bluuebunny/crossref_metadata_2025 huggingface dataset:
Exome sequencing analysis identifies frequent oligogenic involvement andFLNBvariants in adolescent idiopathic scoliosis
Authors: Jiang Heng , Liang Shulun , He Kai , Hu Jinghua , Xu Enjie , Lin Tao , Meng Yichen , Zhao Jianquan , Ma Jun , Gao Rui , Wang Ce , Yang Fu , Zhou Xuhui
Published: May 2020

Background

Adolescent idiopathic scoliosis (AIS) is a genetically heterogeneous disease characterised by three-dimensional deformity of the spine in the absence of a congenital spinal anomaly or neurological musculoskeletal disorder. The clinical variability and incomplete penetrance of some genes linked with AIS indicate that this disease constitutes an oligogenic trait.

Objective

We aimed to explore the oligogenic nature of this disease and identify novel AIS genes.

Methods

We analysed rare damaging variants within AIS-associated genes by using exome sequencing in 40 AIS trios and 183 sporadic patients.

Results

Multiple variants within AIS-associated genes were identified in eight AIS trios, and five individuals harboured rare damaging variants in theFLNBgene. The patients showed more frequent oligogenicity than the controls. In the gene-based burden test, the top signal resided inFLNB. In functional studies, we found that the AIS-associatedFLNBvariants altered the protein’s conformation and subcellular localisation and its interaction with other proteins (TTC26 and OFD1) involved in AIS. The most compelling evidence of an oligogenic basis was that the number of rare damaging variants was recognised as an independent prognostic factor for curve progression in Cox regression analysis.

Conclusion

Our data indicate that AIS is an oligogenic disease and identifyFLNBas a susceptibility gene for AIS.
Human infection challenge studies in endemic settings and/or low-income and middle-income countries: key points of ethical consensus and controversy
Authors: Jamrozik Euzebiusz , Selgelid Michael J
Published: May 2020

Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens (or other micro-organisms). There have been recent calls for more HCS to be conducted in low-income and middle-income countries (LMICs), where many relevant diseases are endemic. HCS in general, and HCS in LMICs in particular, raise numerous ethical issues. This paper summarises the findings of a project that explored ethical and regulatory issues related to LMIC HCS via (i) a review of relevant literature and (ii) 45 qualitative interviews with scientists and ethicists. Among other areas of consensus, we found that there was widespread agreement that LMIC HCS can be ethically acceptable, provided that they have a sound scientific rationale, are accepted by local communities and meet usual research ethics requirements. Unresolved issues include those related to (i) acceptable approaches to trade-offs between the scientific aim to produce generalisable results and the protection of participants, (iii) the sharing of benefits with LMIC populations, (iii) the acceptable limits to risks and burdens for participants, (iv) the potential for third-party risk and whether the degree of acceptable third-party risk is different in endemic settings, (v) the conditions under which (if any) it would be appropriate to recruit children for disease-causing HCS, (v) appropriate levels of payment to participants and (vi) appropriate governance of (LMIC) HCS. This paper provides preliminary analyses of these ethical considerations in order to (i) inform scientists and policymakers involved in the planning, conduct and/or governance of LMIC HCS and (ii) highlight areas warranting future research. Insofar as this article focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided is relevant to HCS (in HICs or LMICs) involving pandemic diseases including COVID19.
Impact of EMS bypass to endovascular capable hospitals: geospatial modeling analysis of the US STRATIS registry
Authors: Mueller-Kronast Nils , Froehler Michael T , Jahan Reza , Zaidat Osama , Liebeskind David , Saver Jeffrey L
Published: May 2020

Background

Routing patients directly to endovascular capable centers (ECCs) would decrease time to mechanical thrombectomy (MT), but may delay intravenous thrombolysis (IVT).

Objective

To study the clinical outcomes of patients with a stroke transferred directly to ECCs compared with those transferred to ECCs from non-endovascular capable centers (nECCs).

Methods

Data from the STRATIS registry were analyzed to evaluate process and clinical outcomes under five routing policies: (1) transport to nearest nECC; (2) transport to STRATIS ECC over any distance or (3) within 20 miles; (4) transport to ideal ECC (iECC), over any distance or (5) within 20 miles.

Results

Among 236 patients, 117 (49.6%) were transferred by ground, of whom 62 (53%) were transferred within 20 miles. Median MT start time was accelerated in all direct transport models. IVT start was prolonged with direct transport across all distances, but accelerated with direct transport to iECC ≤20 miles. With bypass limited to ≤20 miles, the median modeled EMS arrival to IVT interval decreased for both iECCs and ECCs (by 12 min and 6 min, respectively), and median EMS arrival to puncture time decreased by up to 94 min. In this cohort, no patient would have become ineligible for IVT. Bypass to iECC modeling under 20 miles showed a significant reduction in the level of disability at 3 months, with freedom from disability (modified Rankin Scale score 0–1) at 3 months increased by 12%.

Conclusions

Direct routing of patients with a large vessel occlusion to ECCs, especially when within 20 miles, may lead to better clinical outcomes by accelerating the start of MT without any delay of IVT.

