Concentration-and flux-based dose-responses of isoprene emission from poplar leaves and plants exposed to an ozone concentration gradient

Supported by the National Key Research and Development Program of China,Key Research Program of Frontier Sciences,CAS,the Hundred Talents Program,Chinese Academy of Sciences(CAS),and National Natural Science Foundation of China,a cooperative study by the research groups led by Prof.

Higher intakes of lysine,threonine and valine are inversely associated with non-alcoholic fatty liver disease risk:a community-based case-control study in the Chinese elderly

The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.

An Analysis of Specific Categories of Birth Defects and Developmental Disabilities for Children of Participants of the Air Force Health Study

Background: The Air Force Health Study collected reproductive outcomes for live-born children of male Air Force veterans of the Vietnam War. Methods: Dioxin values for participants were obtained from blood samples. Analyses were conducted of occurrence of 16 specific categories of birth defects and developmental disabilities. Children were categorized as conceived before and after the start of participants’ Vietnam War service. Children conceived before the start of Vietnam War service were treated as being conceived when their fathers had unquantifiable dioxin values. Children conceived after the start of Vietnam War service for participants with missing dioxin values were excluded from primary analyses, but were used to assess the impact of their exclusion on conclusions. Correlation between values for specific categories for multiple children fathered by the same participant was accounted for. The dose-response relationship was treated as a step function increasing for dioxin values larger than adaptively identified individual thresholds changing with the specific category. Results: For 15 of 16 specific categories, the probability of occurrence increased substantially for a sufficiently high dioxin level above identified thresholds. Exclusion of children due to missing dioxin likely did not affect these results. Conclusions: Results supported the conclusion of substantial adverse effects on a wide variety of specific categories of birth defects and developmental disabilities due to sufficiently high exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War. Results may hold more generally, but might also have been affected by a variety of limitations.

Standardization of exercise intensity and consideration of a dose-response is essential.Commentary on "Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models”,by Lourenco et al.,published 2019 in Nature Medicine

Over the past decade,several biochemical pathways have been investigated to understand the underlying mechanisms involved in the beneficial effects of physical exercise on cognition.1,2 Lourenco et al.,3 in an elegant study published in Nature Medicine,examined the relationship between exercise training and hippocampal memory function.Mechanistically,the authors showed that FNDC5/irisin is an important mediator of beneficial effects of physical exercise in a mouse model of Alzheimer's disease.

Interpreting Dose-Response Relation for Exposure to Multiple Sound Impulses in the Framework of Immunity

Hearing loss is a common military health problem and it is closely related to exposures to impulse noises from blast explosions and weapon firings. In a study based on test data of chinchillas and scaled to humans (Military Medicine, 181: 59-69), an empirical injury model was constructed for exposure to multiple sound impulses of equal intensity. Building upon the empirical injury model, we conduct a mathematical study of the hearing loss injury caused by multiple impulses of non-uniform intensities. We adopt the theoretical framework of viewing individual sound exposures as separate injury causing events, and in that framework, we examine synergy for causing injury (fatigue) or negative synergy (immunity) or independence among a sequence of doses. Starting with the empirical logistic dose-response relation and the empirical dose combination rule, we show that for causing injury, a sequence of sound exposure events are not independent of each other. The phenomenological effect of a preceding event on the subsequent event is always immunity. We extend the empirical dose combination rule, which is applicable only in the case of homogeneous impulses of equal intensity, to accommodate the general case of multiple heterogeneous sound exposures with non-uniform intensities. In addition to studying and extending the empirical dose combination rule, we also explore the dose combination rule for the hypothetical case of independent events, and compare it with the empirical one. We measure the effect of immunity quantitatively using the immunity factor defined as the percentage of decrease in injury probability attributed to the sound exposure in the preceding event. Our main findings on the immunity factor are: 1) the immunity factor is primarily a function of the difference in SELA (A- weighted sound exposure level) between the two sound exposure events;it is virtually independent of the magnitude of the two SELA values as long as the difference is fixed;2) the immunity factor increases monotonically from 0 to 100% as the first dose is varied from being significantly below the second dose, to being moderately above the second dose. The extended dose-response formulation developed in this study provides a theoretical framework for assessing the injury risk in realistic situations.

