Protein fingerprinting and quantification of ß-casein variants by ultra-performance liquid chromatography-high-resolution mass spectrometry.

Infant formulations are constantly evolving as novel protein ingredients are added to make them more closely mimic the protein profile of human milk; however, precise analytical methods for characterizing and quantifying the major milk proteins in such formulations are currently lacking. This article describes an ultra-performance liquid chromatography-high-resolution mass spectrometry method for intact proteins that can efficiently detect, identify, and characterize the major milk proteins and their proteoforms (phosphorylation status, degree of glycation, genetic variants among others) in ingredients and final products, with an emphasis on detecting and quantifying specific genetic variants of ß-casein in infant formulas. Method sensitivity allows detection of ß-casein A1 in A2-based infant formulas with a limit of detection of 2% (grams of ß-casein A1 per 100 g of total ß-casein). Protein glycation affects signal intensity in a linear fashion, which permits proteins to be quantified from their mass spectrometry signals after correction according to their measured glycation index. The method was validated for the quantification of ß-casein in infant formulas. Repeatability ranged from 2 to 3% and intermediate reproducibility from 5 to 9%. Calculated ß-casein amounts ranged between 77 and 110% of the values based on formulations and published protein profiles for milk. Altogether, this method can be used for general fingerprinting as well as specific characterization and quantification of individual major milk proteins in dairy-based ingredients and products.

Asymmetric distribution of anionic phospholipids in supported lipid bilayers.

Lipid bilayers with a controlled content of anionic lipids are a prerequisite for the quantitative study of hydrophobic-electrostatic interactions of proteins with lipid bilayers. Here, the asymmetric distribution of zwitterionic and anionic lipids in supported lipid bilayers is studied by neutron reflectometry. We prepare POPC/POPS (3:1) unilamellar vesicles in a high-salt-concentration buffer. Initially, no fusion of the vesicles to a SiO(2) surface is observed over hours and days. Once the isotonic buffer is exchanged with hypotonic buffer, vesicle fusion and bilayer formation occur by osmotic shock. Neutron reflectivity on the bilayers formed this way reveals the presence of anionic lipids (d(31)-POPS) in the outer bilayer leaflet only, and no POPS is observed in the leaflet facing the SiO(2) substrate. We argue that this asymmetric distribution of POPS is induced by the electrostatic repulsion of the phosphatidylserines from the negatively charged hydroxy surface groups of the silicon block. Such bilayers with controlled and high contents of anionic lipids in the outer leaflet are versatile platforms for studying anionic lipid protein interactions that are key elements in signal transduction pathways in the cytoplasmic leaflet of eukaryotic cells.

Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis.

BACKGROUND: Probiotics have been associated with prevention and improvement of symptoms in atopic diseases such as atopic dermatitis. However, few studies exist that document their efficacy for upper airways allergies such as allergic rhinitis. OBJECTIVE: To investigate the effect of short-term oral administration of Lactobacillus paracasei ST11 on a nasal provocation test (NPT) with grass pollen. METHODS: Thirty-one adult volunteers with allergic rhinitis were enrolled in a randomized, double-blind, placebo-controlled study, based on two 4-week cross-over periods of product consumption (ST11-fermented milk vs. placebo), separated by a wash-out period of 6-8 weeks. Objective and subjective clinical parameters of NPT as well as systemic and nasal immunological parameters were compared between the two treatment periods (registration number: NCT 011 50 253). RESULTS: Subjects that received ST11-fermented milk had lower nasal congestion than subjects under placebo (visual analogical scale; P<0.05). Nasal pruritus followed the same trend. However, no significant change in combined nasal reaction threshold was observed between the two periods. IL-5 secretion by peripheral blood mononuclear cells and serum allergen-specific IgG4 were significantly lower in ST11-fermented milk group compared to placebo group. IL-8 and IL-10 secretion followed the same trend. CONCLUSION AND CLINICAL RELEVANCE: Short-term treatment with ST11-fermented milk before NPT significantly improved a clinical marker of NPT (subjective nasal congestion) and down-regulated systemic immune markers (IL-5 from peripheral blood mononuclear cells and serum IgG4). These data strongly suggest that probiotics may down modulate key parameters of allergic rhinitis and warrant future evaluation in seasonal trials.

Potentially inappropriate drug prescription in the elderly in France: a population-based study from the French National Insurance Healthcare system.

