322 research outputs found

    Modification of Bennett's Method for the Histochemical Demonstration of Free Sulfhydryl Groups in Skin11

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    Contact Dermatitis from Rubber Caused by Allergic Sensitivity to Thio-Beta-Naphthol*

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    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

    Towards an optimal aiming for molten salt power towers

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    Finding a suitable aiming strategy for receivers of power towers can be challenging, especially for receivers using molten salt as heat transfer fluid as the allowable flux density decreases dramatically with increasing salt temperature. In this paper a very fast, steady-state model for the molten salt receiver is presented. This model is combined with a ray-tracing software and a metaheuristic optimization procedure. The thermal model is used to calculate the actual temperature and mass flow in the receiver which are then used to calculate the operational limits for the flux density. It is demonstrated that such an optimized aiming strategy can outperform a parameter based aiming strategies by more than 2%

    Evaluation of a questionnaire to assess selected infectious diseases and their risk factors: Findings of a multicenter study

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    Background/objectives The risk to die from an infectious disease in Germany has been continuously decreasing over the last century. Since infections are, however, not only causes of death but risk factors for diseases like cardiovascular diseases, it is essential to monitor and analyze their prevalence and frequency, especially in consideration of the increased life expectancy. To gain more knowledge about infectious diseases as risk factors and their implications on the condition and change of the immune status, the German National Cohort (GNC), a population-based prospective cohort study, will recruit 200,000 subjects between 2014 and 2017. In Pretest 1, a feasibility study for the GNC, we evaluated a self-administered and self-report questionnaire on infectious diseases and on the use of health care facilities (hereinafter called “ID Screen”) for feasibility and validity. Methods: From August–November 2011, 435 participants between the ages of 20–69 completed the ID Screen. All subjects had been recruited via a random sample from the local residents’ registration offices by 4 of the 18 participating study centers. The questionnaire encompasses 77 variables in six sections assessing items such as 12-month prevalence of infections, cumulative prevalence of infectious diseases, visit of health care facilities and vaccination. The feasibility was amongst others evaluated by assessing the completeness and comprehensiveness of the questionnaire. To assess the questionnaires ability to measure “immune status” and “susceptibility to infections”, multivariate analysis was used. Results: The overall practicability was good and most items were well understood, demonstrated by 5 % of missing values. However, direct comparison of the items 12-month prevalence and lifetime prevalence of nephritis/pyelitis showed poor agreement and thereby poor understanding by 80 % of the participants, illustrating the necessity for a clear, lay person appropriate description of rare diseases to increase comprehensibility. The questionnaire will be used to support the assessment of immune dysfunction and frequency of infection. An analysis of these constructs in an exploratory factor analysis revealed limited applicability due to low interitem correlation (Cronbach’s α < 0.5). This is corroborated by the extraction of more than one factor with a Kaiser–Meyer–Olkin measure of 0.6 instead of a unidimensional latent construct for “immune status”. Conclusion: All in all, the ID Screen is a good and reliable tool to measure infectious diseases as risk factors and outcome in general, but requires a better translation of infection specific terms into lay person terms. For the assessment of the overall immune status, the tool has strong limitations. Vaccinations status should also rather be assessed based on vaccination certificates than on participants’ recall. Electronic supplementary material The online version of this article (doi: 10.1007/s00103-014-2052-y) contains supplementary material, which is available to authorized users

    Active megadetachment beneath the western United States

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    Geodetic data, interpreted in light of seismic imaging, seismicity, xenolith studies, and the late Quaternary geologic history of the northern Great Basin, suggest that a subcontinental-scale extensional detachment is localized near the Moho. To first order, seismic yielding in the upper crust at any given latitude in this region occurs via an M7 earthquake every 100 years. Here we develop the hypothesis that since 1996, the region has undergone a cycle of strain accumulation and release similar to “slow slip events” observed on subduction megathrusts, but yielding occurred on a subhorizontal surface 5–10 times larger in the slip direction, and at temperatures >800°C. Net slip was variable, ranging from 5 to 10 mm over most of the region. Strain energy with moment magnitude equivalent to an M7 earthquake was released along this “megadetachment,” primarily between 2000.0 and 2005.5. Slip initiated in late 1998 to mid-1999 in northeastern Nevada and is best expressed in late 2003 during a magma injection event at Moho depth beneath the Sierra Nevada, accompanied by more rapid eastward relative displacement across the entire region. The event ended in the east at 2004.0 and in the remainder of the network at about 2005.5. Strain energy thus appears to have been transmitted from the Cordilleran interior toward the plate boundary, from high gravitational potential to low, via yielding on the megadetachment. The size and kinematic function of the proposed structure, in light of various proxies for lithospheric thickness, imply that the subcrustal lithosphere beneath Nevada is a strong, thin plate, even though it resides in a high heat flow tectonic regime. A strong lowermost crust and upper mantle is consistent with patterns of postseismic relaxation in the southern Great Basin, deformation microstructures and low water content in dunite xenoliths in young lavas in central Nevada, and high-temperature microstructures in analog surface exposures of deformed lower crust. Large-scale decoupling between crust and upper mantle is consistent with the broad distribution of strain in the upper crust versus the more localized distribution in the subcrustal lithosphere, as inferred by such proxies as low P wave velocity and mafic magmatism

