present the recommendations worked out by the Société Française de Médecine du Travail, with regard to the medical supervision of pregnant wage-earners. They include: evaluation of the risk on the work place, evaluation of exposure, be it external or internal, presentation of methods of calculation of values guides and of recommendations transmitted to occupational doctors, before and during the pregnancy of their patients. To conclude, it is important to remain rigorous with this reprotoxic risk, by referring to the lawful bases at our disposal and supporting the scientific bases following epidemiologic studies. Adequate information must be given to women but also men pf procreation age. In spite of a well-defined lawful framework, watchfulness is required with the new products put on the market and the new scientific data.

[Occupational risk factors for lung cancer]. / Facteurs de risque professionnels du cancer bronchopulmonaire.

OBJECTIVE: We aimed to review the literature regarding the dose-response relationship between occupational exposure to chemicals classified by the International Agency for Research on Cancer (IARC) as carcinogenic agents and the risk of some lung cancers and on any combined effect with tobacco exposure on lung cancer risk. METHODS: A literature search was performed in three databases as well as in the IARC monographs between January 1990 and April 2015. RESULTS: The literature is abundant for some carcinogens such as asbestos, crystalline silica and diesel exhaust fumes but is more sparse for many carcinogens and particularly any interaction with tobacco on lung cancer risk. CONCLUSION: Few data exist for most lung occupational carcinogens including their interaction with tobacco exposure. In the case of exposure to occupational carcinogens and co-exposure to tobacco smoke, there is a dual primary prevention objective: the elimination of both occupational risk factors and tobacco smoke.

Twenty five year mortality and air pollution: results from the French PAARC survey.

AIMS AND METHODS: Long term effects of air pollution on mortality were studied in 14,284 adults who resided in 24 areas from seven French cities when enrolled in the PAARC survey (air pollution and chronic respiratory diseases) in 1974. Daily measurements of sulphur dioxide, total suspended particles, black smoke, nitrogen dioxide, and nitric oxide were made in 24 areas for three years (1974-76). Cox proportional hazards models controlling for individual confounders (smoking, educational level, body mass index, occupational exposure) were applied, and frailty models used to take into account spatial correlation. Indicators of air pollution were the mean concentration. RESULTS: Models were run before and after exclusion of six area monitors influenced by local traffic (NO/NO2 >3 in ppb). After exclusion of these areas, analyses showed that adjusted risk ratios (95% CI) for TSP, BS, NO2, and NO for non-accidental mortality were 1.05 (1.02 to 1.08), 1.07 (1.03 to 1.10), 1.14 (1.03 to 1.25), and 1.11 (1.05 to 1.17) for 10 microg/m3 respectively. Consistent patterns for lung cancer and cardiopulmonary causes were observed. CONCLUSIONS: Urban air pollution assessed in the 1970s was associated with increased mortality over 25 years in France.

Spirometric changes following the use of pesticides.

We compared the respiratory function of 19 pesticide factory workers and a control group of 43 other factory workers in Lebanon. The groups had no difference in smoking status. Baseline measurements of respiratory function showed significantly lower forced expiratory volume and flow rates (FEV1, FEF(25-75%), and FEV1/FVC ratio) among subjects working with pesticides, i.e. obstruction may be linked to chronic exposure to pesticides. After 4 hours of work, all respiratory variables were still significantly lower in pesticide-exposed subjects, but no acute changes in respiratory function were seen. Pesticide-exposed workers had 5.6 times higher risk of abnormal FEV1/FVC ratio and 16.5 higher risk for abnormal FEF(25-75%). Duration of occupation in the pesticide factory was significantly correlated with abnormal respiratory measures.