Serum Ferritin and the Risk of Metabolic Syndrome:A Systematic Review and Dose-Response Meta-Analysis of Cross-sectional Studies

Objective This study aims to assess the dose-response relationship between serum ferritin(SF)and metabolic syndrome(MetS)in the two sexes.Methods We searched for articles on PubMed,the Cochrane Library,EMBASE,and the Web of Science databases that were published from 1950 to 2020.The summary odds ratio(OR)and 95%confidence interval(CI)of the association between SF and MetS were estimated using a random-effects model through a meta-analysis.Based on the methods described by Greenland and Longnecker,we explored the dose-response relationship between the two sexes.Results This study included 14 studies and 74,710 samples.The results of the classical meta-analysis showed that SF was positively associated with MetS(OR=1.77,95%CI:1.59–1.98).Regarding the components of MetS(8 studies included),the results showed that SF was positively associated with abdominal obesity(OR=1.42,95%CI:1.24–1.62),elevated fasting plasma glucose(OR=1.84,95%CI:1.50–2.25),elevated blood pressure(OR=1.17,95%CI:1.08–1.26),elevated triglycerides(OR=2.09,95%CI:1.72–2.54),and reduced high-density lipoprotein cholesterol(OR=1.33,95%CI:1.19–1.49).In the linear dose-response meta-analysis,the ORs of males,females,and postmenopausal females were 1.14(95%CI:1.13–1.16),1.32(95%CI:1.26–1.39),and 1.34(95%CI:1.22–1.47),respectively.Conclusions Our study shows that SF is significantly and positively associated with MetS,and the risk in the male population is higher than that in the female population.This finding also supports the recommendation of using SF as an early warning marker of MetS.

Atrial fibrillation burden and the risk of stroke:A systematic review and dose-response meta-analysis

BACKGROUND The increased stroke risk associated with atrial fibrillation(AF)burden exceeding 5 min is a matter of debate.In addition,the potential linear or nonlinear relationship between AF burden and stroke risk has been largely unexplored.AIM To determine the association between AF burden>5 min and the increased risk of stroke and explore the potential dose-response relationship between these two factors.METHODS Sixteen studies from six databases with 53141 subjects(mean age 65 years)were included.Fifteen studies were observational studies,and one was a randomized controlled trial study.The potential nonlinear dose-response association was characterized using a restricted cubic splines regression model.AF burden for each 1 h and 2 h was associated with an increased risk of stroke.Trial sequential analysis with a random-effect model was used to evaluate the robustness of the evidence from the included 16 studies.RESULTS AF burden>5 min was associated with an increased risk of clinical AF[adjusted risk ratio(RR)=4.18,95%confidence interval(CI):2.26-7.74].However,no association was found with an increased risk of all-cause mortality(adjusted RR=1.55,95%CI:0.87-2.75).Patients with AF burden>5 min had an increased risk of stroke(adjusted RR=2.49,95%CI:1.79-3.47).Moreover,a dose-response analysis showed that the increased stroke risk was paralleled by an increase in AF burden at a rate of 2.0%per hour(Pnonlinear=0.656,RR=1.02,95%CI:1.01-1.03).Trial sequential analysis provided robust evidence of the association between AF burden>5 min and an increased risk of stroke.CONCLUSION AF burden was a significant risk factor for clinical AF and future stroke.A significant linear association was documented between increased AF burden and risk of future stroke.

