The method of processing and the results of measurements of 131I content in the thyroids of Russian people performed in May-June 1986 are presented. The contribution of radiation from Cs radionuclides in the human body was taken into account in the processing of measurement data with an SRP-68-01 device. The greatest individual 131I content was found in the thyroids of inhabitants of the Bryansk region, up to 250-350 kBq, and in the Tula and Orel regions, up to 100 kBq. The average 131I thyroid activity in the middle of May 1986 reached 80 kBq for inhabitants of some settlements in the Bryansk region, 5-8 kBq in the Tula region and 5 kBq in the Orel region.
Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. Electronic address: email@example.com.
Noninvasive scoring systems are used to identify persons with advanced liver fibrosis. We investigated the ability of scoring systems to identify individuals in the general population at risk for future liver-related events.
We collected data from the Swedish Apolipoprotein Mortality Risk cohort on persons 35 to 79 years old who had blood samples collected from 1985 through 1996. We collected APRI (n = 127,302), BARD (n = 75,303), FIB-4 (n = 126,941), Forns (n = 122,419), and the nonalcoholic fatty liver disease (NAFLD) fibrosis scores (NFS, n = 13,160). We ascertained incident cases of cirrhosis or complications by linking Swedish health data registers. Cox regression was used to estimate hazard ratios (HRs) for severe liver disease at 5, 10, and a maximum follow-up time of 27 years. The predictive ability of the scores was evaluated using area under the receiver operating characteristic (AUROC) curve and C-statistics analyses. Our specific aims were to investigate the predictive capabilities of scoring systems for fatal and nonfatal liver disease, determine which scoring system has the highest level of accuracy, and investigate the predictive abilities of the scoring systems in persons with a higher probability of NAFLD at baseline.
A similar proportion of individuals evaluated by each scoring system developed cirrhosis or complications thereof (1.0%-1.4%). The incidence of any outcome was increased in intermediate- and high-risk groups compared with low-risk groups, with HRs at 10 years in the high-risk group ranging from 1.67 for the BARD score to 45.9 for the APRI score. The predictive abilities of all scoring systems decreased with time and were higher in men. All scoring systems were more accurate in persons with risk factors for NAFLD at baseline, with AUROCs reaching 0.83.
Higher scores from noninvasive scoring systems to evaluate fibrosis are associated with an increased risk of cirrhosis in a general population, but their predictive ability is modest. Performance was better when patients were followed for shorter time periods and in persons with a higher risk of NAFLD, with AUROC values reaching 0.83. New scoring systems are needed to evaluate risk of fibrosis in the general population and in primary care.
Revealing causal effects from correlative data is very challenging and a contemporary problem in human life history research owing to the lack of experimental approach. Problems with causal inference arising from measurement error in independent variables, whether related either to inaccurate measurement technique or validity of measurements, seem not well-known in this field. The aim of this study is to show how structural equation modeling (SEM) with latent variables can be applied to account for measurement error in independent variables when the researcher has recorded several indicators of a hypothesized latent construct.
As a simple example of this approach, measurement error in lifetime allocation of resources to reproduction in Finnish preindustrial women is modelled in the context of the survival cost of reproduction. In humans, lifetime energetic resources allocated in reproduction are almost impossible to quantify with precision and, thus, typically used measures of lifetime reproductive effort (e.g., lifetime reproductive success and parity) are likely to be plagued by measurement error. These results are contrasted with those obtained from a traditional regression approach where the single best proxy of lifetime reproductive effort available in the data is used for inference.
As expected, the inability to account for measurement error in women's lifetime reproductive effort resulted in the underestimation of its underlying effect size on post-reproductive survival.
This article emphasizes the advantages that the SEM framework can provide in handling measurement error via multiple-indicator latent variables in human life history studies.
Bone lead levels for 367 active and 14 retired lead smelter workers were measured in vivo by X-ray fluorescence in May-June 1994. The bone sites of study were the tibia and calcaneus; magnitudes of concentration were used to gauge lead body burden. Whole blood lead readings from the workers generated a cumulative blood lead index (CBLI) that approximated the level of lead exposure over time. Blood lead values for 204 of the 381 workers were gathered from workers returning from a 10-month work interruption that ended in 1991; their blood level values were compared to their tibia and calcaneus lead levels. The resulting relations allowed constraints to be placed on the endogenous release of lead from bone in smelter works. Calcaneus lead levels were found to correlate strongly with those for tibia lead, and in a manner consistent with observations from other lead industry workers. Relations between bone lead concentration and CBLI demonstrated a distinctly nonlinear appearance. When the active population was divided by date of hire, a significant difference in the bone lead-CBLI slope emerged. After a correction to include the component of CBLI existing before the workers' employment at the smelter was made, this difference persisted. This implies that the transfer of lead from blood to bone in the workers has changed over time, possibly as a consequence of varying exposure conditions.
