The fraction of lung cancer incidence attributable to fine particulate air pollution in France: Impact of spatial resolution of air pollution models

Outdoor air pollution is a leading environmental cause of death and cancer incidence in humans. We aimed to estimate the fraction of lung cancer incidence attributable to fine particulate matter (PM2.5) exposure in France, and secondarily to illustrate the influence of the input data and the spatial resolution of information on air pollution levels on this estimate. The population attributable fraction (PAF) was estimated using a nationwide spatially refined chemistry-transport model with a 2-km spatial resolution, neighbourhood-scale population density data, and a relative risk from a published meta-analysis. We used the WHO guideline value for PM2.5 exposure (10??g/m3) as reference. Sensitivity analyses consisted in attributing the nation-wide median exposure to all areas and using alternative input data such as reference of PM2.5 exposure level and relative risk. Population-weighted median PM2.5 level in 2005 was 13.8??g/m3; 87% of the population was exposed above the guideline value. The burden of lung cancer attributable to PM2.5 exposure corresponded to 1466 cases, or 3.6% of all cases diagnosed in 2015. Sensitivity analyses showed that the use of a national median of PM2.5 exposure would have led to an underestimation of the PAF by 11% (population-weighted median) and by 72% (median of raw concentration), suggesting that our estimates would have been higher with even more finely spatially-resolved models. When the PM2.5 reference level was replaced by the 5th percentile of country-scale exposure (4.9??g/m3), PAF increased to 7.6%. Other sensitivity analyses resulted in even higher PAFs. Improvements in air pollution are crucial for quantitative health impacts assessment studies. Actions to reduce PM2.5 levels could substantially reduce the burden of lung cancer in France

Robotically-Assisted Coronary Artery Bypass Grafting

Objectives. Robotic surgery enables to perform coronary surgery totally endoscopically. This report describes our experience using the da Vinci system for coronary artery bypass surgery. Methods. Patients requiring single-or-double vessel revascularization were eligible. The procedure was performed without cardiopulmonary bypass on a beating heart. Results. From April 2004 to May 2008, fifty-six patients were enrolled in the study. Twenty-four patients underwent robotic harvesting of the mammary conduit followed by minimal invasive direct coronary artery bypass (MIDCAB), and twenty-three patients had a totally endoscopic coronary artery bypass (TECAB) grafting. Nine patients (16%) were converted to open techniques. The mean total operating time for TECAB was 372 ± 104 minutes and for MIDCAB was 220 ± 69 minutes. Followup was complete for all patients up to one year. There was one hospital death following MIDCAB and two deaths at follow up. Forty-eight patients had an angiogram or CT scan revealing occlusion or anastomotic stenoses (>50%) in 6 patients. Overall permeability was 92%. Conclusions. Robotic surgery can be performed with promising results

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Objectives. Robotic surgery enables to perform coronary surgery totally endoscopically. This report describes our experience using the da Vinci system for coronary artery bypass surgery. Methods. Patients requiring single-or-double vessel revascularization were eligible. The procedure was performed without cardiopulmonary bypass on a beating heart. Results. From April 2004 to May 2008, fifty-six patients were enrolled in the study. Twenty-four patients underwent robotic harvesting of the mammary conduit followed by minimal invasive direct coronary artery bypass (MIDCAB), and twenty-three patients had a totally endoscopic coronary artery bypass (TECAB) grafting. Nine patients (16%) were converted to open techniques. The mean total operating time for TECAB was 372 ± 104 minutes and for MIDCAB was 220 ± 69 minutes. Followup was complete for all patients up to one year. There was one hospital death following MIDCAB and two deaths at follow up. Forty-eight patients had an angiogram or CT scan revealing occlusion or anastomotic stenoses (>50%) in 6 patients. Overall permeability was 92%. Conclusions. Robotic surgery can be performed with promising results

A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine

International audienceBackground/Aims. Lamivudine resistance has been described in subjects with chronic hepatitis B infections, associated with mutations in the viral polymerase gene. The objective of this study was to estimate the emergence rate of lamivudine-resistant viral strains and their consequences over a two-year period. Methods. We evaluated 283 lamivudine-naive subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every six months thereafter. Viral DNA was characterised using PCR-based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. Results. The annualised incidence rate for viral polymerase mutations was 22%. The only independent risk factor identified was high viral load at inclusion. Detectable viral DNA and elevated transaminases were more frequent in subjects harbouring mutant viral strains, and these underwent a lower rate of HBe seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. Conclusions. This prospective cohort study identified lamivudine resistant mutations emerging in 22% of subjects yearly, which were apparently not associated with clinical aggravation over the study period

Genetic instability triggered by G-quadruplex interacting Phen-DC compounds in Saccharomyces cerevisiae

G-quadruplexes are nucleic acid secondary structures for which many biological roles have been proposed but whose existence in vivo has remained elusive. To assess their formation, highly specific G-quadruplex ligands are needed. Here, we tested Phen-DC3 and Phen-DC6, two recently released ligands of the bisquinolinium class. In vitro, both compounds exhibit high affinity for the G4 formed by the human minisatellite CEB1 and inhibit efficiently their unwinding by the yeast Pif1 helicase. In vivo, both compounds rapidly induced recombination-dependent rearrangements of CEB1 inserted in the Saccharomyces cerevisiae genome, but did not affect the stability of other tandem repeats lacking G-quadruplex forming sequences. The rearrangements yielded simple-deletion, double-deletion or complex reshuffling of the polymorphic motif units, mimicking the phenotype of the Pif1 inactivation. Treatment of Pif1-deficient cells with the Phen-DC compounds further increased CEB1 instability, revealing additional G4 formation per cell. In sharp contrast, the commonly used N-methyl-mesoporphyrin IX G-quadruplex ligand did not affect CEB1 stability. Altogether, these results demonstrate that the Phen-DC bisquinolinium compounds are potent molecular tools for probing the formation of G-quadruplexes in vivo, interfere with their processing and elucidate their biological roles

