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Objective To assess the psychometric properties of the French version of the Hospital Survey on Patient Safety Culture questionnaire (HSOPSC) and study the hierarchical structure of the measured dimensions. Design Cross-sectional survey of the safety culture. Setting 18 acute care units of seven hospitals in South-western France. Participants Full- and part-time healthcare providers who worked in the units. Interventions None. Main outcome measures Item responses measured with 5-point agreement or frequency scales. Data analyses A principal component analysis was used to identify the emerging components. Two structural equation modeling methods [LInear Structural RELations (LISREL) and Partial Least Square (PLS)] were used to verify the model and to study the relative importance of the dimensions. Internal consistency of the retained dimensions was studied. A test–retest was performed to assess reproducibility of the items. Results Overall response rate was 77% (n = 401). A structure in 40 items grouped in 10 dimensions was proposed. The LISREL approach showed acceptable data fit of the proposed structure. The PLS approach indicated that three dimensions had the most impact on the safety culture: ‘Supervisor/manager expectations & actions promoting safety’ ‘Organizational learning—continuous improvement’ and ‘Overall perceptions of safety’. Internal consistency was above 0.70 for six dimensions. Reproducibility was considered good for four items. Conclusions The French HSOPSC questionnaire showed acceptable psychometric properties. Classification of the dimensions should guide future development of safety culture improving action plans. [ABSTRACT FROM AUTHOR]

Sodium-cooled fast reactors (SFRs) remain the favorite candidate in France for a Generation IV (Gen IV) reactor fleet to be deployed within this century. Compared with earlier generations (Phénix, Superphénix, and European fast reactor), Gen IV SFRs require attractive economics together with enhanced safety and nonproliferation criteria. An innovative approach named Mathematical Estimation of Transients for Reactor design Orientation (METRO) has been developed with the objective of taking into account both SFR core economic performance and SFR transient incident behavior at an early stage of the core design process. Loss-of-flow, loss-of-heat-sink, and overpower transients are evaluated. Simplified modeling of transients has been developed and benchmarked against reference calculations with satisfactory results. The METRO approach to assessing the efficiency of design orientations is described in the following and applied to a carbide-fueled reactor core. [ABSTRACT FROM AUTHOR]

The myelin basic protein (MBP) gene is a candidate locus for susceptibility to multiple sclerosis. Several groups have tested a complex (TGGA)[sub n] repeat in the 5' region of this gene for association/linkage with multiple sclerosis, with divergent results. This region of tandem repetitive sequence has been subjected to complex rearrangements, and there is a possibility that alleles of the same size have different internal structures, which reduces the interest of this marker for linkage disequilibrium studies and may at least partly explain the conflicting results obtained so far. To overcome this problem, we isolated a new polymorphic (CA)[sub n] repeat within the Golli-MBP locus. The limited number of alleles identified makes this other marker suitable for transmission disequilibrium studies. We tested this marker for linkage with multiple sclerosis, using the transmission-disequilibrium test (TDT) on a sample of 196 nuclear families in which the genotypes of both parents could be unambiguously defined. We found no evidence of transmission disequilibrium between multiple sclerosis and any of the three alleles of this marker, even when the patients were subdivided according to their HLADRB1[sup *]1501 status. The present data thus provide no evidence for a contribution of the MBP gene to multiple sclerosis susceptibility in French patients. [ABSTRACT FROM AUTHOR]

