Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 49 Records) |
Query Trace: Silverman B[original query] |
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Urinary biomonitoring of glyphosate exposure among male farmers and nonfarmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study
Chang VC , Ospina M , Xie S , Andreotti G , Parks CG , Liu D , Madrigal JM , Ward MH , Rothman N , Silverman DT , Sandler DP , Friesen MC , Beane Freeman LE , Calafat AM , Hofmann JN . Environ Int 2024 187 108644 Glyphosate is the most widely applied herbicide worldwide. Glyphosate biomonitoring data are limited for agricultural settings. We measured urinary glyphosate concentrations and assessed exposure determinants in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study. We selected four groups of BEEA participants based on self-reported pesticide exposure: recently exposed farmers with occupational glyphosate use in the last 7 days (n = 98), farmers with high lifetime glyphosate use (>80th percentile) but no use in the last 7 days (n = 70), farming controls with minimal lifetime use (n = 100), and nonfarming controls with no occupational pesticide exposures and no recent home/garden glyphosate use (n = 100). Glyphosate was quantified in first morning void urine using ion chromatography isotope-dilution tandem mass spectrometry. We estimated associations between urinary glyphosate concentrations and potential determinants using multivariable linear regression. Glyphosate was detected (≥0.2 µg/L) in urine of most farmers with recent (91 %) and high lifetime (93 %) use, as well as farming (88 %) and nonfarming (81 %) controls; geometric mean concentrations were 0.89, 0.59, 0.46, and 0.39 µg/L (0.79, 0.51, 0.42, and 0.37 µg/g creatinine), respectively. Compared with both control groups, urinary glyphosate concentrations were significantly elevated among recently exposed farmers (P < 0.0001), particularly those who used glyphosate in the previous day [vs. nonfarming controls; geometric mean ratio (GMR) = 5.46; 95 % confidence interval (CI): 3.75, 7.93]. Concentrations among high lifetime exposed farmers were also elevated (P < 0.01 vs. nonfarming controls). Among recently exposed farmers, glyphosate concentrations were higher among those not wearing gloves when applying glyphosate (GMR = 1.91; 95 % CI: 1.17, 3.11), not wearing long-sleeved shirts when mixing/loading glyphosate (GMR = 2.00; 95 % CI: 1.04, 3.86), applying glyphosate exclusively using broadcast/boom sprayers (vs. hand sprayer only; GMR = 1.70; 95 % CI: 1.00, 2.92), and applying glyphosate to crops (vs. non-crop; GMR = 1.72; 95 % CI: 1.04, 2.84). Both farmers and nonfarmers are exposed to glyphosate, with recency of occupational glyphosate use being the strongest determinant of urinary glyphosate concentrations. Continued biomonitoring of glyphosate in various settings is warranted. |
Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study
Rhee J , Chang VC , Cheng I , Calafat AM , Botelho JC , Shearer JJ , Sampson JN , Setiawan VW , Wilkens LR , Silverman DT , Purdue MP , Hofmann JN . Environ Int 2023 180 108197 Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993-2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, OR(continuous) = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), P(trend) = 0.04; OR(continuous) = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [OR(continuous) = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations. |
The Diesel Exhaust in Miners Study (DEMS) II: Temporal factors related to diesel exhaust exposure and lung cancer mortality in the Nested Case-Control Study
Silverman DT , Bassig BA , Lubin J , Graubard B , Blair A , Vermeulen R , Attfield M , Appel N , Rothman N , Stewart P , Koutros S . Environ Health Perspect 2023 131 (8) 87002 BACKGROUND: The Diesel Exhaust in Miners Study (DEMS) was an important contributor to the International Agency for Research on Cancer reclassification of diesel exhaust as a Group I carcinogen and subsequent risk assessment. We extended the DEMS cohort follow-up by 18 y and the nested case-control study to include all newly identified lung cancer deaths and matched controls (DEMS II), nearly doubling the number of lung cancer deaths. OBJECTIVE: Our purpose was to characterize the exposure-response relationship with a focus on the effects of timing of exposure and exposure cessation. METHODS: We conducted a case-control study of lung cancer nested in a cohort of 12,315 workers in eight nonmetal mines (376 lung cancer deaths, 718 controls). Controls were selected from workers who were alive when the case died, individually matched on mine, sex, race/ethnicity, and birth year (within 5 y). Based on an extensive historical exposure assessment, we estimated respirable elemental carbon (REC), an index of diesel exposure, for each cohort member. Odds ratios (ORs) were estimated by conditional regression analyses controlling for smoking and other confounders. To evaluate time windows of exposure, we evaluated the joint OR patterns for cumulative REC within each of four preselected exposure time windows, < 5, 5-9, 10-19, and ≥ 20 y prior to death/reference date, and we evaluated the interaction of cumulative exposure across time windows under additive and multiplicative forms for the joint association. RESULTS: ORs increased with increasing 15-y lagged cumulative exposure, peaking with a tripling of risk for exposures of ∼ 950 to < 1,700 μg/m3-y [OR = 3.23; 95% confidence interval (CI): 1.47, 7.10], followed by a plateau/decline among the heavily exposed (OR = 1.85; 95% CI: 0.85, 4.04). Patterns of risk by cumulative REC exposure varied across four exposure time windows (phomogeneity < 0.001), with ORs increasing for exposures accrued primarily 10-19 y prior to death (ptrend < 0.001). Results provided little support for a waning of risk among workers whose exposures ceased for ≥ 20 y. CONCLUSION: DEMS II findings provide insight into the exposure-response relationship between diesel exhaust and lung cancer mortality. The pronounced effect of exposures occurring in the window 10-19 y prior to death, the sustained risk 20 or more years after exposure ceases, and the plateau/decline in risk among the most heavily exposed provide direction for future research on the mechanism of diesel-induced carcinogenesis in addition to having important implications for the assessment of risk from diesel exhaust by regulatory agencies. https://doi.org/10.1289/EHP11980. |
A prospective nested case-control study of serum concentrations of per- and polyfluoroalkyl substances and aggressive prostate cancer risk.
