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Determinants of urinary dialkyl phosphate metabolites in midlife women: the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). 中年妇女尿液中磷酸二烷基代谢物的决定因素:全国妇女健康多污染物研究(SWAN-MPS)。
IF 4.1 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-05-08 DOI: 10.1038/s41370-024-00672-z
Sung-Hee Seo, Stuart Batterman, Carrie A Karvonen-Gutierrez, Sung Kyun Park
<p><strong>Background: </strong>Biomonitoring data and determinants of urinary dialkylphosphate (DAP) metabolites, markers of organophosphate pesticides, in racially diverse, non-occupationally exposed populations are scarce.</p><p><strong>Objective: </strong>This study evaluated urinary concentrations and potential determinants of DAP metabolites of organophosphate pesticides in a multi-site, multi-racial/ethnic cohort of women aged 45-56 years, the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS).</p><p><strong>Methods: </strong>We analyzed 963 urine samples collected in 1999-2000, the baseline of SWAN-MPS for longitudinal studies, and quantified DAP metabolites, including dimethyl alkylphosphates (DMAPs): dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP); and diethyl alkylphosphates (DEAPs): diethylphosphate (DEP), diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), using gas chromatography and triple quadrupole mass spectroscopy. Adjusted least squared geometric means (LSGMs) and 95% confidence intervals (CIs) were computed to compare DAP concentrations by socio-demographic, behavioral and dietary factors.</p><p><strong>Results: </strong>The geometric means (geometric standard deviations) of total DAPs, DMAPs, and DEAPs were 141 (2.63) nmol/L, 102 (2.99) nmol/L, and 26.8 (2.46) nmol/L, respectively. Body mass index (BMI) was inversely associated with DMAPs and DEAPs: LSGM (95% CI) = 68.8 (55.7-84.9) and 21.0 (17.7-25.0) nmol/L for women with obesity vs. 102 (84.7-123) and 30.1 (25.7-35.1) nmol/L for women with normal/underweight, respectively. Fruit consumption was positively (74.9 (62.1-90.2) for less than 5-6 servings/week vs. 105 (84.8-130) nmol/L for 1 serving/day and more) whereas meat consumption was inversely associated with DMAPs (110 (95.0-128) for seldom vs. 82.3 (59.5-114) nmol/L for often consumption). Fresh apple consumption appears to be attributed to the DMAP differences. Alcohol consumption was positively associated with DEAPs (27.5 (23.1-32.7) for 2 drinks/week and more vs. 23.0 (20.0-26.6) nmol/L for less than 1 drink/month). Black women had higher concentrations of DEAPs compared with White women (27.3 (21.2-35.2) vs. 23.2 (20.2-26.7) nmol/L).</p><p><strong>Impact statement: </strong>Organophosphate pesticides (OPs) are synthetic chemicals and currently the most widely used type of insecticides. We examined multi-site, multi-ethnic cohort of midlife women in the U.S. that offers a unique opportunity to evaluate major determinants of OP exposure. We improved OP metabolite detection rates and obtained accurate concentrations using an improved analytical technique. Our findings suggest that consumptions of fruit, meat and alcohol are important determinants of OP exposure for midlife women. Higher concentrations of diethyl OP metabolites in Black women compared to White women, even after accounting for dietary intake, suggests additional, but unknown racial
背景:在不同种族、非职业接触有机磷农药的人群中,尿液中有机磷农药标记物--二烷基磷酸酯(DAP)代谢物的生物监测数据和决定因素很少:本研究评估了多地点、多种族/民族 45-56 岁妇女队列(全国妇女健康多污染物研究(SWAN-MPS))中有机磷农药 DAP 代谢物的尿液浓度和潜在决定因素:我们分析了 1999-2000 年收集的 963 份尿液样本(SWAN-MPS 的纵向研究基线),并量化了 DAP 代谢物,包括二甲基烷基磷酸盐 (DMAP):采用气相色谱法和三重四极杆质谱法,对二甲基烷基磷酸酯(DMAPs):二甲基磷酸酯(DMP)、二甲基硫代磷酸酯(DMTP)、二甲基二硫代磷酸酯(DMDTP);以及二乙基烷基磷酸酯(DEAPs):二乙基磷酸酯(DEP)、二乙基硫代磷酸酯(DETP)、二乙基二硫代磷酸酯(DEDTP)进行了定量分析。计算了调整后的最小平方几何平均数(LSGMs)和 95% 置信区间(CIs),以比较不同社会人口、行为和饮食因素导致的 DAP 浓度:总 DAPs、DMAPs 和 DEAPs 的几何平均数(几何标准偏差)分别为 141 (2.63) nmol/L、102 (2.99) nmol/L 和 26.8 (2.46) nmol/L。体重指数(BMI)与 DMAPs 和 DEAPs 呈反比:肥胖女性的 LSGM(95% CI)=68.8(55.7-84.9)和 21.0(17.7-25.0)毫摩尔/升,而体重正常/偏轻女性的 LSGM(95% CI)=102(84.7-123)和 30.1(25.7-35.1)毫摩尔/升。水果摄入量与 DMAPs 呈正相关(每周少于 5-6 份为 74.9(62.1-90.2)毫摩尔/升,每天 1 份及以上为 105(84.8-130)毫摩尔/升),而肉类摄入量与 DMAPs 呈反相关(很少摄入为 110(95.0-128)毫摩尔/升,经常摄入为 82.3(59.5-114)毫摩尔/升)。食用新鲜苹果似乎是造成 DMAP 差异的原因。饮酒与 DEAP 呈正相关(每周饮酒 2 次及以上为 27.5(23.1-32.7)毫摩尔/升,每月饮酒不足 1 次为 23.0(20.0-26.6)毫摩尔/升)。黑人妇女的 DEAPs 浓度高于白人妇女(27.3 (21.2-35.2) nmol/L vs. 23.2 (20.2-26.7) nmol/L):有机磷杀虫剂(OPs)是一种合成化学品,也是目前使用最广泛的杀虫剂类型。我们对美国中年妇女的多地点、多种族队列进行了研究,为评估 OP 暴露的主要决定因素提供了一个独特的机会。我们利用改进的分析技术提高了 OP 代谢物的检测率,并获得了准确的浓度。我们的研究结果表明,水果、肉类和酒精的摄入量是中年女性暴露于 OP 的重要决定因素。与白人妇女相比,黑人妇女的 OP 二乙基代谢物浓度更高,即使考虑到饮食摄入量也是如此。
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引用次数: 0
Does socioeconomic and environmental burden affect vulnerability to extreme air pollution and heat? A case-crossover study of mortality in California. 社会经济和环境负担是否会影响对极端空气污染和高温的脆弱性?加利福尼亚州死亡率个案交叉研究。