Clinical trial registration number

http://www.clinicaltrials.gov. Unique identifier:NCT02239640.
O4D.3 Bone lead associations with blood lead, kidney function, and blood pressure among U.S., lead-exposed workers in a surveillance program
Authors: Barry Vaughn , Todd Andrew , Steenland Kyle
Published: May 2020

Objectives

Bone lead and past blood lead (BL) levels may be more strongly associated with current health effects than current BL, representing recent exposure. We examined whether current bone lead is correlated with maximum past BL, and compared three measures of lead as predictors for current blood pressure (BP) and kidney function among workers with past occupational exposure to lead.

Methods

Adult men in a lead surveillance program living within 200 miles of New York City were enrolled in this observational study during 2016–2017. We gathered data on current bone and BL, BP, and estimated glomerular filtration rate (eGFR). Maximum past BL was obtained from prior surveillance program data. Regression models were used to determine associations of health endpoints with different measures of lead.

Results

Among 211 participants, median (interquartile range) bone lead, maximum past BL, and current BL were 13.8 (9.4–19.5) µg of lead per gram of bone mineral, 29.0 (14.0–38.0) µg/dl, and 2.5 (1.5–4.4) µg/dl, respectively. Both maximum past and current BL were significantly associated with current bone lead in adjusted analyses (p<0.0001 for both), with associations driven by those with the highest BL levels. Bone lead was associated with increased systolic BP (p=0.02, model R-square=0.16), but quartile analyses were not monotonic. Bone lead was also non-significantly associated with decreased (worse) eGFR (regression coefficient=−0.15, p=0.18, model R-square=0.28).

Conclusions

Bone lead was significantly associated with past maximum and current BL. Bone lead, but not past maximum or current BL, was associated with elevated systolic BP.
O4E.4 Application of probabilistic bias analysis to adjust for exposure misclassification in a cohort of trichlorophenol workers
Authors: Scott Laura , Maldonado George
Published: May 2020

This method was developed to demonstrate the application of probabilistic bias analysis to quantify and adjust for exposure misclassification in a historical cohort mortality study of New Zealand trichlorophenol workers where exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was measured as a multi-level variable. Published exposure information available for this cohort of workers was used to specify the initial bias parameter distributions, which were then varied under 18 different scenarios to assess the potential impact of differing amounts of misclassification as well as both non-differential and differential exposure misclassification. For each scenario, each bias parameter distribution was sampled 50 000 times using Monte Carlo simulation techniques to generate adjusted counts of cases and non-cases of ischemic heart disease (IHD) by exposure group. These counts were then used to calculate odds ratios adjusted for exposure misclassification and the associated exposure misclassification error terms. Given the specified assumptions, the geometric mean (GM) adjusted odds ratio had a range of 2.89 to 5.05, and the GM error term ranged from 0.60 to 1.05. In all non-differential scenarios and scenarios in which non-cases had greater proportions of misclassification, the observed odds ratio of 3.05 was closer to the null (i.e., 1) than the GM adjusted odds ratio. For the differential simulations where cases had higher proportions of misclassification, the direction of the error was dependent on the level of misclassification error, with smaller proportions of misclassification resulting in the observed odds ratio being farther away from the null than the GM adjusted odds ratio. These findings demonstrate that probabilistic bias analysis of historical cohort mortality studies can be an effective tool for understanding trends in study error stemming from exposure misclassification and confirm the importance of quantifying potential sources of systematic error.
O5A.2 Musculoskeletal symptoms and work-related accidents: a hospital-based case-control study
Authors: Dias Adriano , Bernardes João Marcos , Gomez-Salgado Juan , Ruiz-Frutos Carlos
Published: May 2020

This hospital-based case-control study aimed to determine whether self-reports of musculoskeletal symptoms (MSS) were associated with the occurrence of work-related accidents. Study participants were recruited from the emergency department at Botucatu Medical School University Hospital. Cases were workers who suffered work-related accidents that required hospitalization, while controls were selected patients who suffered a non-work-related accident. Participants were interviewed using a standardized structured questionnaire with close-ended questions and a modified version of the Brazilian Portuguese Nordic Musculoskeletal Questionnaire. Associations between self-reports of MSS and work-related accidents were analyzed with two logistic regression models (one for symptoms that occurred in the 12 months period and the other for those that occurred in the previous 7 days). These analyses were performed in two steps: univariate and multiple model. Variables with a P-value ≤0.25 in the univariate analysis were included in the multiple models, using the forward stepwise selection procedure. In the multiple models two-sided P-values less than 0.05 were considered statistically significant. Altogether, 80 cases and 125 controls were included. The participants had a mean age of 36.9 years (SD = 11.4) and 72.2% were men. In the 12 months multiple logistic regression model, self-report of MSS in the upper limbs (OR 2.689 95% CI 1.357-5.326) was associated with increased odds of work-related accidents occurrence, while in the 7 days multiple logistic regression model, self-report of MSS in the upper limbs (OR 2.374 95% CI 1.083-5.201) and in the vertebral column (OR 2.154 95% CI 1.017-4.561) were associated. Thus, this case–control study suggests that MSS in the upper limbs and in the vertebral column are associated with increased odds of work-related accidents; and that the Nordic Musculoskeletal Questionnaire may be used as a complementary screening tool for identifying workers at risk for work-related accidents.
O5B.1 Workplace exposure assessment (WEA), skin barrier function, and occurrence of hand eczema among workers handling drilling waste in norway
Authors: Alfonso Jose Hernan , Olsen Raymond , Graff Pål , Zienolddiny Shan , Anmarkrud Kristine Haugen , Johansen Thea Haugesten , Dag G Ellingsen med
Published: May 2020

Introduction

Knowledge on skin exposure and the occurrence of hand eczema (HE) among workers handling drilling waste from oil and gas drilling is scarce.

