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ObjectivesTo define the prevalence and incidence of asthma in a large working population of pesticide workers and to assess which exposures are potentially of relevance to causing or aggravating this condition.MethodsA baseline cross-sectional study at recruitment (2013–2017, n=5817), with follow-up in 2018 (n=2578), was carried out in predominantly Great Britain based pesticide workers. At baseline, participants completed a health and work questionnaire which included questions on demographic, lifestyle, socioeconomic and work-related factors, pesticide use and doctor diagnosed health conditions. In January 2018, a follow-up questionnaire focused on respiratory ill health, with questions covering self-reported respiratory symptoms and doctor diagnosed respiratory conditions. The associations of various exposures with asthma were estimated using logistic regression adjusting for age as a continuous variable, and for sex where possible. An estimate of hours worked with pesticides in the previous year was calculated for each participant.ResultsAt baseline, 608 (10.4%) had doctor diagnosed asthma. In 2018 the figure was 297 (11.5% of the follow-up population); the incidence of new asthma cases between surveys was 1.7 cases per 1000 participants per year. At follow-up, 18.1% reported wheeze in the last 12 months, 73.2% of those with self-reported asthma noted it to be persistent and using a more specific definition of asthma (doctor diagnosed asthma with at least one asthma-related symptom in the last year); 6.8% (95% CI 5.9% to 7.9%) fulfilled this definition. At follow-up, 127 participants felt that their asthma was caused or made worse by their work, with 77 (63.6%) nominating organic dust, 13 (10.7%) unspecified dust, 12 (9.9%) chemicals, 9 (7.4%) mixed exposures, 7 (5.8%) physical agents and 3 (2.5%) fumes or other irritants. There was little or no association between high pesticide exposure and doctor diagnosed asthma or self-reported recent wheeze, although there was an elevated risk for work-related wheeze (OR for high exposure=2.67; 95% CI 1.16 to 6.18). High pesticide exposure (high vs low exposure category OR 2.68, 95% CI 1.28 to 5.60) was also associated with work-related chest tightness. Exposure to organic dusts was associated (significantly, p=0.026) with persistent asthma when adjusted for the effects of age and smoking.ConclusionsThis large study of pesticide workers has identified expected levels of doctor diagnosed asthma, and high levels of self-reported respiratory symptoms. Pesticide exposure was associated with an increased risk of self-reported work-related wheeze, but not with asthma or wheeze in general. Further work is needed to identify more clearly which exposures within a complex mixed exposure profile are likely causative in order to best focus interventions to reduce work-related asthma and related conditions.

ObjectiveNumerous exposure assessment methods (EAM) exist for investigating health effects of occupational exposure to pesticides. Direct (eg, biomonitoring) and indirect methods (eg, self-reported exposures) are however associated with degrees of exposure misclassification. We systematically reviewed EAM in studies of occupational pesticide exposure.MethodsWe searched for articles reporting observational epidemiological studies in MEDLINE and Embase published 1993 to 2017. The relative frequency of EAM was analysed according to EAM type (direct and indirect methods), health outcome, study design, study location (country) and specificity of assessment. Temporal trends in EAM were analysed.ResultsIn 1298 included articles 1521 EAM occurrences were documented. Indirect EAM (78.3%), primarily self-reported exposures (39.3%) and job titles assessments (9.5%), were mainly applied in case-control studies (95.0%), in high-income countries (85.0%) and in studies of doctor-diagnosed health outcomes (>85%). Direct EAM (20.8%), primarily biomonitoring of blood (15.6%) or urine (4.7%), were predominantly applied in cross-sectional studies (29.8%), in lower middle-income countries (40.9%) and in studies of neurological (50.0%) outcomes. Between 1993 to 2017 no distinct time trends regarding the ratio indirect to direct methods was seen. Within the category of indirect methods use of self-reported exposures and job exposure matrices increased while assessments by job titles and registers decreased. The use of algorithms showed no trend. The specificity of pesticide assessment increased since studies assessing exposure by using job title as a proxy declined. Assessments of type of pesticide increased.ConclusionOver the last 25 years, the ratio (5:1) of indirect to direct EAM applied in articles on occupational pesticide epidemiology stayed relatively constant; changes were mainly attributable to increasing use of self-reported exposures and job exposure matrices. This review, combined with studies assessing EAM validity, will inform on magnitudes of exposure misclassification and help improve the quality of studies on occupational pesticides exposure.

