HLA-F: A New Kid Licensed for Peptide Presentation.

HLA-F, a non-classical MHC molecule, is not known to present peptides. Dulberger et al. (2017) show that HLA-F contains a distinct peptide-binding groove and can present a diverse array of peptides. LIR1, however, recognized HLA-F away from bound peptide, leaving open whether peptide-HLA-F-specific T and NK receptors exist.

Psychometric properties of the Perceived Stress Scale (PSS-10) in silica-exposed workers from diverse cultural and linguistic backgrounds.

BACKGROUND: The Perceived Stress Scale (PSS-10) has been used in a range of occupational cohorts, but only recently in stone benchtop workers undergoing screening for silicosis. The aim of this study was to compare psychometric properties of the PSS-10 in stone benchtop workers amongst those born overseas or who used an interpreter. METHODS: Stone benchtop workers in Melbourne, Australia completed the PSS-10 as part of their occupational screening for silicosis. Internal consistency was assessed with Cronbach's α for the total score and the positive and negative subscales. Validity was assessed using confirmatory factor analysis (CFA). Analysis was performed for the total group and for subgroups according to sex, interpreter use, overseas-born, and language spoken at home. RESULTS: The results of 682 workers with complete PSS-10 scores were included in analysis. Most participants were male (93%), with mean age 36.9 years (SD 11.4), with just over half (51.6%) born in Australia, 10.1% using an interpreter, and 17.5% using a language other than English at home. Cronbach's α for the overall group (α = 0.878) suggested good internal consistency. DISCUSSION: CFA analysis for validity testing suggested PSS-10 performance was good for both sexes, moderate for country of birth and language spoken at home categories, but poorer for those who used an interpreter. Whilst professional interpreters provide a range of benefits in the clinical setting, the use of translated and validated instruments are important, particularly in cohorts with large numbers of migrant workers. CONCLUSION: This study describes the psychometric properties of the PSS-10 in a population of stone benchtop workers, with good internal consistency, and mixed performance from validity testing across various subgroups.

Chest x-ray has low sensitivity to detect silicosis in artificial stone benchtop industry workers.

BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.

Evaluation of a health and social care programme to improve outcomes following critical illness: a multicentre study.

RATIONALE: At present, clinicians aiming to support patients through the challenges after critical care have limited evidence to base interventions. OBJECTIVES: Evaluate a multicentre integrated health and social care intervention for critical care survivors. A process evaluation assessed factors influencing the programme implementation. METHODS: This study evaluated the impact of the Intensive Care Syndrome: Promoting Independence and Return to Employment (InS:PIRE) programme. We compared patients who attended this programme with a usual care cohort from the same time period across nine hospital sites in Scotland. The primary outcome was health-related quality of life (HRQoL) measured via the EuroQol 5-dimension 5-level instrument, at 12 months post hospital discharge. Secondary outcome measures included self-efficacy, depression, anxiety and pain. RESULTS: 137 patients who received the InS:PIRE intervention completed outcome measures at 12 months. In the usual care cohort, 115 patients completed the measures. The two cohorts had similar baseline demographics. After adjustment, there was a significant absolute increase in HRQoL in the intervention cohort in relation to the usual care cohort (0.12, 95% CI 0.04 to 0.20, p=0.01). Patients in the InS:PIRE cohort also reported self-efficacy scores that were 7.7% higher (2.32 points higher, 95% CI 0.32 to 4.31, p=0.02), fewer symptoms of depression (OR 0.38, 95% CI 0.19 to 0.76, p=0.01) and similar symptoms of anxiety (OR 0.58, 95% CI 0.30 to 1.13, p=0.11). There was no significant difference in overall pain experience. Key facilitators for implementation were: integration with inpatient care, organisational engagement, flexibility to service inclusion; key barriers were: funding, staff availability and venue availability. CONCLUSIONS: This multicentre evaluation of a health and social care programme designed for survivors of critical illness appears to show benefit at 12 months following hospital discharge.

