Increased global demand for touch screens, photovoltaics, and optoelectronics has resulted in an increase in the production of indium-tin oxide (ITO). Occupational exposure to indium compounds is associated with the development of indium lung disease. Although many previous epidemiologic investigations highlight an excess of lung abnormalities in workplaces where ITO is produced, few assessments of occupational exposure to respirable and inhalable indium are reported to date. The objective of this study was to identify the determinants of respirable and inhalable indium at an ITO production facility to target exposure interventions. In 2012 and 2014, we conducted exposure assessments at an ITO production facility and collected full-shift personal respirable (n = 159) and inhalable (n = 57) indium samples. We also observed workers and recorded information on task duration and location, materials used, and use of personal protective equipment (PPE). Tasks (n = 121) recorded in task diaries were categorized into 40 similar task groups using the Advanced REACH Tool and process-related information. Mixed-effects models were fit separately for log-transformed respirable and inhalable indium, with random effect of subject and fixed effects of task groups. Overall, respirable and inhalable indium measurements ranged from 0.1 to 796.6 microg m-3 and 1.6 to 10 585.7 microg m-3, respectively, and were highly correlated with Spearman correlation coefficient of 0.90. The final model for respirable indium explained 36.3% of total variance and identified sanding, powder transfer tasks in reclaim, powder transfer tasks in refinery, handling indium materials, and liquid transfer tasks in ITO production as tasks associated with increased respirable indium exposure. The final model for inhalable indium explained 24.6% of total variance and included powder transfer tasks in ITO production, cleaning cylinder or tile, and handling indium material tasks. Tasks identified as strong predictors of full-shift exposure to respirable and inhalable indium can guide the use of engineering, administrative, and PPE controls designed to mitigate occupational exposure to indium. Moreover, since the tasks were aligned with REACH activities, results from this study can also be used to inform REACH activity scenarios.

BACKGROUND: Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. METHODS: A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. RESULTS: Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. CONCLUSIONS: SETA supports public health policy on typhoid immunization strategy in Africa.

Indium-tin oxide production has increased greatly in the last twenty years subsequent to increased global demand for touch screens and photovoltaics. Previous studies used measurements of indium in blood as an indicator of indium exposure and observed associations with adverse respiratory outcomes. However, correlations between measurements of blood indium and airborne respirable indium are inconsistent, in part because of the long half-life of indium in blood, but also because respirable indium measurements do not incorporate inhalable indium that can contribute to the observed biological burden. Information is lacking on relationships between respirable and inhalable indium exposure, which have implications for biological indicators like blood indium. The dual IOM sampler includes the foam disc insert and can simultaneously collect respirable and inhalable aerosol. Here, the field performance of the dual IOM sampler was evaluated by comparing performance with the respirable cyclone and traditional IOM for respirable and inhalable indium and dust exposure, respectively. Side-by-side area air samples were collected throughout an indium-tin oxide manufacturing facility. Cascade impactors were used to determine particle size distribution. Several statistical methods were used to evaluate the agreement between the pairs of samplers including calculating the concordance correlation coefficient and its accuracy and precision components. One-way ANOVA was used to evaluate the effect of dust concentration on sampler differences. Respirable indium measurements showed better agreement (concordance correlation coefficient: 0.932) compared to respirable dust measurements (concordance correlation coefficient: 0.777) with significant differences observed in respirable dust measurements. The dual IOM measurements had high agreement with the traditional IOM for inhalable indium (concordance correlation coefficient: 0.997) but lower agreement for inhalable dust (concordance correlation coefficient: 0.886 and accuracy: 0.896) with a significantly large mean bias (-146.5 microg/m(3)). Dust concentration significantly affected sampler measurements of inhalable dust and inhalable indium. Results from this study suggest that the dual IOM is a useful single sampler for simultaneous measurements of occupational exposure to respirable and inhalable indium.

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

BACKGROUND: Workers manufacturing indium-tin oxide (ITO) are at risk of elevated indium concentration in blood and indium lung disease, but relationships between respirable indium exposures and biomarkers of exposure and disease are unknown. METHODS: For 87 (93%) current ITO workers, we determined correlations between respirable and plasma indium and evaluated associations between exposures and health outcomes. RESULTS: Current respirable indium exposure ranged from 0.4 to 108 mug/m3 and cumulative respirable indium exposure from 0.4 to 923 mug-yr/m3 . Plasma indium better correlated with cumulative (rs = 0.77) than current exposure (rs = 0.54) overall and with tenure ≥1.9 years. Higher cumulative respirable indium exposures were associated with more dyspnea, lower spirometric parameters, and higher serum biomarkers of lung disease (KL-6 and SP-D), with significant effects starting at 22 mug-yr/m3 , reached by 46% of participants. CONCLUSIONS: Plasma indium concentration reflected cumulative respirable indium exposure, which was associated with clinical, functional, and serum biomarkers of lung disease. Am. J. Ind. Med. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

