Experimental measurements of the bacterial oxidation of HT in soils: Impact over a zone influenced by an industrial release of tritium in HT form.

Tritium is a radionuclide released to the atmosphere by nuclear industries in various forms, mainly HTO and to a lesser extent HT. However, some nuclear sites may emit predominantly HT in the atmosphere. The HT is oxidized to HTO essentially in the top cm of soils, and that the formed HTO is then possibly released into the atmosphere. HTO is an assimilable form by plants. Therefore, it is important to understand the environmental behaviour of HT. In this work, we adapt the bacterial oxidation model of HT in soils of Ota et al. (2007) by laboratory experiments on soils typical of western France, and we have in particular adapted the frequency factor A and the Michaelis-Menten enzymatic reaction parameter (Km) on the basis of an Arrhenius equation in function of the porosity of the soil. We then applied this model to the environment near the reprocessing plant of Orano la Hague (France), which emits a significant amount of HT. Based on the adapted model, and knowing the atmospheric variations of HTO and HT over the period 2013-2016, we estimated that the mean HTO activity in soil due to atmospheric HT reached 0.6 Bq.L-1 (with a peak value of 5 Bq.L-1) while the mean value with all sources taken into account is 6.2 Bq.L-1. Then, in an environment such as that surrounding the Orano La Hague plant, where near-field atmospheric HT activity is very high, the bacterial oxydation contribution to produce HTO in the soil can be considered as approximately 10%. The flux to the atmosphere from these source representing approximately. 1.5 Bq.m-2.d-1. If we consider an area of 2 km around the plant (i.e. 13 km2), we estimate 218 Bq.s-1 of HTO was released by the soil, representing less than 0.1% of the direct atmospheric release of HTO around the site. From this work, it appears clear that this secondary source term from the soil is insignificant at this specific site.

Tritium forms discrimination in ryegrass under constant tritium exposure: From seed germination to seedling autotrophy.

Uncertainties remain regarding the fate of atmospheric tritium after it has been assimilated in grasslands (ryegrass) in the form of TFWT (Tissue Free Water Tritium) or OBT (Organically Bound Tritium). One such uncertainty relates to the tritium forms discrimination during transfer from TFWT to OBT resulting from photosynthesis (OBTphoto), corresponding to the OBTphoto/TFWT ratio. In this study, the OBT/TFWT ratio is determined by experiments in the laboratory using a ryegrass model and hydroponic cultures, with constant activity of tritium in the form of tritiated water (denoted as HTO) in the "water" compartment (liquid HTO) and "air" compartment (HTO vapour in the air). The OBTphoto/TFWT ratio and the exchangeable OBT fraction are measured for three parts of the plant: the leaf, seed and root. Plant growth is modelled using dehydrated biomass measurements taken over time in the laboratory and integrating physiological functions of the plant during the first ten days after germination. The results suggest that there is no measurable discrimination of tritium in the plant organic matter produced by photosynthesis.

HTLV-1 infection in Reunion.

OBJECTIVES: Although regularly looked for in blood donors, HTLV infections are very rare in Reunion. We aimed to describe HTLV infections locally. PATIENTS AND METHODS: HTLV infections were identified from the database of the Reunion University Hospital administrative database (PMSI) between 2000 and 2016. Diagnosis was performed with HTLV 1/2 enzyme immunoassay test and confirmed by Western blot. RESULTS: We reported three asymptomatic and four symptomatic HTLV infections, including two tropical spastic paraparesis/HTLV-1 associated myelopathies (TSP/HAM) and two adult T-cell leukemia/lymphoma (ATLL), diagnosed between 2000 and 2016. CONCLUSION: Reunion is a low HTLV prevalence area, which could be explained by its settlement history. The present report underlines the local circulation of HTLV and symptomatic infections.

Genetic, functional, and histopathological evaluation of two C-terminal BRCA1 missense variants.

