Analysis of single nucleotide polymorphisms in chronic beryllium disease.

Sarcoidosis and chronic beryllium disease (CBD) are phenocopies, however the latter one has a clear trigger factor that is beryllium exposure. This study analyses single nucleotide polymorphisms (SNPs) in a large cohort for beryllium-exposed persons. SNPs were chosen for their relevance in sarcoidosis. Even though one of largest cohorts of beryllium-exposed persons was analysed, no statistically relevant association between any SNP and CBD could be verified. Notably, some SNPs exhibit inverse OR for beryllium sensitization and CBD with nominally statistical significance, which allows hypothesizing about pathophysiological role of genes for the disease triggering and development.

Work-related asthma cluster at a syntactic foam manufacturing facility - Massachusetts 2008-2013.

Work-related asthma is asthma that is caused or exacerbated by exposure to specific substances in the workplace. Approximately 10%-16% of adult-onset asthma cases are attributable to occupational factors, and estimates of asthma exacerbated by work range from 13% to 58%. During 2008-2012, the Massachusetts Department of Public Health received nine reports of work-related asthma among workers at a facility that manufactured syntactic foam used for flotation in the offshore oil and gas industry. These reports and a request from facility employees led to a CDC health hazard evaluation during 2012-2013 in which CDC reviewed records, toured the facility, and administered a questionnaire to current employees. Investigators found that workers' risk for asthma increased substantially after hire, possibly because of known asthma triggers (i.e., asthmagens) used in production. The company has since initiated efforts to reduce employee exposures to these substances. This cluster of work-related asthma was identified through CDC-funded, state-based surveillance and demonstrates complementary state and federal investigations.

An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease.

RATIONALE: Beryllium continues to have a wide range of industrial applications. Exposure to beryllium can lead to sensitization (BeS) and chronic beryllium disease (CBD). OBJECTIVES: The purpose of this statement is to increase awareness and knowledge about beryllium exposure, BeS, and CBD. METHODS: Evidence was identified by a search of MEDLINE. The committee then summarized the evidence, drew conclusions, and described their approach to diagnosis and management. MAIN RESULTS: The beryllium lymphocyte proliferation test is the cornerstone of both medical surveillance and the diagnosis of BeS and CBD. A confirmed abnormal beryllium lymphocyte proliferation test without evidence of lung disease is diagnostic of BeS. BeS with evidence of a granulomatous inflammatory response in the lung is diagnostic of CBD. The determinants of progression from BeS to CBD are uncertain, but higher exposures and the presence of a genetic variant in the HLA-DP ß chain appear to increase the risk. Periodic evaluation of affected individuals can detect disease progression (from BeS to CBD, or from mild CBD to more severe CBD). Corticosteroid therapy is typically administered when a patient with CBD exhibits evidence of significant lung function abnormality or decline. CONCLUSIONS: Medical surveillance in workplaces that use beryllium-containing materials can identify individuals with BeS and at-risk groups of workers, which can help prioritize efforts to reduce inhalational and dermal exposures.

Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove.

Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings.

Migration of Beryllium via Multiple Exposure Pathways among Work Processes in Four Different Facilities.

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.].

Long-term efficacy of a program to prevent beryllium disease.

BACKGROUND: In 2000, a manufacturer of beryllium materials and products introduced a comprehensive program to prevent beryllium sensitization and chronic beryllium disease (CBD). We assessed the program's efficacy in preventing sensitization 9 years after implementation. METHODS: Current and former workers hired since program implementation completed questionnaires and provided blood samples for the beryllium lymphocyte proliferation test (BeLPT). Using these data, as well as company medical surveillance data, we estimated beryllium sensitization prevalence. RESULTS: Cross-sectional prevalence of sensitization was 0.7% (2/298). Combining survey results with surveillance results, a total of seven were identified as sensitized (2.3%). Early Program workers were more likely to be sensitized than Late Program workers; one of the latter was newly identified. All sensitization was identified while participants were employed. One worker was diagnosed with CBD during employment. CONCLUSIONS: The combination of increased respiratory and dermal protection, enclosure and improved ventilation of high-risk processes, dust migration control, improved housekeeping, and worker and management education showed utility in reducing sensitization in the program's first 9 years. The low rate (0.6%, 1/175) among Late Program workers suggests that continuing refinements have provided additional protection against sensitization compared to the program's early years.