Mental health and wellbeing of health and aged care workers in Australia, May 2021 - June 2022: a longitudinal cohort study.

OBJECTIVES: To assess the mental health and wellbeing of health and aged care workers in Australia during the second and third years of the coronavirus disease 2019 (COVID-19) pandemic, overall and by occupation group. DESIGN, SETTING, PARTICIPANTS: Longitudinal cohort study of health and aged care workers (ambulance, hospitals, primary care, residential aged care) in Victoria: May-July 2021 (survey 1), October-December 2021 (survey 2), and May-June 2022 (survey 3). MAIN OUTCOME MEASURES: Proportions of respondents (adjusted for age, gender, socio-economic status) reporting moderate to severe symptoms of depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder scale, GAD-7), or post-traumatic stress (Impact of Event Scale-6, IES-6), burnout (abbreviated Maslach Burnout Inventory, aMBI), or high optimism (10-point visual analogue scale); mean scores (adjusted for age, gender, socio-economic status) for wellbeing (Personal Wellbeing Index-Adult, PWI-A) and resilience (Connor Davidson Resilience Scale 2, CD-RISC-2). RESULTS: A total of 1667 people responded to at least one survey (survey 1, 989; survey 2, 1153; survey 3, 993; response rate, 3.3%). Overall, 1211 survey responses were from women (72.6%); most respondents were hospital workers (1289, 77.3%) or ambulance staff (315, 18.9%). The adjusted proportions of respondents who reported moderate to severe symptoms of depression (survey 1, 16.4%; survey 2, 22.6%; survey 3, 19.2%), anxiety (survey 1, 8.8%; survey 2, 16.0%; survey 3, 11.0%), or post-traumatic stress (survey 1, 14.6%; survey 2, 35.1%; survey 3, 14.9%) were each largest for survey 2. The adjusted proportions of participants who reported moderate to severe symptoms of burnout were higher in surveys 2 and 3 than in survey 1, and the proportions who reported high optimism were smaller in surveys 2 and 3 than in survey 1. Adjusted mean scores for wellbeing and resilience were similar at surveys 2 and 3 and lower than at survey 1. The magnitude but not the patterns of change differed by occupation group. CONCLUSION: Burnout was more frequently reported and mean wellbeing and resilience scores were lower in mid-2022 than in mid-2021 for Victorian health and aged care workers who participated in our study. Evidence-based mental health and wellbeing programs for workers in health care organisations are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12621000533897 (observational study; retrospective).

Workers in Australian prebake aluminium smelters: update on risk of mortality and cancer incidence in the Healthwise cohort.

OBJECTIVES: To investigate mortality and the rates of incident cancer among a cohort of aluminium industry workers. METHODS: Among 4507 male employees who worked in either of two Australian prebake smelters for at least 3 months, data linkage was undertaken with the Australian National Death Index and Australian Cancer Database. Standardised Mortality Ratios (SMRs) and Standardised Incidence Rates (SIRs) were estimated for the whole cohort and for: production; maintenance and office workers. SMRs and SIRs were calculated by time since first employment. RESULTS: Among production workers, there was an excess risk of mortality from mesothelioma (SMR 2.8, 95% CI 1.3 to 5.2), lung (SMR 1.4, 95% CI 1.0 to 1.8), prostate (SMR 1.9, 95% CI 1.3 to 2.7) and liver cancer (SMR 2.0, 95% CI 1.1 to 3.4) and the SIR was also increased for overall respiratory cancers, specifically lung cancers. An excess risk of death from stomach cancer (SMR 2.9, 95% CI 1.2 to 6.1) and Alzheimer's disease (SMR 3.4, 95% CI 1.1 to 7.9) was seen among maintenance workers. The overall risk of death was similar to that of the Australian general population, as was mortality from cancers overall and non-malignant respiratory disease. CONCLUSIONS: No excess risk of death from bladder cancer or non-malignant respiratory disease was found. Excess lung cancer mortality and incidence may be explained by smoking and excess mortality from mesothelioma may be explained by asbestos exposure. An excess risk of mortality from liver and prostate cancer has been shown in production workers and requires further investigation.