M and M

WEA included seven waste management plants. Samples of oil drilling waste were analysed with gas chromatography with flame ionization detection (GC-FID). Dry solids from thermal treatment of cuttings fluids were incubated in an artificial sweat solution and analysed with inductively coupled plasma mass spectrometry (ICP-MS). pH of dry solids in the sweat solution was measured with Panpeha™ pH indicator strips.

Sixty-eight workers got an invitation to participate in a structured interview and skin examination. The Nordic Occupational Skin Questionnaire 2002 assessed the occurrence of skin problems and HE. Transepidermal water loss (TEWL) and hydration of the stratum corneum (SC) were measured with Tewameter 300 and Corneometer CM 825 (Courage and Khazaka Electronic GmbH).

Results

WEA identified scenarios for potential skin exposure. The profile of hydrocarbons in oil-based drilling waste was similar among the different plants. The soluble fraction of dry solids in artificial sweat solution contained bioavailable metals such as Cr (from 22 to 210 ng/g), Co (from 20 to 94 ng/g), Ni (from 0,13 to 0,72 µg/g). The pH ranged from 6.5 to 12.0.

The participation frequency was of 97%. The one-year prevalence for HE and work-related HE was 30.3% and 24.2%. Ninety-three percent of the workers reported glove use for two hours or more. TEWL values>25 g/h/m2on the dorsal side of the hands, indicating skin barrier disruption, were measured in 55% of the workers. TEWL and hydration of SC values were associated to the occurrence of HE.

Conclusion

Potential skin exposure to irritants, allergenic metals, skin occlusion from gloves, skin barrier disruption and high occurrence of HE among workers handling oil and drilling waste are of concern.
O5D.2 Occupational exposure of healthcare personnel to nitrous oxide in various pediatric specialty care units: an observational study
Authors: Denis Marie-Agnès , Pete-Bonneton Charlotte , Riche Benjamin , Cadot Robert , Massardier-Pilonchery Amélie , Iwaz Jean , Charbotel Barbara
Published: May 2020

Objectives

Nitrous oxide (N2O) present in anesthetic mixtures (e.g., equimolar mix of oxygen and N2O, EMONO) has been found responsible for various toxicities, including genetic and reproductive toxicities. N2O-containing mixtures are widely used in pediatric care units where most healthcare providers (HCPs) are women of childbearing age. This motivated an investigation of occupational exposure to N2O in search for overexposure and overexposure factors in a pediatric hospital.

Methods

This observational study concerned seven different units. On each of 34 HCPs, air samples were extracted by portable pumps and collected in Tedlar® bags. N2O was quantified by gas chromatography coupled to pulsed discharge ionization detection and infrared spectrometry. The data allowed calculating mainly the instantaneous exposure and the 8 hour time-weighted average (8h-TWA).

Results

The exposure was four times higher in closed than in open treatment rooms and two times higher in case of use vs. non-use of EMONO. The exposure was significantly higher in junior vs. senior HCPs (by 12%) and higher during presumably short vs. presumably long procedures (by 20%). The mean 8h-TWAs were rather higher than the recommended exposure limit (25 ppm/8 hour) in emergency unit and in day hospital for thoracic and abdominal diseases. Overexposures represented 11% of all measurements but reached substantial levels (up to 3.5 times the recommended threshold).

Conclusions

Overexposures to N2O were frequent during short-duration procedures. The causes of overexposure were insufficient air renewal and inappropriate equipment use. This calls for dedicated rooms, more efficient medical/nursing practices, proper training, and regular checks of gas levels.
O1B.2 Parental occupational exposure to extremely low-frequency magnetic fields and the risk of leukaemia in the offspring
Authors: Talibov Madar
Published: May 2020

Background

Leukaemia is the most common cancer diagnosed in children worldwide, accounting for about one third of all paediatric malignancies in economically developed countries. Despite extensive research, the aetiology of this cancer remains largely unknown. Previous studies suggested that parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) may increase leukaemia risk in the offspring.

Objective

We aimed to evaluate the association of parental occupational exposure to ELF-MF with the risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring.

Methods

We pooled data from 11 case-control studies participating in the Childhood Leukaemia International Consortium (CLIC). The studies included 9723 childhood leukaemia cases and 17 099 controls. Data on parental job history and other characteristics of the study population were collected by questionnaires and interviews, except for the Finnish study where data was obtained from population registries and censuses. Parental occupational ELF-MF exposure was estimated by linking job histories to an independently developed international ELF-MF job-exposure matrix. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). We employed two analytical approaches to obtain summary risk estimates. First, we conducted pooled analyses of all studies combined. Second, we summarized ORs from individual studies in meta-analyses.

Results

The summary OR estimates from pooled analyses for paternal ELF-MF exposure at conception were 1.04 (95% CI 0.95–1.13) for ALL and 1.06 (95% CI 0.87–1.29) for AML, at >0.2 microtesla (µT) compared to ≤0.2 µT. Corresponding estimates for maternal ELF-MF exposure during pregnancy, using again the 0.2 µT cut-off, were 1.00 (95% CI 0.89–1.12) for ALL and 0.85 (95% CI 0.61–1.16) for AML. No trends with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses.

