This study was conducted to determine how well the TLV for HAL and the SI predict risk of CTS using a prospective cohort design with survival analysis. Both the TLV for HAL and the SI were found to predict risk of CTS when adjusted for relevant covariates.

We examined the behavior of alternative smoothing methods for modeling environmental epidemiology data. Model fit can only be examined when the true exposure-response curve is known and so we used simulation studies to examine the performance of penalized splines (Psplines), restricted cubic splines (RCS), natural splines (NS), and fractional polynomials (FP). Survival data were generated under six plausible exposure-response scenarios with a right skewed exposure distribution, typical of environmental exposures. Cox models with each spline or FP were fit to simulated datasets. The best models, e.g. degrees of freedom, were selected using default criteria for each method. The root mean-square error (rMSE) and area difference were computed to assess model fit and bias (difference between the observed and true curves). The test for linearity was a measure of sensitivity and the test of the null was an assessment of statistical power. No one method performed best according to all four measures of performance, however, all methods performed reasonably well. The model fit was best for P-splines for almost all true positive scenarios, although fractional polynomials and RCS were least biased, on average.

Background Left truncation occurs when subjects who otherwise meet entry criteria do not remain observable for a later start of follow-up. We investigated left truncation in occupational studies due to inclusion of workers hired before the start of follow-up in a simulation study. Methods Using Monte Carlo methods, we simulated null and positive associations between exposure (work duration) and mortality for 500 datasets of 5000 subjects, assuming the absence and presence of heterogeneity in susceptibility to disease and to the effect of exposure. We examined incident hires (followed since hire) and left-truncated prevalent hires (those hired before baseline and remained employed at baseline). We estimated the association ( β^1∗) as the mean slope using Cox proportional hazards with a linear term for exposure, under scenarios with and without susceptibility. Results With homogeneous susceptibility, there were no differences between incident and prevalent hires. Introducing only disease susceptibility did not change results. However, with heterogeneous susceptibility to the effect of exposure, downward bias was observed among prevalent hires under both the true null and positive exposure-response scenarios. The bias increased with time between hire and baseline (null: β^1∗=0.050.16667emfalse[SD=0.08false],0.16667emβ^1∗=-0.080.16667emfalse[SD=0.24false],0.16667emβ^1∗=-0.180.16667emfalse[SD=0.98false] if hired <15, 15 to <30, and ≥30 years before baseline, respectively), coincident with a decreasing percentage of susceptible subjects. Conclusions: Prevalent hires induce downward bias in an occupational cohort. This occurs because subjects who are less susceptible to the exposure remain exposed the longest, thereby underestimating the association.

JPE is associated with increased risk of LE. The SI and TLV for HAL are useful metrics for estimating JPE.

Objective This paper aimed to quantify exposure–response relationships between the American Conference of Governmental Industrial Hygienists’ (ACGIH) threshold limit value (TLV) for hand-activity level (HAL) and incidence of carpal tunnel syndrome (CTS). Methods Manufacturing and service workers previously studied by six research institutions had their data combined and re-analyzed. CTS cases were defined by symptoms and abnormal nerve conduction. Hazard ratios (HR) were calculated using proportional hazards regression after adjusting for age, gender, body mass index, and CTS predisposing conditions. Results The longitudinal study comprised 2751 incident-eligible workers, followed prospectively for up to 6.4 years and contributing 6243 person-years of data. Associations were found between CTS and TLV for HAL both as a continuous variable [HR 1.32 per unit, 95% confidence interval (95% CI) 1.11–1.57] and when categorized using the ACGIH action limit (AL) and TLV. Those between the AL and TLV and above the TLV had HR of 1.7 (95% CI 1.2–2.5) and 1.5 (95% CI 1.0–2.1), respectively. As independent variables (in the same adjusted model) the HR for peak force (PF) and HAL were 1.14 per unit (95% CI 1.05–1.25), and 1.04 per unit (95% CI 0.93–1.15), respectively. Conclusion Those with exposures above the AL were at increased risk of CTS, but there was no further increase in risk for workers above the TLV. This suggests that the current AL may not be sufficiently protective of workers. Combinations of PF and HAL are useful for predicting risk of CTS.

Despite loss in power and restricted exposure range, decreasing the relative proportion of prevalent to incident hires reduced HWSE bias, resulting in stronger evidence for a dose-response between silica exposure and lung cancer mortality.

This study quantified social life events hypothesized to affect the welfare of zoo African and Asian elephants, focusing on animals that were part of a large multi-disciplinary, multi-institutional elephant welfare study in North America. Age was calculated based on recorded birth dates and an age-based account of life event data for each elephant was compiled. These event histories included facility transfers, births and deaths of offspring, and births and deaths of non-offspring herd mates. Each event was evaluated as a total number of events per elephant, lifetime rate of event exposure, and age at first event exposure. These were then compared across three categories: species (African vs. Asian); sex (male vs. female); and origin (imported vs. captive-born). Mean age distributions differed (p<0.05) between the categories: African elephants were 6 years younger than Asian elephants, males were 12 years younger than females, and captive-born elephants were 20 years younger than imported elephants. Overall, the number of transfers ranged from 0 to 10, with a 33% higher age-adjusted transfer rate for imported African than imported Asian elephants, and 37% lower rate for imported females than males (p<0.05). Other differences (p<0.05) included a 96% higher rate of offspring births for captive-born females than those imported from range countries, a 159% higher rate of birthing event exposures for captive-born males than for their imported counterparts, and Asian elephant females being 4 years younger than African females when they produced their first calf. In summarizing demographic and social life events of elephants in North American zoos, we found both qualitative and quantitative differences in the early lives of imported versus captive-born elephants that could have long-term welfare implications.

Background: Rectal cancer has been previously associated with exposure to metalworking fluids in a cohort mortality study of autoworkers. Objective: To better specify the exposure-response relationship with straight metalworking fluids (mineral oils) by applying non-parametric regression methods that avoid linearity constraints and arbitrary exposure cut points and by lagging exposure to account for cancer latency, in a nested case-control analysis. Methods: In addition to the classical Poisson regression with categorical exposure, survival models with penalised splines were used to estimate the exposure-response relationship between cumulative exposure to straight metalworking fluid and mortality from rectal cancer. Exposures to water-based metalworking fluids were treated as potential confounders, and all exposures were lagged by 5, 10, 15 and 20 years to account for cancer latency. The influence of the highest exposures was dealt with by a log transformation and outlier removal. The sensitivity of the penalised splines to alternative criteria for model selection and to the placement of knots was also examined. Results: The hazard ratio for mortality from rectal cancer increased essentially linearly with cumulative exposure to straight metalworking fluid (with narrow confidence bands) up to a maximum of 2.2 at the 99th centile of exposure and then decreased (with wide confidence bands). Lagging exposure up to 15 years increased the initial steepness of the curve and raised the maximum hazard ratio to 3.2. Conclusions: Non-parametric smoothing of lagged exposures has shown stronger evidence for a causal association between straight metalworking fluid and rectal cancer than was previously described using standard analytical methods. This analysis suggests an exposure-response trend that is close to linear and statistically significant over most of the exposure range and that increases further with lagged exposures. Smoothing should be regularly applied to environmental studies with quantitative exposure estimates to refine characterisation of the dose-response relationship.