IF 4.1 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-05-07 DOI: 10.1038/s41370-024-00676-9
Mehjar Azzouz, Zainab Hasan, Md Mostafijur Rahman, W James Gauderman, Melissa Lorenzo, Frederick W Lurmann, Sandrah P Eckel, Lawrence Palinkas, Jill Johnston, Michael Hurlburt, Sam J Silva, Hannah Schlaerth, Joseph Ko, George Ban-Weiss, Rob McConnell, Leo Stockfelt, Erika Garcia
<p><strong>Background: </strong>Extreme heat and air pollution is associated with increased mortality. Recent evidence suggests the combined effects of both is greater than the effects of each individual exposure. Low neighborhood socioeconomic status ("socioeconomic burden") has also been associated with increased exposure and vulnerability to both heat and air pollution. We investigated if neighborhood socioeconomic burden or the combination of socioeconomic and environmental exposures ("socioenvironmental burden") modified the effect of combined exposure to extreme heat and particulate air pollution on mortality in California.</p><p><strong>Methods: </strong>We used a time-stratified case-crossover design to assess the impact of daily exposure to extreme particulate matter <2.5 μm (PM<sub>2.5</sub>) and heat on cardiovascular, respiratory, and all-cause mortality in California 2014-2019. Daily average PM<sub>2.5</sub> and maximum temperatures based on decedent's residential census tract were dichotomized as extreme or not. Census tract-level socioenvironmental and socioeconomic burden was assessed with the CalEnviroScreen (CES) score and a social deprivation index (SDI), and individual educational attainment was derived from death certificates. Conditional logistic regression was used to estimate associations of heat and PM<sub>2.5</sub> with mortality with a product term used to evaluate effect measure modification.</p><p><strong>Results: </strong>During the study period 1,514,292 all-cause deaths could be assigned residential exposures. Extreme heat and air pollution alone and combined were associated with increased mortality, matching prior reports. Decedents in census tracts with higher socioenvironmental and socioeconomic burden experienced more days with extreme PM<sub>2.5</sub> exposure. However, we found no consistent effect measure modification by CES or SDI on combined or separate extreme heat and PM<sub>2.5</sub> exposure on odds of total, cardiovascular or respiratory mortality. No effect measure modification was observed for individual education attainment.</p><p><strong>Conclusion: </strong>We did not find evidence that neighborhood socioenvironmental- or socioeconomic burden significantly influenced the individual or combined impact of extreme exposures to heat and PM<sub>2.5</sub> on mortality in California.</p><p><strong>Impact: </strong>We investigated the effect measure modification by socioeconomic and socioenvironmental of the co-occurrence of heat and PM<sub>2.5</sub>, which adds support to the limited previous literature on effect measure modification by socioeconomic and socioenvironmental burden of heat alone and PM<sub>2.5</sub> alone. We found no consistent effect measure modification by neighborhood socioenvironmental and socioeconomic burden or individual level SES of the mortality association with extreme heat and PM<sub>2.5</sub> co-exposure. However, we did find increased number of days with extreme PM<sub>2.5</
背景:酷热和空气污染与死亡率上升有关。最近的证据表明,两者的综合影响大于单独暴露的影响。社区社会经济地位低("社会经济负担")也与更容易接触高温和空气污染有关。我们研究了邻里社会经济负担或社会经济与环境暴露的结合("社会环境负担")是否会改变加州极端高温和颗粒空气污染的综合暴露对死亡率的影响:我们采用时间分层病例交叉设计来评估 2014-2019 年加利福尼亚州每日暴露于极端颗粒物 2.5)和高温对心血管、呼吸系统和全因死亡率的影响。根据死者居住的人口普查区,将每日平均 PM2.5 和最高气温二分为极端或非极端。人口普查区一级的社会环境和社会经济负担通过加州环境筛查(CalEnviroScreen,CES)得分和社会贫困指数(SDI)进行评估,而个人教育程度则来自死亡证明。采用条件逻辑回归法估算高温和 PM2.5 与死亡率的关系,并用乘积项来评估效应测量修正:在研究期间,1,514,292 例全因死亡可归因于居住暴露。极端高温和空气污染单独或共同导致死亡率上升,这与之前的报告一致。在社会环境和社会经济负担较重的人口普查区,死者接触 PM2.5 极端天气的天数较多。然而,我们没有发现 CES 或 SDI 对极端高温和 PM2.5 暴晒对总死亡率、心血管死亡率或呼吸系统死亡率的综合或单独影响的一致修正。在个人教育程度方面,也没有观察到任何效应测量修正:我们没有发现证据表明,在加利福尼亚,邻里社会环境或社会经济负担会显著影响极端高温和 PM2.5 暴露对死亡率的个体或综合影响:我们调查了社会经济和社会环境对同时出现的高温和 PM2.5 的影响度量的调节作用,这为之前关于社会经济和社会环境负担对单独的高温和单独的 PM2.5 的影响度量的调节作用的有限文献提供了支持。我们没有发现邻里社会环境和社会经济负担或个人水平的社会经济地位对极端高温和 PM2.5 共同暴露造成的死亡率相关性有一致的影响。不过,我们确实发现,在社会环境和社会经济负担较重的社区,PM2.5 极端暴露的天数有所增加。我们评估了多个地区级和一个个人级的社会经济地位和社会环境负担指标,每个指标对社会环境因素的估计不同,从而使我们的结论更加可靠。
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引用次数: 0
The application of PTR-MS and non-targeted analysis to characterize VOCs emitted from a plastic recycling facility fire. 应用 PTR-MS 和非目标分析来确定塑料回收设施火灾中排放的挥发性有机化合物的特征。
IF 4.1 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-05-06 DOI: 10.1038/s41370-024-00681-y
Eva C M Vitucci, Oladayo Oladeji, Albert A Presto, Carolyn L Cannon, Natalie M Johnson