Soil Pb concentrations at urban agriculture sites (UAS) commonly exceed recommended safe levels. There is a lack of evidence regarding uptake of Pb by gardeners using such sites for food crops. Our study aimed to elucidate whether gardening in soil with raised Pb levels results in Pb body burdens of concern to health, and to assess confounding factors influencing Pb body burden. Our cross-sectional case study measured Pb in saliva and blood of UAS gardeners (n = 43), soil and produce samples from their UAS, and home tap water. Blood and saliva Pb concentrations were compared with those from non-UAS gardener controls (n = 29). A health risk threshold of 5 µg dL−1 blood Pb level (BLL) was selected in keeping with international guidance. Detailed surveys investigated individuals’ anthropometrics and potential Pb exposures from diet, and historic and everyday activities. Saliva was not found to be a suitable biomarker of adult Pb exposure in this context. Predictors of higher BLLs were being older, being male and eating more root vegetables and shrub fruit. Eating more green vegetables predicted a lower BLL, suggesting a protective effect against Pb uptake. UAS gardeners’ BLLs (geometric mean 1.53; range 0.6–4.1 µg dL−1) were not significantly higher (p = 0.39) than the control group (geometric mean 1.43; range 0.7–2.9 µg dL−1). All BLLs were below 5 µg dL−1 except one resulting from occupational exposure. Having paired the UAS gardeners with closely matched controls, we found Pb in UAS soils (with range 62–1300 mg kg−1from common urban sources) unlikely to pose an additional risk to adult health compared to their neighbours who did not access UAS. As such, other Pb sources may be the dominant factor controlling BLL.

To develop an evidence-based program for addressing the concerns of burnout and secondary trauma and building on the concept of resilience in oncology healthcare providers. 164 oncology staff, of which 160 were nurses, at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus, Ohio. Oncology nurses and other providers participated in the THRIVE© program, which consists of an eight-hour retreat designed to teach self-care strategies, a six-week private group study interaction on a social media platform, and a two-hour wrap-up session. The Compassion Fatigue Short Scale and the Connor-Davidson Resilience Scale were used to evaluate the program. In self-assessments prior to THRIVE, nurse managers demonstrated the greatest degree of burnout, and bedside/chairside nurses demonstrated the greatest degree of secondary trauma. The greatest improvement in average scores from pre- to postprogram assessment was in increased resilience and decreased burnout. Increased resilience scores were sustained for a six-month period after THRIVE participation. Oncology healthcare providers must identify self-care strategies that build their resilience for long, successful careers.

A suppressor screen using dwarf mutants of barley (Hordeum vulgare L.) led to the isolation of ‘overgrowth’ derivatives, which retained the original dwarfing gene but grew at a faster rate because of a new mutation. The new mutations were in the Slender1 (Sln1) gene (11/13 cases), which encodes the DELLA protein central to gibberellin (GA) signalling, showed 100% genetic linkage to Sln1 (1/13), or were in the Spindly1 (Spy1) gene (1/13), which encodes another protein involved in GA signalling. The overgrowth mutants were characterized by increased GA signalling, although the extent still depended on the background GA biosynthesis capacity, GA receptor function, and DELLA activity. A comparison between two GA responses, α-amylase production and leaf growth rate, revealed degrees of specificity for both the overgrowth allele and the GA response under consideration. Many overgrowth mutants were also isolated in a dwarf line of bread wheat (Triticum aestivum L.) and 19 new alleles were identified in the Rht-B1 gene, one of the ‘Green Revolution’ semi-dwarfing genes and the orthologue of Sln1. The sites of amino acid substitutions in the DELLA proteins of both species provide insight into DELLA function, and included examples where identical but independent substitutions were observed. In both species, the starting lines were too dwarfed to be directly useful in breeding programmes, but new overgrowth derivatives with semidwarf heights have now been characterized. The variation they exhibit in GA-influenced traits identifies novel alleles with perfect markers that are of potential use in breeding.

Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect methods often rely on workers’ imperfect recall of exposures, or job titles. We investigated how the applied exposure assessment method influenced risk estimates for some chronic diseases. In three meta-analyses the influence of exposure assessment method type on the summary risk ratio (sRR) of prostate cancer (PC) (25 articles), non-Hodgkin’s lymphoma (NHL) (29 articles) and Parkinson’s disease (PD) (32 articles) was investigated. Exposure assessment method types analysed were: group-level assessments (eg, job titles), self-reported exposures, expert-level assessments (eg, job-exposure matrices) and biomonitoring (eg, blood, urine). Additionally, sRRs were estimated by study design, publication year period and geographic location where the study was conducted. Exposure assessment method types were not associated with statistically significant different sRRs across any of the health outcomes. Heterogeneity in results varied from high in cancer studies to moderate and low in PD studies. Overall, case–control designs showed significantly higher sRR estimates than prospective cohort designs. Later NHL publications showed significantly higher sRR estimates than earlier. For PC, studies from North America showed significantly higher sRR estimates than studies from Europe. We conclude that exposure assessment method applied in studies of occupational exposure to pesticides appears not to have a significant effect on risk estimates for PC, NHL and PD. In systematic reviews of chronic health effects of occupational exposure to pesticides, epidemiological study design, publication year and geographic location, should primarily be considered.

