A branching process model of heterogeneous DNA damages caused by radiotherapy in in vitro cell cultures.

This paper deals with the dynamic modeling and simulation of cell damage heterogeneity and associated mutant cell phenotypes in the therapeutic responses of cancer cell populations submitted to a radiotherapy session during in vitro assays. Each cell is described by a finite number of phenotypic states with possible transitions between them. The population dynamics is then given by an age-dependent multi-type branching process. From this representation, we obtain formulas for the average size of the global survival population as well as the one of subpopulations associated with 10 mutation phenotypes. The proposed model has been implemented into Matlab© and the numerical results corroborate the ability of the model to reproduce four major types of cell responses: delayed growth, anti-proliferative, cytostatic and cytotoxic.

[Generating person-years and calculating SMR using SAS: a simple program for exact calculations]. / Décompte des personnes-années avec SAS et calculs de SMR: présentation d'un programme simple pour faire des calculs de façon exacte.

The computation of standardized incidence/mortality ratios or Poisson regression requires the calculation of person-years generated in a cohort. Softwares can do that, but SAS users still need to program this step themselves. Various algorithms were published previously, but they do not perform exact calculations: the present paper describes a simple program, which creates exact person-years, and computes SMRs. This program provides a referenced tool to perform this analysis in a cohort, with SAS or another language (the algorithm used can be easily adapted).

Dilemmas caused by endogenous pararetroviruses regarding the taxonomy and diagnosis of yam (Dioscorea spp.) badnaviruses: analyses to support safe germplasm movement.

The discovery of endogenous pararetroviral sequences (EPRVs) has had a deep impact on the approaches needed for diagnosis, taxonomy, safe movement of germplasm and management of diseases caused by pararetroviruses. In this article, we illustrate this through the example of yam (Dioscorea spp.) badnaviruses. To enable progress, it is first necessary to clarify the taxonomical status of yam badnavirus sequences. Phylogeny and pairwise sequence comparison of 121 yam partial reverse transcriptase sequences provided strong support for the identification of 12 yam badnavirus species, of which ten have not been previously named. Virus prevalence data were obtained, and they support the presence of EPRVs in D. rotundata, but not in D. praehensilis, D. abyssinica, D. alata or D. trifida. Five yam badnavirus species characterised by a wide host range seem to be of African origin. Seven other yam badnavirus species with a limited host range are probably of Asian-Pacific origin. Recombination under natural circumstances appears to be rare. Average values of nucleotide intra-species genetic distances are comparable to data obtained for other RNA and DNA virus families. The dispersion scenarios proposed here, combined with the fact that host-switching events appear common for some yam badnaviruses, suggest that the risks linked to introduction via international plant material exchanges are high.

Use of cpSSRs for the characterisation of yam phylogeny in Benin.

The Dioscorea cayenensis - Dioscorea rotundata species complex is the most widely cultivated yam in West Africa. This species complex has been described as deriving from wild yams belonging to the Enanthiophyllum section through domestication by African farmers. To study patterns of yam evolution and to establish phylogenetic relationships existing between wild and cultivated species sampled in Benin, we investigated changes in chloroplast DNA simple sequence repeats (cpSSR) in 148 yam accessions selected to cover the wider possible genetic diversity existing in the country. Dioscorea cayenensis and D. rotundata share the same haplotype. The morphotype "abyssinica" appeared to be subdivided into 2 haplotypes. One of these haplotypes shares the same haplotype with the Dioscorea cayenensis - Dioscorea rotundata species complex and with morphotypes praehensilis, suggesting that they might belong to the same species. Relationships among sections Lasiophyton, Macrocapaea, Opsophyton, and Enanthiophyllum were clarified, and some taxonomic changes within the Enanthiophyllum section were suggested. Dioscorea minutiflora, D. smilacifolia, and D. burkilliana might be considered as 1 single genetic group, and they are suspected of belonging to the same species.

[Quantitative assessment of the risk of lung cancer and pleural mesothelioma among automobile mechanics]. / Evaluation quantitative du risque de cancer du poumon et de mésothéliome pleural chez les mécaniciens de véhicules automobiles.

