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BackgroundOlder workers experience higher rates of fatal occupational injury than younger workers worldwide. In North Carolina, the population of older workers more than doubled between 2000 and 2017. In 2008, the Great Recession changed occupational patterns among all age groups. We examined annual rates and distribution of fatal occupational injuries experienced by older workers, comparing the pre-recession period (2000–2007) to the post-recession period (2009–2017).MethodsDetailed information on all fatal occupational injuries during the period between 1 January 2000 and 31 December 2017 were abstracted from the records of the North Carolina Office of the Chief Medical Examiner and the office of vital records. The decennial Census and American Community Survey were used to estimate the population at risk and derive annual rates of fatal occupational injury.ResultsDuring the study period, 537 occupational fatalities occurred among workers 55+ years of age. The rate of fatal occupational injury among older workers declined 2.8% per year, with a 7.7% yearly decline in the pre-recession period compared with a 1.4% increase per year in the post-recession period. Workers 65+ years of age experienced rate increases in both periods. The highest rates of unintentional fatal occupational injury (injuries that were not purposefully inflicted) were observed in forestry, fishing hunting and trapping, and wood building manufacturing. Intentional fatal occupational injury rates (homicide, suicide) were highest in transportation, gas/service stations and grocery/food stores.ConclusionsOlder workers have persistently high rates of fatal occupational injury in North Carolina before and after the Great Recession.

We aim to assess the reporting of key patient-level demographic and clinical characteristics among COVID-19 related randomized controlled trials (RCTs).We queried English-language articles from PubMed, Web of Science, clinicaltrials.gov, and the CDC library of gray literature databases using keywords of "coronavirus," "covid," "clinical trial" and "randomized controlled trial" from January 2020 to June 2021. From the search, we conducted an initial review to rule-out duplicate entries, identify those that met inclusion criteria (i.e., had results), and exclude those that did not meet the definition of an RCT. Lastly, we abstracted the demographic and clinical characteristics reported on within each RCT.From the initial 43 627 manuscripts, our final eligible manuscripts consisted of 149 RCTs described in 137 articles. Most of the RCTs (113/149) studied potential treatments, while fewer studied vaccines (29), prophylaxis strategies (5), and interventions to prevent transmission among those infected (2). Study populations ranged from 10 to 38 206 participants (median = 100, IQR: 60-300). All 149 RCTs reported on age, 147 on sex, 50 on race, and 110 on the prevalence of at least one comorbidity. No RCTs reported on income, urban versus rural residence, or other indicators of socioeconomic status (SES).Limited reporting on race and other markers of SES make it difficult to draw conclusions about specific external target populations without making strong assumptions that treatment effects are homogenous. These findings highlight the need for more robust reporting on the clinical and demographic profiles of patients enrolled in COVID-19 related RCTs.

Acquisition of medical data such as blood pressure, ECG, pulse, and other values is currently often carried out in doctor’s offices by physicians or medical staff. This requires valuable time of patients as well as of practices’ personel and can deliver specific data only of the time of the visit. In this paper we describe a different approach. Patients measure their biomedical vital data at home. Therefore a technical infrastructure together with a workflow were developed and applied within a current project with patients in a rural area. Vital data is transferred via smartphone apps to a cloud environment where doctors can easily access and assess the data.

Chemical risk assessment can benefit from integrating data across multiple evidence bases, especially in exposure-response curve (ERC) modeling when data across the exposure range are sparse.We estimated the ERC for benzene and acute myeloid leukemia (AML), by fitting linear and spline-based Bayesian meta-regression models that included summary risk estimates from non-AML and nonhuman studies as prior information. Our complete dataset included six human AML studies, three human leukemia studies, 10 human biomarker studies, and four experimental animal studies.A linear meta-regression model with intercept best predicted AML risks after cross-validation, both for the full dataset and AML studies only. Risk estimates in the low exposure range [40 parts per million (ppm)-years] from this model were comparable, but more precise when the ERC was derived using all available data than when using AML data only. Allowing for between-study heterogeneity, RRs and 95% prediction intervals (95% PI) at 5 ppm-years were 1.58 (95% PI, 1.01-3.22) and 1.44 (95% PI, 0.85-3.42), respectively.Integrating the available epidemiologic, biomarker, and animal data resulted in more precise risk estimates for benzene exposure and AML, although the large between-study heterogeneity hampers interpretation of these results. The harmonization steps required to fit the Bayesian meta-regression model involve a range of assumptions that need to be critically evaluated, as they seem crucial for successful implementation.By describing a framework for data integration and explicitly describing the necessary data harmonization steps, we hope to enable risk assessors to better understand the advantages and assumptions underlying a data integration approach.See related commentary by Keil, p. 695.

