43 research outputs found

    Mortality and life expectancy of professional fire fighters in Hamburg, Germany: a cohort study 1950 – 2000

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    BACKGROUND: The healthy worker effect may hide adverse health effects in hazardous jobs, especially those where physical fitness is required. Fire fighters may serve as a good example because they sometimes are severely exposed to hazardous substances while on the other hand their physical fitness and their strong health surveillance by far exceeds that of comparable persons from the general population. METHODS: To study this effect a historic cohort study was conducted to assess mortality and life expectancy of professional fire fighters of the City of Hamburg, Germany. Fire departments and trade unions questioned the validity of existing studies from outside Germany because of specific differences in the professional career. No mortality study had been conducted so far in Germany and only few in Europe. Information on all active and retired fire fighters was extracted from personnel records. To assure completeness of data the cohort was restricted to all fire fighters being active on January 1, 1950 or later. Follow up of the cohort ended on June 30th 2000. Vital status was assessed by personnel records, pension fund records and the German residence registries. Mortality of fire fighters was compared to mortality of the Hamburg and German male population by means of standardized mortality ratios. Life expectancy was calculated using life table analysis. Multivariate proportional hazard models were used to assess the effect of seniority, time from first employment, and other occupational characteristics on mortality. RESULTS: The cohort consists of 4640 fire fighters accumulating 111796 person years. Vital status could be determined for 98.2% of the cohort. By the end of follow up 1052 person were deceased. Standardized Mortality Ratio (SMR) for the total cohort was 0.79 (95% CI, 0.74–0.84) compared to Hamburg reference data and 0.78 (95% CI, 0.74–0.83) compared to National German reference data. Conditional life expectancy of a 30 year old fire fighter was 45.3 years as compared to 42.9 year of a German male in normal population. Job tasks, rank status and early retirement negatively influenced mortality. For fire fighters with comparably short duration of employment the mortality advantage diminished with longer time since first employment. SMR of persons who retired early was 1.25 (95% CI, 1.13–1.60) in reference to the general German population and the SMR of 1.71 (1.18–2.50) in the multivariate regression model. CONCLUSION: A strong healthy worker effect was observed for the cohort, which diminished with longer time since first employment for fire fighters with shorter duration of employment, as expected. The negative effects on mortality of job tasks, rank status and in particular early retirement indicate the presence of undetermined and specific risks related to occupational hazards of fire fighters

    The Groebke-Blackburn-Bienayme Reaction

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    Imidazo[1,2a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry , we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    Get PDF
    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

    The Sample Analysis at Mars Investigation and Instrument Suite

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    Détermination de l'âge du granite du Bilstein

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    Hée Arlette, Coche A., Jarovoy Michel, Flesch Louis, Kraemer R. Détermination de l'âge du granite du Bilstein. In: Bulletin du Service de la carte géologique d'Alsace et de Lorraine, tome 12, n°2, 1959. pp. 97-102
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