Incidence and mortality from malignant mesothelioma 1982-2020 and relationship with asbestos exposure: the Australian Mesothelioma Registry.

OBJECTIVES: Malignant mesothelioma is an uncommon cancer associated with asbestos exposure, predominantly occupational. Asbestos has been banned in Australia since 2003 but mesothelioma has a long latency and incident cases continue to present. The Australian Mesothelioma Registry was incepted to collect systematic data about incidence and mortality alongside asbestos exposure. METHODS: Benefiting from the Australian national system of cancer notification, all incident cases of mesothelioma in all states and territories are fast-tracked and notified regularly. Notified patients are contacted asking for consent to collect exposure information, initially by postal questionnaire and subsequently by telephone interview. Age-standardised annual incidence rates and mortality rates were calculated. Asbestos exposure was categorised as occupational, non-occupational, neither or, both; and as low, or high, probability of exposure. RESULTS: Mesothelioma incidence appears to have peaked. The age-standardised incidence rates have declined steadily since the early 2000s (peaking in males at 5.9/100 000 and in all-persons at 3.2/100 000), driven by rates in males, who comprise the majority of diagnosed cases. Rates in women have remained fairly stable since that time. Age-standardised mortality rates have followed similar trends. Mesothelioma remains the most common in those aged over 80 years. Nearly all (94%) cases were linked with asbestos exposure (78% occupational in men; 6.8% in women). CONCLUSIONS: With effective control of occupational asbestos use, the decline in age-standardised incidence and death rates has occurred. Incidence rates among women, in whom occupational asbestos exposure is rarely detectable, remain unchanged, pointing to the role of household and /or environmental asbestos exposure.

Ever and cumulative occupational exposure and lung function decline in longitudinal population-based studies: a systematic review and meta-analysis.

OBJECTIVES: Adverse occupational exposures can accelerate age-related lung function decline. Some longitudinal population-based studies have investigated this association. This study aims to examine this association using findings reported by longitudinal population-based studies. METHODS: Ovid Medline, PubMed, Embase, and Web of Science were searched using keywords and text words related to occupational exposures and lung function and 12 longitudinal population-based studies were identified using predefined inclusion criteria. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Lung function decline was defined as annual loss of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) or the ratio (FEV1/FVC). Fixed and random-effects meta-analyses were conducted to calculate pooled estimates for ever and cumulative exposures. Heterogeneity was assessed using the I2 test, and publication bias was evaluated using funnel plots. RESULTS: Ever exposures to gases/fumes, vapours, gases, dusts, fumes (VGDF) and aromatic solvents were significantly associated with FEV1 decline in meta-analyses. Cumulative exposures for these three occupational agents observed a similar trend of FEV1 decline. Ever exposures to fungicides and cumulative exposures to biological dust, fungicides and insecticides were associated with FEV1 decline in fixed-effect models only. No statistically significant association was observed between mineral dust, herbicides and metals and FEV1 decline in meta-analyses. CONCLUSION: Pooled estimates from the longitudinal population-based studies have provided evidence that occupational exposures are associated with FEV1 decline. Specific exposure control and respiratory health surveillance are required to protect the lung health of the workers.

Prevalence and risk factors for silicosis among a large cohort of stone benchtop industry workers.