    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

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    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

    A self administered reliable questionnaire to assess lower bowel symptoms

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    <p>Abstract</p> <p>Background</p> <p>Bowel symptoms are considered indicators of the presence of colorectal cancer and other bowel diseases. Self administered questionnaires that elicit information about lower bowel symptoms have not been assessed for reliability, although this has been done for upper bowel symptoms. Our aim was to develop a self administered questionnaire for eliciting the presence, nature and severity of lower bowel symptoms potentially related to colorectal cancer, and assess its reliability.</p> <p>Methods</p> <p>Immediately before consulting a gastroenterologist or colorectal surgeon, 263 patients likely to have a colonoscopy completed the questionnaire. Reliability was assessed in two ways: by assessing agreement between patient responses and (a) responses given by the doctor at the consultation; and (b) responses given by patients two weeks later.</p> <p>Results</p> <p>There was more than 75% agreement for 78% of the questions for the patient-doctor comparison and for 92% of the questions for the patient-patient comparison. Agreement for the length of time a symptom was present, its severity, duration, frequency of occurrence and whether or not medical consultation had been sought, all had agreement of greater than 70%. Over all questions, the chance corrected agreement for the patient-doctor comparison had a median kappa of 65% (which represents substantial agreement), interquartile range 57–72%. The patient-patient comparison also showed substantial agreement with a median kappa of 75%, interquartile range 68–81%.</p> <p>Conclusion</p> <p>This self administered questionnaire about lower bowel symptoms is a useful way of eliciting details of bowel symptoms. It is a reliable instrument that is acceptable to patients and easily completed. Its use could guide the clinical consultation, allowing a more efficient, comprehensive and useful interaction, ensuring that all symptoms are assessed. It will also be a useful tool in research studies on bowel symptoms and their predictive value for colorectal cancer and other diseases. Studies assessing whether bowel symptoms predict the presence of colorectal cancer should provide estimates of the reliability of the symptom elicitation.</p

    BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

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    Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

    Can user testing of a clinical trial patient information sheet make it fit-for-purpose? - a randomized controlled trial

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    Background: The participant information sheet (PIS) provided to potential trial participants is a critical part of the process of valid consent. However, there is long-standing concern that these lengthy and complex documents are not fit-for-purpose. This has been supported recently through the application of a performance-based approach to testing and improving readability called user testing. This method is now widely used to improve patient medicine leaflets - determining whether people can find and understand key facts. This study applied for the first time a controlled design to determine whether a PIS developed through user testing had improved readability over the original, using a sheet from a UK trial in acute myeloid leukemia (AML16). Methods: In the first phase the performance of the original PIS was tested on people in the target group for the trial. There were three rounds of testing including 50 people in total - with the information revised according to its performance after each of the first 2 rounds. In the second phase, the revised PIS was compared with the original in a parallel groups randomised controlled trial (RCT) A total of 123 participants were recruited and randomly allocated to read one version of the PIS to find and show understanding of 21 key facts. Results: The first, developmental phase produced a revised PIS significantly altered in its wording and layout. In the second, trial phase 66% of participants who read the revised PIS were able to show understanding of all aspects of the trial, compared with 15% of those reading the original version (Odds Ratio 11.2; Chi-square = 31.5 p < .001). When asked to state a preference, 87.1% participants chose the revised PIS (Sign test p < .001). Conclusions: The original PIS for the AML16 trial may not have enabled valid consent. Combining performance-based user testing with expertise in writing for patients and information design led to a significantly improved and preferred information sheet. User testing is an efficient method for indicating strengths and weaknesses in trial information, and Research Ethics Committees and Institutional Review Boards should consider requesting such testing, to ensure that PIS are fit-for-purpose
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