Rhee J , Barry KH , Huang WY , Sampson JN , Hofmann JN , Silverman DT , Calafat AM , Botelho JC , Kato K , Purdue MP , Berndt SI . Environ Res 2023 228 115718 Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested an association between PFAS and prostate cancer, but evidence from population-based studies is limited. We investigated the association between pre-diagnostic serum PFAS concentrations and aggressive prostate cancer risk in a large prospective study. We measured pre-diagnostic serum concentrations of eight PFAS, including perfluorooctanoate (PFOA), for 750 aggressive prostate cancer cases and 750 individually matched controls within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We assessed the reproducibility of PFAS concentrations in serial samples collected up to six years apart among 60 controls using intraclass correlation coefficients (ICCs). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with prostate cancer, adjusting for other PFAS and potential confounders. Concentrations of most PFAS were consistent (ICC>0.7) across the serial samples over time. We observed an inverse association between PFOA and aggressive prostate cancer (OR(continuous) = 0.79, 95% CI = 0.63, 0.99), but the association was limited to cases diagnosed ≤3 years after blood collection and became statistically non-significant for cases diagnosed with later follow-up (>3 years, OR(continuous) = 0.90, 95% CI = 0.79, 1.03). Other PFAS were not associated with aggressive prostate cancer risk. Although we cannot rule out an increased risk at higher levels, our findings from a population with PFAS serum concentrations comparable to the general population do not support an association with increased risk of aggressive prostate cancer. |
Glyphosate Exposure and Urinary Oxidative Stress Biomarkers in the Agricultural Health Study.
Chang VC , Andreotti G , Ospina M , Parks CG , Liu D , Shearer JJ , Rothman N , Silverman DT , Sandler DP , Calafat AM , Beane Freeman LE , Hofmann JN . J Natl Cancer Inst 2023 115 (4) 394-404 BACKGROUND: Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study. METHODS: This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male non-farmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α [8-isoprostane], and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker. RESULTS: Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs. lowest glyphosate quartile; geometric mean ratio [GMR]=1.15, 95% confidence interval [CI]=1.03-1.28, Ptrend=.02) and MDA (GMR = 1.20, 95% CI = 1.03-1.40, Ptrend=.06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with significantly increased 8-OHdG and MDA levels. Compared with non-farmers, we observed elevated 8-isoprostane levels among farmers with recent, high past 12-month, or high lifetime glyphosate use. CONCLUSIONS: Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide. |
Interlaboratory performance and quantitative PCR data acceptance metrics for NIST SRM 2917
Sivaganesan M , Willis JR , Karim M , Babatola A , Catoe D , Boehm AB , Wilder M , Green H , Lobos A , Harwood VJ , Hertel S , Klepikow R , Howard MF , Laksanalamai P , Roundtree A , Mattioli M , Eytcheson S , Molina M , Lane M , Rediske R , Ronan A , D'Souza N , Rose JB , Shrestha A , Hoar C , Silverman AI , Faulkner W , Wickman K , Kralj JG , Servetas SL , Hunter ME , Jackson SA , Shanks OC . Water Res 2022 225 119162 Surface water quality quantitative polymerase chain reaction (qPCR) technologies are expanding from a subject of research to routine environmental and public health laboratory testing. Readily available, reliable reference material is needed to interpret qPCR measurements, particularly across laboratories. Standard Reference Material® 2917 (NIST SRM® 2917) is a DNA plasmid construct that functions with multiple water quality qPCR assays allowing for estimation of total fecal pollution and identification of key fecal sources. This study investigates SRM 2917 interlaboratory performance based on repeated measures of 12 qPCR assays by 14 laboratories (n = 1008 instrument runs). Using a Bayesian approach, single-instrument run data are combined to generate assay-specific global calibration models allowing for characterization of within- and between-lab variability. Comparable data sets generated by two additional laboratories are used to assess new SRM 2917 data acceptance metrics. SRM 2917 allows for reproducible single-instrument run calibration models across laboratories, regardless of qPCR assay. In addition, global models offer multiple data acceptance metric options that future users can employ to minimize variability, improve comparability of data across laboratories, and increase confidence in qPCR measurements. |
Violence against children: multifaceted approaches to a complex problem
Villaveces A , Viswanathan S . Int J Inj Contr Saf Promot 2022 29 (1) 1-2 In this issue of the Journal, we highlight the problem of violence against children globally. We conceptualized this process and the thematic focus and widely disseminated an invitation to submit manuscripts. Each of us took the lead editorial role in a group of manuscripts submitted for this issue. Dr. Viswanathan led the review process for manuscripts submitted by Moe et. al, Seff et. al., Couture et. al, Osborne et. al, Khan et. al., and Friedman et. al. Dr Villaveces led the reviews of Pendharkar et. al, Tang et. al, Ryan et. al, Bravo Sanzana et. al, Flynn O'Brien et. al., Silverman et. al., and Taliep et.al. We hope that readers will see the complexities related to violence against children and get a better sense of the global implications of this problem. |
Arsenic in private well water and birth outcomes in the United States.