Background: On April 11th, 2023, the My Way Trading (MWT) recycling facility in Richmond, Indiana caught fire, mandating the evacuation of local residents and necessitating the U.S. Environmental Protection Agency (EPA) to conduct air monitoring. The EPA detected elevated levels of plastic combustion-related air pollutants, including hydrogen cyanide and benzene.

Objective: We aimed to identify these and other volatile organic compounds (VOCs) present as well as to identify the potential hazard of each compound for various human health effects.

Methods: To identify the VOCs, we conducted air monitoring at sites within and bordering the evacuation zone using proton transfer reaction mass spectrometry (PTR-MS) and non-targeted analysis (NTA). To facilitate risk assessment of the emitted VOCs, we used the EPA Hazard Comparison Dashboard.

Results: We identified 46 VOCs, within and outside the evacuation zone, with average detection levels above local background levels measured in Middletown, OH. Levels of hydrogen cyanide and 4 other VOCs were at least 1.8-fold higher near the incidence site in comparison to background levels and displayed unique temporal and spatial patterns. The 46 VOCs identified had the highest hazardous potential for eye and skin irritation, with approximately 45% and 39%, respectively, of the VOCs classified as high and very high hazards for these endpoints. Notably, all detected VOC levels were below the hazard thresholds set for single VOC exposures; however, hazard thresholds for exposure to VOC mixtures are currently unclear.

Impact: This study serves as a proof-of-concept that PTR-MS coupled with NTA can facilitate rapid identification and hazard assessment of VOCs emitted following anthropogenic disasters. Furthermore, it demonstrates that this approach may augment future disaster responses to quantify additional VOCs present in complex combustion mixtures.