OBJECTIVES: High silica content artificial stone has been found to be associated with silicosis among stone benchtop industry (SBI) workers. The objectives of this study were to determine the prevalence of and risk factors for silicosis among a large cohort of screened SBI workers, and determine the reliability of respiratory function testing (RFT) and chest x-ray (CXR) as screening tests in this industry. METHODS: Subjects were recruited from a health screening programme available to all SBI workers in Victoria, Australia. Workers undertook primary screening, including an International Labour Office (ILO) classified CXR, and subject to prespecified criteria, also underwent secondary screening including high-resolution CT (HRCT) chest and respiratory physician assessment. RESULTS: Among 544 SBI workers screened, 95% worked with artificial stone and 86.2% were exposed to dry processing of stone. Seventy-six per cent (414) required secondary screening, among whom 117 (28.2%) were diagnosed with silicosis (median age at diagnosis 42.1 years (IQR 34.8-49.7)), and all were male. In secondary screening, silicosis was associated with longer SBI career duration (12 vs 8 years), older age, lower body mass index and smoking. In those with silicosis, forced vital capacity was below the lower limit of normal in only 14% and diffusion capacity for carbon monoxide in 13%. Thirty-six (39.6%) of those with simple silicosis on chest HRCT had an ILO category 0 CXR. CONCLUSION: Screening this large cohort of SBI workers identified exposure to dry processing of stone was common and the prevalence of silicosis was high. Compared with HRCT chest, CXR and RFTs had limited value in screening this high-risk population.

Workers' compensation claims for COVID-19 among workers in healthcare and other industries during 2020-2022, Victoria, Australia.

OBJECTIVE: To identify and characterise COVID-19 workers' compensation claims in healthcare and other industries during the pandemic in Victoria, Australia. METHODS: We used workers' compensation claims identified as COVID-19 infection related from 1 January 2020 to 31 July 2022 to compare COVID-19 infection claims and rates of claims by industry and occupation, and in relation to Victorian COVID-19 epidemiology. A Cox proportional hazards model assessed risk factors for extended claim duration. RESULTS: Of the 3313 direct and indirect COVID-19-related claims identified, 1492 (45.0%) were classified as direct COVID-19 infection accepted time-loss claims and were included in analyses. More than half (52.9%) of COVID-19 infection claims were made by healthcare and social assistance industry workers, with claims for this group peaking in July-October 2020. The overall rate of claims was greater in the healthcare and social assistance industry compared with all other industries (16.9 vs 2.4 per 10 000 employed persons) but industry-specific rates were highest in public administration and safety (23.0 per 10 000 employed persons). Workers in healthcare and social assistance were at increased risk of longer incapacity duration (median 26 days, IQR 16-61 days) than in other industries (median 17 days, IQR 11-39.5 days). CONCLUSIONS: COVID-19 infection claims differed by industry, occupational group, severity and timing and changes coincided with different stages of the COVID-19 pandemic. Occupational surveillance for COVID-19 cases is important and monitoring of worker's compensation claims and incapacity duration can contribute to understanding the impacts of COVID-19 on work absence.

Current and projected heatwave-attributable occupational injuries, illnesses, and associated economic burden in Australia.

INTRODUCTION: The costs of global warming are substantial. These include expenses from occupational illnesses and injuries (OIIs), which have been associated with increases during heatwaves. This study estimated retrospective and projected future heatwave-attributable OIIs and their costs in Australia. MATERIALS AND METHODS: Climate and workers' compensation claims data were extracted from seven Australian capital cities representing OIIs from July 2005 to June 2018. Heatwaves were defined using the Excess Heat Factor. OIIs and associated costs were estimated separately per city and pooled to derive national estimates. Results were projected to 2030 (2016-2045) and 2050 (2036-2065). RESULTS: The risk of OIIs and associated costs increased during heatwaves, with the risk increasing during severe and particularly extreme heatwaves. Of all OIIs, 0.13% (95% empirical confidence interval [eCI]: 0.11-0.16%) were heatwave-attributable, equivalent to 120 (95%eCI:70-181) OIIs annually. 0.25% of costs were heatwave-attributable (95%eCI: 0.18-0.34%), equal to $AU4.3 (95%eCI: 1.4-7.4) million annually. Estimates of heatwave-attributable OIIs by 2050, under Representative Concentration Pathway [RCP]4.5 and RCP8.5, were 0.17% (95%eCI: 0.10-0.27%) and 0.23% (95%eCI: 0.13-0.37%), respectively. National costs estimates for 2030 under RCP4.5 and RCP8.5 were 0.13% (95%eCI: 0.27-0.46%) and 0.04% (95%eCI: 0.66-0.60), respectively. These estimates for extreme heatwaves were 0.04% (95%eCI: 0.02-0.06%) and 0.04% (95%eCI: 0.01-0.07), respectively. Cost-AFs in 2050 were, under RCP4.5, 0.127% (95%eCI: 0.27-0.46) for all heatwaves and 0.04% (95%eCI: 0.01-0.09%) for extreme heatwaves. Attributable fractions were approximately similar to baseline when assuming theoretical climate adaptation. DISCUSSION: Heatwaves represent notable and preventable portions of preventable OIIs and economic burden. OIIs are likely to increase in the future, and costs during extreme heatwaves in 2030. Workplace and public health policies aimed at heat adaptation can reduce heat-attributable morbidity and costs.