Higher efficiency in large-scale and long-term biodiversity monitoring can be obtained through the use of Essential Biodiversity Variables, among which species population sizes provide key data for conservation programs. Relevant estimations and assessment of actual population sizes are critical for species conservation, especially in the current context of global biodiversity erosion. However, knowledge on population size varies greatly, depending on species conservation status and ranges. While the most threatened or restricted-range species generally benefit from exhaustive counts and surveys, monitoring common and widespread species population size tends to be neglected or is simply more challenging to achieve. In such a context, citizen science (CS) is a powerful tool for the long-term monitoring of common species through the engagement of various volunteers, permitting data acquisition on the long term and over large spatial scales. Despite this substantially increased sampling effort, detectability issues imply that even common species may remain unnoticed at suitable sites. The use of structured CS schemes, including repeated visits, enables to model the detection process, permitting reliable inferences of population size estimates. Here, we relied on a large French structured CS scheme (EPOC-ODF) comprising 27,156 complete checklists over 3,873 sites collected during the 2021-2023 breeding seasons to estimate the population size of 63 common bird species using hierarchical distance sampling (HDS). These population size estimates were compared to the previous expert-based French breeding bird atlas estimations, which did not account for detectability issues. We found that population size estimates from the former French breeding bird atlas were lower than those estimated using HDS for 65% of species. Such a prevalence of lower estimations is likely due to more conservative estimates inferred from semi-quantitative expert-based assessments used for the previous atlas. We also found that species with long-range songs such as the Common Cuckoo ( Cuculus canorus ), Eurasian Hoopoe ( Upupa epops ) or the Eurasian Blackbird ( Turdus merula ) had, in contrast, higher estimated population sizes in the previous atlas than in our HDS models. Our study highlights the need to rely on sound statistical methodology to ensure reliable ecological inferences with adequate uncertainty estimation and advocates for a higher reliance on structured CS in support of long-term biodiversity monitoring., Competing Interests: The authors declare that they have no competing interests., (© 2024 Nabias et al.)

Background: Relying on capacity increases and patient transfers to deal with the huge and continuous inflow of COVID-19 critically ill patients is a strategy limited by finite human and logistical resources., Rationale: Prioritising both critical care initiation and continuation is paramount to save the greatest number of lives. It enables to allocate scarce resources in priority to those with the highest probability of benefiting from them. It is fully ethical provided it relies on objective and widely shared criteria, thus preventing arbitrary decisions and guaranteeing equity. Prioritisation seeks to fairly allocate treatments, maximise saved lives, gain indirect life benefits from prioritising exposed healthcare and similar workers, give priority to those most penalised as a last resort, and apply similar prioritisation schemes to all patients., Prioritisation Strategy: Prioritisation schemes and their criteria are adjusted to the level of resource scarcity: strain (level A) or saturation (level B). Prioritisation yields a four level priority for initiation or continuation of critical care: P1-high priority, P2-intermediate priority, P3-not needed, P4-not appropriate. Prioritisation schemes take into account the patient's wishes, clinical frailty, pre-existing chronic condition, along with severity and evolution of acute condition. Initial priority level must be reassessed, at least after 48h once missing decision elements are available, at the typical turning point in the disease's natural history (ICU days 7 to 10 for COVID-19), and each time resource scarcity levels change. For treatments to be withheld or withdrawn, a collegial decision-making process and information of patient and/or next of kin are paramount., Perspective: Prioritisation strategy is bound to evolve with new knowledge and with changes within the epidemiological situation., (Copyright © 2020 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Depending on their theatre of operation, French soldiers may potentially be exposed to scorpion stings and snakebites. Following the recommendations of a French military health service (FMHS) technical committee for envenomation, the FMHS provides antivenoms appropriate to each deployment. This work aimed to evaluate this risk of envenomation and to assess the antivenoms used by the FMHS in operational theatres since the creation of this committee in 2015., Methods: Cases were identified based on a review of temporary authorization of use application forms for the use of antivenom. Data were collected retrospectively from these forms, and prescribing physicians were contacted for any missing data., Results: Between 2015 and 2017, 28 requests for temporary authorization of use were identified: 19 for Scorpifav (Sanofi-Pasteur, Lyon, France) and 9 for Fav-Afrique (Sanofi-Pasteur). The FMHS treated 15 soldiers and 4 civilians for scorpion envenomation with Scorpifav: 15 in Mali, 3 in Chad, and 1 in Niger. Systemic signs were observed in 7 patients. Two soldiers and 7 civilians were treated with Fav-Afrique for ophidian envenomation: 5 in Djibouti, 3 in Mali, and 1 in the Republic of Côte d'Ivoire. These 28 patients were treated without sequelae. Other than moderate erythema that resolved with an antihistamine, no adverse effects were reported. Medical evacuation to France was unnecessary., Conclusions: This study shows that the risk of envenomation for soldiers on deployment is low but real. Antivenoms used by the FMHS were efficient and well tolerated, preserving the operational capacity of deployed troops., (Copyright © 2020 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Despite growing concern over consequences of global changes, we still know little about potential interactive effects of anthropogenic perturbations and diversity loss on the stability of local communities, especially for taxa other than plants. Here we analyse the relationships among landscape composition, biodiversity and community stability looking at time series of three types of communities, i.e., bats, birds and butterflies, monitored over the years by citizen science programs in France. We show that urban and intensive agricultural landscapes as well as diversity loss destabilize these communities but in different ways: while diversity loss translates into greater population synchrony, urban and intensive agricultural landscapes mainly decrease mean population stability. In addition to highlight the stabilizing effects of diversity on ecologically important but overlooked taxa, our results further reveal new pathways linking anthropogenic activities to diversity and stability.