Bulka CM , ScannellBryan M , Lombard MA , Bartell SM , Jones DK , Bradley PM , Vieira VM , Silverman DT , Focazio M , Toccalino PL , Daniel J , Backer LC , Ayotte JD , Gribble MO , Argos M . Environ Int 2022 163 107176 BACKGROUND: Prenatal exposure to drinking water with arsenic concentrations >50g/L is associated with adverse birth outcomes, with inconclusive evidence for concentrations 50g/L. In a collaborative effort by public health experts, hydrologists, and geologists, we used published machine learning model estimates to characterize arsenic concentrations in private wells-federally unregulated for drinking water contaminants-and evaluated associations with birth outcomes throughout the conterminous U.S. METHODS: Using several machine learning models, including boosted regression trees (BRT) and random forest classification (RFC), developed from measured groundwater arsenic concentrations of 20,000 private wells, we characterized the probability that arsenic concentrations occurred within specific ranges in groundwater. Probabilistic model estimates and private well usage data were linked by county to all live birth certificates from 2016 (n=3.6 million). We evaluated associations with gestational age and term birth weight using mixed-effects models, adjusted for potential confounders and incorporated random intercepts for spatial clustering. RESULTS: We generally observed inverse associations with term birth weight. For instance, when using BRT estimates, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 5g/L was associated with a -1.83g (95% CI: -3.30, -0.38) lower term birth weight after adjusting for covariates. Similarly, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 10g/L was associated with a -2.79g (95% CI: -4.99, -0.58) lower term birth weight. Associations with gestational age were null. CONCLUSION: In this largest epidemiologic study of arsenic and birth outcomes to date, we did not observe associations of modeled arsenic estimates in private wells with gestational age and found modest inverse associations with term birth weight. Study limitations may have obscured true associations, including measurement error stemming from a lack of individual-level information on primary water sources, water arsenic concentrations, and water consumption patterns. |
COVID-19 vaccines in children and adolescents
Maldonado YA , O'Leary ST , Ardura MI , Banerjee R , Bryant KA , Campbell JD , Caserta MT , John CC , Gerber JS , Kourtis AP , Ratner AJ , Romero JR , Shah SS , Zangwill KM , Kimberlin DW , Barnett ED , Lynfield R , Sawyer MH , Bernstein HH , Cohn AC , Farizo KM , Halasa NB , Kafer LM , Kim D , LpezMedina E , Moore D , Panagiotakopoulos L , Sauv L , Silverman NS , Starke JR , Tomashek KM , Frantz JM , CommitteeonInfectious Diseases . Pediatrics 2022 149 (1) Vaccines are safe and effective in protecting individuals and populations against infectious diseases. New vaccines are evaluated by a long-standing, rigorous, and transparent process through the US Food and Drug Administration and the Centers for Disease Control and Prevention (CDC), by which safety and efficacy data are reviewed before authorization and recommendation. |
The relationship between commercial sexual exploitation of children (CSEC) and childhood sexual abuse (CSA) among boys and girls in Haiti
Silverman JG , Boyce SC , Fonseka RW , Triplett D , Chiang LF , Caslin SS , Raj A . Int J Inj Contr Saf Promot 2021 29 (1) 1-7 To test the hypothesis that childhood sexual abuse (CSA) is a risk factor for commercial sexual exploitation of children (CSEC), we analysed data from the Haiti Violence Against Children Survey (VACS), a population-based sample of adolescents and young adults ages 13-24 (1459 males and 1457 females). Twenty-one percent of males and 25% of females reported CSA; 6% of males and 4% of females reported CSEC. The adjusted odds ratios (AORs) for CSEC based on exposure to CSA were 5.6 (95% confidence interval/CI: 3.1-10.2) for males and 5.9 (CI: 2.6-13.0) for females. For each year earlier that males first experienced CSA, the odds of CSEC increased 60% (AOR 1.6, CI 1.2-2.0). In this first nationally-representative study of lifetime CSEC, both boys and girls victimised by CSA in Haiti were more likely to have also experienced CSEC than other youth, with children who experienced CSA at younger ages at the greatest risk. |
SARS-CoV-2 Wastewater Surveillance for Public Health Action.
McClary-Gutierrez JS , Mattioli MC , Marcenac P , Silverman AI , Boehm AB , Bibby K , Balliet M , de Los Reyes FL 3rd , Gerrity D , Griffith JF , Holden PA , Katehis D , Kester G , LaCross N , Lipp EK , Meiman J , Noble RT , Brossard D , McLellan SL . Emerg Infect Dis 2021 27 (9) 1-8 Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has garnered extensive public attention during the coronavirus disease pandemic as a proposed complement to existing disease surveillance systems. Over the past year, methods for detection and quantification of SARS-CoV-2 viral RNA in untreated sewage have advanced, and concentrations in wastewater have been shown to correlate with trends in reported cases. Despite the promise of wastewater surveillance, for these measurements to translate into useful public health tools, bridging the communication and knowledge gaps between researchers and public health responders is needed. We describe the key uses, barriers, and applicability of SARS-CoV-2 wastewater surveillance for supporting public health decisions and actions, including establishing ethics consideration for monitoring. Although wastewater surveillance to assess community infections is not a new idea, the coronavirus disease pandemic might be the initiating event to make this emerging public health tool a sustainable nationwide surveillance system, provided that these barriers are addressed. |
Machine Learning Models of Arsenic in Private Wells Throughout the Conterminous United States As a Tool for Exposure Assessment in Human Health Studies