Long-term impact of the 2014 Hazelwood coal mine fire on emergency department presentations in Australia.

BACKGROUND: In 2014, wildfires ignited a coal mine in Australia, burning for 6 weeks, releasing large amounts of fine particulate matter ≤2.5 µm in diameter (PM2.5). We investigated the association between individual PM2.5 exposure and emergency department presentations (EDPs) within 5 years post-fire. METHODS: Survey and exposure data for 2725 residents from an exposed and unexposed town were linked with ED administrative data from 2009 to 2019. The association between individual PM2.5 and EDPs was assessed using recurrent survival analysis. RESULTS: A 10 µg/m3 increase in PM2.5 was associated with a 10% increase in respiratory EDPs (HR = 1.10; 95%CI:1.00-1.22) over 5 years post-fire. Increased risks of EDPs for ischaemic heart disease (HR = 1.39; 95%CI:1.12-1.73), atherothrombotic disease (HR = 1.27; 95%CI:1.08-1.50), and cardiovascular disease (HR = 1.10, 95%CI:0.99-1.22) were evident within 2.5 years. CONCLUSION: PM2.5 exposure from a 6-week mine fire increased the 5-year risk of respiratory conditions. An increased risk of CVD within 2.5 years post-fire subsided after this time.

High-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D.

Complete cancer regression occurs in a subset of patients following adoptive T cell therapy (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs). However, the low success rate presents a great challenge to broader clinical application. To provide insight into TIL-based immunotherapy, we studied a successful case of ACT where regression was observed against tumors carrying the hotspot mutation G12D in the KRAS oncogene. Four T cell receptors (TCRs) made up the TIL infusion and recognized two KRAS-G12D neoantigens, a nonamer and a decamer, all restricted by human leukocyte antigen (HLA) C*08:02. Three of them (TCR9a, 9b, and 9c) were nonamer-specific, while one was decamer-specific (TCR10). We show that only mutant G12D but not the wild-type peptides stabilized HLA-C*08:02 due to the formation of a critical anchor salt bridge to HLA-C. Therapeutic TCRs exhibited high affinities, ranging from nanomolar to low micromolar. Intriguingly, TCR binding affinities to HLA-C inversely correlated with their persistence in vivo, suggesting the importance of antigenic affinity in the function of therapeutic T cells. Crystal structures of TCR-HLA-C complexes revealed that TCR9a to 9c recognized G12D nonamer with multiple conserved contacts through shared CDR2ß and CDR3α. This allowed CDR3ß variation to confer different affinities via a variable HLA-C contact, generating an oligoclonal response. TCR10 recognized an induced and distinct G12D decamer conformation. Thus, this successful case of ACT included oligoclonal TCRs of high affinity recognizing distinct conformations of neoantigens. Our study revealed the potential of a structural approach to inform clinical efforts in targeting KRAS-G12D tumors by immunotherapy and has general implications for T cell-based immunotherapies.

Exposure to wildfire-related PM2.5 and site-specific cancer mortality in Brazil from 2010 to 2016: A retrospective study.