BACKGROUND: Inappropriate prescribing is a known risk factor for adverse drug event occurrence in the elderly. In various countries, several studies have used insurance healthcare databases to estimate the national prevalence of potentially inappropriate medications (PIM) in the elderly, as defined by explicit PIM lists. Recently, a representative sample of the French National Insurance Healthcare database, known as the "Echantillon Généraliste des Bénéficiaires" (EGB), was created, making it possible to assess the quality of drug prescription in France. Our objective was to evaluate the prevalence and the regional distribution of PIM prescription in the elderly aged 75 years and over in France, using the French PIM list and the EGB database. METHODS: The list of drugs reimbursed to patients aged 75 years and over from 1 March 2007 to 29 February 2008 was extracted from the EGB. Drugs were classified as inappropriate using the French PIM list. A PIM user was defined as a person receiving at least one PIM reimbursement during the study period. Interregion variability was estimated from logistic regression. RESULTS: In 53.6% (95% CI: 53.0-54.1) of the elderly aged 75 years and over, at least one PIM was given during the study period. The three main drug groups identified were cerebral vasodilators (19.4%), drugs with antimuscarinic properties (19.3%), and long half-life benzodiazepines (17.8%). There was an important disparity in PIM prescription among the French regions. In 14 out of 22 regions, the risk of PIM prescription was significantly elevated. This geographical variation differed for the different drug groups. CONCLUSION: PIM prescription in the elderly is a major and worrying problem in France. As in other countries, recent accessibility of the National Insurance Healthcare database makes it possible to create local indicators that the regional health agencies could use to manage public health policy in closer alignment to the needs of the patients within each French region.

Lung cancer mortality and iron oxide exposure in a French steel-producing factory.

OBJECTIVE: To study the possible association between iron oxide exposures and lung cancer risk among workers in a French carbon steel-producing factory. METHODS: 16 742 males and 959 females ever employed for at least 1 year between 1959 and 1997 were followed up for mortality from January 1968 to December 1998. Causes of death were ascertained from death certificates. Job histories and smoking habits were available for 99.7% and 72.3% of subjects, respectively. Occupational exposures were assessed by a factory-specific job-exposure matrix (JEM) validated with atmospheric measurements. Standardised mortality ratios (SMRs) were computed using local death rates (external references). Poisson regressions were used to estimate the relative risks (RRs) for occupational exposures (internal references), adjusted on potential confounding factors. RESULTS: Among males, observed mortality was lower than expected for lung cancer compared to the local population (233 deaths, SMR 0.89, 95% CI 0.78 to 1.01) and higher than expected compared to the French population (SMR 1.30, 95% CI 1.15 to 1.48) No lung cancer excess was observed for exposure to iron oxides (RR 0.80, 95% CI 0.55 to 1.17) and no dose-response relationship with intensity, duration of exposure or cumulative index was found. A significant bladder cancer excess was observed among workers exposed to oil mist (RR 2.44, 95% CI 1.06 to 5.60), increasing significantly with intensity, duration of exposure and cumulative index. CONCLUSION: This study did not detect any relationship between exposure to iron oxides and lung cancer mortality. An excess of mortality from bladder cancer was found among workers exposed to oil mist.

[Job insecurity, unemployment and health: results from the health examination centers of the French General Health Insurance]. / Santé et instabilité professionnelle : résultats issus des centres d'examens de santé de l'assurance-maladie.

BACKGROUND: Job insecurity has increased over the last 30 years. Socioeconomic changes have led to various insecure employment categories, including fixed term employment, part time employment and government sponsored jobs. This study was aimed at investigating relationships between employment status and health. METHODS: The study population was composed of 767,184 people, aged 26 to 59 years, examined between 2003 and 2005 in the Health Examination Centers of the French General Health Insurance. Employment status was defined using insecure employment (combining permanent/fixed-term contracts and part-time/full time), government sponsored jobs and duration of unemployment (from <6 months to > or =3 years). Health indicators were poor perceived health, smoking, lack of gynecological follow-up, obesity, untreated caries and high blood pressure. Data were analysed by logistic regression (odds ratios [OR]) adjusted on age, occupational social class and education level, the reference category being permanent full time contracts (OR=1). RESULTS: Significant level-dependent relations with health were observed between non permanent versus permanent employments, part time versus full time. Most OR of unemployed people were higher than those of having employment and increased with duration of unemployment. For example, for poor perceived health in men, OR ranged between 1.00 and 1.68 (95%CI 1.57-1.78) according to job insecurity categories, and between 1.75 (95%CI 1.67-1.83) and 2.80 (95%CI 2.72-2.89) according to duration of unemployment. For obesity in women, OR increased from 1.00 to 1.48 (95%CI 1.37-1.60) in active women and from 1.35 (95%CI 1.27-1.44) to 1.77 (95%CI 1.70-1.84) in unemployed. CONCLUSIONS: This study showed quantitative relationships between job insecurity, unemployment and health. In particular, workers having government-sponsored jobs and long-time unemployed people were at high risk of health problems.