Introduction: The aim of this study was to compare the efficacy and maternal-neonatal morbidity between balloon catheter and oxytocin for induction of labor in women with a previous cesarean section and an unfavorable cervix., Material and Methods: This open-label randomized controlled trial took place in seven French hospitals. Inclusion criteria were medical indication for labor induction in pregnant women, ≥37 weeks, with lower segment cesarean section, Bishop score ≤4, no pre-labor rupture of membranes, singleton fetus in cephalic presentation. Women were allocated randomly to induction with a 50-mL balloon catheter for 12 hours or a low-dose oxytocin infusion. Primary outcome was the rate of vaginal birth. Secondary outcomes were maternal and neonatal complications., Results: The study enrolled 204 women from 26 December 2010 to 31 December 2013: 101 were allocated to receive balloon catheter and 103 to oxytocin. Vaginal birth rate was 50% (n = 51) in the balloon catheter group vs 37% (n = 38) in the oxytocin group (P = 0.050). Maternal and neonatal morbidity did not differ between balloon catheter and oxytocin groups: two uterine dehiscences vs one, one vs four maternal infections, five vs two hemorrhages and 11 vs five neonatal transfers, respectively. Heterogeneity of treatment effect for vaginal delivery was observed across initial Bishop scores. Balloon catheter was more effective for low values of bishop score., Conclusions: Balloon catheter tended to be associated with a higher probability of vaginal delivery as compared with low-dose intravenous oxytocin when used for induction of labor in women with a previous cesarean section and low Bishop score at induction., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

The care of multiple sclerosis (MS) in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists. The routine use of European database for multiple sclerosis (EDMUS) in all those centers has paved the way for the constitution of a national registry, designated as Observatoire Français de la Sclérose En Plaques (OFSEP). It promotes a prospective, standardized, high-quality, and multimodal collection of data. On June 2018, there were 68.097 files, with 71.1% females, representing 761,185 person-years. This huge database is open to the scientific community and might contribute exploring unresolved issues and unmet needs in MS.