背景:2023 年 4 月 11 日,位于印第安纳州里士满(Richmond)的 My Way Trading (MWT) 回收设施起火,当地居民被迫疏散,美国环保署(EPA)也不得不对其进行空气监测。EPA 检测到与塑料燃烧有关的空气污染物水平升高,其中包括氰化氢和苯:我们的目标是确定这些和其他挥发性有机化合物 (VOC),并确定每种化合物对各种人体健康影响的潜在危害:为了确定挥发性有机化合物,我们使用质子转移反应质谱法(PTR-MS)和非目标分析法(NTA)对疏散区内和疏散区周边的地点进行了空气监测。为了便于对排放的挥发性有机化合物进行风险评估,我们使用了美国环保局的危害比较仪表板:结果:我们发现在俄亥俄州米德尔敦测量到的疏散区域内外有 46 种挥发性有机化合物的平均检测水平高于当地背景水平。与背景水平相比,氰化氢和其他 4 种挥发性有机化合物在事发地点附近的水平至少高出 1.8 倍,并呈现出独特的时空模式。已确定的 46 种挥发性有机化合物对眼睛和皮肤的潜在危害最大,分别有约 45% 和 39% 的挥发性有机化合物被归类为对这些终点的高危和极高危。值得注意的是,所有检测到的挥发性有机化合物水平都低于为接触单一挥发性有机化合物而设定的危害阈值;然而,接触挥发性有机化合物混合物的危害阈值目前尚不明确:本研究证明了 PTR-MS 与 NTA 联用可促进对人为灾害后排放的挥发性有机化合物进行快速识别和危害评估。此外,该研究还表明,这种方法可以增强未来的灾难应对能力,对复杂燃烧混合物中的其他挥发性有机化合物进行量化。
{"title":"The application of PTR-MS and non-targeted analysis to characterize VOCs emitted from a plastic recycling facility fire.","authors":"Eva C M Vitucci, Oladayo Oladeji, Albert A Presto, Carolyn L Cannon, Natalie M Johnson","doi":"10.1038/s41370-024-00681-y","DOIUrl":"10.1038/s41370-024-00681-y","url":null,"abstract":"<p><strong>Background: </strong>On April 11th, 2023, the My Way Trading (MWT) recycling facility in Richmond, Indiana caught fire, mandating the evacuation of local residents and necessitating the U.S. Environmental Protection Agency (EPA) to conduct air monitoring. The EPA detected elevated levels of plastic combustion-related air pollutants, including hydrogen cyanide and benzene.</p><p><strong>Objective: </strong>We aimed to identify these and other volatile organic compounds (VOCs) present as well as to identify the potential hazard of each compound for various human health effects.</p><p><strong>Methods: </strong>To identify the VOCs, we conducted air monitoring at sites within and bordering the evacuation zone using proton transfer reaction mass spectrometry (PTR-MS) and non-targeted analysis (NTA). To facilitate risk assessment of the emitted VOCs, we used the EPA Hazard Comparison Dashboard.</p><p><strong>Results: </strong>We identified 46 VOCs, within and outside the evacuation zone, with average detection levels above local background levels measured in Middletown, OH. Levels of hydrogen cyanide and 4 other VOCs were at least 1.8-fold higher near the incidence site in comparison to background levels and displayed unique temporal and spatial patterns. The 46 VOCs identified had the highest hazardous potential for eye and skin irritation, with approximately 45% and 39%, respectively, of the VOCs classified as high and very high hazards for these endpoints. Notably, all detected VOC levels were below the hazard thresholds set for single VOC exposures; however, hazard thresholds for exposure to VOC mixtures are currently unclear.</p><p><strong>Impact: </strong>This study serves as a proof-of-concept that PTR-MS coupled with NTA can facilitate rapid identification and hazard assessment of VOCs emitted following anthropogenic disasters. Furthermore, it demonstrates that this approach may augment future disaster responses to quantify additional VOCs present in complex combustion mixtures.</p>","PeriodicalId":15684,"journal":{"name":"Journal of Exposure Science and Environmental Epidemiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Monitoring human exposure to four parabens and triclosan: comparing silicone wristbands with spot urine samples as predictors of internal dose 监测人体接触四种对羟基苯甲酸酯和三氯生的情况:比较硅胶腕带和定点尿样作为体内剂量预测指标的作用。
IF 4.1 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-05-04 DOI: 10.1038/s41370-024-00663-0
Jessica L. Levasseur, Kate Hoffman, Sharon Zhang, Ellen M. Cooper, Heather M. Stapleton
People are exposed to a variety of chemicals each day as a result of their personal care product (PCP) use. This study was designed to determine if silicone wristbands provide a quantitative estimate of internal dose for phenols commonly associated with PCPs, with a focus on triclosan and four parabens: methyl-, ethyl-, propyl-, and butylparaben. Uptake of these compounds into wristbands and correlations with internal dose were assessed. Ten adults from central North Carolina wore five silicone wristbands, with one wristband removed each day for 5 days. Each participant provided a 24 h urine sample and a random spot urine sample each day, in which paraben and triclosan metabolites were evaluated. All parabens and triclosan were detected frequently in wristbands and, except for butylparaben, in urine samples. Wristband and spot urine concentrations of parabens and triclosan were both compared to a measurement of internal dose (i.e., the total metabolite mass excreted over 5 days as a measurement of internal dose). The two most hydrophobic compounds investigated, butylparaben and triclosan, displayed significant linear uptake in wristbands over 5 days, whereas concentrations of methyl- and ethylparaben displayed a steady state concentration. In general, wristbands and spot urine samples were similarly correlated to internal dose for frequently detected parabens and triclosan.  However, wristbands have additional advantages including higher detection rates and reduced participant burden that may make them more suitable tools for assessing exposure to PCPs.