Hospital-based home care for young children newly diagnosed with type 1 diabetes: Assessing expectations and obstacles in families and general practitioners.

AIMS: This study aimed to evaluate whether hospital-based home care was desired by the parents of children diagnosed with type 1 diabetes (T1D) under the age of 5 years and their general practitioners, and to identify the main expectations and obstacles to its implementation. METHODS: This descriptive bicentric study in France was performed between November 2016 and November 2017. Data were collected by interviewing 57 families of children diagnosed with diabetes before the age of 5 years and the corresponding 30 general practitioners. The primary endpoint was the families' or general practitioners' acceptance of home-based care after diagnosis. RESULTS: A high proportion of families and physicians (86% and 93%, respectively) expressed a wish for hospital-based home care, most of whom considered it essential (79% and 87%, respectively). Low-income families were less likely to accept this care pathway (P<0.001). The families' expectations regarding home care were help with social care, the management of emergencies, and return to school. The physicians' main request was improved interprofessional collaboration. CONCLUSION: Hospital-based home care seems to be an acceptable transition after conventional care for children just diagnosed with T1D. Multidisciplinary support, personalized social care, and access to welfare benefits may improve acceptance rates, especially among low-income families.

Flow at interfaces: a new device for x-ray surface scattering investigations.

A fluidic cell based setup is described which allows for microbeam grazing incidence small angle x-ray scattering characterization of the interface between a solid substrate and a flowing liquid. This cell can potentially be used to study in situ a wide variety of systems ranging from synthetic and natural colloids to biological molecules. The selected channel geometry enables the characterization of the solid-liquid interface during mixing of different solutions. As a proof of concept, measurements on an aqueous gold nanoparticle solution in contact with a glass surface are presented that show that the structure at the interface can be probed during flow.

Transvaginal ultrasound-guided embryo transfer in IVF.

OBJECTIVES: To determine whether transvaginal ultrasound-guided embryo transfer is a technique that can be used routinely, whether it improves IVF outcomes and whether it makes difficult transfers easier and more successful. MATERIAL AND METHOD: Non-randomized retrospective study conducted between 2012 and 2016 in the fertility center of the Diaconesses-Croix St-Simon hospital group. The outcomes of 3910 transfers, performed by 5 senior operators, under transabdominal ultrasound guidance are compared with those of 800 transfers, performed by 1 senior operator under transvaginal ultrasound guidance. The criteria studied are the feasibility of the technique and the percentage of pregnancies per transfer in the two populations described, as well as in the difficult and very difficult transfer populations. RESULTS: All the transfers were feasible under transvaginal ultrasound guidance without the use of forceps or additional instruments. The percentage of pregnancies per transfer is significantly increased, when the transfer is performed under transvaginal ultrasound guidance compared with that performed under transabdominal ultrasound guidance, in the general population (38%, n=800 vs 30%, n=3910; P 0.0004) and in the reference population characterized by age <38 years and >6 oocytes collected per puncture (45%, n=490 vs 36%, n=1968; P 0.002). The percentage of pregnancies per transfer (P/T) is not significantly different in the populations of easy transfers (n 695, 38% P/T), difficult transfers (n 58, 46% P/T; P=ns) and very difficult transfers (n 47, 34% P/T; P=ns). CONCLUSIONS: Embryo transfer is a key stage in IVF, in which the quality of performance determines the outcome. In this study, transvaginal ultrasound guidance of the transfer, which is the reference procedure in gynaecological imaging, significantly increases the percentage of pregnancies per transfer, both in the general population and in the reference population, compared with transfers performed under transabdominal ultrasound guidance. Transvaginal ultrasound facilitates the performance of difficult transfers and in particular achieves outcomes in these situations that are not significantly different from those of easy transfers. Visual monitoring of transcervical passage, which is rendered more precise and less traumatic and precision of embryo deposition are the factors that probably account for the improvement in outcomes.

Expression and tumorigenicity of the Epstein-Barr virus BARF1 gene in human Louckes B-lymphocyte cell line.