Finite Mixture Normal Models, with Application to Dose-Response Studies

In this paper, we consider the risk assessment problem under multi-levels and multiple mixture subpopulations. Our result is the generalization of the results of [1-5].1 Finite Mixture Normal ModelsIn dose-response studies, a class of phenomena that frequently occur are that experimental subjects (e.g., mice) may have different responses like ’none, mild, severe’ after a toxicant experiment, or ’getting worse, no change, getting better’ after a medical treatment, etc. These phenomena have attracted the attention of many researchers in recent years. Finite

Generalized Estimating Equations for Repeated Measures Logistic Regression in Mosquito Dose-Response

Dose-response studies in arthropod research usually involve observing and collecting successive information at different times on the same group of insects exposed to different concentrations of stimulus. When the same measure is collected repeatedly over time, the data become correlated and Probit Analysis technique which is the standard method in analyzing bioassay experiments data cannot be used. Lethal time is estimated when the speed of kill is of interest since mortality varies over time. We evaluate a complementary approach, repeated measures logistic regression using Generalized Estimating Equations (GEE), for lethal time determination in mosquito dose response. Mortality data from anopheles larva exposed to 3 botanical extracts (B,C,E) at 4 concentration levels: 500 mg/ml, 250 mg/ml, 50 mg/ml and 12.5 mg/ml were used. The result shows the estimated LT50 values with concentration 500 mg/ml being the most virulent chemical for extract B (LT50 = 10.3 hrs), C (LT50 = 7.2 hrs) and E (LT50 = 10.3 hrs). The least virulent chemical was concentration 12.5 mg/ml for extract B (LT50 = 52.1 hrs), C (LT50 = 70.7 hrs) and E (LT50 = 55.0 hrs). We conclude that repeated measures of logistic regression via GEE can be used as a tool to estimate LT50 more effectively in repeated measures of arthropod data.

A Dose-response Meta-analysis of Egg Intake and Breast Cancer Risk

Aim Eggs are one of the most nutritious foods in nature,but there is no unified conclusion about the association between egg intake and breast cancer risk.Methods The PubMed and Web of Science databases for the literature on egg intake and breast cancer risk were searched for papers published during the last 10 years.These were then filtered according to the inclusion and exclusion criteria.Stata16.0 software was applied to perform a meta-analysis,the generalized least squares method and constrained cubic spline model were used to assess the dose-response trends between egg intake and breast cancer risk.Results A total of 9 articles were included:6 case control studies and 3 cohort studies.The Newcastle-Ottawa scale(NOS)values of the included articles were all≥6 points.The pooled relative risks(RR)of egg intake and breast cancer risk was 0.91(95%CI:0.69-1.19).The dose-response analysis showed a linear trend for egg intake and breast cancer risk(P=0.689).With every 10 g/day increase in egg intake,the incidence of breast cancer increased by 2%(RR=1.02,95%CI:0.99-1.05).However,these results were not statistically significant.Conclusion This meta-analysis found no significant association between egg intake and breast cancer.

Biological transformation,kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure

Low levels (ng/g) of musk ketone (MK),used as a fragrance additive in the formulation of personal care products,are frequently detected in the water and other environment.Thus,aquatic organisms can be continuously exposed to MK.In this study,kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite,bound to cysteine-hemoglobin (Hb) in rainbow trout,formed by enzymatic nitro-reduction of MK have been demonstrated.Trout were exposed to a single exposure of 0.010,0.030,0.10,and 0.30 mg MK/g fish.Tw...

24-Hour Urinary Sodium Excretion Association with Cardiovascular Events:A Systematic Review and Dose-Response Meta-Analysis

Objective The relationship between sodium intake and cardiovascular(CV)events remains unconfirmed.Therefore,we carried out a systematic review and dose-response meta-analysis for evaluating the potential impact of 24-hour sodium excretion on CV risk.Besides,24-hour sodium excretion was used to replace daily sodium diet intake.Methods We searched ISI Web of Science,Embase,Pub Med,and the Cochrane Library.Our study included cohort studies reporting hazard ratio(HR).The random-effects model was used for summarizing the total relative risks(RRs)between the included studies.In addition,the generalized least-squares regression was employed to fit the study model.Results A total of 9 studies involving 645,006 participants were included in this study.A significant non-linear relationship was observed between sodium excretion and CV events(P^(non-linearity)<0.001).In studies collecting 24-h urine samples,the sodium excretion and CV events risk were associated linearly(RR:1.04;95%CI:1.01,1.07).Conclusion In a linear dose-response manner,every 1 g increase in sodium intake was associated with an increased risk of CV events up to 4%.Further studies are required to validate our conclusions further.