2022 National Occupational Injury Research Symposium (NOIRS): Preventing workplace injuries in a changing world.

About NOIRS: The National Occupational Injury Research Symposium (NOIRS) is the only conference solely dedicated to occupational injury research and prevention. The 8th NOIRS, sponsored by the National Institute for Occupational Safety and Health (NIOSH) and several partners, was held on May 10-12, 2022. NOIRS was held entirely virtually in response to concerns of the COVID-19 pandemic and honoring the symposium theme "Preventing Workplace Injuries in a Changing World." About this Special Issue: The intent of this issue is to highlight the breadth of high-quality presentations at NOIRS, and to make them available to those who did not participate in the conference. This issue includes three short communication articles and nine research articles. Featured research articles in this special issue span a wide variety of methods, data sources, and worker populations. They address leading and emerging causes and contributors to occupational injury in a range of industries and occupations. Concluding Remarks: We hope that this special issue provides readers with a view into some of the research presented at the 2022 NOIRS. We also hope the articles are useful for research and practice, and thinking toward the future.

Characteristics of beryllium exposure to small particles at a beryllium production facility.

Epidemiological studies have reported process-specific elevated prevalence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) among workers. However, exposure-response relationships have been inconsistent, possibly due to incomplete characterization of many biologically relevant aspects of exposure, including particle size. In 1999, two surveys were conducted 3-5 months apart at a beryllium metal, oxide, and alloy production facility during which personal impactor samples (n = 198) and personal 37-mm closed-face cassette (CFC) 'total' samples (n = 4026) were collected. Among process areas, median particle mass median aerodynamic diameter ranged from 5 to 14 µm. A large fraction of the beryllium aerosol was in the nonrespirable size range. Respirable beryllium concentrations were among the highest for oxide production [geometric mean (GM) = 2.02 µg m⁻³, geometric standard deviation (GSD) = 1.3] and pebbles plant (GM = 1.05 µg m⁻³, GSD = 2.9), areas historically associated with high risk of BeS and CBD. The relationship between GM 'CFC total' and GM respirable beryllium for jobs varied by process areas; the rank order of the jobs showed high overall consistency (Spearman r = 0.84), but the overall correlation was moderate (Pearson r = 0.43). Total beryllium concentrations varied greatly within and between workers among process areas; within-worker variance was larger than between-worker variance for most processes. A review of exposure characteristics among process areas revealed variation in chemical forms and solubility. Process areas with high risk of BeS and CBD had exposure to both soluble and insoluble forms of beryllium. Consideration of biologically relevant aspects of exposure such as beryllium particle size distribution, chemical form, and solubility will likely improve exposure assessment.

Efficacy of a program to prevent beryllium sensitization among new employees at a copper-beryllium alloy processing facility.

OBJECTIVES: In 2000, 7% of workers at a copper-beryllium facility were beryllium sensitized. Risk was associated with work near a wire annealing/pickling process. The facility then implemented a preventive program including particle migration control, respiratory and dermal protection, and process enclosure. We assessed the program's efficacy in preventing beryllium sensitization. METHODS: In 2000, the facility began testing new hires (program workers) with beryllium lymphocyte proliferation tests (BeLPTs) at hire and at intervals during employment. We compared sensitization incidence rates (IRs) and prevalence rates for workers hired before the program (legacy workers) with rates for program workers, including program worker subgroups. We also examined trends in BeLPTs from a single laboratory. RESULTS: In all, five of 43 legacy workers (IR = 3.8/1,000 person-months) and three of 82 program workers (IR = 1.9/1,000 person-months) were beryllium sensitized, for an incidence rate ratio (IRR) of 2.0 (95% confidence interval [CI] 0.5, 10.1). Two of 37 pre-enclosure program workers (IR = 2.4/1,000 person-months) and one of 45 post-enclosure program workers (IR = 1.4/1,000 person-months) were beryllium sensitized, for IRRs of 1.6 (95% CI 0.3, 11.9) and 2.8 (95% CI 0.4, 66.2), respectively, compared with legacy workers. Test for trend in prevalence rates was significant. Among 2,159 first-draw BeLPTs during 95 months, we identified seven months when high numbers of redraws were required, with one possible misclassification in this facility. CONCLUSIONS: Fewer workers became sensitized after implementation of the preventive program. However, low statistical power due to the facility's small workforce prevents a definitive conclusion about the program's efficacy. These findings have implications for other copper-beryllium facilities, where program components may merit application.

Associations of Metrics of Peak Inhalation Exposure and Skin Exposure Indices With Beryllium Sensitization at a Beryllium Manufacturing Facility.