Conclusion

Our study did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia.
O5D.4 Exposure profiles of workers in indium-tin oxide powder manufacturing, target manufacturing and recycling factories in taiwan
Authors: Hsu Yuan-Ting , Su Ting-Yao , Liao Hui-Yi , Kuo Yu-Chieh , Liou Saou-Hsing
Published: May 2020

We aimed to investigate indium exposure profiles and the relationship between ambient exposure and internal dose of indium among workers with different job characteristics in order to improve the work environment and protect workers from overexposure.

We recruited 329 workers from indium-tin oxide (ITO) powder and target manufacturing and recycling factories. The workers were categorized into six groups, as powder, ITO target, bonding, processing, recycling process and administration department as reference group. Field and personal air sampling were performed to monitor indium concentrations of work environments and breathing zones of workers. Cumulative exposure were evaluated by respirable dust concentrations in personal sampling, exposure duration and work duration. Plasma indium (P-In), urine indium (U-In) and U-In adjusted for creatinine (U-In/creatinine) were used as internal dose.

One-fourth of air indium concentrations of ITO manufacturing and recycling factories were exceeded permissible exposure limit (PEL) in Taiwan. Thirty-six percent of workers in this study exposed to unacceptable airborne concentration of indium. Over one-fifth of workers had P-In higher than Japanese biological exposure index (BEI) of 3 µg/L. After adjusting for potential confounders, significant positive were found between indium cumulative exposure and P-In (β=0.56, p<0.001), U-In (β=0.38, p<0.001), and U-In/creatinine (β=0.34, p<0.001) in bonding process. A significant positive were found between indium cumulative exposure and P-In (β=0.53, p=0.003), U-In (β=0.39, p=0.047) and U-In/creatinine (β=0.34, p=0.01) in processing process.

We suggest that U-In was an useful biomarker to assess indium exposure of indium manufacturing workers. The distribution and elimination of indium differed by its chemical form, which lead to characterization of the chemical form of indium is important for biomonitoring. Notably, although workers were exposed to indium below PEL, P-In still exceeded Japanese BEI. An appropriate exposure index need to be specified.
O5E.2 A hospital occupational diseases unit: an experience to increase the recognition of occupational disease
Authors: Benavides FG , Ramada JM , Ubalde-Lopez M , Delclos GL , Serra C
Published: May 2020

Background

Under-reporting and recognition of occupational diseases is a problem in countries with workers’ compensation schemes.

Aims

To describe the role of a public hospital Occupational Disease Unit (ODU) in Barcelona that resulted in improved reporting and official recognition of occupational diseases from 2010 to 2017.

Methods

Hospital physicians referred possible cases of work-related disease to the ODU, where in-depth medical evaluations were then performed, and a detailed report addressing causation was generated. Patients with confirmed cases of occupational disease were counselled and followed while pursuing official recognition and benefits claims by the Spanish Social Security System.

Results

Between 2010 and 2017, 149 cases were referred to the ODU for evaluation. Of these, 80 (53.7%) were confirmed to have an occupational disease, 54 (67.5%) patients pursued official recognition, and to date 26 (48.1%) were accepted by the Social Security System. The predictive positive value varied by diagnosis group (p=0.003), and was highest for skin diseases (71.4%) and cancer (66.7%), and lowest for hearing loss (29.4%) and musculoskeletal disorders (16.7%).

Conclusions

A hospital ODU can improve reporting and official recognition of occupational diseases, that otherwise might not have been recognized. Expanding this experience to other Spanish and European hospitals could improve the efficiency of workers’ compensation schemes and better support preventive policies.
O6A.4 Risk of postmenopausal breast cancer and occupational exposure to chemicals in swedish women
Authors: Gustavsson Per , Videnros Cecilia , Wiebert Pernilla , Plato Nils , Borgquist Signe , Manjer Jonas , Albin Maria , Selander Jenny
Published: May 2020

Earlier studies have led to a hypothesis of an increased risk of breast cancer after exposure to organic solvents. This study aimed to investigate if exposure to various chemicals in the workplace was associated with an increased risk of breast cancer.

The study comprised 14 119 women born 1923–1950 and living in Malmö city, Sweden, who were enrolled for a prospective population cohort study between 1991 and 1996. Oc cupational exposure to various chemicals was assessed from a job-exposure matrix. Individual data on other breast cancer risk factors (age, parity, age at first pregnancy, breastfeeding, hormonal replacement therapy, physical activity, alcohol consumption, height and BMI) were collected at baseline and used for confounding control. Diagnoses of invasive breast cancer were obtained from the Swedish Cancer Registry until end of follow-up at 2013–12–31.

Women exposed to any type of chemical (organic solvents, pesticides, fumes or oil mist) for more than 10 years (66 cases) showed an increased adjusted breast cancer risk, HR=1.43, (95% CI 1.10–1.85), and the risk correlated positively with duration of exposure. Investigation of risk in association with organic solvents showed a small and non-significantly elevated risk after >10 years of exposure, HR=1.18 (95% CI 0.81–1.71). The risk tended to be higher, but not significantly elevated, after >10 year of exposure than after 1–10 years of exposure for most of the studied chemicals. More than 10 years of exposure to diesel exhaust was associated with an increased risk (adjusted HR=1.69, 95% CI 1.01–2.82).