背景:人们每天都会因使用个人护理产品(PCP)而接触到各种化学物质:本研究旨在确定硅胶腕带是否能定量估算与五氯苯酚常见的酚类物质的体内剂量,重点是三氯生和四种对羟基苯甲酸酯:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯和对羟基苯甲酸丁酯。评估了这些化合物在腕带中的吸收情况以及与体内剂量的相关性:来自北卡罗来纳州中部的 10 名成年人佩戴了 5 条硅胶腕带,每天取下一条,共佩戴 5 天。每位参与者每天提供一份 24 小时尿样和一份随机定点尿样,对其中的对羟基苯甲酸酯和三氯生代谢物进行评估:结果:所有对羟基苯甲酸酯和三氯生都能在腕带中频繁检测到,除对羟基苯甲酸丁酯外,在尿样中也能检测到。对羟基苯甲酸酯和三氯生的腕带浓度和定点尿液浓度均与体内剂量测量值(即 5 天内排出的代谢物总量作为体内剂量测量值)进行了比较:所研究的两种疏水性最强的化合物(丁基苯甲酸酯和三氯生)在 5 天内对腕带的吸收呈显著的线性吸收,而甲基苯甲酸酯和乙基苯甲酸酯的浓度则呈稳定状态。总体而言,对于经常检测到的对羟基苯甲酸酯和三氯生,腕带和定点尿样与体内剂量的相关性相似。 不过,腕带还具有其他优点,包括检测率更高,参与者负担更轻,因此可能更适合作为评估五氯苯酚暴露的工具。
{"title":"Monitoring human exposure to four parabens and triclosan: comparing silicone wristbands with spot urine samples as predictors of internal dose","authors":"Jessica L. Levasseur,&nbsp;Kate Hoffman,&nbsp;Sharon Zhang,&nbsp;Ellen M. Cooper,&nbsp;Heather M. Stapleton","doi":"10.1038/s41370-024-00663-0","DOIUrl":"10.1038/s41370-024-00663-0","url":null,"abstract":"People are exposed to a variety of chemicals each day as a result of their personal care product (PCP) use. This study was designed to determine if silicone wristbands provide a quantitative estimate of internal dose for phenols commonly associated with PCPs, with a focus on triclosan and four parabens: methyl-, ethyl-, propyl-, and butylparaben. Uptake of these compounds into wristbands and correlations with internal dose were assessed. Ten adults from central North Carolina wore five silicone wristbands, with one wristband removed each day for 5 days. Each participant provided a 24 h urine sample and a random spot urine sample each day, in which paraben and triclosan metabolites were evaluated. All parabens and triclosan were detected frequently in wristbands and, except for butylparaben, in urine samples. Wristband and spot urine concentrations of parabens and triclosan were both compared to a measurement of internal dose (i.e., the total metabolite mass excreted over 5 days as a measurement of internal dose). The two most hydrophobic compounds investigated, butylparaben and triclosan, displayed significant linear uptake in wristbands over 5 days, whereas concentrations of methyl- and ethylparaben displayed a steady state concentration. In general, wristbands and spot urine samples were similarly correlated to internal dose for frequently detected parabens and triclosan. &nbsp;However, wristbands have additional advantages including higher detection rates and reduced participant burden that may make them more suitable tools for assessing exposure to PCPs.","PeriodicalId":15684,"journal":{"name":"Journal of Exposure Science and Environmental Epidemiology","volume":"34 4","pages":"670-678"},"PeriodicalIF":4.1,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece 金属混合物暴露与儿童期血清脂质水平:希腊雷亚母子队列。
IF 4.1 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-05-02 DOI: 10.1038/s41370-024-00674-x
Gyeyoon Yim, Katerina Margetaki, Megan E. Romano, Maria Kippler, Marina Vafeiadi, Theano Roumeliotaki, Vicky Bempi, Shohreh F. Farzan, Leda Chatzi, Caitlin G. Howe
Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures. To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood. This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log2-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated. BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood. Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.
背景:越来越多的证据表明,心血管疾病在人的一生中都会发生,通常从儿童时期就开始了。金属暴露与心血管疾病和包括血脂异常在内的重要风险因素有关,但之前的研究主要集中在成人群体和单一金属暴露上:调查多种金属暴露对儿童期血脂水平的个体和联合影响:这项横断面研究包括希腊伊拉克利翁瑞亚队列研究中的 291 名 4 岁儿童。采用电感耦合等离子体质谱法测量了全血中的七种金属(锰、钴、硒、钼、镉、汞和铅)。血清脂质水平包括总胆固醇、甘油三酯、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇。为了确定儿童金属暴露(经对数 2 转换)对血脂水平的联合和单独影响,采用了贝叶斯核机器回归 (BKMR) 作为主要的多污染物方法。此外,还评估了儿童性别和童年环境烟草烟雾暴露对影响的潜在修正作用:结果:BKMR 发现金属混合物与总胆固醇和低密度脂蛋白胆固醇之间存在正相关。在所研究的七种金属中,硒(中位数为 90.6 [IQR = 83.6, 96.5] µg/L)被认为与总胆固醇和低密度脂蛋白胆固醇的后纳入概率最高。将血液中硒的含量设定为第 75 百分位数与第 25 百分位数时,低密度脂蛋白胆固醇的差异为 8.22 mg/dL (95% CI = 1.85, 14.59),所有其他金属的含量保持在中值。在分层分析中,硒与低密度脂蛋白胆固醇之间的正相关仅在男孩或童年时期接触过环境烟草烟雾的儿童中观察到:越来越多的证据表明,成年后的心血管事件是始于童年的终生动脉粥样硬化过程的结果。因此,针对儿童期心血管风险因素的公共卫生干预措施可能会对减轻心血管疾病负担产生特别深远的影响。尽管越来越多的证据表明,基本金属和非基本金属都会导致心血管疾病和血脂异常等风险因素,但之前的研究主要集中在成人群体的单一金属暴露上。针对这一研究空白,本研究调查了多种金属暴露对幼儿期血脂浓度的共同影响。
{"title":"Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece","authors":"Gyeyoon Yim,&nbsp;Katerina Margetaki,&nbsp;Megan E. Romano,&nbsp;Maria Kippler,&nbsp;Marina Vafeiadi,&nbsp;Theano Roumeliotaki,&nbsp;Vicky Bempi,&nbsp;Shohreh F. Farzan,&nbsp;Leda Chatzi,&nbsp;Caitlin G. Howe","doi":"10.1038/s41370-024-00674-x","DOIUrl":"10.1038/s41370-024-00674-x","url":null,"abstract":"Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures. To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood. This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log2-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated. BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood. Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.","PeriodicalId":15684,"journal":{"name":"Journal of Exposure Science and Environmental Epidemiology","volume":"34 4","pages":"688-698"},"PeriodicalIF":4.1,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In-silico prediction of dislodgeable foliar residues and regulatory implications for plant protection products. 可脱落叶面残留物的硅内预测及对植保产品的监管影响。
IF 4.5 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-04-27 DOI: 10.1038/s41370-024-00675-w
Yi Shi, Kanak Choudhury, Xiaoyi Sopko, Sarah Adham, Edward Chikwana