Objective: To assess the impact of a vignette-based analysis of adverse events (AEs) on the safety climate (SC) of care units., Design: Prospective, open, cluster (a unit) randomised controlled trial., Setting: Eighteen acute care units of seven hospitals in France., Participants: Healthcare providers who worked in the units., Intervention: Vignette-based analyses of AEs were conducted with unit's providers once per month for six consecutive months. The AEs were real cases that occurred in other hospitals. The hospital risk manager conducted each analysis as follows: analysis of the immediate and root causes of the AE; assessment of the care unit's vulnerabilities and existing barriers in the occurrence of an identical AE and search for solutions., Main Outcome Measure: SC was measured using the French version of the Hospital Survey on Patient Safety Culture questionnaire. The primary outcome was the difference in the 'Organisational learning and continuous improvement' dimension score, from before to after the analyses., Results: Median participation rate in the analyses was 20% (range: 7-45%). Before intervention, the response rate to the SC survey was 80% (n = 210) in the intervention group and 73% (n = 191) in the control group. After intervention, it was 59% (n = 141) and 63% (n = 148), respectively. The dimension score evolved differently for the groups from before to after intervention (intervention: +10.2 points ±8.8; control: -3.0 points ±8.5, P = 0.04). Side effects were not measured., Conclusions: Vignette-based analysis was associated with the improvement of the perception of participants regarding their institution's capacity for organisational learning and continuous improvement., (© The Author(s) 2018. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The purpose of our study was to assess the influence of pregnancy on the course of neuromyelitis optica (NMO) and the impact of epidural analgesia and breastfeeding on its activity in the postpartum period., Methods: We performed a retrospective study of patients with NMO diagnosed according to Wingerchuk criteria. We noted the number of relapses during the year before pregnancy (BP), during pregnancy (first trimester, second trimester, third trimester), and the year after (Y + 1: first trimester, second trimester [PP2], and third and fourth trimesters postpartum). Epidural analgesia and breastfeeding were recorded. Disability was evaluated with the Kurtzke Expanded Disability Status Scale (EDSS). The annualized relapse rate (ARR) was calculated., Results: We identified 124 patients (85 female) in the French NOMADMUS cohort on November 1, 2010. A total of 20 women (including 25 pregnancies) were informative with complete files. Comparisons between the ARR of each period and BP (1.0 ± 0.09) only showed an increased tendency for PP2 (0.8 ± 0.06, p = 0.07). Epidural analgesia and breastfeeding had no influence on the course of NMO. The EDSS score increased from 1.5 ± 1.7 BP to 2.6 ± 1.9 Y + 1 (p = 0.027)., Conclusion: This study shows that pregnancy influences the activity of NMO, a finding that justifies close medical monitoring. We found no evidence to suggest that either epidural analgesia or breastfeeding has an aggravating effect on NMO.

The tyrosine kinase 2 variant rs34536443 has been established as a genetic risk factor for multiple sclerosis in a variety of populations. However, the functional effect of this variant on disease pathogenesis remains unclear. This study replicated the genetic association of tyrosine kinase 2 with multiple sclerosis in a cohort of 1366 French patients and 1802 controls. Furthermore, we assessed the functional consequences of this polymorphism on human T lymphocytes by comparing the reactivity and cytokine profile of T lymphocytes isolated from individuals expressing the protective TYK2(GC) genotype with the disease-associated TYK2(GG) genotype. Our results demonstrate that the protective C allele infers decreased tyrosine kinase 2 activity, and this reduction of activity is associated with a shift in the cytokine profile favouring the secretion of Th2 cytokines. These findings suggest that the rs34536443 variant effect on multiple sclerosis susceptibility might be mediated by deviating T lymphocyte differentiation toward a Th2 phenotype. This impact of tyrosine kinase 2 on effector differentiation is likely to be of wider importance because other autoimmune diseases also have been associated with polymorphisms within tyrosine kinase 2. The modulation of tyrosine kinase 2 activity might therefore represent a new therapeutic approach for the treatment of autoimmune diseases.