We previously showed that the Epstein-Barr virus, which encodes the BARF1 gene, could transform rodent fibroblasts. In this work, the expression of the BARF1 gene was studied in the human Louckes B-lymphocyte cell line. Introduction of the BARF1 open reading frame under the control of the Mo-MuLV LTR promotor into nontumorigenic Louckes lymphoid cells led to the activation of the c-myc protooncogene and increased expression of the B-cell surface proteins, the transferrin receptor, CD21, and CD23. BARF1-expressing cells induced a diffuse lymphoma-like tumor in newborn rats treated with anti-thymocyte serum that was, however, transient and regressed after 3-4 weeks as the immune system recovered. The tumor induction was similar to that observed with lymphoid cell lines in vitro generated by infection with the B95-8 virus strain, in which lytic antigens are expressed at low levels. After long-term culture, Louckes cell clones lost expression of the BARF1 gene and were unable to induce tumors.

[Comparison of the individual deprivation index of the French Health Examination Centres and the administrative definition of deprivation]. / Comparaison du score individuel de précarité des centres d'examens de santé, EPICES, à la définition socio- administrative de la précarité.

In French Health Examination Centres, populations in deprived situation were usually defined by administrative criteria The aim of the study was to investigate whether EPICES, a new individual index of deprivation, was more strongly related to health status than an administrative classification. The EPICES score was calculated on the basis of 11 weighted questions related to material and social deprivation. Participants were 197, 389 men and women, aged over 18, encountered in 2002 in French Health Examination Centres. Relationships between health status, health-related behaviours, access to health care, EPICES and the administrative classification of deprivation were analyzed by logistic regression. The associations between EPICES and the study variables were stronger than those observed for the administrative definition. The comparison also showed socially disadvantaged people with poor health identified by the EPICES score who were not by the administrative classification. These results showed that the EPICES score can be a useful tool to improve the identification of deprived people having health problems associated to deprivation.

Thermal Inactivation of Feline Calicivirus in Pet Food Processing.

Extrusion is the most common manufacturing process used to produce heat-treated dry dog and cat food (pet food) for domestic use and international trade. Due to reoccurring outbreaks of notifiable terrestrial animal diseases and their impact on international trade, experiments were undertaken to demonstrate the effectiveness of heat-treated extruded pet food on virus inactivation. The impact of extrusion processing in a pet food matrix on virus inactivation has not been previously reported and very few inactivation studies have examined the thermal inactivation of viruses in complex food matrices. The feline calicivirus vaccine strain FCV F-9 was used as a surrogate model RNA virus pathogen. Small-scale heat inactivation experiments using animal-derived pet food raw materials showed that a > 4 log10 reduction (log10 R) in infectivity occurred at 70 °C prior to reaching the minimum extrusion manufacturing operating temperature of 100 °C. As anticipated, small-scale pressure studies at extrusion pressure (1.6 MPa) showed no apparent effect on FCV F-9 inactivation. Additionally, FCV F-9 was shown not to survive the acidic conditions used to produce pet food palatants of animal origin that are typically used as a coating after the extrusion process.

Occupational cancer in France: epidemiology, toxicology, prevention, and compensation.

This article is a description of the current situation in France with regard to occupational cancer: research, prevention, and occupation. Toxicologic experiments are carried out using (italic)in vitro(/italic) and (italic)in vivo(/italic) tests, particularly using transgenic mice. Several epidemiologic studies have been conducted over the last decades: population-based case-control studies; mortality studies and cancer incidence studies carried out in historical cohorts of workers employed in the industry; and case-control studies nested in occupational cohorts. French ethical aspects of toxicologic and epidemiologic studies are described. The results thus obtained are used to establish regulations for the prevention and the compensation of cancers attributable to occupational exposure. This French regulation for prevention of occupational cancer involves several partners: (italic)a(/italic)) the states authorities, including labor inspectors, responsible for preparing and implementing the labor legislation and for supervising its application, particularly in the fields of occupational health and safety and working conditions; (italic)b(/italic)) the Social Security Organisation for the analysis of present or potential occupational risks based on tests, visits in plants, complaints or requests from various sources, and statistics. These activities are performed within the framework of the general French policy for the prevention of occupational cancer. This organization includes the National Institute for Research and Safety, particularly involved in research in the various fields of occupational risks--animal toxicology, biologic monitoring, exposure measurements epidemiology, psychology, ergonomy, electronic systems and machineries, exposure to chemicals, noise, heat, vibration, and lighting; and (italic)c(/italic)) companies where the regulation defines the role of the plant manager, the occupational physician, and the Health, Safety and Working Conditions Committee (comprising the manager, employees' representatives, the occupational physician, and the safety department) in dealing with any problem regarding safety, occupational hygiene, and working conditions. These organizations along with medical practitioners are involved with the compensation of occupational cancers. The regulation for compensation includes the tables of occupational cancer, the possibility of recognition of a cancer case when the requirements of the tables are not met, and the postprofessional follow-up of workers exposed to a carcinogenic agent.