Occupational exposure to chemicals in general was associated with an elevated risk of postmenopausal breast cancer, but the study gives no firm support for the hypothesis of an association with exposure to organic solvents. An elevated risk after >10 years of exposure to diesel exhaust was an unexpected finding that needs to be investigated further.
O1B.3 Hyperactivity disorder in children was related to maternal employment status during pregnancy and postpartum depressive symptoms: a prospective cohort study
Authors: Shih Ping , Huang Ching-Chun , Chiang Tung-liang , Chen Pau-Chung , Guo Yue-Liang Leon
Published: May 2020

Background

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders globally. Although some investigations implied a relationship between ADHD and maternal psychosocial stress exposure during pregnancy, little is known about the effects of maternal occupational exposure and even postpartum mental health. This study aimed to investigate whether maternal employment status during pregnancy and postpartum depressive symptoms are related to offspring hyperactivity, one of the key early symptoms of children ADHD.

Methods

Taiwan Birth Cohort Study recruited representative mother-infant pairs, as a result of approximately 12% of all deliveries in 2005 using multistage stratified sampling. Employment status with or without job stress during pregnancy and postpartum depressive symptoms were inquired when the child was six months of age by face-to-face interview. Ever having hyperactivity syndrome as evaluated by physicians, psychologists, or special educators was inquired when the child was eight years of age. Factors of hyperactivity, including maternal employment, job stress, and postpartum depression were studied by adjusted odds ratios (aORs) and 95% confidence interval (CI) using logistic regression, adjusting for gender, urban/rural residence, birth season and household income.

Results

18 215 mother-infant pairs were included in the final analysis, where 421 (2.3%) of children had been diagnosed as having hyperactivity before 8 years of age. Comparing to mothers employed and without job stress during pregnancy, the aOR (95% CI) of child hyperactivity was 1.47 (95%CI: 1.12, 1.94) for mothers with job stress and 1.43 (95%CI: 1.12, 1.84) for mothers with no employment during pregnancy, respectively. Besides, children were 1.36 (95% CI: 1.07, 1.73) times more likely to receive an ADHD diagnosis if their mother experienced postpartum depressive symptoms.

Conclusions

In this prospective birth cohort study, mothers’ employment status, job stress during pregnancy, and postpartum depressive symptoms were risk factors for the occurrence of hyperactivity in their children.
O6A.6 Mortality experience of in women in south african mining: 2013 – 2015
Authors: Wilson Kerry , Kootbodien Tahira , Naicker Nisha
Published: May 2020

Mining is a high-risk industry with both continued accidents and occupational disease, despite controls introduced in the industry. In this study, we looked at the sex differences in mortality between male and female miners in South Africa.

Methods

The use of vital registration data for monitoring mortality in miners has largely been unexplored in South Africa. Statistics South Africa provides data from 2013 to 2015 which was used in students-t-tests along with proportion tests to investigate differences between death in all women and women miners along with differences in deaths in male miners and women miners. Multiple logistic regression analysis was performed to calculate mortality odds ratios (MORs) for the underlying cause of death in these groups, with adjustments for age, education level, province of death and smoking status.

Results

Of the 8769 deaths recorded with occupation miner ion the years 2013–2015, only 5.7% were in females. Significant differences between all women and women miners were found in age at death (58.8 vs 47.8), no 1 cause of death (ill-defined vs TB) and education (43.6% vs 63.6%). MORs were significantly increased in women miners for TB, HIV and external causes of death compared to all women while being protected from lifestyle and chronic diseases. Women miners compared to male miners had increased odds of HIV death and lifestyle diseases but a similar risk of external causes of death.

Discussion

Women miners appear to die at significantly younger ages than both male miners and other women despite a higher level of education. This may be due to the increased mortality due to HIV and external causes of death. Thus increased controls are required on mines to protect the health of women miners.
O6B.1 Use of arsenical pesticides and risk of lung cancer among french farmers
Authors: Boulanger Mathilde , Tual Severine , Pons Romain , Busson Amandine , Delafosse Patricia , Guizard Anne Valerie , Marcotullio Elisabeth , Piel Clement , Pouchieu Camille , Renier Marine , Baldi Isabelle , Lebailly Pierre ,   AGRICAN group
Published: May 2020

Context

Exposure to inorganic arsenicals, including occupational use of pesticides, is carcinogenic to the lung (IARC group 1). However epidemiological data are scarce for agricultural exposures. This work assesses lung cancer (LC) risk, including duration-effect relationships, associated to arsenicals use in farming, by gender and histology.

Methods

We linked data from two French projects: (1) the Agriculture and Cancer (AGRICAN) cohort, a large prospective cohort of farmers and people affiliated to the French agricultural insurance scheme and (2) the Pesticide Matrix (PESTIMAT), a crop-exposure matrix. Incident lung cancer cases were collected and their histological subtype ascertained from cancer registries, from enrolment (2005–2007) to December 31 st 2013. The enrolment questionnaire included items on smoking history, and the involvement in 18 different breedings/crops and specific tasks, including pesticide application, with years of beginning and end. We performed Cox models, with age as timescale, adjusted on gender, smoking, and two activities found to be protective in previous analyses – cattle breeding and corn growing. The reference group included farmers having never applied any pesticide on any crop. We assessed risks for each inorganic compound (lead, sodium, aluminum, copper and calcium arsenate) and for overall exposure.