Background: When experimentally determined dislodgeable foliar residue (DFR) values are not available, regulatory agencies use conservative default DFR values as a first-tier approach to assess post-application dermal exposures to plant protection products (PPPs). These default values are based on a limited set of field studies, are very conservative, and potentially overestimate exposures from DFRs.

Objective: Use Random Forest to develop classification and regression-type ensemble models to predict DFR values after last application (DFR0) by considering experimentally-based variability due to differences in physical and chemical properties of PPPs, agronomic practices, crop type, and climatic conditions.

Methods: Random Forest algorithm was used to develop in-silico ensemble DFR0 prediction models using more than 100 DFR studies from Corteva AgriscienceTM. Several variables related to the active ingredient (a.i.) that was applied, crop, and climate conditions at the time of last application were considered as model parameters.

Results: The proposed ensemble models demonstrated 98% prediction accuracy that if a DFR0 is predicted to be less than the European Food Safety Authority (EFSA) default DFR0 value of 3 µg/cm2/kg a.i./ha, it is highly indicative that the measured DFR value will be less than the default if the study is conducted. If a value is predicted to be larger than or equal to the EFSA default, the model has an 83% prediction accuracy.

Impact statement: This manuscript is expected to have significant impact globally as it provides: A framework for incorporating in silico DFR data into worker exposure assessment, A roadmap for a tiered approach for conducting re-entry exposure assessment, and A proof of concept for using existing DFR data to provide a read-across framework that can easily be harmonized across all regulatory agencies to provide more robust assessments for PPP exposures.