Dose-response relationship between risk factors and incidence of COVID-19 in 325 hospitalized patients:A multicenter retrospective cohort study

BACKGROUND The epidemiological and clinical characteristics of coronavirus disease 2019(COVID-19)patients have been widely reported,but the assessment of doseresponse relationships and risk factors for mortality and severe cases and clinical outcomes remain unclear.AIM To determine the dose-response relationship between risk factors and incidence of COVID-19.METHODS In this retrospective,multicenter cohort study,we included patients with confirmed COVID-19 infection who had been discharged or had died by February 6,2020.We used multivariable logistic regression and Cox proportional hazard models to determine the dose-response relationship between risk factors and incidence of COVID-19.RESULTS It clarified that increasing risk of in-hospital death were associated with older age(HR:1.04,95%CI:1.01-1.09),higher lactate dehydrogenase[HR:1.04,95%confidence interval(CI):1.01-1.10],C-reactive protein(HR:1.10,95%CI:1.01-1.23),and procalcitonin(natural log-transformed HR:1.88,95%CI:1.22-2.88),and D-dimer greater than 1μg/m L at admission(natural log transformed HR:1.63,95%CI:1.03-2.58)by multivariable regression.D-dimer and procalcitonin were logarithmically correlated with COVID-19 mortality risk,while there was a linear dose-response correlation between age,lactate dehydrogenase,D-dimer and procalcitonin,independent of established risk factors.CONCLUSION Higher lactate dehydrogenase,D-dimer,and procalcitonin levels were independently associated with a dose-response increased risk of COVID-19 mortality.

Dose-response relationship of lung cancer to amount smoked, duration and age starting

AIM: To quantify smoking/lung cancer relationships accurately using parametric modelling. METHODS: Using the International Epidemiological Studies on Smoking and Lung Cancer database of all epidemiological studies of 100+ lung cancer cases published before 2000, we analyzed 97 blocks of data for amount smoked, 35 for duration of smoking, and 27 for age started. Pseudo-numbers of cases and controls(or at risk) estimated from RRs by dose level formed the data modelled. We fitted various models relating loge RR to dose(d), including βd, βdY and βloge(1 + Wd),and investigated goodness-of-fit and heterogeneity between studies. RESULTS: The best-fitting models for loge RR were0.833 loge [1 +(8.1c/10)] for cigarettes/d(c), 0.792(y/10)0.74 for years smoked(y) and 0.176 [(70- a)/10]1.44 for age of start(a). Each model fitted well overall, though some blocks misfitted. RRs rose from 3.86 to 22.31 between c = 10 and 50, from 2.21 to 13.54 between y = 10 and 50, and from 3.66 to 8.94 between a = 30 and 12.5. Heterogeneity(P < 0.001) existed by continent for amount, RRs for 50 cigarettes/d being 7.23(Asia), 26.36(North America) and 22.16(Europe). Little heterogeneity was seen for duration of smoking or age started. CONCLUSION: The models describe the dose-relationships well, though may be biased by factors including misclassification of smoking status and dose.