Inhalation of beryllium is associated with the development of sensitization; however, dermal exposure may also be important. The primary aim of this study was to elucidate relationships among exposure pathways in four different manufacturing and finishing facilities. Secondary aims were to identify jobs with increased levels of beryllium in air, on skin, and on surfaces; identify potential discrepancies in exposure pathways, and determine if these are related to jobs with previously identified risk. Beryllium was measured in air, on cotton gloves, and on work surfaces. Summary statistics were calculated and correlations among all three measurement types were examined at the facility and job level. Exposure ranking strategies were used to identify jobs with higher exposures. The highest air, glove, and surface measurements were observed in beryllium metal production and beryllium oxide ceramics manufacturing jobs that involved hot processes and handling powders. Two finishing and distribution facilities that handle solid alloy products had lower exposures than the primary production facilities, and there were differences observed among jobs. For all facilities combined, strong correlations were found between air-surface (rp ≥ 0.77), glove-surface (rp ≥ 0.76), and air-glove measurements (rp ≥ 0.69). In jobs where higher risk of beryllium sensitization or disease has been reported, exposure levels for all three measurement types were higher than in jobs with lower risk, though they were not the highest. Some jobs with low air concentrations had higher levels of beryllium on glove and surface wipe samples, suggesting a need to further evaluate the causes of the discrepant levels. Although such correlations provide insight on where beryllium is located throughout the workplace, they cannot identify the direction of the pathways between air, surface, or skin. Ranking strategies helped to identify jobs with the highest combined air, glove, and/or surface exposures. All previously identified high-risk jobs had high air concentrations, dermal mass loading, or both, and none had low dermal and air. We have found that both pathways are relevant. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a file describing the forms of beryllium materials encountered during production and characteristics of the aerosols by process areas.].

Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

OBJECTIVES: Exposure-response relations for beryllium sensitization (BeS) and chronic beryllium disease (CBD) using aerosol mass concentration have been inconsistent, although process-related risks found in most studies suggest that exposure-dependent risks exist. We examined exposure-response relations using personal exposure estimates in a beryllium worker cohort with limited work tenure to minimize exposure misclassification. METHODS: The population comprised workers employed in 1999 with six years or less tenure. Each completed a work history questionnaire and was evaluated for immunological sensitization and CBD. A job-exposure matrix was combined with work histories to create individual estimates of average, cumulative, and highest-job-worked exposure for total, respirable, and submicron beryllium mass concentrations. We obtained odds ratios from logistic regression models for exposure-response relations, and evaluated process-related risks. RESULTS: Participation was 90.7% (264/291 eligible). Sensitization prevalence was 9.8% (26/264), with 6 sensitized also diagnosed with CBD (2.3%, 6/264). A general pattern of increasing sensitization prevalence was observed as exposure quartile increased. Both total and respirable beryllium mass concentration estimates were positively associated with sensitization (average and highest job), and CBD (cumulative). Increased sensitization prevalence was identified in metal/oxide production, alloy melting and casting, and maintenance, and for CBD in melting and casting. Lower sensitization prevalence was observed in plant-area administrative work. CONCLUSIONS: Sensitization was associated with average and highest job exposures, and CBD was associated with cumulative exposure. Both total and respirable mass concentrations were relevant predictors of risk. New process-related risks were identified in melting and casting and maintenance.

OBJECTIVES: Previous epidemiologic studies of beryllium sensitization (BeS) and chronic beryllium disease (CBD) have reported inconsistent exposure-response relationships, likely due to exposure misclassification. The objective of this study was to develop historical estimates of size-selective personal exposure to beryllium for an epidemiologic study. METHODS: In 1999, a cross-sectional survey of workers hired after 1 January 1994 was conducted at a beryllium production facility. Personal exposure data from two air sampling surveys conducted in 1999 were used to obtain total, respirable, and submicron particle baseline exposure estimates (BEE) for a job-exposure matrix (JEM). General area air samples collected from 1994-1999 were used to estimate annual changes in exposures (temporal factors) for 24 different process areas. Historical exposure estimates (HEE) were calculated by applying the temporal factors to the BEE. Workers were assigned HEE based on their work history, and their historical exposure profile was summarized as cumulative, average, or highest-ever job exposure. RESULTS: Changes in exposure over a 6-year period were observed in 10 of the 24 process areas with an overall mean decline of 18% per year. The overall total exposure for study participants over their work tenure ranged from: 0.001-34.44 mcg/m (3)-year, 0.01-16.26 mcg/m (3), and 0.01-17.54 mcg /m (3)for cumulative, average, and highest-ever job, respectively. For respirable exposures, the ranges were: 0.001-15.54 mcg/m (3)-year, 0.01-3.56 mcg/m (3), 0.01-5.54 mcg /m (3)for cumulative, average, and highest-ever job, respectively. CONCLUSIONS: Using this JEM, exposure-response relationships for BeS and CBD can be explored over a range of exposure metrics such as total, respirable, and submicron beryllium mass concentrations, including summary measures such as cumulative, average, or highest exposures, with the ultimate objective of elucidating a quantitative exposure-response relationship.