背景:当无法获得实验确定的可剥落叶面残留物 (DFR) 值时,监管机构会使用保守的默认 DFR 值作为评估施用后皮肤接触植物保护产品 (PPP) 的第一级方法。这些默认值基于有限的实地研究,非常保守,可能会高估 DFR 的暴露量:使用随机森林开发分类和回归型集合模型,以预测最后一次施用(DFR0)后的 DFR 值,同时考虑到基于实验的变异性,这些变异性是由 PPPs 的物理和化学特性、农艺实践、作物类型和气候条件的差异造成的:方法:使用随机森林算法,利用 Corteva AgriscienceTM 提供的 100 多项 DFR 研究结果,建立室内 DFR0 预测模型。与施用的活性成分 (a.i.)、作物和最后一次施用时的气候条件有关的几个变量被视为模型参数:建议的集合模型显示,如果预测的 DFR0 小于欧洲食品安全局(EFSA)默认的 DFR0 值 3 µg/cm2/kg a.i./ha,则表明如果进行研究,测得的 DFR 值将小于默认值,预测准确率为 98%。如果预测值大于或等于 EFSA 默认值,则模型的预测准确率为 83%:本手稿预计将对全球产生重大影响,因为它提供了将硅学 DFR 数据纳入工人暴露评估的框架、进行再进入暴露评估的分层方法路线图,以及利用现有 DFR 数据提供一个可轻松在所有监管机构之间统一的可读框架的概念验证,从而为购买力平价暴露提供更稳健的评估。
{"title":"In-silico prediction of dislodgeable foliar residues and regulatory implications for plant protection products.","authors":"Yi Shi, Kanak Choudhury, Xiaoyi Sopko, Sarah Adham, Edward Chikwana","doi":"10.1038/s41370-024-00675-w","DOIUrl":"https://doi.org/10.1038/s41370-024-00675-w","url":null,"abstract":"<p><strong>Background: </strong>When experimentally determined dislodgeable foliar residue (DFR) values are not available, regulatory agencies use conservative default DFR values as a first-tier approach to assess post-application dermal exposures to plant protection products (PPPs). These default values are based on a limited set of field studies, are very conservative, and potentially overestimate exposures from DFRs.</p><p><strong>Objective: </strong>Use Random Forest to develop classification and regression-type ensemble models to predict DFR values after last application (DFR0) by considering experimentally-based variability due to differences in physical and chemical properties of PPPs, agronomic practices, crop type, and climatic conditions.</p><p><strong>Methods: </strong>Random Forest algorithm was used to develop in-silico ensemble DFR0 prediction models using more than 100 DFR studies from Corteva Agriscience<sup>TM</sup>. Several variables related to the active ingredient (a.i.) that was applied, crop, and climate conditions at the time of last application were considered as model parameters.</p><p><strong>Results: </strong>The proposed ensemble models demonstrated 98% prediction accuracy that if a DFR0 is predicted to be less than the European Food Safety Authority (EFSA) default DFR0 value of 3 µg/cm<sup>2</sup>/kg a.i./ha, it is highly indicative that the measured DFR value will be less than the default if the study is conducted. If a value is predicted to be larger than or equal to the EFSA default, the model has an 83% prediction accuracy.</p><p><strong>Impact statement: </strong>This manuscript is expected to have significant impact globally as it provides: A framework for incorporating in silico DFR data into worker exposure assessment, A roadmap for a tiered approach for conducting re-entry exposure assessment, and A proof of concept for using existing DFR data to provide a read-across framework that can easily be harmonized across all regulatory agencies to provide more robust assessments for PPP exposures.</p>","PeriodicalId":15684,"journal":{"name":"Journal of Exposure Science and Environmental Epidemiology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prenatal exposure to environmental contaminants and cord serum metabolite profiles in future immune-mediated diseases 产前接触环境污染物与未来免疫介导疾病的脐带血清代谢物特征
IF 4.1 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-04-27 DOI: 10.1038/s41370-024-00680-z
Bagavathy Shanmugam Karthikeyan, Tuulia Hyötyläinen, Tannaz Ghaffarzadegan, Eric Triplett, Matej Orešič, Johnny Ludvigsson
Prenatal exposure to environmental contaminants is a significant health concern because it has the potential to interfere with host metabolism, leading to adverse health effects in early childhood and later in life. Growing evidence suggests that genetic and environmental factors, as well as their interactions, play a significant role in the development of autoimmune diseases. In this study, we hypothesized that prenatal exposure to environmental contaminants impacts cord serum metabolome and contributes to the development of autoimmune diseases. We selected cord serum samples from All Babies in Southeast Sweden (ABIS) general population cohort, from infants who later developed one or more autoimmune-mediated and inflammatory diseases: celiac disease (CD), Crohn’s disease (IBD), hypothyroidism (HT), juvenile idiopathic arthritis (JIA), and type 1 diabetes (T1D) (all cases, N = 62), along with matched controls (N = 268). Using integrated exposomics and metabolomics mass spectrometry (MS) based platforms, we determined the levels of environmental contaminants and metabolites. Differences in exposure levels were found between the controls and those who later developed various diseases. High contaminant exposure levels were associated with changes in metabolome, including amino acids and free fatty acids. Specifically, we identified marked associations between metabolite profiles and exposure levels of deoxynivalenol (DON), bisphenol S (BPS), and specific per- and polyfluorinated substances (PFAS). Abnormal metabolism is a common feature preceding several autoimmune and inflammatory diseases. However, few studies compared common and specific metabolic patterns preceding these diseases. Here we hypothesized that exposure to environmental contaminants impacts cord serum metabolome, which may contribute to the development of autoimmune diseases. We found differences in exposure levels between the controls and those who later developed various diseases, and importantly, on the metabolic changes associated with the exposures. High contaminant exposure levels were associated with specific changes in metabolome. Our study suggests that prenatal exposure to specific environmental contaminants alters the cord serum metabolomes, which, in turn, might increase the risk of various immune-mediated diseases.
背景产前暴露于环境污染物是一个重大的健康问题,因为它有可能干扰宿主的新陈代谢,从而导致幼儿期和日后对健康产生不良影响。越来越多的证据表明,遗传和环境因素以及它们之间的相互作用在自身免疫性疾病的发展中起着重要作用。方法我们从瑞典东南部所有婴儿(All Babies in Southeast Sweden,ABIS)普通人群队列中选取了脐带血清样本,这些样本来自后来患上一种或多种自身免疫介导的炎症性疾病的婴儿:乳糜泻(CD)、克罗恩病(IBD)、甲状腺功能减退症(HT)、幼年特发性关节炎(JIA)和 1 型糖尿病(T1D)(所有病例,N = 62),以及匹配的对照组(N = 268)。我们利用基于暴露组学和代谢组学质谱(MS)的综合平台,测定了环境污染物和代谢物的水平。污染物暴露水平高与代谢组(包括氨基酸和游离脂肪酸)的变化有关。具体而言,我们发现代谢物特征与脱氧雪腐镰刀菌烯醇(DON)、双酚 S(BPS)以及特定全氟和多氟化合物(PFAS)的暴露水平之间存在明显关联。然而,很少有研究对这些疾病发生前的常见和特殊代谢模式进行比较。在此,我们假设暴露于环境污染物会影响脐带血清代谢组,这可能会导致自身免疫性疾病的发生。我们发现,对照组与后来患上各种疾病的对照组之间在暴露水平上存在差异,重要的是,与暴露相关的代谢变化也存在差异。污染物暴露水平高与代谢组的特定变化有关。我们的研究表明,产前暴露于特定环境污染物会改变脐带血清代谢组,进而可能增加各种免疫介导疾病的风险。
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引用次数: 0
Associations between satellite-derived estimates of PM2.5 species concentrations for organic carbon, elemental carbon, nitrate, and sulfate with birth weight and preterm birth in California during 2005-2014. 2005-2014 年间加利福尼亚州 PM2.5 有机碳、元素碳、硝酸盐和硫酸盐物种浓度的卫星估计值与出生体重和早产之间的关系。
IF 4.1 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-04-25 DOI: 10.1038/s41370-024-00673-y
Patrick S Reuther, Guannan Geng, Yang Liu, Lyndsey A Darrow, Matthew J Strickland

Background: Characterizing the spatial distribution of PM2.5 species concentrations is challenging due to the geographic sparsity of the stationary monitoring network. Recent advances have enabled valid estimation of PM2.5 species concentrations using satellite remote sensing data for use in epidemiologic studies.

Objective: In this study, we used satellite-based estimates of ambient PM2.5 species concentrations to estimate associations with birth weight and preterm birth in California.

Methods: Daily 24 h averaged ground-level PM2.5 species concentrations of organic carbon, elemental carbon, nitrate, and sulfate were estimated during 2005-2014 in California at 1 km resolution. Birth records were linked to ambient pollutant exposures based on maternal residential zip code. Linear regression and Cox regression were conducted to estimate the effect of 1 µg/m3 increases in PM2.5 species concentrations on birth weight and preterm birth.