Acid-sensing ion channels (ASICs) are Na+ channels activated by changes in pH within the peripheral and central nervous systems. Several different isoforms of ASICs combine to form trimeric channels, and their properties are determined by their subunit composition. ASIC2 subunits are widely expressed throughout the brain, where they heteromultimerize with their partnering subunit, ASIC1a. However, ASIC2 contributes little to the pH sensitivity of the channels, and so its function is not well understood. We found that ASIC2 increased cell surface levels of the channel when it is coexpressed with ASIC1a, and genetic deletion of ASIC2 reduced acid-evoked current amplitude in mouse hippocampal neurons. Additionally, ASIC2a interacted with the neuronal synaptic scaffolding protein PSD-95, and PSD-95 reduced cell surface expression and current amplitude in ASICs that contain ASIC2a. Overexpression of PSD-95 also reduced acid-evoked current amplitude in hippocampal neurons. This result was dependent upon ASIC2 since the effect of PSD-95 was abolished in ASIC2-/- neurons. These results lend support to an emerging role of ASIC2 in the targeting of ASICs to surface membranes, and allows for interaction with PSD-95 to regulate these processes.

ObjectivesAsbestos is an inflammatory agent, and there is evidence that inflammatory processes are involved in the development of cardiovascular disease. Whether asbestos is a risk factor for cardiovascular disease has not been established. The objective of this study was to investigate cardiovascular disease mortality in a large cohort of workers occupationally exposed to asbestos.MethodsCardiovascular disease mortality in a cohort of 98 912 asbestos workers, with median follow-up of 19 years, was analysed. Unadjusted and smoking-adjusted standardised mortality ratios (SMRs) were calculated. The association between indicators of asbestos exposure and mortality was analysed with Poisson regression models, for deaths occurring during the period 1971–2005.ResultsAltogether 15 557 deaths from all causes, 1053 deaths from cerebrovascular disease and 4185 deaths from ischaemic heart disease (IHD) occurred during follow-up. There was statistically significant excess mortality from cerebrovascular disease (SMR: men 1.63, women 2.04) and IHD (SMR: men 1.39, women 1.89). Job and birth cohort were associated with the risk of cerebrovascular and IHD mortality in the Poisson regression model including sex, age, smoking status, job, cohort and duration of exposure. For IHD only, duration of exposure was also statistically significant in this model.ConclusionsCerebrovascular and IHD mortality was significantly higher among these asbestos workers than in the general population and within the cohort mortality was associated with indicators of asbestos exposure. These findings provide some evidence that occupational exposure to asbestos was associated with cardiovascular disease mortality in this group of workers.

Cardiac afferent neurons have been shown to trigger overactivation of neurohormonal systems known to drive adverse cardiac remodeling following myocardial infarction (MI). Acid‐sensing ion channels (ASICs) that are highly expressed in cardiac sympathetic afferents sense ischemia‐induced myocardial acidosis. We hypothesized that genetic deletion of ASICs might abrogate disadvantageous remodeling after MI by disrupting afferent signaling pathways otherwise resulting in overactivation of neurohormonal responses. To test this, we induced MI in wild type (WT) and ASIC3−/− mice and assessed cardiac remodeling by serial echocardiography. We found that ASIC3−/− mice had less LV dilation relative to ischemic zone fraction, increased LV mass and wall thickness, and increased stroke volume compared to WT mice after MI. To investigate a potential role of the autonomic nervous system, we measured renal and splanchnic sympathetic nerve activity (SNA), heart rate and systolic blood pressure variability (sBPV), and hemodynamic responses to atropine and propranolol. Following MI, ASIC3−/− mice had lower baroreceptor‐renal SNA reflex sensitivity than WT mice, associated with elevated sBPV. Our data show that ASIC3 plays an important role in cardiac remodeling after MI potentially via modulation of baroreflex sensitivity and sBPV. ASIC3 may be further investigated as a potential therapeutic target in heart failure.

Objective To describe the results of two reliability studies and to assess the effect of training on interrater reliability scores. Design The first study (1) examined interrater and intrarater reliability scores (weighted and unweighted kappas) and (2) compared interrater reliability scores before and after training on the use of the Cleft Audit Protocol for Speech–Augmented (CAPS-A) with British English-speaking children. The second study examined interrater and intrarater reliability on a modified version of the CAPS-A (CAPS-A Americleft Modification) with American and Canadian English-speaking children. Finally, comparisons were made between the interrater and intrarater reliability scores obtained for Study 1 and Study 2. Participants The participants were speech-language pathologists from the Americleft Speech Project. Results In Study 1, interrater reliability scores improved for 6 of the 13 parameters following training on the CAPS-A protocol. Comparison of the reliability results for the two studies indicated lower scores for Study 2 compared with Study 1. However, this appeared to be an artifact of the kappa statistic that occurred due to insufficient variability in the reliability samples for Study 2. When percent agreement scores were also calculated, the ratings appeared similar across Study 1 and Study 2. Conclusion The findings of this study suggested that improvements in interrater reliability could be obtained following a program of systematic training. However, improvements were not uniform across all parameters. Acceptable levels of reliability were achieved for those parameters most important for evaluation of velopharyngeal function.