Developing a company-specific job exposure matrix for the Asbest Chrysotile Cohort Study

ObjectivesExposure assessment for retrospective industrial cohorts are often hampered by limited availability of historical measurements. This study describes the development of company-specific job-exposure matrices (JEMs) based on measurements collected over five decades for a cohort study of 35 837 workers (Asbest Chrysotile Cohort Study) in the Russian Federation to estimate their cumulative exposure to chrysotile containing dust and fibres.MethodsAlmost 100 000 recorded stationary dust measurements were available from 1951-2001 (factories) and 1964–2001 (mine). Linear mixed models were used to extrapolate for years where measurements were not available or missing. Fibre concentrations were estimated using conversion factors based on side-by-side comparisons. Dust and fibre JEMs were developed and exposures were allocated by linking them to individual workers’ detailed occupational histories.ResultsThe cohort covered a total of 515 355 employment-years from 1930 to 2010. Of these individuals, 15% worked in jobs not considered professionally exposed to chrysotile. The median cumulative dust exposure was 26 mg/m3 years for the entire cohort and 37.2 mg/m3 years for those professionally exposed. Median cumulative fibre exposure was 16.4 fibre/cm3 years for the entire cohort and 23.4 fibre/cm3 years for those professionally exposed. Cumulative exposure was highly dependent on birth cohort and gender. Of those professionally exposed, women had higher cumulative exposures than men as they were more often employed in factories with higher exposure concentrations rather than in the mine.ConclusionsUnique company-specific JEMs were derived using a rich measurement database that overlapped with most employment-years of cohort members and will enable estimation of quantitative exposure–response.

Metabolism is not a Major Contributor to the Toxicity of Piperaquine, a Major Partner Antimalarial in Artemisinin-Based Combination Therapy

Background: Hepatocellular damage has been reported for the antimalarial piperaquine (PQ) in the clinic after cumulative doses. Objectives: The role of metabolism in PQ toxicity was evaluated, and the mechanism mediating PQ hepatotoxicity was investigated. Method: The toxicity of PQ and its major metabolite (PQ N-oxide; M1) in mice was evaluated in terms of serum biochemical parameters. The role of metabolism in PQ toxicity was investigated in mice pretreated with an inhibitor of CYP450 (ABT) and/or FMO enzyme (MMI). The dose-dependent pharmacokinetics of PQ and M1 were studied in mice. Histopathological examination was performed to reveal the mechanism mediating PQ hepatotoxicity. Results: Serum biochemical levels (ALT and BUN) increased significantly (P < 0.05) in mice after three-day oral doses of PQ (> 200 mg/kg/day), indicating hepatotoxicity and nephrotoxicity of PQ at a high dose. Weaker toxicity was observed for M1. Pretreatment with ABT and/or MMI did not increase PQ toxicity. PQ and M1 showed linear pharmacokinetics in mice after a single oral dose, and multiple oral doses led to their cumulative exposures. Histopathological examination showed that a high dose of PQ (> 200 mg/kg/day for three days) could induce hepatocyte apoptosis. The mRNA levels of targets in NF-κB and p53 pathways could be up-regulated by 2-30-fold in mice by PQ or M1. Conclusions: PQ metabolism led to detoxification of PQ, but there was a low possibility of altered toxicity induced by metabolism inhibition. The hepatotoxicity of PQ and its N-oxidation metabolite was partly mediated by NF-κB inflammatory pathway and p53 apoptosis pathway.

