The primary aim of this laboratory-based human subject study was to evaluate the biomechanical loading associated with mining vehicles' multi-axial whole body vibration (WBV) by comparing joint ...torque and muscle activity in the neck and low back during three vibration conditions: mining vehicles' multi-axial, on-road vehicles' vertical-dominant, and no vibration. Moreover, the secondary aim was to determine the efficacy of a vertical passive air suspension and a prototype multi-axial active suspension seat in reducing WBV exposures and associated biomechanical loading measures. The peak joint torque and muscle activity in the neck and low back were higher when exposed to multi-axial vibration compared to the vertical-dominant or no vibration condition. When comparing the two suspension seats, there were limited differences in WBV, joint torque, and muscle activity. These results indicate that there is a need to develop more effective engineering controls to lower exposures to multi-axial WBV and related biomechanical loading.
Practitioner Summary: This study found that mining vehicles' multi-axial WBV can increase biomechanical loading in the neck and back more so than on-road vehicles' vertical-dominant WBV. While a newly-developed multi-axial active suspension seat slightly reduced the overall WBV exposures, the results indicate that more effective engineering controls should be developed.
Abbreviation: APDF: amplitude probability density function; Aw: weighted average vibration; BMI: body mass index; C7: The 7th cervical vertebra; EMG: electromyography; ES: erector spinae; IRB: institutional review board; ISO: International Organization for Standardization; L5/S1: the fifth lumbar vertebra (L5)/the first sacral vertebra(S1); MSDs: musculoskeletal disorders; MVC: maximum voluntary contraction; PSD: power spectral density; RVC: reference voluntary contraction; SCM: sternocleidomastoid; SD: standard deviation; SPL: splenius capitis; TRAP: trapezius; VDV: vibration dose value; WBV: whole body vibration
Background and Aims
As average temperatures rise and wildfire events increase in the United States, outdoor workers may be at an increased risk of injury. Recent research suggests that heat exposure ...increases outdoor workers' risk of traumatic injuries, but co‐exposures of heat and wildfire smoke have not been evaluated.
Methods
Oregon workers' compensation data from 2009 to 2018 were linked to satellite data by the date of injury to determine if acute heat (maximum Heat Index) and wildfire smoke (presence/absence) were associated with a traumatic injury. North American Industry Classification System (NAICS) codes were utilized to identify accepted, disabling injury claims from construction (NAICS 23) and agriculture, forestry, fishing, and hunting (NAICS 11). Claims from April to October were analyzed using negative binomial models to calculate incident rate ratios (IRR) by heat and wildfire exposure for All workers and specifically for Agricultural (Ag)/Construction workers.
Results
During the study period, 91,895 accepted, traumatic injury claims were analyzed. All workers had an injury IRR of 1.04 (95% confidence interval CI: 1.02–1.06) while Ag/Construction workers had an IRR of 1.11 (95% CI: 1.06–1.16) when wildfire smoke was present. When the maximum Heat Index was 75°F or greater, the IRR significantly increased as temperatures increased. When the maximum Heat Index was above 80–84°F, All workers had an IRR of 1.04 (95% CI: 1.01–1.06) while Ag/construction workers had an IRR of 1.14 (95% CI: 1.08–1.21) with risk increasing with increased temperatures. In joint models, heat remained associated with injury rates, but not wildfire smoke. No multiplicative interactions between exposures were observed.
Conclusion
Increasing temperature was associated with increased rates of traumatic injury claims in Oregon that were more pronounced in Ag/Construction workers. Future work should focus on further understanding these associations and effective injury prevention strategies.
Individuals with respiratory conditions, such as asthma, are particularly susceptible to adverse health effects associated with higher levels of ambient air pollution and temperature. This study ...evaluates whether hourly levels of fine particulate matter (PM.sub.2.5) and dry bulb globe temperature (DBGT) are associated with the lung function of adult participants with asthma. Global positioning system (GPS) location, respiratory function (measured as forced expiratory volume at 1 second (FEV.sub.1 )), and self-reports of asthma medication usage and symptoms were collected as part of the Exposure, Location, and Lung Function (ELF) study. Hourly ambient PM.sub.2.5 and DBGT exposures were estimated by integrating air quality and temperature public records with time-activity patterns using GPS coordinates for each participant (n = 35). The relationships between acute PM.sub.2.5, DBGT, rescue bronchodilator use, and lung function collected in one week periods and over two seasons (summer/winter) were analyzed by multivariate regression, using different exposure time frames. Short-term increases in PM.sub.2.5 were associated with increased rescue bronchodilator use, while DBGT was associated with higher lung function (i.e. FEV.sub.1). Further studies are needed to continue to elucidate the mechanisms of acute exposure to PM.sub.2.5 and DBGT on lung function in asthmatics.