OBJECTIVES: Peak beryllium inhalation exposures and exposure to the skin may be relevant for developing beryllium sensitization (BeS). The objective of this study was to identify risk factors associated with BeS to inform the prevention of sensitization, and the development of chronic beryllium disease (CBD). METHODS: In a survey of short-term workers employed at a primary beryllium manufacturing facility between the years 1994-1999, 264 participants completed a questionnaire and were tested for BeS. A range of qualitative and quantitative peak inhalation metrics and skin exposure indices were created using: personal full-shift beryllium exposure measurements, 15 min to 24 h process-specific task and area exposure measurements, glove measurements as indicator of skin exposure, process-upset information gleaned from historical reports, and self-reported information on exposure events. Hierarchical clustering was conducted to systematically group participants based on similarity of patterns of 16 exposure variables. The associations of the exposure metrics with BeS and self-reported skin symptoms (in work areas processing beryllium salts as well as in other work areas) were evaluated using correlation analysis, log-binomial and logistic regression models with splines. RESULTS: Metrics of peak inhalation exposure, indices of skin exposure, and using material containing beryllium salts were significantly associated with skin symptoms and BeS; skin symptoms were a strong predictor of BeS. However, in this cohort, we could not tease apart the independent effects of skin exposure from inhalation exposure, as these exposures occurred simultaneously and were highly correlated. Hierarchical clustering identified groups of participants with unique patterns of exposure characteristics resulting in different prevalence of BeS and skin symptoms. A cluster with high skin exposure index and use of material containing beryllium salts had the highest prevalence of BeS and self-reported skin symptoms, followed by a cluster with high inhalation and skin exposure index and a very small fraction of jobs in which beryllium salts were used. A cluster with low inhalation and skin exposure and no workers using beryllium salts had no cases of BeS. CONCLUSION: Multiple pathways and types of exposure were associated with BeS and may be important for informing BeS prevention. Prevention efforts should focus on controlling airborne beryllium exposures with attention to peaks, use of process characteristics (e.g. the likelihood of upset conditions to design interventions) minimize skin exposure to beryllium particles, and in particular, eliminate skin contact with beryllium salts to interrupt potential exposure pathways for BeS risk.

Impact of negatively charged patches on the surface of MHC class II antigen-presenting proteins on risk of chronic beryllium disease.

Chronic beryllium disease (CBD) is a granulomatous lung disease that occurs primarily in workers who are exposed to beryllium dust or fumes. Although exposure to beryllium is a necessary factor in the pathobiology of CBD, alleles that code for a glutamic acid residue at the 69th position of the HLA-DPbeta1 gene have previously been found to be associated with CBD. To date, 43 HLA-DPbeta1 alleles that code for glutamic acid 69 (E69) have been described. Whether all of these E69 coding alleles convey equal risk of CBD is unknown. The present study demonstrates that, on the one hand, E69 alleloforms of major histocompatibility complex class II antigen-presenting proteins with the greatest negative surface charge convey the highest risk of CBD, and on the other hand, irrespective of allele, they convey equal risk of beryllium sensitization (BeS). In addition, the data suggest that the same alleles that cause the greatest risk of CBD are also important for the progression from BeS to CBD. Alleles convey the highest risk code for E26 in a constant region and for E69, aspartic acid 55 (D55), E56, D84 and E85 in hypervariable regions of the HLA-DPbeta1 chain. Together with the calculated high binding affinities for beryllium, these results suggest that an adverse immune response, leading to CBD, is triggered by chemically specific metal-protein interactions.

Enhanced preventive programme at a beryllium oxide ceramics facility reduces beryllium sensitisation among new workers.

BACKGROUND: A 1998 survey at a beryllium oxide ceramics manufacturing facility found that 10% of workers hired in the previous 6 years had beryllium sensitisation as determined by the beryllium lymphocyte proliferation test (BeLPT). In response, the facility implemented an enhanced preventive programme to reduce sensitisation, including increased respiratory and dermal protection and particle migration control. AIM: To assess the programme's effectiveness in preventing sensitisation. METHODS: In 2000, the facility began testing newly hired workers for beryllium sensitisation with the BeLPT at time of hire and during employment. The sensitisation rate and prevalence for workers hired from 2000 to 2004 were compared with that for workers hired from 1993 to 1998, who were tested in the 1998 survey. Facility environmental conditions for both time periods were evaluated. RESULTS: Newly hired workers in both cohorts worked for a mean of 16 months. Of the 97 workers hired from 2000 to 2004 with at least one employment BeLPT result, four had abnormal results at time of hire and one became sensitised during employment. Of the 69 workers hired from 1993 to 1998 and tested in 1998, six were found to be sensitised. The sensitisation rate for the 2000-4 workers was 0.7-2.7/1000 person-months of employment, and that for the 1993-8 workers was 5.6/1000 person-months, at least 2.1 (95% confidence interval (CI) 0.6 to 8.4) and up to 8.2 (95% CI 1.2 to 188.8) times higher than that for the 2000-4 workers. The sensitisation prevalence for the 2000-4 workers was 1% and that for the 1993-8 workers was 8.7%, 8.4 (95% CI 1.04 to 68.49) times higher than that for the 2000-4 workers. Airborne beryllium levels for production workers for the two time periods were similar. CONCLUSIONS: A comprehensive preventive programme reduced beryllium sensitisation in new workers during the first years of employment, despite airborne beryllium levels for production workers that were similar to pre-programme levels.