Lombard MA , Bryan MS , Jones DK , Bulka C , Bradley PM , Backer LC , Focazio MJ , Silverman DT , Toccalino P , Argos M , Gribble MO , Ayotte JD . Environ Sci Technol 2021 55 (8) 5012-5023 Arsenic from geologic sources is widespread in groundwater within the United States (U.S.). In several areas, groundwater arsenic concentrations exceed the U.S. Environmental Protection Agency maximum contaminant level of 10 μg per liter (μg/L). However, this standard applies only to public-supply drinking water and not to private-supply, which is not federally regulated and is rarely monitored. As a result, arsenic exposure from private wells is a potentially substantial, but largely hidden, public health concern. Machine learning models using boosted regression trees (BRT) and random forest classification (RFC) techniques were developed to estimate probabilities and concentration ranges of arsenic in private wells throughout the conterminous U.S. Three BRT models were fit separately to estimate the probability of private well arsenic concentrations exceeding 1, 5, or 10 μg/L whereas the RFC model estimates the most probable category (≤5, >5 to ≤10, or >10 μg/L). Overall, the models perform best at identifying areas with low concentrations of arsenic in private wells. The BRT 10 μg/L model estimates for testing data have an overall accuracy of 91.2%, sensitivity of 33.9%, and specificity of 98.2%. Influential variables identified across all models included average annual precipitation and soil geochemistry. Models were developed in collaboration with public health experts to support U.S.-based studies focused on health effects from arsenic exposure. |
Analytical considerations and plans to standardize or harmonize assays for the reference bone turnover markers PINP and -CTX in blood
Bhattoa HP , Cavalier E , Eastell R , Heijboer AC , Jørgensen NR , Makris K , Ulmer CZ , Kanis JA , Cooper C , Silverman SL , Vasikaran SD . Clin Chim Acta 2020 515 16-20 Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (β-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and β-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of β-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and β-CTX. |
Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma
Shearer JJ , Callahan CL , Calafat AM , Huang WY , Jones RR , Sabbisetti VS , Freedman ND , Sampson JN , Silverman DT , Purdue MP , Hofmann JN . J Natl Cancer Inst 2020 113 (5) 580-587 BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are highly persistent chemicals that have been detected in the serum of > 98% of the U.S. population. Studies among highly exposed individuals suggest an association with perfluorooctanoic acid (PFOA) exposure and kidney cancer. It remains unclear whether PFOA or other PFAS are renal carcinogens, or if they influence risk of renal cell carcinoma (RCC) at concentrations observed in the general population. METHODS: We measured pre-diagnostic serum concentrations of PFOA and seven additional PFAS in 324 RCC cases and 324 individually matched controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) relating serum PFAS concentrations and RCC risk. Individual PFAS were modeled continuously (log2-transformed) and categorically, with adjustment for kidney function and additional potential confounders. All statistical tests were two-sided. RESULTS: We observed a positive association with RCC risk for PFOA (doubling in serum concentration, ORcontinuous = 1.71, 95% CI = 1.23 to 2.37; P = .002), and a greater than two-fold increased risk among those in the highest quartile vs. the lowest (OR = 2.63, 95% CI = 1.33 to 5.20; Ptrend = .007). The association with PFOA was similar after adjustment for other PFAS (ORcontinuous = 1.68, 95% CI = 1.07 to 2.63; P = .02), and remained apparent in analyses restricted to individuals without evidence of diminished kidney function and in cases diagnosed ≥8 years after phlebotomy. CONCLUSIONS: Our findings add substantially to the weight of evidence that PFOA is a renal carcinogen and may have important public health implications for the many individuals exposed to this ubiquitous and highly persistent chemical. |
Harmonization of commercial assays for PINP; the way forward
Vasikaran SD , Bhattoa HP , Eastell R , Heijboer AC , Jørgensen NR , Makris K , Ulmer C , Kanis JA , Cooper C , Silverman S , Cavalier E . Osteoporos Int 2020 31 (3) 10.1007/s00198-020-05310-6 International Federation of Clinical Chemistry and Laboratory Medicine and The International Osteoporosis Foundation Joint Committee on Bone Metabolism believes that the harmonization of PINP assays is an achievable and practical goal. INTRODUCTION: In order to examine the agreement between current commercial assays, a multi-center study was performed for PINP in serum and plasma. METHODS: The automated methods for PINP (Roche Cobas and IDS iSYS) gave similar results. A significant proportional bias was observed between the two automated assays and the Orion radioimmunoassay (RIA) for PINP. RESULTS: Results from other published studies comparing PINP values among these three assays broadly support our findings. Taken together, these results confirm that harmonized PINP measurements exist between the two automated assays (Roche Cobas and IDS iSYS) when the eGFR is > 30 mL/min/1.73m(2), but a significant bias exists between the Orion RIA and the two automated assays. CONCLUSION: Therefore, in subjects with normal renal function, PINP results reported by the Roche Cobas and IDS iSYS assays are similar and may be used interchangeably, and similar reference intervals and treatment targets could be applied for the two automated assays. Harmonization between the automated assays and the RIA is potentially possible with the use of common calibrators and the development of a reference method for PINP. This should also help ensure that any new commercial assay developed in the future will attain similar results. IOF and IFCC are committed to working together towards this goal with the cooperation of the reagent manufacturing industry. |
Technology-enabled outreach to patients taking high-risk medications reduces a quality gap in completion of clinical laboratory testing
Raebel MA , Shetterly SM , Bhardwaja B , Sterrett AT , Schroeder EB , Chorny J , Hagen TP , Silverman DJ , Astles R , Lubin IM . Popul Health Manag 2019 23 (1) 3-11 Clinical laboratory quality improvement (QI) efforts can include population test utilization. The authors used a health care organization's Medical Data Warehouse (MDW) to characterize a gap in guideline-concordant laboratory testing recommended for safe use of antirheumatic agents, then tested the effectiveness of laboratory-led, technology-enabled outreach to patients at reducing this gap. Data linkages available through the Kaiser Permanente Colorado MDW and electronic health record were used to identify ambulatory adults taking antirheumatic agents who were due/overdue for alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC), or serum creatinine (SCr) testing. Outreach was implemented using an interactive voice response system to send patients text or phone call reminders. Interrupted time series analysis was used to estimate reminder effectiveness. Rates of guideline-concordant testing and testing timeliness in baseline vs. intervention periods were determined using generalized linear models for repeated measures. Results revealed a decrease in percentage of 3763 patients taking antirheumatic agents due/overdue for testing at any given time: baseline 24.3% vs. intervention 17.5% (P < 0.001). Among 3205 patients taking conventional antirheumatic agents, concordance for all ALT testing was baseline 52.8% vs. intervention 65.4% (P < 0.001) among patients chronically using these agents and baseline 20.6% vs. intervention 26.1% (P < 0.001) among patients newly starting these agents. The 95(th) percentiles for days to ALT testing were baseline 149 vs. intervention 117 among chronic users and baseline 134 vs. intervention 92 among new starts. AST, CBC, and SCr findings were similar. Technology-enabled outreach reminding patients to obtain laboratory testing improves health care system outcomes. |