BACKGROUND: The vast majority of BRCA1 missense sequence variants remain uncharacterized for their possible effect on protein expression and function, and therefore are unclassified in terms of their pathogenicity. BRCA1 plays diverse cellular roles and it is unlikely that any single functional assay will accurately reflect the total cellular implications of missense mutations in this gene. OBJECTIVE: To elucidate the effect of two BRCA1 variants, 5236G>C (G1706A) and 5242C>A (A1708E) on BRCA1 function, and to survey the relative usefulness of several assays to direct the characterisation of other unclassified variants in BRCA genes. METHODS AND RESULTS: Data from a range of bioinformatic, genetic, and histopathological analyses, and in vitro functional assays indicated that the 1708E variant was associated with the disruption of different cellular functions of BRCA1. In transient transfection experiments in T47D and 293T cells, the 1708E product was mislocalised to the cytoplasm and induced centrosome amplification in 293T cells. The 1708E variant also failed to transactivate transcription of reporter constructs in mammalian transcriptional transactivation assays. In contrast, the 1706A variant displayed a phenotype comparable to wildtype BRCA1 in these assays. Consistent with functional data, tumours from 1708E carriers showed typical BRCA1 pathology, while tumour material from 1706A carriers displayed few histopathological features associated with BRCA1 related tumours. CONCLUSIONS: A comprehensive range of genetic, bioinformatic, and functional analyses have been combined for the characterisation of BRCA1 unclassified sequence variants. Consistent with the functional analyses, the combined odds of causality calculated for the 1706A variant after multifactorial likelihood analysis (1:142) indicates a definitive classification of this variant as "benign". In contrast, functional assays of the 1708E variant indicate that it is pathogenic, possibly through subcellular mislocalisation. However, the combined odds of 262:1 in favour of causality of this variant does not meet the minimal ratio of 1000:1 for classification as pathogenic, and A1708E remains formally designated as unclassified. Our findings highlight the importance of comprehensive genetic information, together with detailed functional analysis for the definitive categorisation of unclassified sequence variants. This combination of analyses may have direct application to the characterisation of other unclassified variants in BRCA1 and BRCA2.

[Some ideas for taking in charge accidental blood exposures in the French blood establishment]. / Quelques idées pour la prise en charge des accidents d'exposition au sang au sein des établissements français du sang.

Accidental blood exposures (ABE) are one of the most important problems when talking about industrial accidents in institutions such as the French blood establishment. The three major viruses concerned by these exposures are the AIDS virus (HIV) and Hepatitis viruses: HIV; HCV and HBV. There are universal prevention's ways for the three viruses, a vaccination way for Hepatitis B, and a way of prophylaxis, using triple therapy, for HIV. For the best taking in charge of ABE, it is important to be able to assess quickly the risk, using serology of the source (blood donor or patient), to be able, if needed, to treat with triple therapy, within two hours, members of staff exposed to HIV, and to be able to follow-up these persons in the next four months. French blood establishment has very certainly a critical role in this strategy of prevention, following-up and, above all, taking in charge in the very first therapeutic instants.

[Female general practitioners in Maine-et-Loire: "1990-2000"]. / Les femmes médecins généralistes dans le Maine-et-Loire: "1990-2000".

In 1990, there were approximately 60 female general practitioners in the Maine-et-Loire region, 58 of which participated in the survey that year. By the year 2000, the number had risen to 137. A new study was conducted involving 70 women who had opened practices over that decade. Analyses of the responses to the questionnaire and a comparison with the results of the previous survey demonstrate distinct changes and a real evolution in the working conditions of this new generation of female general practitioners and in their relationships with their colleagues and families. More involved in their work and professional lives, they are now more accepted by other physicians and enjoy real family support. They are fulfilled and appear to succeed fully in all of their roles--those of physician, mother and wife. More active participation in social and political life would enable these professionals to achieve greater self-fulfillment and satisfaction; it is perhaps still too early to comprehend the true specificity, if any, of the private general practice of medicine by women. A new survey is planned to be conducted in ten years.