Cumulative exposure to psychosocial stressors at work and global cognitive function: the PROspective Quebec Study on Work and Health

ObjectivesPsychosocial stressors at work have been proposed as modifiable risk factors for mild cognitive impairment (MCI). This study aimed to evaluate the effect of cumulative exposure to psychosocial stressors at work on cognitive function.MethodsThis study was conducted among 9188 white-collar workers recruited in 1991–1993 (T1), with follow-ups 8 (T2) and 24 years later (T3). After excluding death, losses to follow-up and retirees at T2, 5728 participants were included. Psychosocial stressors at work were measured according to the Karasek’s questionnaire. Global cognitive function was measured with the Montreal Cognitive Assessment. Cumulative exposures to low psychological demand, low job control, passive job and high strain job were evaluated using marginal structural models including multiple imputation and inverse probability of censoring weighting.ResultsIn men, cumulative exposures (T1 and T2) to low psychological demand, low job control or passive job were associated with higher prevalences of more severe presentation of MCI (MSMCI) at T3 (Prevalence ratios (PRs) and 95% CIs of 1.50 (1.16 to 1.94); 1.38 (1.07 to 1.79) and 1.55 (1.20 to 2.00), respectively), but not with milder presentation of MCI. In women, only exposure to low psychological demand or passive job at T2 was associated with higher prevalences of MSMCI at T3 (PRs and 95% CI of 1.39 (0.97 to 1.99) and 1.29 (0.94 to 1.76), respectively).ConclusionsThese results support the deleterious effect of a low stimulating job on cognitive function and the cognitive reserve theory. Psychosocial stressors at work could be part of the effort for the primary prevention of cognitive decline.

Abstract P218: The Association Of Mid-life Cumulative Exposure To Systolic Blood Pressure, Myocardial Oxygen Demand, And Hypertension With Later-life Central Arterial Stiffness And Its 5-year Change: The Atherosclerosis Risk In Communities Study - Neurocognitive Study (ARIC-NCS)

Background: Greater central artery stiffness predicts cardiovascular disease and all-cause mortality, thus understanding arterial stiffness determinants has prevention implications. Reports of the temporal association of blood pressure with arterial stiffness are conflicting and the association with myocardial oxygen demand has not been evaluated. Objective: Characterize the association of mid- to later-life cumulative exposure to systolic blood pressure (SBP), myocardial oxygen demand, and hypertension (HTN) with arterial stiffness and its 5-year change in older adults. Methods: We included 1,975 adults (1151 women; 359 Black; visit 5 mean age 74 years) examined in visits 5 (2011-13) and 6 or 7 (2016-19) of the population-based ARIC-NCS with measures of arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)). Higher cfPWV indicates greater arterial stiffness. We calculated cumulative exposures as the sum of averages from four consecutive visits from 1987-89 to 1996-98 divided by total time. Myocardial oxygen demand was calculated as the rate pressure product (RPP): (SBP x heart rate)/1,000. We derived HTN duration as the time since first HTN detection. Associations of cumulative exposures with visit 5 cfPWV and the 5-year cfPWV change were evaluated by multivariable linear regression adjusted for demographics and cardiometabolic factors. Results: Over the mean 5.7 years between visits 5 and 6 or 7, cfPWV increased by 144.9 cm/s (SD: 276.0; range -680.0, 961.5 cm/s). HTN at any visit, duration, and the time-weighted cumulative measures were associated with higher visit 5 cfPWV (Table). Prevalent HTN was inversely associated with cfPWV change. No statistically significant associations were observed for the other exposures and cfPWV change. Conclusion: Cumulative exposure to SBP, RPP, and HTN are modifiable traits associated with higher cfPWV at later-life, but not with rate of cfPWV change in older adulthood. HTN at visit 5 was associated with lower cfPWV change, albeit the change is of small magnitude.

Optimizing Helmet Pad Placement Using Computational Predicted Injury Pattern to Reduce Mild Traumatic Brain Injury

ABSTRACT Introduction This effort, motivated and guided by prior simulated injury results of the unprotected head, is to assess and compare helmet pad configurations on the head for the effective mitigation of blast pressure transmission in the brain in multiple blast exposure environments. Materials and Methods A finite element model of blast loading on the head with six different helmet pad configurations was used to generate brain model biomechanical responses. The blast pressure attenuation performance of each pad configuration was evaluated by using the calculated pressure exposure fraction in the brain model. Monte Carlo simulations generated repetitive blast cumulative exposures. Results Significant improvement of a 6-Pad Modified configuration compared to a 6-Pad Baseline configuration indicates the importance of providing protection against the side blast. Both 12-Pad configurations are very effective in mitigating pressure in the brain. Repetitive blast exposure statistics for operational exposures shows that pad configurations with a larger number of pads and smaller gaps between pads perform better than the configurations with a smaller number of pads and larger gaps between pads. Conclusions Optimizing helmet pad size and/or placement could provide an improved protection by minimizing the side blast orientation effects and mitigating high-pressure fields in the brain from repeated blast exposures.