Diesel exhaust, respirable dust, and ischemic heart disease: an application of the parametric g-formula
Neophytou AM , Costello S , Picciotto S , Brown DM , Attfield MD , Blair A , Lubin JH , Stewart PA , Vermeulen R , Silverman DT , Eisen EA . Epidemiology 2018 30 (2) 177-185 BACKGROUND: Although general population studies of air pollution suggest that particulate matter - diesel exhaust emissions in particular - is a potential risk factor for cardiovascular disease, direct evidence from occupational cohorts using quantitative metrics of exposure is limited. In this study, we assess counterfactual risk of ischemic heart disease (IHD) mortality under hypothetical scenarios limiting exposure levels of diesel exhaust and of respirable mine/ore dust in the Diesel Exhaust in Miners Study (DEMS) cohort. METHODS: We analyzed data on 10,779 male miners from 8 non-metal, non-coal mines - hired after diesel equipment was introduced in the respective facilities - and followed from 1948 to 1997, with 297 observed IHD deaths in this sample. We applied the parametric g-formula to assess risk under hypothetical scenarios with various limits for respirable elemental carbon (a surrogate for diesel exhaust), and respirable dust, separately and jointly. RESULTS: The risk ratio comparing the observed risk to cumulative IHD mortality risk at age 80 under a hypothetical scenario where exposures to elemental carbon and respirable dust are eliminated was 0.79 (95% confidence interval (CI): 0.64, 0.97). The corresponding risk difference was -3.0% (95% CI: -5.7, -0.3). CONCLUSION: Our findings, based on data from a cohort of non-metal miners, are consistent with the hypothesis that interventions to eliminate exposures to diesel exhaust and respirable dust would reduce IHD mortality risk. |
Secular changes in physical education attendance among U.S. high school students, 1991-2015
Clennin MN , Demissie Z , Michael SL , Wright C , Silverman S , Chriqui J , Pate RR . Res Q Exerc Sport 2018 89 (4) 1-8 PURPOSE: The purpose of this study was to examine changes in school-based physical education (PE) attendance over time among nationally representative samples of U.S. high school students and how changes in PE attendance have varied across demographic subgroups. METHOD: Student demographic information and PE attendance data were obtained from 13 biennial cycles (1991-2015) of the national Youth Risk Behavior Survey (YRBS). Physical education variables derived from YRBS data included PE attendance, daily PE, average PE days/week, and PE frequency. Logistic regression models examined trends in PE attendance, daily PE, and PE frequency for the overall sample and demographic subgroups. Linear regression models examined trends in average PE days/week in the overall sample only. RESULTS: Overall, there was no significant change in the percentage of students reporting PE attendance during 1991 to 2015. However, daily PE and average PE days/week declined significantly from 1991 to 1995 (41.6% to 25.4% and 4.64 days to 3.64 days, respectively) and then remained stable through 2015 (29.8% and 4.11 days, respectively). The percentage of students reporting a PE frequency of 3 days per week increased significantly from 1991 to 1995 (1.5% to 19.0%) before stabilizing through 2015 (9.1%). Trends across demographic subgroups revealed notable differences in PE attendance. CONCLUSIONS: Study findings showed that U.S. schools have not substantially reduced PE amounts in recent years. Still, the prevalence of PE attendance among U.S. high school students is well below recommendations. For PE to contribute to increased adolescent compliance with national physical activity guidelines, significant policy actions are needed to improve PE access for all students. |
Using eHealth to reach black and Hispanic men who have sex with men regarding treatment as prevention and preexposure prophylaxis: Protocol for a small randomized controlled trial
van den Berg JJ , Silverman T , Fernandez MI , Henny KD , Gaul ZJ , Sutton MY , Operario D . JMIR Res Protoc 2018 7 (7) e11047 BACKGROUND: Black and Hispanic men who have sex with men in the United States continue to be disproportionately affected by HIV and AIDS. Uptake of and knowledge about biobehavioral HIV prevention approaches, such as treatment as prevention and preexposure prophylaxis, are especially low in these populations. eHealth campaigns and social media messaging about treatment as prevention and preexposure prophylaxis may help to fill this gap in knowledge and lead to increased uptake of such strategies; however, no evidence exists of the effects of these targeted forms of communication on treatment as prevention and preexposure prophylaxis uptake in these populations. OBJECTIVE: We describe the protocol for a 3-part study aiming to develop and evaluate an eHealth intervention with information about treatment as prevention and preexposure prophylaxis for HIV-positive and HIV-negative black and Hispanic men who have sex with men. METHODS: Phases 1 and 2 will involve focus groups and cognitive interviews with members of the target populations, which we will use to create a culturally tailored, interactive website and applicable social media messaging for these men. Phase 3 will be a small randomized controlled trial of the eHealth intervention, in which participants will receive guided social media messages plus the newly developed website (active arm) or the website alone (control arm), with assessments at baseline and 6 months. RESULTS: Participant recruitment began in August 2017 and will end in August 2020. CONCLUSIONS: Public health interventions are greatly needed to increase knowledge about and uptake of biobehavioral HIV prevention strategies such as treatment as prevention and preexposure prophylaxis among black and Hispanic men who have sex with men. eHealth communication campaigns offer a strategy for engaging these populations in health communication about biobehavioral HIV prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT03404531; https://www.clinicaltrials.gov/ct2/show/NCT03404531 (Archived by WebCite at http://www.webcitation.org/70myofp0R). REGISTERED REPORT IDENTIFIER: RR1-10.2196/11047. |