OBJECTIVE: The aim of this study was to evaluate the validity of a job exposure matrix (JEM) constructed for the period 1994-1999. Historical exposure estimates (HEE) for the JEM were constructed for all job and year combinations by applying temporal factors reflecting annual change in area air measurements (1994-1998) to the personal baseline exposure estimates (BEE) collected in 1999. The JEM was generated for an epidemiologic study to examine quantitative exposure-response relationships with sensitization and chronic beryllium disease. METHODS: The validity of the BEE and HEE was evaluated by comparing them with a validation dataset of independently collected personal beryllium exposure measurements from 1999 and 1994-1998, respectively. Agreement between the JEM and validation data was assessed using relative bias and concordance correlation coefficients (CCC). RESULTS: The BEE and HEE overestimated the measured exposures in their respective validation datasets by 8% and 6%, respectively. The CCC reflecting the deviation of the fitted line from the concordance line, showed good agreement for both BEE (CCC=0.80) and HEE (CCC=0.72). Proportional difference did not change with exposure levels or by process area and year. Overall, the agreement between the JEM and validation estimates (from combined HEE and BEE) was high (CCC=0.77). CONCLUSIONS: This study demonstrated that the reconstructed beryllium exposures at a manufacturing facility were reliable and can be used in epidemiologic studies.

Friction stir welding (FSW) is considered one of the most significant developments in joining technology over the last half century. Its industrial applications are growing steadily and so are the number of workers using this technology. To date, there are no reports on airborne exposures during FSW. The objective of this study was to investigate possible emissions of nanoscale (<100 nm) and fine (<1 microm) aerosols during FSW of two aluminum alloys in a laboratory setting and characterize their physicochemical composition. Several instruments measured size distributions (5 nm to 20 microm) with 1-s resolution, lung deposited surface areas, and PM(2.5) concentrations at the source and at the breathing zone (BZ). A wide range aerosol sampling system positioned at the BZ collected integrated samples in 12 stages (2 nm to 20 microm) that were analyzed for several metals using inductively coupled plasma mass spectrometry. Airborne aerosol was directly collected onto several transmission electron microscope grids and the morphology and chemical composition of collected particles were characterized extensively. FSW generates high concentrations of ultrafine and submicrometer particles. The size distribution was bimodal, with maxima at approximately 30 and approximately 550 nm. The mean total particle number concentration at the 30 nm peak was relatively stable at approximately 4.0 x 10(5) particles cm(-3), whereas the arithmetic mean counts at the 550 nm peak varied between 1500 and 7200 particles cm(-3), depending on the test conditions. The BZ concentrations were lower than the source concentrations by 10-100 times at their respective peak maxima and showed higher variability. The daylong average metal-specific concentrations were 2.0 (Zn), 1.4 (Al), and 0.24 (Fe) microg m(-3); the estimated average peak concentrations were an order of magnitude higher. Potential for significant exposures to fine and ultrafine aerosols, particularly of Al, Fe, and Zn, during FSW may exist, especially in larger scale industrial operations.

The Transmission Electron Microscopy (TEM) and Energy Dispersive Spectroscopy (EDS) were used to determine morphology and elemental composition of a variety of freshly emitted soot particles ( acetylene flame, candle flame, kerosene flame, diesel exhaust, electric arc, plastic burning, styrofoam burning, wood burning [white oak and pine bark], and rice straw burning), which can be possible candidate soot in the ambient atmosphere, and ultrafine particles sampled in urban, industrial, and coastal sites during ultrafine particle formation events ( combustion and photochemical events). By using mobility-classified non-refractory ((NH4)(2)SO4) and refractory ( Polystyrene latex (PSL) and salt ( NaCl)) particles, limitation of the TEM was tested. Data showed that the TEM method can be used to examine shapes of both volatile particles such as (NH4)(2)SO4 (100 nm) at low, but not high magnification ( refer to low and high beam intensity, respectively), and nonvolatile particles like NaCl ( 100 nm) and PSL ( 84 nm) at either low or high magnification. Distinct differences in morphological properties such as primary particle diameter, fractal dimension, and microstructure were observed among the different types of fresh soot particles. The atmospheric ultrafine particles were classified as agglomerates, sulfate mixtures ( spherical), metallic oxides ( spherical and polygonal), C-rich refractory ( not agglomerated), C-rich non-refractory ( not agglomerated), Si-rich ( spherical), Na-rich ( porous), or P-containing (non-spherical) particles. At the urbanGwangju site, a higher fraction of fresh and aged agglomerates was observed than at other sites. The C-rich non-refractory and sulfate mixtures were often observed in the photochemical event. The C-rich refractory particles were abundant at the Gwangju and Yeosu sites. The coastal Taean site had few agglomerates due to limited anthropogenic combustion source.