Results

Nearly 10% (n=14 359 people) of the population was potentially exposed to arsenicals, in vineyard growing before 2001, or in fruit-tree or potato growing before 1973. We observed 98 incident LC among exposed people. Only women exhibited a higher risk of LC (HR 3.14 95% CI(1.42–6.96) for exposure to any compound, n=7 exposed cases, all adenocarcinomas), but with no duration-effect relationship. Risks were significantly elevated for lead, copper and sodium arsenate.

Conclusion

We found an increased risk of LC, especially adenocarcinomas, among women. At this stage, exposure assessment was broad: the use of an exposure index, based on probability, frequency and intensity of use, will help refine the analyses.
O6B.2 Cancer risk by ore type in a mixed miners cohort
Authors: Demers Paul A , Berriault Colin , Ramkissoon Avinash , Do Minh T , Lightfoot Nancy , Zeng Xiaoke , Arrandale Victoria
Published: May 2020

Background and objectives

Mining may involve exposure to many carcinogens, including respirable crystalline silica (RSC), diesel engine exhaust (DEE), nickel (Ni), chromium (Cr), radon (Rn), and arsenic (As), which vary by ore being mined. The province of Ontario, Canada has a diverse mining sector with associated exposures including gold (RSC/DEE/As/Cr), uranium (RSC/DEE/Rn), and nickel-copper (DEE/Ni), and other ores (RSC/DEE). The study aim was to examine the risk of cancer by ore type in a mixed mining cohort.

Methods

From 1928–1987 workers in the Ontario minerals industry were required to undergo an annual physical examination and chest x-ray, as well as record their mining work history in order to receive certification. Data from these exams was used to create the Mining Master File (MMF) cohort. Cancers were identified through linkage of the MMF with the Ontario Cancer Registry (1964–2017). Cancer risk among miners was compared to provincial rates using Standardized Incidence Ratios (SIR); internal analyses were conducted using Poisson regression.

Results

Individuals who died or were lost before 1964, had missing or invalid data, or employment of less than two weeks were excluded. Too few women (n=161) were available for analysis. In total, 61 397 men were included in the analysis. Gold miners had excesses of lung (SIR=1.30, 95%CI=1.23–1.38) and nasopharyngeal cancer (SIR=2.34, 95%CI=1.39–3.70). Uranium miners had excesses of lung (SIR=1.57, 95%CI=1.45–1.70), bladder (SIR=1.20, 95%CI=1.02–1.40), and bone (SIR=2.45, 95%CI=1.30–4.19) cancers. Nickel-copper miners had excesses of lung (SIR=1.13, 95%CI=1.08–1.19), bone (SIR=2.02, 95%CI=1.32–2.96), and sinonasal cancer (SIR=1.73, 95%CI=1.12–2.56).

Conclusions

Increased risks for specific cancers were observed among people who mined many different ore types. Most of the associations were as expected, but several (e.g., bone cancers) will undergo further investigation. Future analyses will examine the impact of combined exposures among miners of multiple ore types.
O6B.3 Risk of leukemia after chronic exposure to gamma radiation among ontario uranium miners?
Authors: Do Minh , Ramkissoon Avinash , Berriault Colin , Villeneuve Paul , Demers Paul
Published: May 2020

Background and objectives

Increases in leukemia risk after exposure to gamma radiation have been well-demonstrated among nuclear energy workers and atomic bomb survivors. Although uranium miners are also exposed to gamma radiation, its health effects are not well characterized, and assumed to be insignificant relative to the effects of radon decay products. The objective of this study is to quantify the effects of whole-body gamma radiation exposure on the incident risk of leukemia among Ontario Uranium Miners.

Methods

Based on a retrospective cohort of 28 546 uranium miners, leukemia cases were identified through record linkages with the Canadian Cancer Registry and Canadian Mortality Database. Gamma doses were estimated through dose prediction models and badge dosimeter readings collated by the National Dose Registry, blinded from case status. Person-years at risk of leukemia were stratified by exposure category, calendar period of employment, and attained age at risk. Poisson regression was used to model the risk (RR) of incident leukemia at increasing levels of cumulative gamma radiation exposure, adjusting for calendar period and attained age.

Results

Between 1969 and 2005, 116 incident cases of leukemia were identified. On average, these miners were employed for 4.4 years with a mean cumulative dose of 5.25 millisieverts (mSv). With exposure lagged by 2 years, preliminary analyses showed that when compared to the referent group (0 mSv), those with >30 mSv of cumulative gamma dose had a non-statistically significant increase in the risk of leukemia diagnosis (RR=2.04, 95% CI: 0.93, 4.51) with increasing, linear trend (p=0.08).