TNF-alpha polymorphisms in chronic beryllium disease and beryllium sensitization.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine involved in normal immune functions. The aim of this study was to investigate if there is an association between chronic beryllium disease or beryllium sensitization and two variants of the TNF-alpha gene located at -308 and -238 called TNF-alpha-308*02 and TNF-alpha-238*02. METHODS: TNF-alpha-308 and TNF-alpha-238 genotyping was conducted in a large, population-based cohort consisting of 886 beryllium workers (92 individuals with chronic beryllium disease, 64 who were beryllium sensitized, and 730 individuals without sensitization or disease). RESULTS: The odds of chronic beryllium disease in the presence of at least one TNF-alpha-308*02 or TNF-alpha-238*02 allele was not significant (OR=1.0; 95% CI=0.7, 1.7 and OR=0.8; 95% CI=0.4, 1.6). This was true regardless of whether a worker was homozygous or heterozygous for TNF-alpha-308*02 or TNF-alpha-238*02. Similarly, neither allele was associated with sensitization (P>0.05). CONCLUSIONS: Unlike an earlier report, there was no association between these specific TNF-alpha alleles and either chronic beryllium disease or sensitization to beryllium.

6th National Occupational Injury Research Symposium: Advancing Occupational Injury Research Through Integration and Partnership.

INTRODUCTION: The National Occupational Injury Research Symposium (NOIRS) is the only regularly held forum exclusively dedicated to occupational injury research and prevention. METHOD: The 2015 conference theme, advancing occupational injury research through integration and partnership, shaped the conference and is reflected in articles selected for this special issue. RESULTS' CONCLUSION: The 6th NOIRS, held May 19-21, 2015, brought together more than 250 researchers, occupational safety practitioners and students to share and discuss occupational injury research. Articles in this special issue highlight some of the research presented at the conference, reflect multiple scientific disciplines and approaches, cover a breadth of occupational injury causes and worker populations, and provide examples of research advanced by partnerships. PRACTICAL APPLICATIONS: The next NOIRS, tentatively scheduled for 2018, will build upon the theme of integration and partnership as well as feedback from conference attendees.

A post-conference evaluation of the 2015 National Occupational Injury Research Symposium.

INTRODUCTION: The National Occupational Injury Research Symposium (NOIRS) is the only national forum focused on occupational injury research findings, data and methods, and prevention strategies; it has been convened every 3-5years since 1997. Held in May 2015, the 6th symposium's theme was "Advancing Occupational Injury Research through Integration and Partnership." Organizers requested that attendees complete a post-meeting evaluation to assess meeting impact, and gather information useful in planning subsequent meetings and activities. METHOD: The questionnaire was publicized via a quick response code and link to the survey on symposium book cover, and mentioned at each scientific session. The online survey was designed to be completed in ≤15min; no identifying information was collected. Survey link remained open for seven days post-symposium. RESULTS: About 50% of registered attendees responded. Almost half were attending their first NOIRS. Most were researchers (69%); 45% were affiliated with government and 38% with university or research institute. Five of six reported that the symposium mostly or completely met expectations. Reasons for attending included gaining exposure to new areas of research (87%), sharing their research (80%), and to develop new ideas for conducting research (79%). The majority (90%) reported that the symposium provided adequate networking opportunities. The conference venue was reported as good or better by 69%, moreso among repeat attendees (77%) compared to first-timers (61%). DISCUSSION: The evaluation demonstrated that NOIRS was valuable to attendees, and provided a forum for sharing research results, developing new research ideas, and networking. Respondents provided input on different aspects of NOIRS and suggestions useful in planning next NOIRS, tentatively scheduled for 2018. NOIRS 2015 objectives for integration across disciplines and partnership with industry and safety professionals were partially met. In planning NOIRS 2018, more attention should be paid to attracting and engaging a broader spectrum of attendees.

Sensitization and chronic beryllium disease among workers in copper-beryllium distribution centers.