Investigation of a slaughterhouse-related outbreak of Q fever in the French Alps.

The aim of the study presented here was to describe the different epidemiological methods used to investigate an outbreak of Q fever that occurred in the spring of 1996 among inhabitants of Briançon, a small town in the French Alps. Three approaches were used: (i) a comparison between a 2-month exhaustive serological survey among blood donors and a retrospective serological survey performed on frozen plasma collected by the transfusion centre in the spring of 1995; (ii) a serological survey performed in the general population by cluster sampling, using dried blood on blotting paper; and (iii) a case-control study. A total of 29 cases of acute Q fever were diagnosed by physicians during hospitalisations of the patients or ambulatory care. The case-con-trol study suggested that the outbreak resulted from airborne transmission of contaminated sheep waste, which had been left uncovered in the slaughterhouse area. Such transmission may have been facilitated by the nearby heliport. The comparison between the cumulative incidence of Q fever among blood donors during the spring seasons of 1995 and 1996 confirmed the outbreak (0.38% vs. 2.58%, respectively; P<0.0001). Health authorities promptly decided to close the slaughterhouse. The use of complementary epidemiological methods allows investigators to focus on major issues related to an outbreak: timely detection of cases, identification of the source, estimations of incidence, and public health intervention. Rapid recognition and management of outbreaks in the general population of a rural region need to be improved, particularly at a time when airborne agents could be used as biological weapons.

Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study.

The genetic basis for nonmedullary forms of thyroid cancer (NMTC) is less well established than that of medullary thyroid cancer. However, epidemiological and family studies suggest that a proportion of NMTC may be due to inherited predisposition. To estimate the familial risk of thyroid cancer, we conducted a hospital-based case-control study at the Princess Margaret Hospital in Toronto, Ontario, Canada, and at 2 university hospitals in Montréal, Québec, Canada. We obtained pedigrees from 339 unselected patients diagnosed with NMTC and from 319 unaffected ethnically matched controls. Family histories of cancer were obtained from the cases and controls for 3292 first degree relatives of cases and controls. Seventeen cases (5.0%) and 2 controls (0.6%) reported at least one first degree relative with thyroid cancer. In relatives of patients with thyroid cancer, the incidence of any type of cancer (including NMTC) was 38% higher than in relatives of controls (incidence rate ratio, 1.4; 95% confidence interval, 1.1-1.7). The relative risk for thyroid cancer was 10-fold higher in relatives of cancer patients than in controls (incidence rate ratio, 10.3; 95% confidence interval, 2.2-47.6). Our findings suggest that hereditary or other familial factors are important in a small proportion of NMTC. Molecular studies are needed to determine the genetic basis of cancer susceptibility in these families.

Absence of evidence for a familial breast cancer susceptibility gene at chromosome 8p12-p22.

Several recent studies indicate that the majority of families with five or fewer cases of breast cancer and no cases of ovarian cancer are not due to BRCA1 or BRCA2. It has been proposed that a further breast cancer susceptibility gene that may account for some of these families is located on chromosome 8p12-p22. We have identified 31 site-specific breast cancer families that have a greater than 80% posterior probability of being due to genes other than BRCA1 or BRCA2. These families have been examined for linkage to 8p12-p22 using markers flanking the putative location of the gene. The overall multi-point LOD score is strongly negative across the whole 44 cM. The individual multi-point LOD score is negative in 23 families and only exceeds 0.5 in a single family (with a multi-point LOD score of 1.22). The maximum heterogeneity LOD score was 0.03 at marker D8S136 with estimated proportion linked (alpha) of 3% (95% CI 0 - 30%). These data do not lend support to the hypothesis that chromosome 8p12-p22 harbours a familial breast cancer susceptibility gene. Oncogene (2000) 19, 4170 - 4173

Trends in cancer incidence and mortality.