Mortality of aluminium reduction plant workers in France.

The mortality between 1950 and 1976 of 6455 French aluminium plant workers was analysed in order to assess occupational risks (especially lung cancer) associated with electrolysis, particularly with the Söderberg process. Mortality from all causes (SMR = 0.85), was lower in this cohort than in the French male population ('healthy worker effect'), and cancer mortality (SMR = 1.09) was only slightly higher. There was an excess of mortality from accidents (mainly non-occupational) in electrolysis workers (SMR = 1.38) and from cirrhosis of the liver in maintenance workers (SMR = 1.63). Among electrolysis workers, only those who had worked less than 10 years had a relative excess mortality from lung cancer (SMR = 1.94), but this did not seem to be associated with a particular electrolysis process. However a substantial underlying risk of lung cancer in Söderberg workers could not be excluded, although such a risk appeared unlikely for prebake workers.

The defective glucose sensitivity of the B cell in non insulin dependent diabetes. Improvement after twenty hours of normoglycaemia.

In non insulin dependent diabetics (N.I.D.D.) of normal body weight, the acute insulin response to glucose is defective while that to pharmacologic agents such as tolbutamide is less impaired. This specific B-cell insensitivity to glucose results from unknown and perhaps multiple mechanisms. Hyperglycemia may be itself aggravate this phenomenon. To test this hypothesis acute insulin release (delta I: sum of increment at 2, 5, 10 min) after intravenous and tolbutamide injection was studied in 5 N.I.D.D. with fasting blood glucose averaging 12.1 mM/I (range 10.7-13.7) before and after 20 hours of glycemic normalization by an artificial pancreas. Intravenous injection of .3 g/k glucose did not elicit an acute insulin or C-peptide response, but following Tolbutamide (20 mg/kg) delta I was 44 +/- 21 microU/ml and delta C-peptide 0.84 +/- 0.37 nM/I. After 20 hr of normoglycemia a response to glucose was apparent (delta I 60 +/- 24 and delta CP 0.86 +/- 26) that to Tolbutamide was unchanged (delta I 58 +/- 26 and delta CP 0.97 +/- 0.27). These results suggest that 20 hr of normoglycemia improve significantly the "glucoreceptor" function of the B-cell in N.I.D.D.

A meta-analysis of epidemiologic studies of lung cancer in welders.

OBJECTIVE: A meta-analysis of epidemiologic studies was carried out on lung cancer risk among shipyard, mild steel, and stainless steel welders, and the role of asbestos exposure and smoking was considered. METHODS: The meta-analysis consisted of calculating combined relative risks (RR) and their variances through a logarithm transformation of published RR values and a weighing using the inverted variance of each RR. RESULTS: The literature provided 18 case-referent and 31 cohort studies. The combined RR values were 1.38 [observed 1028, 95% confidence interval (95% CI) 1.29-1.48] for "all or unspecified welding categories", 1.30 (observed 305, 95% CI 1.14-1.48) for shipyard welders, and 1.35 (observed 173, 95% CI 1.15-1.58) for nonshipyard welders. Similar combined RR values (RR) were observed for mild steel welders (combined RR 1.50, observed 137, 95% CI 1.18-1.91) and stainless steel welders (combined RR 1.50 observed 114, 95% CI 1.10-2.05). No significant heterogeneity was discerned between studies of any welding or study design category. A marked healthy worker effect may also lead to an underestimation of the standardized mortality ratio for lung cancer among stainless steel welders. Furthermore, welders of any category are likely to be exposed to asbestos. Welders also seem to smoke more than the general male population, and therefore the hypothesis of tobacco overconsumption among welders could not be discarded. CONCLUSIONS: A 30-40% increase in the RR of lung cancer among welders cannot be explained by hexavalent chromium and nickel exposure among stainless steel welders. The combination of the carcinogenic effects of asbestos exposure and smoking may account for part of the lung cancer excess observed.