Enhancing individual and community disaster preparedness: Individuals with disabilities and others with access and functional needs
Kruger J , Hinton CF , Sinclair LB , Silverman B . Disabil Health J 2017 11 (2) 170-173 Preparedness planning is essential to minimizing the impact of disasters on communities and individuals. Attention to the needs of people with disabilities is vital as they have additional needs before, during and after a disaster that are specific to the disabling condition. In this Commentary, we emphasize national guidelines on disability inclusion in emergency preparedness. We examine some potential areas of planning and response that need attention as suggested by preparedness data for people with self-reported disabilities (also referred to as access and functional needs) and highlight selected resources (e.g., tools, trainings, and online webinars) to enhance whole community preparedness and disability inclusion efforts. This Commentary intends to bridge the gap between those various facets of preparedness, at all levels of government and among individuals, with the aim of ensuring that the whole community is prepared to adapt, withstand and rapidly recover from disruptions due to disasters. |
Improvements in state and local planning for mass dispensing of medical countermeasures: The Technical Assistance Review Program, United States, 2007-2014
Renard PG Jr , Vagi SJ , Reinold CM , Silverman BL , Avchen RN . Am J Public Health 2017 107 S200-s207 OBJECTIVES: To evaluate and describe outcomes of state and local medical countermeasure preparedness planning, which is critical to ensure rapid distribution and dispensing of a broad spectrum of life-saving medical assets during a public health emergency. METHODS: We used 2007 to 2014 state and local data collected from the Centers for Disease Control and Prevention's Technical Assistance Review. We calculated descriptive statistics from 50 states and 72 local Cities Readiness Initiative jurisdictions that participated in the Technical Assistance Review annually. RESULTS: From 2007 to 2014, the average overall Technical Assistance Review score increased by 13% for states and 41% for Cities Readiness Initiative jurisdictions. In 2014, nearly half of states achieved the maximum possible overall score (100), and 94% of local Cities Readiness Initiative jurisdictions achieved a score of 90 or more. CONCLUSIONS: Despite challenges, effective and timely medical countermeasure distribution and dispensing is possible with appropriate planning, staff, and resources. However, vigilance in training, exercising, and improving plans from lessons learned in a sustained, coordinated way is critical to ensure continued public health preparedness success. |
Sentinel events preceding youth firearm violence: An investigation of administrative data in Delaware
Sumner SA , Maenner MJ , Socias CM , Mercy JA , Silverman P , Medinilla SP , Martin SS , Xu L , Hillis SD . Am J Prev Med 2016 51 (5) 647-655 INTRODUCTION: Accurately identifying youth at highest risk of firearm violence involvement could permit delivery of focused, comprehensive prevention services. This study explored whether readily available city and state administrative data covering life events before youth firearm violence could elucidate patterns preceding such violence. METHODS: Four hundred twenty-one individuals arrested for homicide, attempted homicide, aggravated assault, or robbery with a firearm committed in Wilmington, Delaware, from January 1, 2009 to May 21, 2014, were matched 1:3 to 1,259 Wilmington resident controls on birth year and sex. In 2015, descriptive statistics and a conditional logistic regression model using Delaware healthcare, child welfare, juvenile services, labor, and education administrative data examined associations between preceding life events and subsequent firearm violence. RESULTS: In a multivariable adjusted model, experiencing a prior gunshot wound injury (AOR=11.4, 95% CI=2.7, 48.1) and being subject to community probation (AOR=13.2, 95% CI=5.7, 30.3) were associated with the highest risk of subsequent firearm violence perpetration, though multiple other sentinel events were informative. The mean number of sentinel events experienced by youth committing firearm violence was 13.0 versus 1.9 among controls (p<0.0001). Within the sample, 84.1% of youth experiencing a sentinel event in all five studied domains ultimately committed firearm violence. CONCLUSIONS: Youth who commit firearm violence have preceding patterns of life events that markedly differ from youth not involved in firearm violence. This information is readily available from administrative data, demonstrating the potential of data sharing across city and state institutions to focus prevention strategies on those at greatest risk. |
School district crisis preparedness, response, and recovery plans - United States, 2012
Silverman B , Chen B , Brener N , Kruger J , Krishna N , Renard P Jr , Romero-Steiner S , Avchen RN . MMWR Morb Mortal Wkly Rep 2016 65 (36) 949-953 The unique characteristics of children dictate the need for school-based all-hazards response plans during natural disasters, emerging infectious diseases, and terrorism. Schools are a critical community institution serving a vulnerable population that must be accounted for in public health preparedness plans; prepared schools are adopting policies and plans for crisis preparedness, response, and recovery. The importance of having such plans in place is underscored by the development of a new Healthy People 2020 objective (PREP-5) to "increase the percentage of school districts that require schools to include specific topics in their crisis preparedness, response, and recovery plans". Because decisions about such plans are usually made at the school district level, it is important to examine district-level policies and practices. Although previous reports have provided national estimates of the percentage of districts with policies and practices in place, these estimates have not been analyzed by U.S. Census region* and urbanicity.dagger Using data from the 2012 School Health Policies and Practices Study (SHPPS), this report examines policies and practices related to school district preparedness, response, and recovery. In general, districts in the Midwest were less likely to require schools to include specific topics in their crisis preparedness plans than districts in the Northeast and South. Urban districts tended to be more likely than nonurban districts to require specific topics in school preparedness plans. Southern districts tended to be more likely than districts in other regions to engage with partners when developing plans. No differences in district collaboration (with the exception of local fire department engagement) were observed by level of urbanicity. School-based preparedness planning needs to be coordinated with interdisciplinary community partners to achieve Healthy People 2020 PREP-5 objectives for this vulnerable population. |
