The National Registry for Radiation Workers (NRRW) is the largest epidemiological study of UK radiation workers. Following the first analysis published in 1992, a second analysis has been conducted using an enlarged cohort of 124,743 workers, updated dosimetry and personal data for some workers, and a longer follow-up. Overall levels of mortality were found to be less than those expected from national rates; the standardised mortality ratio for all causes was 82, increasing to 89 after adjusting for social class. This 'healthy worker effect' was particularly strong for lung cancer and for some smoking-related non-malignant diseases. Analysis of potential radiation effects involved testing for any trend in mortality risk with external dose, after adjusting for likely confounding factors. For leukaemia, excluding chronic lymphatic leukaemia (CLL), the central estimate of excess relative risk (ERR) per Sv was similar to that estimated for the Japanese atomic bomb survivors at low doses (without the incorporation of a dose-rate correction factor); the corresponding 90% confidence limits for this trend were tighter than in the first analysis, ranging from just under four times the risk estimated at low doses from the Japanese atomic bomb survivors to about zero. For the grouping of all malignancies other than leukaemia, the central estimate of the trend in risk with dose was closer to zero than in the first analysis; also, the 90% confidence limits were tighter than before and included zero. Since results for lung cancer and non-malignant smoking-related diseases suggested the possibility of confounding by smoking, an examination was made, as in the first analysis, of all malignancies other than leukaemia and lung cancer. In this instance the central estimate of the ERR per Sv was similar to that from the A-bomb data (without the incorporation of a dose-rate correction factor), with a 90% confidence interval ranging from about four times the A-bomb value to less than zero. For multiple myeloma there was an indication of an increasing trend in risk with external dose (p = 0.06), although the evidence for this trend disappeared after omitting workers monitored for exposure to internal emitters. The second NRRW analysis provides stronger inferences than the first on occupational radiation exposure and cancer mortality; the 90% confidence intervals for the risk per unit dose are tighter than before, and now exclude values which are greater than four times those seen among the Japanese A-bomb survivors, although they are also generally consistent with an observation of no raised risk. Furthermore, there is evidence, of borderline statistical significance, of an increasing risk for leukaemia excluding CLL, and, as with solid cancers, the data are consistent with the A-bomb findings.
We asked if the higher work of breathing (Wb) during exercise in women compared with men is explained by biological sex. We created a statistical model that accounts for both the viscoelastic and the resistive components of the total Wb and independently compares the effects of biological sex. We applied the model to esophageal pressure-derived Wb values obtained during an incremental cycle test to exhaustion. Subjects were healthy men (n = 17) and women (n = 18) with a range of maximal aerobic capacities (V̇o2 max range: men = 40-68 and women = 39-60 ml·kg(-1)·min(-1)). We also calculated the dysanapsis ratio using measures of lung recoil and forced expiratory flow as index of airway caliber. By applying the model we found that the differences in the total Wb during exercise in women are due to a higher resistive Wb rather than viscoelastic Wb. We also found that the higher resistive Wb is independently explained by biological sex. To account for the known effect of lung volumes on the dysanapsis ratio we compared the sexes with an analysis of covariance procedures and found that when vital capacity was accounted for the adjusted mean dysanapsis ratio is statistically lower in women (0.17 vs. 0.25 arbitrary units; P < 0.05). Our collective findings suggest that innate sex-based differences may exist in human airways, which result in significant male-female differences in the Wb during exercise in healthy subjects.
The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.
The Alpha-Risk study required the reconstruction of doses to lung and red bone marrow for lung cancer and leukaemia cases and their matched controls from cohorts of nuclear workers in the UK, France and Belgium. The dosimetrists and epidemiologists agreed requirements regarding the bioassay data, biokinetic and dosimetric models and dose assessment software to be used and doses to be reported. The best values to use for uncertainties on the monitoring data, setting of exposure regimes and characteristics of the exposure material, including lung solubility, were the responsibility of the dosimetrist responsible for each cohort. Among 1721 subjects, the median absorbed dose to the lung from alpha radiations was 2.1 mGy, with a maximum dose of 316 mGy. The lung doses calculated reflect the higher levels of exposure seen among workers in the early years of the nuclear industry compared to today.
Europium (152,154Eu) was intravenously injected into rats as: (i) the chloride salt at pH 7.4, (ii) the chloride salt at pH 3, (iii) the albumin complex and (iv) the DTPA complex, and tissue uptake was determined 24 h later. For the chlorides, the target organ for uptake was liver (about 60% of dose) whilst europium complexes were rapidly excreted in urine and were predominantly taken up into the kidney (about 0.5% of dose) and bone. Liver uptake of EuCl3, pH 7.4, corresponded to that of a colloidal material with most 152Eu present in the non-hepatocyte population; however, EuCl3, pH 3, was handled in a different manner, with significant uptake by hepatocytes. The differing tissue distributions of EuCl3 and Eu-albumin suggest that plasma albumin does not readily bind injected EuCl3. Renal uptake of europium, although a relatively low proportion of the injected dose, was associated with many subcellular fractions, including lysosomes, suggesting significant intracellular uptake and thus possible retention.
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