Background: There have been few epidemiologic studies on neuromyelitis optica (NMO) and none used the recent 2006 diagnostic criteria. Here we describe the clinical, laboratory, MRI, and disability course of NMO in a French cohort of 125 patients., Methods: We performed an observational, retrospective, multicenter study. Data were collected from September 2007 through August 2008, corresponding to the endpoint of the study. We identified 125 patients fulfilling the 2006 NMO criteria. Selection was made using hospital files and a specific clinical questionnaire for NMO., Results: Mean age at onset was 34.5 years (range 4-66) with a mean disease duration of 10 +/- 7.8 years at the endpoint. The patients were mainly (87%) Caucasian, with a female:male ratio of 3:1. In 90% of cases, the association of optic neuritis, longitudinal extensive myelitis, and a Paty-negative initial brain MRI was sufficient to fulfill the supportive criteria. Eighty-eight percent of patients were treated with immunosuppressive therapies. Median delay from onset to Expanded Disability Status Scale (EDSS) score 4 was 7 years; score 6, 10 years; and score 7, 21 years. The first episode of myelitis was immediately followed by an EDSS score > or = 4 in 37.3% of cases, and a severe residual visual loss was observed in 22% of patients after the first episode of optic neuritis. Multivariate analysis did not reveal any predictors of a poor evolution other than a high number of MRI brain lesions at diagnosis, which were predictive of a residual visual acuity < or = 1/10., Conclusions: Our demographic data provide new data on disability in patients with neuromyelitis optica, most of whom were receiving treatment.

Both genetic and environmental factors contribute to multiple sclerosis, the most common neurodegenerative disorder with onset in young adults. The objective of the current study is, based on the hypothesis that environmentally predisposed individuals are at risk for multiple sclerosis, to investigate whether they also carry genetic variants within the vitamin D machinery. Using medical files and DNA samples from 583 trios (a patient and both parents) of the French Multiple Sclerosis Genetics Group as well as data from the French Statistics Bureau, we aimed to assess whether: (1) a seasonality of birth was observed in French multiple sclerosis patients; (2) three single nucleotide polymorphisms within the promoter region of the vitamin D receptor were associated with multiple sclerosis susceptibility; and (3) the combination of a high risk month of birth and vitamin D receptor polymorphisms were correlated to multiple sclerosis incidence. We observed a significantly reduced number of individuals born in November who were later diagnosed as multiple sclerosis patients. However, we found no association between the three studied vitamin D receptor polymorphisms and multiple sclerosis. In conclusion, our data suggest that high levels of vitamin D during the third trimester of pregnancy could be a protective factor for multiple sclerosis.

Multiple sclerosis (MS) is the most common chronic inflammatory neurologic disorder diagnosed in young adults and, due to its chronic course, is responsible for a substantial economic burden. MS is considered to be a multifactorial disease in which both genetic and environmental factors intervene. The well-established human leukocyte antigen (HLA) association does not completely explain the genetic impact on disease susceptibility. However, identification and validation of non-HLA-genes conferring susceptibility to MS has proven to be difficult probably because of the small individual contribution of each of these genes. Recently, associations with two single nucleotide polymorphisms (SNPs) in the IL2RA gene (rs12722489, rs2104286) and one SNP in the IL7RA gene (rs6897932) have been reported by several groups. These three SNPs were genotyped in a French and a German population of MS patients using the hME assay by the matrix-assisted laser desorption/ionization time of flight technology (Sequenom, San Diego, CA, USA). We show that these SNPs do contribute to the risk of MS in these two unrelated European MS patient populations with odds ratios varying from 1.1 to 1.5. The discovery and validation of new genetic risk factors in independent populations may help toward the understanding of MS pathogenesis by providing valuable information on biological pathways to be investigated.