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.
Machiela MJ , Zhou W , Karlins E , Sampson JN , Freedman ND , Yang Q , Hicks B , Dagnall C , Hautman C , Jacobs KB , Abnet CC , Aldrich MC , Amos C , Amundadottir LT , Arslan AA , Beane-Freeman LE , Berndt SI , Black A , Blot WJ , Bock CH , Bracci PM , Brinton LA , Bueno-de-Mesquita HB , Burdett L , Buring JE , Butler MA , Canzian F , Carreon T , Chaffee KG , Chang IS , Chatterjee N , Chen C , Chen C , Chen K , Chung CC , Cook LS , Crous Bou M , Cullen M , Davis FG , De Vivo I , Ding T , Doherty J , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF , Friedenreich CM , Fuchs CS , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Gaudet MM , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Henriksson R , Holly EA , Hong YC , Hoover RN , Hsiung CA , Hu N , Hu W , Hunter DJ , Hutchinson A , Jenab M , Johansen C , Khaw KT , Kim HN , Kim YH , Kim YT , Klein AP , Klein R , Koh WP , Kolonel LN , Kooperberg C , Kraft P , Krogh V , Kurtz RC , LaCroix A , Lan Q , Landi MT , Marchand LL , Li D , Liang X , Liao LM , Lin D , Liu J , Lissowska J , Lu L , Magliocco AM , Malats N , Matsuo K , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Moore L , Olson SH , Orlow I , Park JY , Patino-Garcia A , Peplonska B , Peters U , Petersen GM , Pooler L , Prescott J , Prokunina-Olsson L , Purdue MP , Qiao YL , Rajaraman P , Real FX , Riboli E , Risch HA , Rodriguez-Santiago B , Ruder AM , Savage SA , Schumacher F , Schwartz AG , Schwartz KL , Seow A , Wendy Setiawan V , Severi G , Shen H , Sheng X , Shin MH , Shu XO , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Van Den Berg D , Visvanathan K , Wacholder S , Wang JC , Wang Z , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolpin BM , Wong MP , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xia L , Yang HP , Yang PC , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Ziegler RG , Perez-Jurado LA , Caporaso NE , Rothman N , Tucker M , Dean MC , Yeager M , Chanock SJ . Nat Commun 2016 7 11843 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. |
Adapting the Get Yourself Tested Campaign to reach black and Latino sexual-minority youth
Garbers S , Friedman A , Martinez O , Scheinmann R , Bermudez D , Silva M , Silverman J , Chiasson MA . Health Promot Pract 2016 17 (5) 739-50 BACKGROUND: Culturally appropriate efforts are needed to increase sexually transmitted disease (STD) testing and care among Black and Latino sexual-minority youth, who are at high risk for STDs. Get Yourself Tested, a national testing campaign, has demonstrated success among youth, but it has yet to be assessed for relevance or impact among this population. METHOD: This effort included (1) formative and materials-testing research through focus groups; (2) adaptation of existing Get Yourself Tested campaign materials to be more inclusive of Black and Latino sexual-minority youth; (3) a 3-month campaign in four venues of New York City, promoting STD testing at events and through mobile testing and online and social media platforms; (4) process evaluation of outreach activities; and (5) an outcome evaluation of testing at select campaign venues, using a preexperimental design. RESULTS: During the 3-month campaign period, the number of STD tests conducted at select campaign venues increased from a comparable 3-month baseline period. Although testing uptake through mobile vans remained low in absolute numbers, the van drew a high-prevalence sample, with positivity rates of 26.9% for chlamydia and 11.5% for gonorrhea. This article documents the process and lessons learned from adapting and implementing a local campaign for Black and Latino sexual-minority youth. |
Isolation of Onchocerca lupi in dogs and black flies, California, USA
Hassan HK , Bolcen S , Kubofcik J , Nutman TB , Eberhard ML , Middleton K , Wekesa JW , Ruedas G , Nelson KJ , Dubielzig R , De Lombaert M , Silverman B , Schorling JJ , Adler PH , Unnasch TR , Beeler ES . Emerg Infect Dis 2015 21 (5) 789-96 In southern California, ocular infections caused by Onchocerca lupi were diagnosed in 3 dogs (1 in 2006, 2 in 2012). The infectious agent was confirmed through morphologic analysis of fixed parasites in tissues and by PCR and sequencing of amplicons derived from 2 mitochondrially encoded genes and 1 nuclear-encoded gene. A nested PCR based on the sequence of the cytochrome oxidase subunit 1 gene of the parasite was developed and used to screen Simulium black flies collected from southern California for O. lupi DNA. Six (2.8%; 95% CI 0.6%-5.0%) of 213 black flies contained O. lupi DNA. Partial mitochondrial16S rRNA gene sequences from the infected flies matched sequences derived from black fly larvae cytotaxonomically identified as Simulium tribulatum. These data implicate S. tribulatum flies as a putative vector for O. lupi in southern California. |
Characterization of large structural genetic mosaicism in human autosomes.
Machiela MJ , Zhou W , Sampson JN , Dean MC , Jacobs KB , Black A , Brinton LA , Chang IS , Chen C , Chen C , Chen K , Cook LS , Crous Bou M , De Vivo I , Doherty J , Friedenreich CM , Gaudet MM , Haiman CA , Hankinson SE , Hartge P , Henderson BE , Hong YC , Hosgood HD 3rd , Hsiung CA , Hu W , Hunter DJ , Jessop L , Kim HN , Kim YH , Kim YT , Klein R , Kraft P , Lan Q , Lin D , Liu J , Le Marchand L , Liang X , Lissowska J , Lu L , Magliocco AM , Matsuo K , Olson SH , Orlow I , Park JY , Pooler L , Prescott J , Rastogi R , Risch HA , Schumacher F , Seow A , Setiawan VW , Shen H , Sheng X , Shin MH , Shu XO , VanDen Berg D , Wang JC , Wentzensen N , Wong MP , Wu C , Wu T , Wu YL , Xia L , Yang HP , Yang PC , Zheng W , Zhou B , Abnet CC , Albanes D , Aldrich MC , Amos C , Amundadottir LT , Berndt SI , Blot WJ , Bock CH , Bracci PM , Burdett L , Buring JE , Butler MA , Carreon T , Chatterjee N , Chung CC , Cook MB , Cullen M , Davis FG , Ding T , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF Jr , Freedman ND , Fuchs CS , Gao YT , Gapstur SM , Patino-Garcia A , Garcia-Closas M , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Greene MH , Hallmans G , Harris CC , Henriksson R , Holly EA , Hoover RN , Hu N , Hutchinson A , Jenab M , Johansen C , Khaw KT , Koh WP , Kolonel LN , Kooperberg C , Krogh V , Kurtz RC , LaCroix A , Landgren A , Landi MT , Li D , Liao LM , Malats N , McGlynn KA , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Peplonska B , Peters U , Petersen GM , Prokunina-Olsson L , Purdue M , Qiao YL , Rabe KG , Rajaraman P , Real FX , Riboli E , Rodriguez-Santiago B , Rothman N , Ruder AM , Savage SA , Schwartz AG , Schwartz KL , Sesso HD , Severi G , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Viswanathan K , Wacholder S , Wang Z , Weinstein SJ , Wheeler W , White E , Wiencke JK , Wolpin BM , Wu X , Wunder JS , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Ziegler RG , de Andrade M , Barnes KC , Beaty TH , Bierut LJ , Desch KC , Doheny KF , Feenstra B , Ginsburg D , Heit JA , Kang JH , Laurie CA , Li JZ , Lowe WL , Marazita ML , Melbye M , Mirel DB , Murray JC , Nelson SC , Pasquale LR , Rice K , Wiggs JL , Wise A , Tucker M , Perez-Jurado LA , Laurie CC , Caporaso NE , Yeager M , Chanock SJ . Am J Hum Genet 2015 96 (3) 487-97 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. |
Investing in prospective cohorts for etiologic study of occupational exposures
Blair A , Hines CJ , Thomas KW , Alavanja MC , Freeman LE , Hoppin JA , Kamel F , Lynch CF , Lubin JH , Silverman DT , Whelan E , Zahm SH , Sandler DP . Am J Ind Med 2015 58 (2) 113-22 Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures. |
RE: the Diesel Exhaust in Miners Study (DEMS): a nested case-control study of lung cancer and diesel exhaust
Silverman DT , Lubin JH , Blair AE , Vermeulen R , Stewart PA , Schleiff PL , Attfield MD . J Natl Cancer Inst 2014 106 (8) Because our original publication (1) generated considerable interest over the past two years, we now provide additional data from our nested case-control study that are valuable in evaluating the relation between diesel exhaust exposure and lung cancer. Here we include results based on alternative exposure metrics (Table 1) and alternative approaches for adjusting for cigarette smoking as a confounder (Table 2), for comparison with results that appeared in Table 3 of Silverman et al. (1). |
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Wang Z , Zhu B , Zhang M , Parikh H , Jia J , Chung CC , Sampson JN , Hoskins JW , Hutchinson A , Burdette L , Ibrahim A , Hautman C , Raj PS , Abnet CC , Adjei AA , Ahlbom A , Albanes D , Allen NE , Ambrosone CB , Aldrich M , Amiano P , Amos C , Andersson U , Andriole G Jr , Andrulis IL , Arici C , Arslan AA , Austin MA , Baris D , Barkauskas DA , Bassig BA , Beane Freeman LE , Berg CD , Berndt SI , Bertazzi PA , Biritwum RB , Black A , Blot W , Boeing H , Boffetta P , Bolton K , Boutron-Ruault MC , Bracci PM , Brennan P , Brinton LA , Brotzman M , Bueno-de-Mesquita HB , Buring JE , Butler MA , Cai Q , Cancel-Tassin G , Canzian F , Cao G , Caporaso NE , Carrato A , Carreon T , Carta A , Chang GC , Chang IS , Chang-Claude J , Che X , Chen CJ , Chen CY , Chen CH , Chen C , Chen KY , Chen YM , Chokkalingam AP , Chu LW , Clavel-Chapelon F , Colditz GA , Colt JS , Conti D , Cook MB , Cortessis VK , Crawford ED , Cussenot O , Davis FG , De Vivo I , Deng X , Ding T , Dinney CP , Di Stefano AL , Diver WR , Duell EJ , Elena JW , Fan JH , Feigelson HS , Feychting M , Figueroa JD , Flanagan AM , Fraumeni JF Jr , Freedman ND , Fridley BL , Fuchs CS , Gago-Dominguez M , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Garcia-Closas R , Gastier-Foster JM , Gaziano JM , Gerhard DS , Giffen CA , Giles GG , Gillanders EM , Giovannucci EL , Goggins M , Gokgoz N , Goldstein AM , Gonzalez C , Gorlick R , Greene MH , Gross M , Grossman HB , Grubb R 3rd , Gu J , Guan P , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Hartge P , Hattinger C , Hayes RB , He Q , Helman L , Henderson BE , Henriksson R , Hoffman-Bolton J , Hohensee C , Holly EA , Hong YC , Hoover RN , Hosgood HD 3rd , Hsiao CF , Hsing AW , Hsiung CA , Hu N , Hu W , Hu Z , Huang MS , Hunter DJ , Inskip PD , Ito H , Jacobs EJ , Jacobs KB , Jenab M , Ji BT , Johansen C , Johansson M , Johnson A , Kaaks R , Kamat AM , Kamineni A , Karagas M , Khanna C , Khaw KT , Kim C , Kim IS , Kim YH , Kim YC , Kim YT , Kang CH , Jung YJ , Kitahara CM , Klein AP , Klein R , Kogevinas M , Koh WP , Kohno T , Kolonel LN , Kooperberg C , Kratz CP , Krogh V , Kunitoh H , Kurtz RC , Kurucu N , Lan Q , Lathrop M , Lau CC , Lecanda F , Lee KM , Lee MP , Le Marchand L , Lerner SP , Li D , Liao LM , Lim WY , Lin D , Lin J , Lindstrom S , Linet MS , Lissowska J , Liu J , Ljungberg B , Lloreta J , Lu D , Ma J , Malats N , Mannisto S , Marina N , Mastrangelo G , Matsuo K , McGlynn KA , McKean-Cowdin R , McNeill LH , McWilliams RR , Melin BS , Meltzer PS , Mensah JE , Miao X , Michaud DS , Mondul AM , Moore LE , Muir K , Niwa S , Olson SH , Orr N , Panico S , Park JY , Patel AV , Patino-Garcia A , Pavanello S , Peeters PH , Peplonska B , Peters U , Petersen GM , Picci P , Pike MC , Porru S , Prescott J , Pu X , Purdue MP , Qiao YL , Rajaraman P , Riboli E , Risch HA , Rodabough RJ , Rothman N , Ruder AM , Ryu JS , Sanson M , Schned A , Schumacher FR , Schwartz AG , Schwartz KL , Schwenn M , Scotlandi K , Seow A , Serra C , Serra M , Sesso HD , Severi G , Shen H , Shen M , Shete S , Shiraishi K , Shu XO , Siddiq A , Sierrasesumaga L , Sierri S , Sihoe AD , Silverman DT , Simon M , Southey MC , Spector L , Spitz M , Stampfer M , Stattin P , Stern MC , Stevens VL , Stolzenberg-Solomon RZ , Stram DO , Strom SS , Su WC , Sund M , Sung SW , Swerdlow A , Tan W , Tanaka H , Tang W , Tang ZZ , Tardon A , Tay E , Taylor PR , Tettey Y , Thomas DM , Tirabosco R , Tjonneland A , Tobias GS , Toro JR , Travis RC , Trichopoulos D , Troisi R , Truelove A , Tsai YH , Tucker MA , Tumino R , Van Den Berg D , Van Den Eeden SK , Vermeulen R , Vineis P , Visvanathan K , Vogel U , Wang C , Wang C , Wang J , Wang SS , Weiderpass E , Weinstein SJ , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolk A , Wolpin BM , Wong MP , Wrensch M , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xiang YB , Xu J , Yang HP , Yang PC , Yatabe Y , Ye Y , Yeboah ED , Yin Z , Ying C , Yu CJ , Yu K , Yuan JM , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Mirabello L , Savage SA , Kraft P , Chanock SJ , Yeager M , Landi MT , Shi J , Chatterjee N , Amundadottir LT . Hum Mol Genet 2014 23 (24) 6616-33 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. |
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