OBJECTIVE: Little is known about the risk of sensitization and chronic beryllium disease (CBD) among workers performing limited processing of copper-beryllium alloys downstream of the primary beryllium industry. In this study, we performed a cross-sectional survey of employees at three copper-beryllium alloy distribution centers. METHODS: One hundred workers were invited to be tested for beryllium sensitization using the beryllium blood lymphocyte proliferation test (BeLPT); a sensitized worker was further evaluated for CBD. Available beryllium mass concentration air sampling data were obtained for characterization of airborne exposure. RESULTS: One participant, who had exposure to other forms of beryllium, was found to be sensitized and to have CBD, resulting in a prevalence of sensitization/CBD of 1% for all tested. CONCLUSIONS: The overall prevalence of beryllium sensitization and CBD for workers in these three copper-beryllium alloy distribution centers is lower than for workers in primary beryllium production facilities.

Research to Practice Implications of High-Risk Genotypes for Beryllium Sensitization and Disease.

OBJECTIVE: Beryllium workers may better understand their genetic susceptibility to chronic beryllium disease (CBD) expressed as population-based prevalence, rather than odds ratios from case-control studies. METHODS: We calculated CBD prevalences from allele-specific DNA sequences of 853 workers for Human Leukocyte Antigen (HLA)-DPB1 genotypes and groups characterized by number of E69-containing alleles and by calculated surface electronegativity of HLA-DPB1. RESULTS: Of 18 groups of at least 10 workers with specific genotypes, CBD prevalence was highest, 72.7%, for the HLA-DPB102:01:02/DPB117:01 genotype. Population-based grouped genotypes with two E69 alleles wherein one allele had -9 surface charge had a beryllium sensitization (BeS) of 52.6% and a CBD prevalence of 42.1%. CONCLUSIONS: The high CBD and BeS prevalences associated with -9-charged E69 alleles and two E69s suggest that workers may benefit from knowing their genetic susceptibility in deciding whether to avoid future beryllium exposure.

Immunogenetic factors in beryllium sensitization and chronic beryllium disease.

Exposure to beryllium in the workplace can cause beryllium sensitization and chronic beryllium disease. Sensitization to beryllium can be detected in the laboratory using the beryllium lymphocyte proliferation test. It was shown that anti-HLA antibodies could block the beryllium-specific response in the beryllium lymphocyte proliferation test, thereby implicating HLA genes in chronic beryllium disease. A supratypic genetic marker, HLA-DPB1*E69, was found to be strongly associated with immunologic sensitization to beryllium and chronic beryllium disease in beryllium workers. However, there are 40 HLA-DPB1 gene variants that have E69 but that also have other DNA sequence variations. The purpose of the study was to evaluate the evidence for potential differential susceptibility that may be associated with the physical characteristics of HLA protein molecules for which different HLA-DPB1*E69 variants code; that is, do some HLA-DPB1*E69 variants convey higher risk of beryllium sensitization and chronic beryllium disease than others. To do this, two approaches were pursued: first, detailed analysis of the findings from the published literature was performed, and second, computational chemistry was used to seek clues concerning the physical properties of the HLA protein molecules for which these alleles code. Among the 40 HLA-DPB1 gene variants that code for E69, molecular epidemiological studies have suggested a risk hierarchy, where some variants appear to convey low to moderate risk of chronic beryllium disease (e.g., HLA-DPB1*0201, approximately 3-fold increased risk), some convey an intermediate risk (e.g., HLA-DPB1*1901, approximately 5-fold) and others convey high risk (e.g., HLA-DPB1*1701, >10-fold). Molecular modeling has been used to further investigate a potential mechanistic basis for these observations. We found a strong correlation between the hierarchical order of risk of chronic beryllium disease associated with specific alleles and the predicted surface electrostatic potential and charge of the corresponding isotypes. Therefore, when alleles were grouped by the relative negative charge on the molecules for which they code, the data suggest that those alleles associated with the most negatively charged proteins carry the greatest risk of beryllium sensitization and disease.

A decision process for determining whether to conduct responder health research following large disasters.

Disasters often set the stage for scientific inquiry within the field of occupational safety and health. This is especially true when the long-term consequences of exposures associated with a particular disaster are unclear. However, a responder research study can be costly and difficult to design, and researchers must consider whether the proposed study will produce useful, reliable results and is a prudent public health investment. The decision process can be segregated into various components, including scientific rationale that should be formally recognized as critical to efficiently and effectively determine whether a research study is warranted. The scientific rationale includes certain controlling or "gatekeeper" factors that should be present to proceed with research.