Conclusions

Although our results did not show a statistically significant relationship between gamma radiation and leukemia incidence, it is likely due to low statistically power. Future work may include pooling the Ontario Uranium Miners cohort with other similar cohorts to better quantify the potential associated risks.
O6B.4 Laryngeal cancer risks in workers exposed to lung carcinogens: exposure-effect analyses using a quantitative job exposure matrix
Authors: Hall Amy , Kromhout Hans , Schüz Joachim , Portengen Lützen , Peters Susan , Vermeulen Roel , Boffetta Paolo , Brennan Paul , Luce Danièle , Stücker Isabelle , Ramroth Heribert , Yuan-Chin Amy Lee , Hashibe Mia , Straif Kurt , Olsson Ann
Published: May 2020

Background

Various occupational agents are suspected risk factors for laryngeal cancer. However, individual studies are often inadequate to investigate how such exposures relate to this relatively rare outcome. Important limitations include small sample sizes, lack of detail on exposure, and inadequate adjustment for confounders.

Methods

This study applied quantitative estimates via SYN-JEM for four established occupational lung carcinogens to case-control data from five (Western European and Latin American) studies within the International Head and Neck Cancer Epidemiology Consortium. Participant job histories for n=2256 laryngeal cancer cases and n=7857 controls recruited from 1989–2007 were linked with quantitative SYN-JEM estimates via ISCO-68 codes. Logistic regression models were applied to assess the effects of occupational exposure to asbestos, respirable crystalline silica (RCS), chromium-VI, and nickel on laryngeal cancer risk while controlling for tobacco and alcohol consumption.

Results

Increased ORs were observed for all agents evaluated. In males, a positive exposure-effect relationship was observed with duration of RCS exposure (p-value for trend <0.01). Relatively strong effects were also observed in the highest categories of career-cumulative chromium-VI exposure (>90%ile: OR=2.21, 95% CI=1.13–4.33) and career-average exposure (>90%ile: OR=2.96, 95% CI=1.51–5.79), and in the highest category of career-cumulative nickel/chromium-VI combined exposure (>90%ile: OR=1.51, 95% CI=1.01–2.26). These relationships weakened in analyses restricted to blue collar workers but interpretations remained unchanged.

Conclusions

These results support causal links between exposure to known lung carcinogens and laryngeal cancer. Measures to reduce such exposures in workplaces could decrease the risk of both laryngeal and lung cancers.
O1B.4 Health effects of prenatal occupational noise exposure: a systematic review
Authors: Stokholm Zara Ann , Iversen Inge Brosbøl , Kolstad Henrik
Published: May 2020

Current legislation and threshold limits for occupational noise exposure may not sufficiently account for higher vulnerability of the foetus. We conducted a systematic literature review and identified 20 relevant studies of prenatal noise exposure levels and health. Maternal tissues attenuate industrial noise by about 30 dB. The foetus responds the earliest to noise exposure from the 19th week of gestational age. There is some evidence of an increased risk of hearing loss at prenatal noise levels≥85 dBA (8 hour average) and little evidence at lower levels. Increased risks for preterm birth, small-for-gestational-age and congenital malformations are seen as single study findings at levels≥90 dBA. There is little evidence for how noise exposure may increase the risk of extra-auditive effects in the foetus. Methodological shortcomings and the scarce number of studies limit the conclusions that can be drawn. Still, we recommend pregnant women avoid working at noise levels≥85 dBA.
O6D.2 Evidence of dna methylation changes by carbon nanotubes in a translational study design
Authors: Ghosh Manosij , Öner Deniz , Godderis Lode , Hoet Peter
Published: May 2020

Introduction

While studies have addressed genotoxic effects of CNT, only limited information are available on epigenetic effects. We designed a study to investigate DNA methylation alterationsin vitro,in vivoand in occupationally exposed workers.

Material and methods

In vitrostudies were performed in 16-HBE and THP-1 cells. For thein vivostudy, BALB/c mice were administered intratracheally with single-wall CNT (SWCNTs) and multi-wall (MWCNTs) at high (2.5 mg/kg) and low (0.25 mg/kg) doses. For the cross sectional study, 24 workers exposed to aggregates of MWCNT of 500 nm–100 µm with concentrations of 4.6–42.6 µg/m3 and 43 unexposed referents were recruited. Global DNA methylation and demethylation patterns were analysed by LC-MS/MS. Methylation of specific genes was measured by Pyromark 24® (Qiagen). Genome-wide assessment of DNA methylation was performed with Infinium HumanMethylation450 BeadChip Array.

Results

In general, we did not find global DNA methylation alteration for both CNTs. In 16-HBE cells, differentially methylated and expressed genes (MWCNTs>SWCNTs) from p53 signalling, DNA damage repair and cell cycle pathways were observed. In THP-1 cells, CNTs induced promoter-specific methylation of genes involved in several signaling cascade, vascular endothelial growth factor and platelet activation pathways. In lungs of BALB/c mice CNTs affected methylation of ATM gene. Finally, analysis of gene-specific DNA methylation in exposed workers revealed significant changes for DNMT1, ATM, SKI, and HDAC4 promoter CpGs.

Conclusions

Epigenetic changes seem to occur at sub cyto-genotoxic concentrationsin vitro. Alteration in DNA methylation pattern could be a natural reaction of cells but could also silence critical genes and reprogram cellular functions.
O6D.3 Evaluation of polycyclic aromatic hydrocarbons exposure across occupations in korea using urinary metabolite 1-hydroxypyrene
Authors: Koh Dong-Hee , Park Ju-Hyun , Lee Sang-Gil , Kim Hwan-Cheol , Choi Sang-Jun , Jung Hyejung , Park Dong-Uk
Published: May 2020

Objectives

Polycyclic aromatic hydrocarbons are a well-known carcinogen causing lung and skin cancers in exposed workers. Several occupations such as coke production have been reported to be associated with high PAHs exposure. However, previous reports have been confined in several occupations. Thus, we aimed to evaluate PAHs exposure across a wide range of occupations using its urinary metabolite 1-hydroxypyrene (1-OHP).