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Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibition of bone resorption without inhibition of bone formation. We investigated the role of acidification in human osteoclastic resorption and life span in vitro using inhibitors of chloride channels (NS5818/NS3696), the proton pump (bafilomycin) and cathepsin K. We found that bafilomycin and NS5818 dose dependently inhibited acidification of the osteoclastic resorption compartment and bone resorption. Inhibition of bone resorption by inhibition of acidification, but not cathepsin K inhibition, augmented osteoclast survival, which resulted in a 150 to 300% increase in osteoclasts compared to controls. We investigated the effect of inhibition of osteoclastic acidification in vivo by using the rat ovariectomy model with twice daily oral dosing of NS3696 at 50 mg/kg for 6 weeks. We observed a 60% decrease in resorption (DPYR), increased tartrate-resistant acid phosphatase levels, and no effect on bone formation evaluated by osteocalcin. We speculate that attenuated acidification inhibits dissolution of the inorganic phase of bone and results in an increased number of nonresorbing osteoclasts that are responsible for the coupling to normal bone formation. Thus, we suggest that acidification is essential for normal bone remodeling and that attenuated acidification leads to uncoupling with decreased bone resorption and unaffected bone formation.
Sex allocation theory predicts that in a population with a biased operational sex ratio (OSR), parents will increase their fitness by adjusting the sex ratio of their progeny towards the rarer sex, until OSR has reached a level where the overproduction of either sex no longer increases a parent's probability of having grandchildren. Furthermore, in a monogamous mating system, a biased OSR is expected to lead to lowered mean fecundity among individuals of the more abundant sex. We studied the influence of OSR on the sex ratio of newborns and on the population birth rate using an extensive data set (n = 14,420 births) from pre-industrial (1775-1850) Finland. The overall effect of current OSR on sex ratio at birth was significant, and in the majority of the 21 parishes included in this study, more sons were produced when males were rarer than females. This suggests that humans adjusted the sex ratio of their offspring in response to the local OSR to maximize the reproductive success of their progeny. Birth rate and, presumably, also population growth rate increased when the sex ratio (males:females) among reproductive age classes approached equality. However, the strength of these patterns varied across the parishes, suggesting that factors other than OSR (e.g. socioeconomic or environmental factors may also have influenced the sex ratio at birth and the birth rate.
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The antagonistic pleiotropy theory of senescence postulates genes or traits that have opposite effects on early-life and late-life performances. Because selection is generally weaker late in life, genes or traits that improve early-life performance but impair late-life performance should come to predominate. Variation in the strength of age-specific selection should then generate adaptive variation in senescence. We demonstrate this mechanism by comparing early and late breeders within a population of semelparous capital-breeding sockeye salmon (Oncorhynchus nerka). We show that early breeders (but not late breeders) are under strong selection for a long reproductive lifespan (RLS), which facilitates defence of their nests against disturbance by later females. Accordingly, early females invest less energy in egg production while reserving more for nest defence. Variation along this reproductive trade-off causes delayed or slower senescence in early females (average RLS of 26 days) than in late females (reproductive lifespan of 12 days). We use microsatellites to confirm that gene flow is sufficiently limited between early and late breeders to allow adaptive divergence in response to selection. Because reproductive trade-offs should be almost universal and selection acting on them should typically vary in time and space, the mechanism described herein may explain much of the natural variation in senescence.
Several methods exist to quantitate small-solute clearance by daily hemodialysis (HD) regimens, but these have not been empirically applied or compared.
In the London Daily/Nocturnal Hemodialysis Study, dosing and adequacy of quotidian HD regimens, both short daily HD (n = 11) and long nocturnal HD (n = 12), were compared with conventional thrice-weekly HD (n = 22) using several models. Urea clearance was computed by percentage of reduction in urea, kinetic modeling (single-pool Kt/V [spKt/V]), Daugirdas rate equation (equilibrated Kt/V [eKt/V]), and Gotch standardized Kt/V (stdKt/V).
Nocturnal HD patients maintained a mean single-session spKt/V of 1.64 throughout the study, similar to that of conventional HD patients (1.73), whereas daily HD patients showed a significant decrease in mean single-session spKt/V (0.93) compared with baseline (t(0)) values. Mean weekly spKt/V values increased from t(0) for both quotidian HD groups (9.08 for nocturnal HD, 5.55 for daily HD) and were higher in both quotidian HD groups compared with conventional HD patients. Weekly eKt/V, stdKt/V, and normalized protein equivalent of nitrogen appearance values showed similar trends. Comparison of the 3 different adequacy models showed an increase in weekly HD doses for both quotidian HD regimens compared with conventional HD; however, percentages of increases from t(0) to follow-up differed according to the model used. The calculated efficiency of dose delivery at the 10-month follow-up comparing daily HD with conventional HD was 257 +/- 26 minutes versus 306 +/- 17 stdKt/V unit delivered, respectively, amounting to almost 1 dialysis-hour saved per stdKt/V unit delivered for daily HD.
These results show that both quotidian HD regimens are more effective than conventional HD in improving weekly urea clearance measured by spKt/V, stdKt/V, and eKt/V.
The purpose of this study are to analyse adherence to antidepressant treatment over 2 years in Sweden among women and men who initiated treatment with citalopram and to identify groups at risk of non-adherence using trajectory models.
The study population, including individuals 18-85 years who initiated citalopram use between 1 July 2006 and 30 June 2007, was identified in the Swedish Prescribed Drug Register and followed for 2 years. Adherence was estimated with continuous measure of medication acquisition (CMA) and group-based trajectory modelling, a method which describes adherence patterns over time by estimating trajectories of adherence and the individual's probability of belonging to a specific trajectory.
The study population included 54,248 individuals, 64 % women. Mean CMA was 52 % among women and 50 % among men (p