Oral cavity and laryngeal cancers among man-made mineral fiber production workers.

From 1975 to 1984, the incidence of cancer was determined among workers employed in a French man-made mineral fiber (MMMF) production plant. The cohort, including 1 374 fully active or retired men, represented 12 793 person-years. Forty-one patients had cancer, 19 of which were in the upper respiratory and alimentary tract and five of which were lung cancers. The number of lung cancers observed did not significantly differ from that expected [standardized incidence ration (SIR) 0.7]. However the incidence of upper respiratory and alimentary tract cancers was significantly higher (SIR 2.2), especially for those in the larynx (SIR = 2.3), pharynx (SIR 1.4), and buccal cavity (SIR 3.0). The relative risk of cancers in the upper respiratory and alimentary tracts seemed to increase with the length of exposure to glass fibers and exceeded the value of 3.0 for more than 10 years of exposure. This result does not seem to be attributable to an excess of tobacco and/or alcohol consumption. No previous survey of the MMMF industry has shown such a risk, except in Italy. Thus this finding has to be confirmed.

Risk of lung, larynx, pharynx and buccal cavity cancers among carbon electrode manufacturing workers.

Among workers employed in factories producing carbon graphite products the risk of cancer due to exposure to polycyclic aromatic hydrocarbons was estimated. In one cohort (plant A), a cancer incidence study was carried out; the number of cases were not significantly increased for lung cancers [7 cases, standardized incidence ratio (SIR) 79] or for cancers of the upper respiratory and alimentary tract (10 cases, SIR 103). In another cohort (plant B), a mortality study was carried out; neither the mortality from lung cancer [13 deaths, standardized mortality ratio (SMR) 118] nor that from upper respiratory and alimentary tract cancers (10 deaths, SMR 125) was significantly higher than expected. Within each cohort, a case-referent study was carried out. In plant A the odds ratios were high but nonsignificant for lung cancers (odds ratio 3.42) and upper respiratory and alimentary tract cancers (odds ratio 2.19) and they showed a nonsignificant relationship with duration of exposure. In plant B, the odds ratios were low for every cancer site.

[Comparative epidemiology, in Europe, of cancers related to tobacco (lung, larynx, pharynx, oral cavity)]. / Epidémiologie comparée, en Europe, des cancers liés au tabac (poumon, larynx, pharynx, cavité buccale).

In 25 European countries, annual age-adjusted mortality and incidence rates, in males, for tobacco-related cancers (lung, larynx, oral cavity), were used in order to study geographic variations in the occurrence of those diseases, from 1952 to 1977. Neither in 1952 (mortality rates), nor in 1977 (mortality and incidence rates), was there any significant geographical correlation between lung cancer on the one hand, and laryngeal or oral cavity cancers on the other hand. Over the 25 years, all countries experienced a sharp increase in lung cancer mortality, especially in association with trends in tobacco consumption. On the contrary, mortality from cancers of the larynx or of the oral cavity showed divergent trends according to countries, since ten of them had steady or decreasing rates. The validity of the method, and the role of alcohol consumption are discussed. Moreover, it is suggested that, in southern european countries, some occupational exposures may be causative factors for laryngeal and oral cavity cancers.

[Survey of the effects of smoking in an occupational cohort study. Value and limits of a new method]. / Prise en compte des effets du tabagisme dans les études de cohortes professionnelles. Intérêt et limites d'une nouvelle méthode.

BACKGROUND: This paper proposes a method to take smoking into account in occupational cohort studies when a lung cancer excess is observed and no information on smoking is available. METHODS: The model consists in assessing the proportion of smokers in the study cohort on the basis of (i) the relative risk observed for lung cancer (P1), and (ii) relative risks due to other smoking related diseases (P2). If P1 is higher than P2, it is concluded that the observed lung cancer excess is unlikely to be due to smoking. RESULTS: The model was applied to nine epidemiological studies, of which five showed a lung cancer excess (ranged between 1.12 et 1.32). The P2 proportions of four of these five studies ranged between 0.29 and 0.46, and were lower than P1 that ranged between 0.57 and 0.69. These differences reached statistical significance. These results suggest that occupational lung cancer risks might have existed. The model was validated by applying to cohorts without lung cancer excess and to cohorts of smokers and non smokers. The robustness was assessed using different values of the basic parameters: proportion of smokers in the general population and risks due to smoking for smoking related diseases. CONCLUSION: This model is an assessment of the relative importance of smoking and occupational factors in occupational cohort studies, in the absence of information on smoking.