10 years of CEMARA database in the AnDDI-Rares network: a unique resource facilitating research and epidemiology in developmental disorders in France

Background : In France, the Ministry of Health has implemented a comprehensive program for rare diseases (RD) that includes an epidemiological program as well as the establishment of expert centers for the clinical care of patients with RD. Since 2007, most of these centers have entered the data for patients with developmental disorders into the CEMARA population-based registry, a national online data repository for all rare diseases. Through the CEMARA web portal, descriptive demographic data, clinical data, and the chronology of medical follow-up can be obtained for each center. We address the interest and ongoing challenges of this national data collection system 10 years after its implementation. Methods : Since 2007, clinicians and researchers have reported the “minimum dataset (MDS)” for each patient presenting to their expert center. We retrospectively analyzed administrative data, demographic data, care organization and diagnoses. Results : Over 10 years, 228,243 RD patients (including healthy carriers and family members for whom experts denied any suspicion of RD) have visited an expert center. Among them, 167,361 were patients affected by a RD (median age 11 years, 54% children, 46% adults, with a balanced sex ratio), and 60,882 were unaffected relatives (median age 37 years). The majority of patients (87%) were seen no more than once a year, and 52% of visits were for a diagnostic procedure. Among the 2,869 recorded rare disorders, 1,907 (66.5%) were recorded in less than 10 patients, 802 (28%) in 10 to 100 patients, 149 (5.2%) in 100 to 1,000 patients, and 11 (0.4%) in > 1,000 patients. Overall, 45.6% of individuals had no diagnosis and 6.7% had an uncertain diagnosis. Children were mainly referred by their pediatrician (46%; n = 55,755 among the 121,136 total children referrals) and adults by a medical specialist (34%; n = 14,053 among the 41,564 total adult referrals). Given the geographical coverage of the centers, the median distance from the patient’s home was 25.1 km (IQR = 6.3 km-64.2 km). Conclusions : CEMARA provides unprecedented support for epidemiological, clinical and therapeutic studies in the field of RD. Researchers can benefit from the national scope of CEMARA data, but also focus on specific diseases or patient subgroups. While this endeavor has been a major collective effort among French RD experts to gather large-scale data into a single database, it provides tremendous potential to improve patient care

Weber (Eugen) - Action Française, Royalism and reaction in twentieth century France

Slama Alain-Gérard. Weber (Eugen) - Action Française, Royalism and reaction in twentieth century France. In: Revue française de science politique, 20ᵉ année, n°3, 1970. pp. 570-573

Un quotidien républicain sous Vichy : Le Temps (juin 1940 -novembre 1942)

A republican daily newspaper under Vichy. "Le Temps" (June 1940 - November 1942), by Alain-Gérard Slama By what process did a parliamentary, republican and liberal daily newspaper as important as Le Temps become, between June 1940 and November 1942, one of the main props of the Vichy regime? The ordeal of defeat and their anxiety to defend their threatened interests led the middle class elite, of which Le Temps was the mouthpiece, to sacrifice all that was not essential in their ideology; thus, republicanism transpired to be weaker than industrialism, the protection of liberty was superseded by the defense of authority, parliamentary government suffered the consequences of the fear of universal suffrage and the decadence of the party system. The lesson to be learnt from this behaviour is more far-reaching than the experience of Vichy. It shows that old reactions persist in spite of an apparent adjustment to new problems, and that while basic principles may be asserted, in the political order temperaments outweigh ideas. [Revue française de science politique XXII (4), août 1972, pp. 719-749.]Un quotidien républicain sous Vichy. "Le Temps" (juin 1940 - novembre 1942), par Alain-Gérard Slama Par quels cheminements un quotidien parlementaire, républicain et libéral, de l'importance du Temps est-il devenu, entre juin 1940 et novembre 1942, un des principaux soutiens du régime de Vichy ? L'épreuve de la défaite et le souci de défendre ses intérêts menacés ont amené l'élite bourgeoise du pays, dont Le Temps était l'expression, à sacrifier dans son idéologie tout ce qui n'était pas l'essentiel : le républicanisme s'est révélé moins fort que l'industrialisme, la défense de la liberté a cédé le pas à la protection de l'autorité, le parlementarisme lui-même a subi le contrecoup de la crainte du suffrage universel et de la dégradation du système des partis. La leçon de ce comportement dépasse l'expérience de Vichy. Elle révèle, sous l'apparence d'une adaptation à des problèmes nouveaux, la continuité de réflexes anciens et, derrière l'affirmation des grands principes, la prédominance, dans l'ordre politique, des tempéraments sur les idées. [Revue française de science politique XXII (4), août 1972, pp. 719-749.]Slama Alain-Gérard. Un quotidien républicain sous Vichy : Le Temps (juin 1940 -novembre 1942). In: Revue française de science politique, 22ᵉ année, n°4, 1972. pp. 719-749

Girardet (Raoul) - L'idée coloniale en France de 1871 à 1962.

Slama Alain-Gérard. Girardet (Raoul) - L'idée coloniale en France de 1871 à 1962.. In: Revue française de science politique, 22ᵉ année, n°3, 1972. pp. 602-605