A previous study conducted in 1995 showed that psychoactive drug use by workers was higher in safety/security workstations than in the rest of the labour force. In order to verify this finding, we conducted a new study in 2003-2004 in the Nord-Pas-de-Calais region, restricted to truck drivers. The aim of this study was to allow harmonizing the professional practice of the occupational physicians, proposing drug prevention and drug testing policies, validating the analytical methods and the guidelines in case of positive testing results. One thousand truck drivers were studied. Urines were tested for amphetamines, cannabinoids, cocaine, opiates, benzodiazepines, buprenorphine and methadone by immunoassay. Urine ethanol determinations were performed by an ADH method. Positive urines for drugs of abuse, methadone or buprenorphine were then tested by gas chromatography or liquid chromatography coupled to mass spectrometry. Out of the 1000 drivers, cannabinoids were detected in 85 cases, opiates in 41 cases, amphetamines in 3 cases and cocaine in only one case. Buprenorphine was detected in 18 cases, methadone in 5 cases and benzodiazepines in 4 cases. Urine ethanol was positive in 50 cases. We found only one case with 6-monoacetylmorphine. Other positive opiates were metabolites of antitussives. The relatively low number of benzodiazepine positive urines could be explained by the lack of sensitivity of the test we used. All these results confirm those of the previous study for cannabinoids and ethanol in safety/security workstations. Positive results for methadone and buprenorphine are eight times higher than in the general population. In conclusion, the authors think that it will be of a great interest to test urine of truck drivers for other classes of psychoactive drugs, using a liquid chromatography-mass spectrometry method.

In multiple sclerosis (MS) MBP is heavily citrullinated by peptidylarginine deiminase (PAD). This post-translational modification may be crucial for its pathogenesis. PADI4 is the isoform expressed in inflammatory infiltrates. The aim of this study was to analyse the role of PADI4 gene in conferring susceptibility to MS, by means of a family-based association study, testing three SNPs by RFLP. No association was found either with single SNPs or haplotypes. Similarly no significant association was detected partitioning the patients according to DRB1*15 positivity or disease severity. These results do not support a major role of the PADI4 gene, but further studies may contribute to clarify the genetic factors that regulate deimination.

Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disorder. Despite substantial evidence for polygenic inheritance of the disease, the major histocompatibility complex is the only region that clearly and consistently demonstrates linkage and association in MS studies. The goal of this study was to identify additional chromosomal regions that harbor susceptibility genes for MS. With a panel of 390 microsatellite markers genotyped in 245 U.S. and French multiplex families (456 affected relative pairs), this is the largest genomic screen for MS conducted to date. Four regions met both of our primary criteria for further interest (heterogeneity LOD [HLOD] and Z scores >2.0): 1q (HLOD=2.17; Z=3.38), 6p (HLOD=4.21; Z=2.26), 9q (HLOD; Z=2.71), and 16p (HLOD=2.64; Z=2.05). Two additional regions met only the Z score criterion: 3q (Z=2.39) and 5q (Z=2.17). Further examination of the data by country (United States vs. France) identified one additional region demonstrating suggestive linkage in the U.S. subset (18p [HLOD=2.39]) and two additional regions generating suggestive linkage in the French subset (1p [HLOD=2.08] and 22q [HLOD=2.06]). Examination of the data by human leukocyte antigen (HLA)-DR2 stratification identified four additional regions demonstrating suggestive linkage: 2q (HLOD=3.09 in the U.S. DR2- families), 6q (HLOD=3.10 in the French DR2- families), 13q (HLOD=2.32 in all DR2+ families and HLOD=2.17 in the U.S. DR2+ families), and 16q (HLOD=2.32 in all DR2+ families and HLOD=2.13 in the U.S. DR2+ families). These data suggest several regions that warrant further investigation in the search for MS susceptibility genes.

Introduction: A quality insurance program has been set up in order to improve the relief of pain in patients with perineal injury after childbirth., Patients and Methods: The program has been developed according to the French standards of accreditation. After elaboration of a referential, a first study (103 patients) allowed to evaluate the ongoing practices and to appreciate the pain intensities. After analysis of the results, an action strategy has been elaborated, with a brand new therapeutic standard and a pain-monitoring program for nurses. Six months later, a second study (105 patients) measured the efficiency of the accomplished actions. The statistic analysis used chi2 and Kruskal-Wallis tests and a multivariate analyse (p <0.05)., Results: Several indicators led to conclude to the success of this program: analgesics prescribed systematically and earlier, best observance, larger utilisation of the NSAI, decrease of the analgesics requests, improvement of the satisfaction referred to the relief of pain. The multivariate analyse showed a risk twice as little as in the second study to have a 36th hour VAS score superior to four (p =0.03)., Conclusion: The apply of this quality insurance program allowed to improve the analgesia after obstetric perineal injuries. A few adaptations are needed, and also more formations of the medical and paramedical staff. The durability of the accomplished actions shall be evaluated in the future.