BACKGROUND: Long-term exposure to fine particles ≤2.5 µm in diameter (PM2.5) has been linked to cancer mortality. However, the effect of wildfire-related PM2.5 exposure on cancer mortality risk is unknown. This study evaluates the association between wildfire-related PM2.5 and site-specific cancer mortality in Brazil, from 2010 to 2016. METHODS AND FINDINGS: Nationwide cancer death records were collected during 2010-2016 from the Brazilian Mortality Information System. Death records were linked with municipal-level wildfire- and non-wildfire-related PM2.5 concentrations, at a resolution of 2.0° latitude by 2.5° longitude. We applied a variant difference-in-differences approach with quasi-Poisson regression, adjusting for seasonal temperature and gross domestic product (GDP) per capita. Relative risks (RRs) and 95% confidence intervals (CIs) for the exposure for specific cancer sites were estimated. Attributable fractions and cancer deaths were also calculated. In total, 1,332,526 adult cancer deaths (age ≥ 20 years), from 5,565 Brazilian municipalities, covering 136 million adults were included. The mean annual wildfire-related PM2.5 concentration was 2.38 µg/m3, and the annual non-wildfire-related PM2.5 concentration was 8.20 µg/m3. The RR for mortality from all cancers was 1.02 (95% CI 1.01-1.03, p < 0.001) per 1-µg/m3 increase of wildfire-related PM2.5 concentration, which was higher than the RR per 1-µg/m3 increase of non-wildfire-related PM2.5 (1.01 [95% CI 1.00-1.01], p = 0.007, with p for difference = 0.003). Wildfire-related PM2.5 was associated with mortality from cancers of the nasopharynx (1.10 [95% CI 1.04-1.16], p = 0.002), esophagus (1.05 [95% CI 1.01-1.08], p = 0.012), stomach (1.03 [95% CI 1.01-1.06], p = 0.017), colon/rectum (1.08 [95% CI 1.05-1.11], p < 0.001), larynx (1.06 [95% CI 1.02-1.11], p = 0.003), skin (1.06 [95% CI 1.00-1.12], p = 0.003), breast (1.04 [95% CI 1.01-1.06], p = 0.007), prostate (1.03 [95% CI 1.01-1.06], p = 0.019), and testis (1.10 [95% CI 1.03-1.17], p = 0.002). For all cancers combined, the attributable deaths were 37 per 100,000 population and ranged from 18/100,000 in the Northeast Region of Brazil to 71/100,000 in the Central-West Region. Study limitations included a potential lack of assessment of the joint effects of gaseous pollutants, an inability to capture the migration of residents, and an inability to adjust for some potential confounders. CONCLUSIONS: Exposure to wildfire-related PM2.5 can increase the risks of cancer mortality for many cancer sites, and the effect for wildfire-related PM2.5 was higher than for PM2.5 from non-wildfire sources.

Cancer and mortality in coal mine workers: a systematic review and meta-analysis.

Coal mine workers are exposed to a number of workplace hazards which may increase the risk of cancer and mortality. We conducted a systematic review and meta-analysis to investigate cancer and mortality in coal mine workers We searched in Ovid Medline, PubMed, Embase and Web of Science databases using keywords and text words related to coal mines, cancer and mortality and identified 36 full-text articles using predefined inclusion criteria. Each study's quality was assessed using the Newcastle-Ottawa Scale. We performed random-effect meta-analyses including 21 of the identified articles evaluating cancer and/or mortality of coal mine workers. The meta-analysis showed an increased risk of all-cause mortality (SMR 1.14, 95% CI 1.00 to 1.30) and mortality from non-malignant respiratory disease (NMRD) (3.59, 95% CI 3.00 to 4.30) in cohorts with coal workers' pneumoconiosis (CWP). We found a somewhat increased risk of stomach cancer (1.11, 95% CI 0.97 to 1.35) and of mortality from NMRD (1.26, 95% CI 0.99 to 1.61) in the cohorts of coal miners with unknown CWP status. The meta-analysis also showed a decreased risk of prostate cancer and cardiovascular and cerebrovascular mortality among coal miners. This may be a result of the healthy worker effect and possible lower smoking rates, and perhaps also reflect the physically active nature of many jobs in coal mines. The meta-analysis for lung cancer did not show increased risk in coal miners with CWP (1.49, 95% CI 0.70 to 3.18) or for coal miners of unknown CWP status (1.03, 95% CI 0.91 to 1.18). Lower smoking rates in coal mine workers could explain why case-control studies where smoking was controlled for showed higher risks for lung cancer than were seen in cohort studies. Coal mine workers are at increased risk of mortality from NMRD but decreased risk of prostate cancer and cardiovascular and cerebrovascular mortality. Studies of coal mine workers need long-term follow-up to identify increased mortality and cancer incidence.