We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, by aggregating data from four centenarian studies. The ...combined data included 2304 EL cases and 5879 controls. The analysis identified a locus in CDKN2B-AS1 (rs6475609,
= 7.13 × 10
) that almost reached genome-wide significance and four additional loci that were suggestively significant. Among these, a novel rare variant (rs145265196) on chromosome 11 had much higher longevity allele frequencies in cases of Ashkenazi Jewish and Southern Italian ancestry compared to cases of other European ancestries. We also correlated EL-associated SNPs with serum proteins to link our findings to potential biological mechanisms that may be related to EL and are under genetic regulation. The findings from the proteomic analyses suggested that longevity-promoting alleles of significant genetic variants either provided EL cases with more youthful molecular profiles compared to controls or provided some form of protection from other illnesses, such as Alzheimer's disease, and disease progressions.
Performing a genome-wide association study (GWAS) with a binary phenotype using family data is a challenging task. Using linear mixed effects models is typically unsuitable for binary traits, and ...numerical approximations of the likelihood function may not work well with rare genetic variants with small counts. Additionally, imbalance in the case-control ratios poses challenges as traditional statistical methods such as the Score test or Wald test perform poorly in this setting. In the last couple of years, several methods have been proposed to better approximate the likelihood function of a mixed effects logistic regression model that uses Saddle Point Approximation (SPA). SPA adjustment has recently been implemented in multiple software, including GENESIS, SAIGE, REGENIE and fastGWA-GLMM: four increasingly popular tools to perform GWAS of binary traits. We compare Score and SPA tests using real family data to evaluate computational efficiency and the agreement of the results. Additionally, we compare various ways to adjust for family relatedness, such as sparse and full genetic relationship matrices (GRM) and polygenic effect estimates. We use the New England Centenarian Study imputed genotype data and the Long Life Family Study whole-genome sequencing data and the binary phenotype of human extreme longevity to compare the agreement of the results and tools' computational performance. The evaluation suggests that REGENIE might not be a good choice when analyzing correlated data of a small size. fastGWA-GLMM is the most computationally efficient compared to the other three tools, but it appears to be overly conservative when applied to family-based data. GENESIS, SAIGE and fastGWA-GLMM produced similar, although not identical, results, with SPA adjustment performing better than Score tests. Our evaluation also demonstrates the importance of adjusting by full GRM in highly correlated datasets when using GENESIS or SAIGE.
Case control studies of nonagenarians and centenarians provide evidence that long-lived individuals do not differ in the rate of disease associated variants compared to population controls. These ...results suggest that an enrichment of novel protective variants, rather than a lack of disease associated variants, determine the genetic predisposition to exceptionally long lives. Using data from the Long Life Family Study (LLFS), we sought to replicate these findings and extend them to include a larger number of disease-specific risk alleles. To accomplish this goal, we built a genetic risk score for each of four age-related disease groups: Alzheimer's disease, cardiovascular disease and stroke, type 2 diabetes, and various cancers and compared the distribution of these scores between older participants of the LLFS, their offspring and their spouses. The analyses showed no significant differences in distribution of the genetic risk scores for cardiovascular disease and stroke, type 2 diabetes, or cancer between the groups, while participants of the LLFS appeared to carry an average 1% fewer risk alleles for Alzheimer's disease compared to spousal controls and, while the difference may not be clinically relevant, it was statistically significant. However, the statistical significance between familial longevity and the Alzheimer's disease genetic risk score was lost when a more stringent linkage disequilibrium threshold was imposed to select independent genetic variants.
Recent work shows strong evidence of ancestry-based assortative mating in spouse pairs of the older generation of the Framingham Heart Study. Here, we extend this analysis to two studies of human ...longevity: the Long Life Family Study (LLFS), and the New England Centenarian Study (NECS). In the LLFS, we identified 890 spouse pairs spanning two generations, while in the NECS we used data from 102 spouse pairs including offspring of centenarians. We used principal components of genome-wide genotype data to demonstrate strong evidence of ancestry-based assortative mating in spouse pairs of the older generation and also confirm the decreasing trend of endogamy in more recent generations. These findings in studies of human longevity suggest that spouses marrying into longevous families may not be powerful controls for genetic association studies, and that there may be important ethnicity-specific, genetic influences and/or gene-environment interactions that influence extreme survival in old generations. In addition, the decreasing trend of genetic similarity of more recent generations might have ramifications for the incidence of homozygous rare variants necessary for survival to the most extreme ages.
Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we ...performed a genome-wide association study (GWAS) on personality factors assessed by NEO-five-factor inventory in individuals enrolled in the Long Life Family Study (LLFS), a study of 583 families (N up to 4595) with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p < 10(-8)) and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241) failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2 × 10(-7) was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value <10(-4) and 10(-5)), were also marginally significantly associated in this study (p-value <0.05), although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene-gene interactions affecting personality traits and longevity.
Linear mixed models have become a popular tool to analyze continuous data from family-based designs by using random effects that model the correlation of subjects from the same family. However, mixed ...models for family data are challenging to implement with the BUGS (Bayesian inference Using Gibbs Sampling) software because of the high-dimensional covariance matrix of the random effects. This paper describes an efficient parameterization that utilizes the singular value decomposition of the covariance matrix of random effects, includes the BUGS code for such implementation, and extends the parameterization to generalized linear mixed models. The implementation is evaluated using simulated data and an example from a large family-based study is presented with a comparison to other existing methods.
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