Multiple sclerosis (MS) is a demyelinating autoimmune disease with a strong yet complex genetic component. To date only the HLA-DR locus, and specifically the HLA-DR15 allele, has been identified and confirmed as influencing the risk of developing MS. Genomic screens on several datasets have been performed and have identified several chromosomal regions with interesting results, but none have yet been confirmed. We tested seven of the most-promising regions (on chromosomes 1p, 2p, 3p, 3q, 5q, 19q, and Xp) identified from several genomic screens in a dataset of 98 multiplex MS families from the United States and 90 multiplex MS families from France. The results did not confirm linkage to 2p, 3q, 5q, or Xp in the overall dataset, or in subsets defined by geographic origin or HLA-DR15 status. Regions on 1p34, 3p14, and 19q13 produced lod scores >0.90 in at least one subset of the data, suggesting that these regions should be examined in more detail.

Intercellular adhesion molecule-1 (ICAM-1) and its receptors are adhesion molecules that play a key role in the transmigration of inflammatory cells through the blood-brain barrier, one of the earliest events in multiple sclerosis (MS), which leads to demyelination in the central nervous system. To investigate the role of genes encoding ICAM-1 and its receptors, we used a strategy of genetic linkage and association in 439 case-parent MS families of French origin, well characterized according to HLA status and severity. We demonstrate that the genes encoding ICAM-1 receptors do not influence MS susceptibility or severity. ICAM-1 had a modest, but significant effect on MS genetic susceptibility, independent of HLA and disease severity. We observed a rare, and an as yet unreported, ICAM-1 gene haplotype defined by amino acids K469 and R241 that was never transmitted to patients suggesting a protective effect against MS in our population.

We report the results of a genome-wide screen for linkage disequilibrium (LD) in multiple sclerosis (MS) performed on 200 cases, 200 controls and 200 case-parent trios from France employing pooled DNA methodology. A total of 3510 microsatellite markers supplied through the GAMES collaborative were analysed and ranked according to their evidence for association. The most promising 117 markers were then followed up in a two-step validation process. In the first step, additional PCR of the DNA pools was performed in order to refine the ranking order. In the second step, markers were genotyped in individual cases and parents from the trio families. Seven markers showing nominally significant allele frequency differences between affected and unaffected emerged-D6S265, D12S1064, TNFa, D7S1824, D14S1426, D14S605 and D21S2051. These potential associations will require confirmation in further studies.

Aetiological factors of the myelodysplastic syndromes (MDS) are largely unknown, with the exception of alkylating agents, ionizing radiation and benzene. Some other risk factors have been suggested by the few epidemiological studies reported (solvents, ammonia, exhaust gases, metals, pesticides, alcohol). We performed a case-control study to assess the relationship between occupational or environmental factors and MDS. Two hundred and four patients with newly diagnosed MDS, and 204 sex- and age-matched controls were included. Medical history, demographic data, lifetime exposure and hobbies were obtained. Qualitative and quantitative exposure to chemical and physical hazards were evaluated with the patients and reviewed by a group of experts in occupational exposure. The median age was 70 years and 62% of the patients were men. In univariate analyses, we found relationships between MDS and smoking habits, gardening, occupations such as health professionals, technical and sale representatives, machine operators, agricultural workers, textile workers, qualitative occupational exposures (exposed/non-exposed) to oil, solvents, ammonia, pesticides, fertilizers, cereal dusts, contact with poultry or livestock and infective risk, and lifetime cumulative exposure to solvents, oil, textile dust and infective risk. The main risk factors of MDS determined by multivariate analyses (conditional logistic regression) were, being an agricultural worker [odds ratio (OR) = 3.66; 95% confidence interval (CI) 1.9-7.0], textile operator (OR = 3.66; 95% CI 1.9-7.9), health professional (OR = 10.0; 95% CI 2.1-48.7), commercial and technical sale representative (OR = 4.45; 95% CI 1.4-14.6), machine operator (OR = 2.69; 95% CI 1.2-6.0), living next to an industrial plant (OR = 2.45; 95% CI 1.5-4.1), smoking (OR = 1.74; 95% CI 1.1-2.7) and lifetime cumulative exposure to oil (OR = 1.1; 95% CI 1.0-1.2). Further studies should be performed to assess specific exposures more precisely and it would be of interest to develop a map of haematological malignancies according to industrial background.