Time trends in cancer risk have often been summarised by the observation that mortality from cancers associated with tobacco is increasing rapidly, while mortality from all other cancers is either stable or falling slightly, this slight decline being dominated by the decrease in mortality from stomach cancer. Until recently, and with some variation between the sexes, this simple summary of cancer mortality trends would have been broadly correct for a number of developed countries, and it remains useful in dismissing claims of an impending and unexplained epidemic of cancer, but it does not apply to all countries, and in some there have recently been striking changes in the trends in mortality from cancers associated with tobacco. Cancer mortality has been widely accepted as the most important measure of progress against cancer, since it reflects the impact of cancer on people, and has been considered less subject to distortion than incidence or survival, although this is open to question. Cancer mortality also reflects trends in incidence and survival to a greater or lesser extent. There has been controversy, however, over how cancer mortality trends should be interpreted, as well as over which measures should be used to assess progress in cancer control. An overall summary of trends in mortality from all cancers combined is of limited value in assessing progress against cancer, in any case. Increases in a common lethal cancer may numerically dominate overall mortality trends, perhaps concealing declines in less common or less lethal cancers, while opposite trends in cancers of the lung and stomach, for example, might lead to an overall impression that little has changed. Further, up to a third of cancer patients will not die of cancer, and cancer mortality statistics do not reflect their experience at all. Cancer mortality trends only indirectly reflect trends in the number of people who are diagnosed with cancer in a given year, and those who do die of cancer in a given year may have been diagnosed more than 3 years previously, even though many die earlier: this blurs the responsiveness of routine cancer mortality statistics as a measure of recent progress, and alternative measures have been proposed. Trends in competing risks of death, especially at higher ages, may also complicate the interpretation of cancer mortality trends. The chance of developing cancer, and in that event, the chances of surviving it, are of direct interest to individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Cancer in the European Community and its member states.

The European Community (EC) mounted the "Europe Against Cancer" programme in 1987 to control cancer. Information on mortality rates is available for all member countries and the incident number of cancers was estimated for each site, for each country and for the EC as a whole. In 1980 there were 730,000 deaths from cancer and an estimated 1,222,120 [corrected] new cases (excluding non-melanoma skin cancers). Among men, cancer of the lung is the leading cancer site with some 135,000 cases per year followed by prostate, colon and bladder cancer. Breast cancer is the leading site in women, with 135,000 cases per year, followed by colon, stomach and genital cancer. Among men, melanoma of the skin, and lung, pancreas and rectum cancer are more frequent in the north in contrast to larynx, oesophagus, buccal cavity and liver cancer, which are more frequent in the south. There are additional contrasts between Southern European countries. The contrasts are less striking for women. This study provides an estimate of the true number of cases only. The establishment of a network of European cancer registries should eventually lead to more comprehensive incidence information form the EC.

Synthetic human growth hormone releasing factor (h-GRF-I-44-NH2) dose response effect on growth hormone and prolactin secretion in healthy adult men.

The dose-effect relationship of an i.v. bolus of synthetic h-GRF-44 on growth-hormone and prolactin secretion has been studied. Seven healthy adult volunteers received in a random order h-GRF-44 2.5, 5, 10, 20, 40 and 80 micrograms and a placebo. Plasma growth hormone (GH) was determined between 30 min before and 240 min after injection, the area under the curve (AUC) and the peak GH level being used to assess the response. For both parameters a dose-effect relationship was observed. Doses as low as 2.5 micrograms were capable of eliciting a rise in GH plasma levels in few patients. Above 40 micrograms the dose-effect curves tended to plateau, although the decrease in the slope of the dose-effect curve at the peak was more marked. Intersubject variability was large, so precise determination of the minimal effective dose as well as the lowest dose giving a maximal effect was not possible. The available evidence suggests that the i.v. dose of synthetic h-GRF-44 (SR 95228) which is likely to promote GH release into the blood stream in most healthy adults is within the range 40-100 micrograms. In these healthy adults unwanted effects were infrequent with these low doses. Unlike previous experience with higher doses of another synthetic h-GRF-44, prolactin secretion in this study was not affected.