Predictors of psychological stress in silica-exposed workers in the artificial stone benchtop industry.

BACKGROUND AND OBJECTIVE: Artificial stone benchtops are a popular kitchen product, but dust from their preparation and installation contains respirable crystalline silica, which causes silicosis. Silicosis is a preventable, permanent lung disease. The aim of this study was to assess mental health in workers from the artificial stone benchtop industry at risk of silicosis. METHODS: Workers from the artificial stone benchtop industry undergoing assessment for silica-associated disease were included. Information on demographics; occupational, medical and smoking history; modified Medical Research Council dyspnoea scale; Perceived Stress Scale (PSS-10) questionnaire; spirometry; and chest x-ray was collected. Univariate and multivariate regression analyses were conducted. RESULTS: Of the 547 participants, the majority were men, aged under 45 years, in the industry for less than 10 years. With each increase of dyspnoea score, PSS-10 scores increased. Higher PSS-10 scores were also observed in those no longer in the industry, with a history of anxiety or depression, attending assessment early in the programme and a medium exposure duration. Participants who used an interpreter reported lower stress. No difference was observed across job title, age, sex, smoking, spirometry or chest x-ray categories after multivariate analysis. CONCLUSION: This study identified workers with dyspnoea as likely to report higher stress. Other factors, such as leaving the industry, early attendance and a history of anxiety or depression, are also helpful in identifying workers at risk of poorer mental health outcomes.

Changes in work and health of Australians during the COVID-19 pandemic: a longitudinal cohort study.

BACKGROUND: Engagement in work is an important determinant of health. In response to the COVID-19 pandemic, public health measures imposed to reduce viral transmission resulted in large-scale loss of work during the early stages of the pandemic, contributing to declined mental and physical health. As the pandemic unfolded, the Australian economy began to recover and some people could return to work, whilst localised lockdowns resulted in further loss of work for others. The long-term health effects of work loss remain unexplored within the COVID-19 pandemic context, in addition to whether any health effects are persistent upon returning to work. METHODS: A prospective longitudinal cohort study of 2603 participants across Australia monitored changes in health and work between March and December 2020, with participants completing surveys at baseline and 1, 3 and 6 months later. Outcomes described psychological distress, and mental and physical health. Linear mixed regression models examined associations between changes in health and experiences of work loss, and return to work, over time. RESULTS: Losing work during the early stages of the pandemic was associated with long-term poorer mental health, which began to recover over time as some returned to work. Physical health deteriorated over time, greater for people not working at baseline. Being out of work was associated with poorer mental health, but better physical health. These effects were larger for people that had recently lost work than for people with sustained work loss, and retaining employment played a protective role. Generally, returning to work resulted in poorer physical health and improvements in mental health, although this depended on the broader context of changes in work. CONCLUSIONS: Work cessation during the pandemic led to poor health outcomes and had long-lasting effects. Returning to work benefits mental health but may reduce physical activity in the short-term. We encourage the provision of accessible mental health supports and services immediately following loss of work, and for people with prolonged forms of work loss. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12620000857909 .

Human NK cell receptor KIR2DS4 detects a conserved bacterial epitope presented by HLA-C.