This paper reports the clinico-pathological data in a French family with orthochromatic leukodystrophy. The parents were first cousins and had seven children. Among those, two sisters and one brother presented with neurological signs, with onset around the 5(th) decade, including a dementing syndrome of frontal type, a tetrapyramidal syndrome, seizures, and, in one sibling, a cerebellar syndrome. CT scan or MRI showed diffuse involvement of the white matter. The neurological signs worsened progressively leading to death within 11 and 22 months. Neuropathological examination was performed in two cases. It revealed characteristic orthochromatic leukodystrophy. In one case, the presence of pigmented macrophages and astrocytes was suggestive of Van Bogaert and Nyssen disease. However there were some atypical features including the absence of pigmented cells in the second case whose clinical course was shorter, and the cavitary appearance of the white matter changes with a relative increase in the number of oligodendrocytes raising the issue of a possible link between this condition and cavitary orthochromatic leukodystrophies.

Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous disorders causing progressive spasticity and weakness of the lower limbs. We report a large family of French descent with autosomal dominant pure HSP. We excluded genetic linkage to the known loci causing HSP and performed a genomewide search. We found evidence for linkage of the disorder to polymorphic markers on chromosome 2q24-q34: a maximum LOD score of 3. 03 was obtained for marker D2S2318. By comparison with families having linkage to the major locus of pure autosomal dominant HSP (SPG4 on chromosome 2p), there were significantly more patients without Babinski signs, with increased reflexes in the upper limbs, and with severe functional handicaps.

Recently, genome-wide searches for multiple sclerosis (MS) susceptibility genes have suggested that the chromosome 17q22-q24 region might contain susceptibility genes in two sets of families of different ethnic backgrounds (Finnish and British). Therefore, we decided to test this region in two sets of families of different ethnic backgrounds (American and French), but collected according to the same diagnostic criteria. All lod-score values were non-significant. Moreover, we could exclude that the 17q22-24 region might contain a gene increasing the sibling recurrence risk of MS over 1.4, rendering the existence of such a gene very unlikely, at least in the group of tested families.

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.

Hereditary spastic paraplegias are neurological hereditary conditions of unknown aetiology. In pure spastic paraplegia, most of the pedigrees display an autosomal dominant mode of inheritance. A gene for pure autosomal dominant spastic paraplegia (ADSP), termed FSP1, was mapped to chromosome 14q in a large pedigree with early-onset disease. This locus was tested by linkage analysis in six large French kindreds of ADSP with late-onset disease, using four microsatellites spanning a 9 cM interval including FSP1. FSP1 could be excluded in five of the six families, while no evidence for linkage was found in the remaining family. These results suggest that FSP1 is not involved in late onset ADSP, at least in the six families studied.

Autosomal dominant familial spastic paraplegia (AD-FSP) is a genetically heterogeneous neurodegenerative disorder characterized by a spasticity of the lower limbs. A locus causing AD-FSP (FSP1) has been previously mapped to chromosome 14q. We now report linkage of a second AD-FSP locus (FSP2) to chromosome 2p21-p24 in five of seven French families and one large Dutch pedigree. The analysis of recombination events and multipoint linkage place FSP2 within a 4 cM interval flanked by loci D2S400 and D2S367.