Association of alcohol consumption with colorectal cancer risk: a dose-response meta-analysis

Background:Currently,there are many meta-analyses on the correlation between alcohol conception and the risk of colorectal cancer,but the findings are inconsistent.We conducted a dose-response meta-analysis to investigate the association between alcohol intake and the risk of colorectal cancer.Methods:A literature search was performed on PubMed and EMBASE databases to identify relevant articles published before December 09,2019.Summarized relative risks(RRs)and 95%confidence intervals(CIs)were calculated using a fixed or random-effects model for the dose-response meta-analysis.The Cochran Q and I2 statistics were used to assess statistical heterogeneity among studies.Results:Five cohort and 19 case-control studies were included in the meta-analysis.An increased intake of 15-39.9g of daily alcohol was related to a 21%growth risk of CRC(RR=1.21,95%CI:1.05-1.38).Our dose-response analysis indicated that for drinkers of light,moderate and heavy level of alcohol drinking,the estimated RRs of CRC were 0.94(95%CI:0.69-1.27),1.08(95%CI:0.93-1.26)and 1.90(95%CI:1.29-2.97)respectively and for drinkers of moderate beer,heavy beer,moderate wine and heavy wine intake,the estimated RRs of CRC were 0.98(95%CI:0.72-1.34),1.48(95%CI:1.05-2.07),0.86(95%CI:0.56-1.34)and 1.04(95%CI:0.83-1.29)respectively.The risks with no significant association were consistent in the subgroup analyses of general alcohol consumption status and frequency.Conclusions:Heavy level of alcohol consumption,especially heavy beer intake seems to be associated with an increased the risk of CRC.

A Study on the Dose-Response Relationship between Asbestos Exposure Level and Asbestosis among Workers in a Chinese Chrysotile Product Factory

The dose-response relationship for asbestos exposure in a chrysotile product factory was studied. The past gravimetric dust concentration values, obtained from different worksites, were converted into fiber concentration values according to conversion factors that were worked out by simultaneous sampling in this study. The conversions were made so that exposure could be expressed in fiber-years (f-yr). Asbestosis was diagnosed on the basis of chest radiographs and occupational histories. Cumulative dust exposure (f-yr) was calculated up to the date of diagnosis for asbestosis patients, and up to September 1982 for the remaining workers. A dose-response relationship expressed as fiber-years exposed vs cumulative prevalence of asbestosis was established by the life table method on the basis of these data. Predicted 3 and 1% prevalence of asbestosis corresponded to 43 and 22 f-yr exposure, respectively. Considering that a worker can work for 35 years, these doses are commensurate with dust concentrations of 1.22 and 0.63 f/ml, respectively. It is recommended that 1 f/ml be taken as the maximum allowable concentration of airborne asbestos dust for the workplace with an anticipated prevalence of about 2% asbestosis after 35 years of exposure. 1990 Academic Press, Inc.

NiuHuangJiangYa capsule for hypertension:a Bayesian dose-response analysis of multiple N-of-1 trials

Background:There is the limited evidence available from randomized controlled trials on the dose-response relationship of NiuHuangJiangYa capsule for hypertension.The objective of this study is to investigate the dose-response relationship of NiuHuangJiangYa capsule for hypertension based on multiple N-of-1 trials.Methods:This study was a secondary analysis of the data from a series of N-of-1 trials examining the efficacy of high-dose versus low-dose NiuHuangJiangYa capsule for hypertension.Hierarchical Bayesian models were used to aggregate these N-of-1 trials for estimating the population and individual treatment effects synchronously.Results:It showed that overall population estimates of the posterior mean difference in Systolic Blood Pressure reduction,Diastolic Blood Pressure reduction,and traditional Chinese medicine symptom score reduction were 3.18 mmHg(95%CIs:-4.69 to 9.04,posterior probability(>0):83.33%),0.8636 mmHg(95%CIs:-5.19 to 6.79,posterior probability(>0):63.38%),and 0.8384(95%CIs:-2.21 to 3.84,posterior probability(>0):77.05%)respectively.Individual posterior mean difference ranged from 1.237 to 5.628 with posterior probability(>0)ranging from 63.63%to 92.95%in Systolic Blood Pressure reduction,-0.714 to 3.423 with posterior probability(>0)ranging from 43.03%to 84.04%in Diastolic Blood Pressure reduction,and-0.5179 to 2.733 with posterior probability(>0)ranging from 27.02%to 97.73%in traditional Chinese medicine symptom score reduction.Conclusion:The efficacy of high-dose versus low-dose NiuHuangJiangYa capsule for hypertension may be various across patients.Further studies are warranted to investigate these findings.Moreover,Bayesian N-of-1 trial may be helpful to explore the optimal and personalized dosage of anti-hypertensive drugs.