Natural killer (NK) cells have an important role in immune defense against viruses and cancer. Activation of human NK cell cytotoxicity toward infected or tumor cells is regulated by killer cell immunoglobulin-like receptors (KIRs) that bind to human leukocyte antigen class I (HLA-I). Combinations of KIR with HLA-I are genetically associated with susceptibility to disease. KIR2DS4, an activating member of the KIR family with poorly defined ligands, is a receptor of unknown function. Here, we show that KIR2DS4 has a strong preference for rare peptides carrying a Trp at position 8 (p8) of 9-mer peptides bound to HLA-C*05:01. The complex of a peptide bound to HLA-C*05:01 with a Trp at p8 was sufficient for activation of primary KIR2DS4+ NK cells, independent of activation by other receptors and of prior NK cell licensing. HLA-C*05:01+ cells that expressed the peptide epitope triggered KIR2DS4+ NK cell degranulation. We show an inverse correlation of the worldwide allele frequency of functional KIR2DS4 with that of HLA-C*05:01, indicative of functional interaction and balancing selection. We found a highly conserved peptide sequence motif for HLA-C*05:01-restricted activation of human KIR2DS4+ NK cells in bacterial recombinase A (RecA). KIR2DS4+ NK cells were stimulated by RecA epitopes from multiple human pathogens, including Helicobacter, Chlamydia, Brucella, and Campylobacter. We predict that over 1,000 bacterial species could activate NK cells through KIR2DS4, and propose that human NK cells also contribute to immune defense against bacteria through recognition of a conserved RecA epitope presented by HLA-C*05:01.

Sleep disturbances and disability following work-related injury and illness: Examining longitudinal relationships across three follow-up waves.

Despite the high burden of sleep disturbances among the general population, there is limited information on prevalence and impact of poor sleep among injured workers. This study: (a) estimated the prevalence of sleep disturbance following work-related injury; and (b) examined the longitudinal association between sleep disturbances and disability/functioning, accounting for reciprocal relationships and mental illness. Longitudinal survey data were collected from workers' compensation claimants with a time-loss claim in Victoria, Australia (N = 700). Surveys were conducted at baseline, 6 months and 12 months. Sleep disturbance was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire. Disability/functioning was based on self-reported activity limitations, participation restrictions and emotional functioning. Path models examined the association between disability/functioning and sleep. Mean sleep disturbance T-scores were 55.2 (SD 11.4) at 6 months, with 36.4% of the sample having a T-score of 60+. Longitudinal relationships were observed between disability (specifically, emotional functioning) and sleep disturbances across successive follow-up waves. For example, each unit increase in T2 emotional functioning (five-point scale) was associated with a 1.1 unit increase in T3 sleep disturbance (approximately 29-76 scale). Cross-lagged path models found evidence of a reciprocal relationship between disability and sleep, although adjustment for mental illness attenuated the estimates to the null. In conclusion, sleep disturbances are common among workers' compensation claimants with work injuries/illnesses. Given the links between some dimensions of disability, mental health and sleep disturbances, the findings have implications for the development of interventions that target the high prevalence of sleep problems among working populations.

A Metabolomics approach for the diagnosis Of SecondAry InfeCtions in COVID-19 (MOSAIC): a study protocol.

BACKGROUND: Critically ill patients with COVID-19 are at an increased risk of developing secondary bacterial infections. These are both difficult to diagnose and are associated with an increased mortality. Metabolomics may aid clinicians in diagnosing secondary bacterial infections in COVID-19 through identification and quantification of disease specific biomarkers, with the aim of identifying underlying causative microorganisms and directing antimicrobial therapy. METHODS: This is a multi-centre prospective diagnostic observational study. Patients with COVID-19 will be recruited from critical care units in three Scottish hospitals. Three serial blood samples will be taken from patients, and an additional sample taken if a patient shows clinical or microbiological evidence of secondary infection. Samples will be analysed using LC-MS and subjected to bioinformatic processing and statistical analysis to explore the metabolite changes associated with bacterial infections in COVID-19 patients. Comparisons of the data sets will be made with standard microbiological and biochemical methods of diagnosing infection. DISCUSSION: Metabolomics analyses may provide additional strategies for identifying secondary infections, which might permit faster initiation of specific tailored antimicrobial therapy to critically ill patients with COVID-19.