BACKGROUND: A quantitative assessment of the risk of lung cancer and pleural mesothelioma among mechanics exposed to dust released from automobile asbestos-containing parts was performed. METHODS: The population of automobile mechanics in France, according to profession and industrial sectors codes, was estimated from the data of the 1999 census. Risks were computed for a total male population of 242,360 automobile mechanics aged 16 to 60 years. Exposure to asbestos among these workers comes from maintenance tasks involving asbestos-containing parts produced before 1997 (date of the asbestos ban in France). Airborne asbestos concentration data available from the literature were highly variable. No data reporting the distribution of time spent for such tasks over a typical week of work were available. Therefore, different weekly exposure profiles were simulated, based on data from the 1994 SUMER survey. Risk models were those used for assessing asbestos health effects by all national and international agencies. Exposure scenarios mixed different levels of exposure, periods of time, proportions of exposed workers and dates of the "natural" disappearance of the automobile fleet built before asbestos was banned in brakes and other parts. The most realistic scenario hypothesizes that all automobile mechanics were exposed to asbestos, that the exposure levels ranged from 0.06 and 0.25 fibers/liter per week for the period before 1997, and between 0.01 and 0.06 fibers/liter per week afterwards until 2010. RESULTS: According to this scenario, the number of lifelong cancer deaths (lung and pleura) induced by asbestos exposure in this population is estimated at 602 "unavoidable" cases, due to exposure experienced before 2003; 43 other cases will occur if asbestos is not removed from existing automobiles.

[Causes of death in a cohort of EDF-GDF employees: comparison between occupational medicine and official statistics data]. / Causes de décès dans une cohorte de travailleurs EDF-GDF: comparaison des données de la médecine du travail et de la statistique nationale.

BACKGROUND: In an epidemiological study, medical causes of death may be obtained from different sources. In a study on French gas and electricity company (EDF-GDF) workers, they were obtained from the national INSERM database. Additionally, the causes collected by the EDF-GDF occupational physicians were available for a subset of 1,330 deaths, which occurred between 1989 and 1994. The data from the two sources were compared with each other, in order to assess whether they were globally equivalent, and the potential impact of their differences on the results of epidemiological analyses. METHODS: Concordance rates between causes of death in the INSERM and EDF-GDF physicians databases were calculated according to the International Classification of Diseases (ICD) ninth revision codes and for various causes groups. Causes of death records were also examined in order to clarify the observed divergences. SMRs were computed in order to evaluate the consequences of using each database in epidemiological analyses. Finally, some SMRs were computed with the two sources and compared with each other. RESULTS: INSERM and EDF-GDF physicians causes belonged to the same causes group in 81% of cases, but the exact cause was different for more than half of them. The concordance rate was high for the deaths by AIDS and by cancer, and low for deaths by respiratory system and digestive system diseases. More causes of death were coded as "unknown" in EDF-GDF physicians data than in INSERM data. The SMRs varied widely depending on whether the INSERM or EDF-GDF physicians causes of death databases were used. CONCLUSIONS: Causes of death recorded in the INSERM and EDF-GDF physicians databases are very different. Therefore, using the national mortality rates computed by INSERM with the EDF-GDF physicians causes of death to calculate SMRs is not valid, and it is observed that they may be very different from those computed with INSERM data. In a general way, it should be better to use the INSERM database, which is a common source, in order to generate results comparable with other studies. However, this database has its own limitations, and it may be better, in particular situations and for internal analyses, to use another source if it seems to be a better one.

IgG anti-beta2-glycoprotein I antibodies in adult patients with systemic lupus erythematosus: prevalence and diagnostic value for the antiphospholipid syndrome.

OBJECTIVE: To investigate the prevalence of serum anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies and other antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). To study their diagnostic value for the antiphospholipid syndrome (APS). METHODS: Anti-beta2-GPI and IgG anticardiolipin (aCL) were determined in sera from 102 consecutive patients with SLE using ELISA. Serum and plasma tests were also done for lupus anticoagulant (LAC), syphilis, and antibodies to dsDNA. Clinical and laboratory features of APS were observed. RESULTS: Prevalences were 23.5% for aCL and 18.6% for anti-beta2-GPI. Correlations between the presence of aCL and anti-beta2-GPI and between their titers were statistically significant (p<0.0001). No associations were found between anti-beta2-GPI and disease activity criteria (SLEDAI, ECLAM, dsDNA). Anti-beta2-GPI were significantly associated with LAC (p = 0.005), APS (p = 0.005), and a high aCL titer (aCL > 5 SD; p< or =0.001). LAC was the best diagnostic criterion for APS. CONCLUSION: These data suggest that determination of anti-beta2-GPI in addition to aCL and LAC is unlikely to improve the diagnosis of APS in patients with SLE.