Results: Analyses included 4.7 million live singleton births having a median 28 days with exposure measurements per pregnancy. In single pollutant models, the observed changes in mean birth weight (per 1 µg/m3 increase in speciated PM2.5 concentrations) were: organic carbon -3.12 g (CI: -4.71, -1.52), elemental carbon -14.20 g (CI: -18.76, -9.63), nitrate -5.51 g (CI: -6.79, -4.23), and sulfate 9.26 g (CI: 7.03, 11.49). Results from multipollutant models were less precise due to high correlation between pollutants. Associations with preterm birth were null, save for a negative association between sulfate and preterm birth (Hazard Ratio per 1 µg/m3 increase: 0.973 CI: 0.958, 0.987).

背景:由于固定监测网络的地理稀疏性,确定 PM2.5 物种浓度的空间分布具有挑战性。最近的进展使我们能够利用卫星遥感数据对 PM2.5 物种浓度进行有效估算,并将其用于流行病学研究:在这项研究中,我们使用基于卫星的环境 PM2.5 浓度估算值来估算加利福尼亚州出生体重和早产的相关性:2005-2014年期间,我们以1公里的分辨率估算了加利福尼亚州每天24小时平均地面PM2.5中有机碳、元素碳、硝酸盐和硫酸盐的浓度。根据母亲居住地的邮政编码,将出生记录与环境污染物暴露联系起来。通过线性回归和 Cox 回归来估计 PM2.5 浓度增加 1 µg/m3 对出生体重和早产的影响:分析包括 470 万名单胎活产婴儿,每次妊娠的暴露测量时间中位数为 28 天。在单一污染物模型中,观察到的平均出生体重变化(PM2.5特定浓度每增加1微克/立方米)为:有机碳-3.12克(CI:-4.71,-1.52),元素碳-14.20克(CI:-18.76,-9.63),硝酸盐-5.51克(CI:-6.79,-4.23),硫酸盐9.26克(CI:7.03,11.49)。由于污染物之间的高度相关性,多污染物模型的结果不够精确。除了硫酸盐与早产之间存在负相关外(每增加 1 µg/m3 的危险比:0.973 CI:0.958, 0.987),其他污染物与早产的相关性均为零。
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引用次数: 0
Developing a geographical–meteorological indicator system and evaluating prediction models for alveolar echinococcosis in China 建立中国肺泡棘球蚴病地理气象指标体系并评估预测模型
IF 4.5 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-04-23 DOI: 10.1038/s41370-024-00664-z
Chuizhao Xue, Baixue Liu, Yan Kui, Weiping Wu, Xiaonong Zhou, Ning Xiao, Shuai Han, Canjun Zheng

Background

Geographical and meteorological factors have been reported to influence the prevalence of echinococcosis, but there’s a lack of indicator system and model.

Objective

To provide further insight into the impact of geographical and meteorological factors on AE prevalence and establish a theoretical basis for prevention and control.

Methods

Principal component and regression analysis were used to screen and establish a three-level indicator system. Relative weights were examined to determine the impact of each indicator, and five mathematical models were compared to identify the best predictive model for AE epidemic levels.

Results

By analyzing the data downloaded from the China Meteorological Data Service Center and Geospatial Data Cloud, we established the KCBIS, including 50 basic indicators which could be directly obtained online, 15 characteristic indicators which were linear combination of the basic indicators and showed a linear relationship with AE epidemic, and 8 key indicators which were characteristic indicators with a clearer relationships and fewer mixed effects. The relative weight analysis revealed that monthly precipitation, monthly cold days, the difference between negative and positive temperature anomalies, basic air temperature conditions, altitude, the difference between positive and negative atmospheric pressure anomalies, monthy extremely hot days, and monthly fresh breeze days were correlated with the natural logarithm of AE prevalence, with sequential decreases in their relative weights. The multinomial logistic regression model was the best predictor at epidemic levels 1, 3, 5, and 6, whereas the CART model was the best predictor at epidemic levels 2, 4, and 5.

背景有报道称,地理和气象因素对棘球蚴病的流行有影响,但缺乏指标体系和模型。结果通过对中国气象数据服务中心和地理空间数据云下载的数据进行分析,建立了KCBIS,包括50个可直接在线获取的基本指标,15个由基本指标线性组合而成、与AE流行呈线性关系的特征指标,以及8个关系较为明确、混合效应较少的特征指标。相对权重分析表明,月降水量、月寒冷日数、气温异常正负差、基本气温条件、海拔高度、气压异常正负差、月酷热日数和月微风日数与 AE 流行率的自然对数相关,且相对权重依次减小。多项式逻辑回归模型是流行程度 1、3、5 和 6 的最佳预测模型,而 CART 模型是流行程度 2、4 和 5 的最佳预测模型。
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引用次数: 0
What is the safe noise exposure level to prevent noise-induced hearing loss? 预防噪音引起的听力损失的安全噪音暴露水平是多少?
IF 4.1 3区 医学 Q2 ENVIRONMENTAL SCIENCES Pub Date : 2024-04-18 DOI: 10.1038/s41370-024-00660-3
Daniel Fink
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引用次数: 0
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Journal of Exposure Science and Environmental Epidemiology
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