Occupational and non-occupational risk factors of sickness absence due to a shoulder lesion

ObjectivesTo determine the associations of lifestyle factors and cumulative physical workload exposures with sickness absence (SA) due to a shoulder lesion and to calculate their population attributable fractions (PAF).MethodsOur nationally representative cohort consisted of 4344 individuals aged 30–62 years who participated in the Finnish Health 2000 Survey. Education, smoking, chronic diseases and work exposures were assessed during interviews and leisure time physical activity with a questionnaire. Weight and height were measured. We followed the individuals for 15 years for the first SA due to a shoulder lesion. We used competing risk regression models. We calculated PAFs to assess the proportion of SA that was attributed to modifiable risk factors.ResultsIn the entire study population, risk factors of SA were age, daily smoking, being exposed for more than 10 years to physically heavy work and being exposed for more than 10 years to at least two specific physical workload factors. The overall PAF for the modifiable risk factors was 49%. In men, number of specific cumulative exposures, obesity and daily smoking predicted SA with PAF values of 34%, 30% and 14%, respectively. Among women, being exposed for more than 10 years to physically heavy work, number of specific cumulative exposures and daily smoking accounted for 23%, 22% and 15% of SA, respectively.ConclusionsReducing significantly prolonged exposure to physical workload factors, avoiding regular smoking in both genders and obesity in men has a high potential to prevent SA due to a shoulder lesion.

Simulation of Cumulative Exposure Statistics for Blast Pressure Transmission Into the Brain

Introduction This study develops and demonstrates an analysis approach to understand the statistics of cumulative pressure exposure of the brain to repetitive blasts events. Materials and Methods A finite element model of blast loading on the head was used for brain model biomechanical responses. The cumulative pressure exposure fraction (CPEF), ranging from 0.0 to 1.0, was used to characterize the extent and repetition of high pressures. Monte Carlo simulations were performed to generate repetitive blast cumulative exposures. Results The blast orientation effect is as influential as the blast overpressure magnitudes. A 75° (from the side) blast orientation can produce CPEF values exceeding traumatic brain injury pressure thresholds &gt;0.95 while, for the same blast overpressure, a 0° (front) blast orientation results in a CPEF &lt;0.25. Monte Carlo results for different sequences reflecting notional operational and training environments show that both mean values and standard deviations of CPEF reach the statistically equilibrium state at a finite value of n exposures for each sequence. Conclusions Statistical convergence of the brain pressure response metrics versus number of blasts for different exposures characterizes the transitions from “low” to “high” number of blasts and quantitatively highlights the differences between operational and training exposures.

“Losing Your Land You Feel Like You’re Losing Your Identity, Like You’re Experiencing Slow Death”: An Interview With Chief Thomas Dardar—Houma Nation

The Houma Nation was a major community hub for the Citizen Science Network seafood sampling conducted as part of the Gulf Coast Health Alliance: Health Risks Related to the Macondo Spill (GC-HARMS) research project. They also managed a clinical cohort to facilitate wellness checkups and collection of biological samples during the project. In this interview, Thomas Dardar, Principal Chief of the Houma Nation, outlines the historical and evolving changes—cultural as well as geophysical—that the Houma Nation must address in an uncharted era of climate-related impacts on weather patterns, sea levels, and sustainable land uses. He explores tribal efforts to cope with cumulative exposures, risks, and outcomes of industrial practices that have led to land loss and deterioration of natural marshlands. These changes challenge the perpetuation of traditional values based on multigenerational ties to their land base, and the bayous and estuarial waters they fish.