食品微波加热杀菌动力学描述模型的选择

该文基于微波加热在不同温度条件下的大肠杆菌和金黄色葡萄球菌菌数减少的对数周期变化,选取SWeibull、Slogistic和Dose-response 3种数学模型来拟合微波杀菌的动力学过程,以精确因子、偏差因子、均方差和决定系数作为模型拟合度优劣的评判指标。数据分析结果表明,Slogistic模型的拟合度较其他两个模型的拟合度更好,更适于描述微波加热杀菌的动力学过程。

Evaluation of Cytogenetic Effects of Isoproturon on the Root Meristem Cells of Allium sativum

Objective\ To validate the use of Allium sativum as a reliable test model for genotoxicity, isoproturon, a substituted phenylalkylurea herbicide, was evaluated on the root meristem cells by this plant system. Method\ Test concentrations were selected by determining EC50 and root tips were exposed to various concentrations for 6 or 24 hr. EC50 concentration was calculated to be 70.8 ppm for the root growth. In addition to root growth retardation exposure to isoproturon induced morpholoogical changes like discolouration and stiffness of roots. Results\ Exposure to various experimental concentrations of isoproturon (35-280 ppm), including EC50, significantly and dose-dependently inhibited the mitotic index and induced chromosome breaks/mitotic aberrations at 6 or 24 hr. Conclusion\ The frequency of aberrations was found to be decreased in a dose dependant manner at 24 or 48 hr post exposure, however in comparison of control cells the frequency of aberrations was considerably high which indicates genotoxicity potentials of isoproturon. Further, present study also suggests that Allium sativum is a sensitive, efficient, and reliable test system for measuring the genotoxicity potential of environmental chemicals.

Toxicity threshold of lead(Pb) to nitrifying microorganisms in soils determined by substrate-induced nitrification assay and prediction model

Lead （Pb） contamination has often been recorded in Chinese field soils. In recent years, efforts have been made to inves- tigate Pb toxicity thresholds in soils with plant growth and microbial assays. However, the influence of soil properties on Pb toxicity impacts on soil microbial processes is poorly understood. In this study ten soils with different properties were collected in China to investigate the relationships between thresholds of Pb toxicity to soil microbes and soil properties. The effect of soil leaching on Pb toxicity was also investigated to determine the possible influence of added anions on Pb toxicity during dose-response tests. Toxicity was inferred by measuring substrate-induced nitrification in leached and non-leached soils after Pb addition. We found that soil microbe Pb toxicity thresholds （ECx, x=10, 50） differed significantly between the soils; the 10% inhibition ratio values （ECI0） ranged from 86 to 218 mg kg-1 in non-leached soils and from 101 to 313 mg kg in leached soils. The 50% inhibition ratio values （EC50） ranged from 403 to 969 mg kg^-1 in non-leached soils and from 494 to 1 603 mg kg^-1 in leached soils. Soil leaching increased EC50 and EC50 values by an average leaching factor （LF） of 1.46 and 1.33, respectively. Stepwise multiple regression models predicting Pb toxicity to soil microbes were developed based on ECx and soil properties. Based on these models, soil pH and organic carbon are the most important soil properties af- fecting Pb toxicity thresholds （R2〉0.60）. The quantitative relationship between Pb toxicity and soil properties will be helpful for developing soil-specific guidance on Pb toxicity thresholds in Chinese field soils.