Methods

To evaluate PAHs exposure across occupations, we collected the urine 1-OHP data from the Korean National Environmental Health Survey which is a nationwide bio-monitoring survey. The data contained information about urine 1-OHP levels, cigarette smoking status, and standard occupational codes. We calculated summary statistics of urine 1-OHP levels for each occupation. In addition, we calculated the relative exposure indicators which are the proportions of exceeding the quartile levels. Since cigarette smoking is a single most influential factor of PAHs exposure, we repeated the analyses by excluding current smokers.

Results

Overall geometric means (GM) of all populations and non-smoker populations were 0.13µg/L and 0.10µg/L, respectively. For the major group of occupation, ‘Craft and Related Trades Workers’ and ‘Equipment, Machine Operating and Assembling Workers’ showed the highest urine 1-OHP levels, while ‘Homemaker’ showed the lowest level. For the sub-major group of occupation, ‘Video and Telecommunications Equipment Related Occupations’ showed the highest percentage (61%) of exceeding the third quartile (Q3) level of all populations. While ‘Legal and Administration Professional Occupations’ showed the lowest percentage of exceeding the Q3 level of all populations. For the minor group of occupation, ‘Horticultural and Landscape Workers’ showed the highest percentage (64%) of exceeding the Q3 level of all populations. While ‘Kindergarten teachers’ showed the lowest percentage of exceeding the Q3 level of all populations.

Conclusions

Our results will provide ancillary information about PAHs exposure across occupations, especially in occupations where PAHs exposure has not well known.
O6D.4 Association of occupational exposures with ex vivo functional immune response in workers handling carbon nanotubes and nanofibers
Authors: Schubauer-Berigan Mary , Dahm Matthew , Beard John , Kodali Vamsi , Zeidler-Erdely Patti , Erdely Aaron
Published: May 2020

Animal toxicology studies suggest that workers exposed to carbon nanotubes or nanofibers (CNT/F) may experience pulmonary or systemic health effects; however, direct human evidence is lacking. Our study’s objective was to evaluate associations between CNT/F exposure andex vivoresponses of leukocytes challenged with secondary stimulants, adjusting for potential confounders, in a cross-sectional study. We measured multi-day exposure using CNT/F structure count (SC) and elemental carbon air concentrations among 102 U.S. workers. Demographic, lifestyle, and other occupational information was obtained via in-person interview. Workers’ whole blood was incubated for 18 hours with and without two microbial stimulants (lipopolysaccharide and staphylococcal enterotoxin type B) using TruCulture® technology to evaluate immune cell activity. Following incubation, collected supernatants were preserved and subsequently analyzed for cytokine and chemokine concentrations. The ratio of stimulant:null response for each protein was analyzed using multiple linear regression, principal components (PC) analysis, and Ingenuity® Pathway Analysis (IPA) to determine whether patterns of protein response were associated with CNT/F exposure. We found that CNT/F metrics (most consistently, the SC-based) were significantly (p<0.05) inversely associated with stimulant:null ratios of GM-CSF, IFN-γ, interleukin (IL)−2, IL-4, IL-5, IL-10, IL-17, and IL-23. CNT/F metrics were significantly inversely associated with PC1 (a weighted mean of most biomarkers that explained 25% of the variance in the set of protein ratios) and PC2 (a biomarker contrast that explained 14%). Among other occupational exposures, only solvent exposure was significantly (and was inversely) related to PC2. IPA suggested a CNT/F-associated generalized inhibition of all leukocyte responses when challenged with a secondary stimulus. We found that CNT/F exposure metrics were uniquely related to a pattern of reduced stimulant responses in challenged circulating leukocytes. This approach, if replicated in other exposed populations, may present a relatively sensitive method to evaluate human response to CNT/F or other occupational exposures.
O6E.2 Exposure assessment for a study of cognitive impairment in former professional footballers in england
Authors: Mcelvenny Damien , Basinas Ioannis , Graveling Richard , Cherrie John , Gallo Valeintina , Kemp Simon , Pearce Neil
Published: May 2020

Evidence is accumulating on the possible increased risks of neurodegenerative disease in former (professional) sportspersons. This study will assess the associations between a history of repetitive low-level head trauma and general and neurological health in retired professional footballers aged 50+in England. The main exposure measures are concussions and cumulative lifetime repeated sub-concussive head impacts (RSHIs), either from heading footballs or other forces applied to the head. Information on factors associated with concussions and RSHIs will be collected via a structured questionnaire during face-to-face interviews.

Our approach will include:

Literature search to identify potentially important proxy measures of RSHI during training and matches;

Developing a model of cumulative RSHIs, based on the more strongly predictive variables, which may include playing position, the frequency of heading, the number of games played and training sessions attended, decade of play and the type of ball used.

The model will be developed from analyses of head contacts from video footage of matches and training, at the individual level and in general, and from statistics on playing career. We will also consult a panel of former professional footballers on the exposure assessment.

The exposure data will be crucial to assess whether those with higher exposure within the study cohort are at increased risk compared to those with lower exposure.