The main objective of this work was the construction of a numerical model using Advanced Process Simulation Software to represent the dynamic behaviour of a thermal storage system (TSS). The storage model was validated by comparing the results with the measured data of the storage process of the Andasol 2 solar power plant. Subsequently, a system analysis and system optimisation were carried out, and the stand-alone concept of the thermal storage system is presented. Stand-alone refers to an isolated use of the storage system without a solar power plant. During power peaks, this storage medium is heated with excess electrical power and later returned to the electrical grid through a steam cycle. Then, the system was optimised by modelling four models based on the type of storage medium and the temperature difference of the storage system. The four models, Andasol 2, SSalt max, Hitec, and Carbonate, were evaluated and compared in terms of the improvement in capacity and efficiency that can be achieved. The comparison shows that the preferred storage medium is carbonate salt due to the increases in both efficiency and capacity. The greatest increase in efficiency in terms of power generation can also be achieved with the Carbonate model (18.2%), whereas the amount of increase was 9.5% and 7.4% for each of SSalt max and Hitec, respectively. The goal of this analysis and system optimisation of a thermal salt storage system is to stabilise and relieve the local power grid.

BackgroundRespiratory exposure to silica is associated with the risk of death due to malignant and non-malignant disease. 2.3 million U.S. workers are exposed to silica. Occupational exposure limits for silica are derived from a number of lines of evidence, including observational studies. Observational studies may be subject to healthy worker survivor bias, which could result in underestimates of silica’s impact on worker mortality and, in turn, bias risk estimates for occupational exposure limits.MethodsUsing data on 65 999 workers pooled across multiple industries, we estimate the impacts of several hypothetical occupational exposure limits on silica exposure on lung cancer and all-cause mortality. We use the parametric g-formula, which can account for healthy worker survivor bias.ResultsAssuming we could eliminate occupational exposure, we estimate that there would be 20.7 fewer deaths per 1000 workers in our pooled study by age 80 (95% confidence interval: 14.5, 26.8), including 3.91 fewer deaths due to lung cancer (95% CI: 1.53, 6.30). Less restrictive interventions demonstrated smaller, but still substantial risk reductions.ConclusionsOur results suggest that occupational exposure limits for silica can be further strengthened to reduce silica-associated mortality and illustrate how current risk analysis for occupational limits can be improved.

Mutations of NPHS1 or NPHS2, the genes encoding nephrin and podocin, as well as the targeted disruption of CD2-associated protein (CD2AP), lead to heavy proteinuria, suggesting that all three proteins are essential for the integrity of glomerular podocytes, the visceral glomerular epithelial cells of the kidney. It has been speculated that these proteins participate in common signaling pathways; however, it has remained unclear which signaling proteins are actually recruited by the slit diaphragm protein complex in vivo. We demonstrate that both nephrin and CD2AP interact with the p85 regulatory subunit of phosphoinositide 3-OH kinase (PI3K) in vivo, recruit PI3K to the plasma membrane, and, together with podocin, stimulate PI3K-dependent AKT signaling in podocytes. Using two-dimensional gel analysis in combination with a phosphoserine-specific antiserum, we demonstrate that the nephrin-induced AKT mediates phosphorylation of several target proteins in podocytes. One such target is Bad; its phosphorylation and inactivation by 14-3-3 protects podocytes against detachment-induced cell death, suggesting that the nephrin-CD2AP-mediated AKT activity can regulate complex biological programs. Our findings reveal a novel role for the slit diaphragm proteins nephrin, CD2AP, and podocin and demonstrate that these three proteins, in addition to their structural functions, initiate PI3K/AKT-dependent signal transduction in glomerular podocytes.

Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria.

Radon is estimated to cause over 20,000 lung cancer deaths per year in the United States. Occupational studies have been used to estimate population risks. These studies may be subject to healthy w...

Workers employed at the Oak Ridge National Laboratory (ORNL) were potentially exposed to a range of chemical and physical hazards, many of which are poorly characterized. We compared the observed deaths among workers to expectations based upon US mortality rates.The cohort included 22,831 workers hired between January 1, 1943 and December 31, 1984. Vital status and cause of death information were ascertained through December 31, 2008. Standardized mortality ratios (SMRs) were computed separately for males and females using US and Tennessee mortality rates; SMRs for men were tabulated separately for monthly-, weekly-, and hourly-paid workers.Hourly-paid males had more deaths due to cancer of the pleura (SMR = 12.09, 95% CI: 4.44, 26.32), cancer of the bladder (SMR = 1.89, 95% CI: 1.26, 2.71), and leukemia (SMR = 1.33, 95% CI: 0.87, 1.93) than expected based on US mortality rates. Female workers also had more deaths than expected from cancer of the bladder (SMR = 2.20, 95% CI: 1.20, 3.69) and leukemia (SMR = 1.64, 95% CI: 1.09, 2.36). The pleural cancer excess has only appeared since the 1980s, approximately 40 years after the start of operations. The bladder cancer excess was larger among workers who also had worked at other Oak Ridge nuclear weapons facilities, while the leukemia excess was among people who had not worked at other DOE facilities.Occupational hazards including asbestos and ionizing radiation may contribute to these excesses.