Laryngeal and hypopharyngeal cancer and occupational exposure to asbestos and man-made vitreous fibers: results of a case-control study.

BACKGROUND: The data from a case-control study performed in France between 1989 and 1991 were used to test whether exposure to either asbestos or to man-made vitreous fibers (MMVF) is a risk factor for cancer of the larynx or the hypopharynx. METHODS: This study involved 315 incident cases of laryngeal cancer, 206 cases of hypopharyngeal cancer, and 305 hospital-based controls with other types of cancer, all recruited in 15 hospitals in six French cities. The subjects' past occupational exposure to asbestos and to four types of MMVF (mineral wool, refractory ceramic fibers, glass filaments, and microfibers) was evaluated based on their job history, with the aid of a job-exposure matrix. Odds ratios were calculated with unconditional logistic regression, with adjustment for smoking and drinking levels. RESULTS: Exposure to asbestos resulted in a significant increase in the risk of hypopharyngeal cancer (OR = 1.80, 95% CI: 1.08-2.99) and a nonsignificant increase in the risk of laryngeal cancer (OR = 1.24, 95% CI: 0.83-1.90). Risk was highest for the epilarynx (highest cumulative level of exposure: OR = 2.22, 95% CI: 1.05-4.71). Exposure to mineral wools was of borderline significance for the risk of hypopharyngeal cancer (OR = 1.55, 95% CI: 0.99-2.41), and nonsignificantly associated with the risk of laryngeal cancer (OR-1.33, 95% CI: 0.91-1.95). The risk was again highest for the epilarynx (OR = 1.85, 95% CI: 1.08-3.17). No significant results were observed for the other MMVF. CONCLUSIONS: These results suggest that asbestos exposure increases the risk of epilaryngeal and hypopharyngeal cancers. It is difficult to reach a conclusion about the effects of mineral wools, because nearly all the exposed subjects were also exposed to asbestos. The possible effects of other MMVF were difficult to assess in this study, because of the paucity of exposed subjects.

Genetic mapping of maize streak virus resistance from the Mascarene source. I. Resistance in line D211 and stability against different virus clones.

Maize streak virus (MSV) disease may cause significant grain yield reductions in maize in Africa. Réunion island maize germplasm is a proven source of strong resistance. Its genetic control was investigated using 123 RFLP markers in an F(2) population of D211 (resistant) × B73 (susceptible). This population of 165 F(2:3) families was carefully evaluated in Harare (Zimbabwe) and in Réunion. Artificial infestation was done with viruliferous leafhoppers. Each plant was rated weekly six times after infestation on a 1-9 scale previously adjusted by image analysis. QTL analyses were conducted for each scoring date, and for the areas under the disease, incidence and severity progress curves. The composite interval mapping method used allowed the estimation of the additive and dominance effects and QTL × environment interactions. Heritabilities ranged from 73% to 98%, increasing with time after infestation. Resistance to streak virus in D211 was provided by one region on chromosome 1, with a major effect, and four other regions on chromosomes 2, 3 (two regions) and 10, with moderate or minor effects. Overall, they explained 48-62% of the phenotypic variation for the different variables. On chromosome 3, one of the two regions seemed to be more involved in early resistance, whereas the second was detected at the latest scoring date. Other QTLs were found to be stable over time and across environments. Mild QTL × environment interactions were detected. Global gene action appeared to be partially dominant, in favor of resistance, except at the earliest scoring dates, where it was additive. From this population, 32 families were chosen, representing the whole range of susceptibility to MSV. They were tested in Réunion against three MSV clones, along with a co-inoculation of two of them. Virulence differences between clones were significant. There were genotype × clone interactions, and these were more marked for disease incidence than for severity. Although these interactions were not significant for the mean disease scores, it is suggested that breeders should select for completely resistant genotypes.

Genetic mapping of maize streak virus resistance from the Mascarene source. II. Resistance in line CIRAD390 and stability across germplasm.

The streak disease has a major effect on maize in sub-Saharan Africa. Various genetic factors for resistance to the virus have been identified and mapped in several populations; these factors derive from different sources of resistance. We have focused on the Réunion island source and have recently identified several factors in the D211 line. A second very resistant line, CIRAD390, was crossed to the same susceptible parent, B73. The linkage map comprised 124 RFLP markers, of which 79 were common with the D211×B73 map. A row-column design was used to evaluate the resistance to maize streak virus (MSV) of 191 F(2:3) families under artificial infestation at two locations: Harare (Zimbabwe) and in Réunion island. Weekly ratings of resistance were taken and disease incidence and severity calculated. QTL analyses were conducted for each scoring date and for the integration over time of the disease scores, of incidence, and of severity. Heritability estimates (71-98%) were as high as for the D211×B73 population. Eight QTLs were detected on chromosomes 1, 2, 3, 5 (two QTLs), 6, 8, and 10. The chr1-QTL explained the highest proportion of phenotypic variation, about 45%. The QTLs on chromosomes 1, 2, and 10 were located in the same chromosomal bin as QTLs for MSV resistance in the D211×B73 population. In a simultaneous fit, QTLs explained together 43-67% of the phenotypic variation. The QTLs on chromosomes 3, 5, and 6 appeared to be specific for one or the other component of the resistance. For the chr3-QTL, resistance was contributed by the susceptible parent. There were significant QTL × environment interactions for some of the variables studied, but QTLs were stable in the two environments. They also appeared to be stable over time. Global gene action ranged from partial dominance to overdominance, except for disease severity. Some additional putative QTLs were also detected. The major QTL on chromosome 1 seemed to be common to the other sources of resistance, namely Tzi4, a tolerant line from IITA, and CML202 from CIMMYT. However, the distribution of the other QTLs within the genome revealed differences in Réunion germplasm and across these other resistance sources. This diversity is of great importance when considering the durability of the resistance.

[Automatic quantitative analysis of vascular stenosis. Experimental study of a digital angiography system applied to cardiology]. / Analyse quantitative automatique d'une sténose vasculaire. Etude expérimentale d'un système d'angiographie numérisée appliquée à la cardiologie.

The purpose of this study was to test the measurement reliability of the automatic stenosis quantitation program present in a digital angiography system (DG 300 General Electric CGR SA). The experimental study was performed on models mimicking circular, elliptic and irregular stenoses; it made it possible to measure the percentage of stenosis by geometric and densitometric methods. The parameters studied were the size and shape of the stenoses, the contrast medium concentration, the positioning of the stenosis in relation to the image intensifier, the number of Kvp and the angle of projection of X-ray beams in the case of elliptic and irregular stenoses. The results showed a perfect linear correlation between the thickness traversed by the X-ray beams and the value in grey level at the output of the optico-radiological chain (r between 0.987 and 0.997, p less than 0.001), using different Kvp (65 Kvp, 85 Kvp, 90 Kvp) and different X-ray doses (1 milliRoentgen and 80 microRoentgen). With all concentrations of contrast medium (320 mg I/ml to 5 mg I/ml), the values of the circular stenoses measured were very close to real values (75 p. 100) for vessels of all diameters, except those of 1.5 mm in a 22 cm field. When 16 cm and 11 cm fields were used, the results were very close to the 75 p. 100 real value (3 to 4 p. 100 of relative error), even with the 1.5 mm diameter. The values of elliptic stenoses measured by densitometry were very close to real values (1 to 4 p. 100 of relative error) with contrast medium concentrations ranging from 320 mg I/ml to 20 mg I/ml) and with three angles of projection (0 degrees, 30 degrees, 60 degrees). In contrast, the geometric method gave very different results with the three angles of projection. In the case of irregular stenosis (17 percentages of stenosis ranging from 26.2 p. 100 to 77.1 p. 100) the real values correlated very well with the estimated values (r = 0.999, p less than 0.0001). Some of the results were compared with those obtained with a digital cineradiology system (Pie Data) and were found to be equivalent.