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The increasing availability of portable air pollution monitoring devices has greatly enhanced the ability to measure personal exposures in real time. However, these devices vary considerably in their cost and specifications, and questions remain as to their reliability and practicality for use in epidemiological investigations. In this field study, three personal PM(2.5) exposure monitors (two nephelometers, one optical particle counter) were compared in an urban setting to assess their feasibility for use in future studies. In total, 3963 1-min measurements were collected over 12 days from locations of several types (e.g., above and below-ground subway stations, sidewalks next to urban traffic, outdoor construction sites) in the Washington, D.C. metropolitan area. Overall, we observed moderate-to-high agreement in pairwise comparisons of PM(2.5) concentrations between devices (R(2) range: 0.37 to 0.75). Bland-Altman plots showed that differences in device agreement varied over the range of mean concentrations. In linear mixed models adjusting for temperature and relative humidity, we saw significant interaction between device and location (p

Meta-analysis, a statistical procedure that compares, combines, and synthesizes research findings from multiple studies in a principled manner, has become popular in a variety of fields. Meta-analyses using study-level (or equivalently aggregate) data are of particular interest due to data availability and modeling flexibility. In this paper, we describe an R package metapack that introduces a unified formula interface for both meta-analysis and network meta-analysis. The user interface—and therefore the package—allows flexible variance-covariance modeling for multivariate meta-analysis models and univariate network meta-analysis models. Complicated computing for these models has prevented their widespread adoption. The package also provides functions to generate relevant plots and perform statistical inferences like model assessments. Use cases are demonstrated using two real data sets contained in metapack.

SummaryIn this discussion, we examine the contributions of Qian et al. (2021) and potential applications of the newly developed estimator for the causal excursion effect in binary outcome data. Specifically, we consider extension of their method to count outcomes and observational data, propose an alternative use of their method for analysing excursion effect trajectories and discuss ways of improving estimator efficiency.

Network meta-analysis (NMA) is gaining popularity in evidence synthesis and network meta-regression (NMR) allows us to incorporate potentially important covariates into network meta-analysis. In this paper, we propose a Bayesian network meta-regression hierarchical model and assume a general multivariate t distribution for the random treatment effects. The multivariate t distribution is desired for heavy-tailed random effects and converges to the multivariate normal distribution when the degrees of freedom go to infinity. Moreover, in NMA, some treatments are compared only in a single study. To overcome such sparsity, we propose a log-linear regression model for the variances of the random effects and incorporate aggregate covariates into modeling the variance components. We develop a Markov chain Monte Carlo sampling algorithm to sample from the posterior distribution via the collapsed Gibbs technique. We further use the Deviance Information Criterion (DIC) and the logarithm of the Pseudo-marginal likelihood (LPML) for model comparison. A simulation study is conducted and a detailed analysis from our motivating case study is carried out to further demonstrate the proposed methodology.

A flexible class of multivariate meta-regression models are proposed for Individual Patient Data (IPD). The methodology is well motivated from 26 pivotal Merck clinical trials that compare statins (cholesterol lowering drugs) in combination with ezetimibe and statins alone on treatment-naïve patients and those continuing on statins at baseline. The research goal is to jointly analyze the multivariate outcomes, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG). These three continuous outcome measures are correlated and shed much light on a subject’s lipid status. The proposed multivariate meta-regression models allow for different skewness parameters and different degrees of freedom for the multivariate outcomes from different trials under a general class of skew t-distributions. The theoretical properties of the proposed models are examined and an efficient Markov chain Monte Carlo (MCMC) sampling algorithm is developed for carrying out Bayesian inference under the proposed multivariate meta-regression model. In addition, the Conditional Predictive Ordinates (CPOs) are computed via an efficient Monte Carlo method. Consequently, the logarithm of the pseudo marginal likelihood and Bayesian residuals are obtained for model comparison and assessment, respectively. A detailed analysis of the IPD meta data from the 26 Merck clinical trials is carried out to demonstrate the usefulness of the proposed methodology.

Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r2 = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections.

Human exposure to persistent environmental pollutants often results in concentrations with a range of values below the laboratory detection limits. Growing evidence suggests that inadequate handling of concentrations below the limit of detection (LOD) may bias assessment of health effects in relation to environmental exposures. We seek to quantify such bias in models focusing on the day-specific probability of pregnancy during the fertile window and propose a model-based approach to reduce such bias. A multivariate skewed generalized t-distribution constrained by the LOD is assumed for the chemical concentrations, which realistically represents the underlying distribution. A latent variable-based framework is used to model fecundibility, which nonlinearly relates conception probability to chemical concentrations, daily intercourses, and other important covariates. The advantages of the proposed approach include the use of multiple chemical concentrations to aid the estimation of left censored chemical exposures, as well as the model-based feedback mechanism for fecundibility outcome to inform the estimations, and an adequate handling of model uncertainty through a joint modeling framework. A Markov chain Monte Carlo sampling algorithm is developed for implementing the Bayesian computations and the logarithm of pseudo-marginal likelihood measure is used for model choices. We conduct simulation studies to demonstrate the performance of the proposed approach and apply the framework to the Longitudinal Investigation of Fertility and the Environment study which evaluates the effects of exposures to environmental pollutants on the probability of pregnancy. We found that p,p'-DDT is negatively associated with the day-specific probability of pregnancy.

Background: Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices. Methods: MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons. Results: Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia (P < 0.004). Conclusions: MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results. Impact: MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.

Summary Background The timepoint at which fetal growth begins to differ by maternal glycaemic status is not well understood. To address this lack of data, we examined gestational diabetes, impaired glucose tolerance, and early pregnancy glucose concentrations in relation to fetal growth trajectories. Methods This cohort study included 2458 pregnant women from the NICHD Fetal Growth Studies-Singletons study, which took place between 2009 and 2013. Women were recruited from 12 clinical centres in the USA. Women aged 18–40 years without major chronic conditions when entering pregnancy were included and those with records of neither glucose screening test or glucose tolerance test were excluded from the study. Women were enrolled at gestational weeks 8–13 and randomly assigned to four ultrasonogram schedules (Group A; weeks 16, 24, 30, 34; Group B: weeks 18, 26, 31, 35, 39; Group C: weeks 20, 28, 32, 36; Group D: weeks 22, 29, 33, 37, 41) to capture weekly fetal growth. Gestational diabetes, impaired glucose tolerance, and normal glucose tolerance were defined by medical record review. Glucose was measured in a subsample of women at weeks 10–14. We modelled fetal growth trajectories using linear mixed models with cubic splines. This study is registered with ClinicalTrials.gov , NCT00912132 . Findings Of the 2458 women included in this study, 107 (4·4%) had gestational diabetes, 118 (4·8%) had impaired glucose tolerance, and 2020 (82·2%) had NGT. 213 women were excluded from the main analysis. The cohort with gestational diabetes was associated with a larger estimated fetal weight that started at week 20 and was significant at week 28–40 (at week 37: 3061 g [95% CI 2967–3164] for women with gestational diabetes vs 2943 g [2924–2962] for women with normal glucose tolerance, adjusted p=0·02). In addition, glucose levels at weeks 10–14 were positively associated with estimated fetal weight starting at week 23 and the association became significant at week 27 (at week 37: 3073 g [2983–3167] in the highest tertile vs 2853 g [2755–2955] in the lowest tertile, adjusted p=0·0009. Interpretation Gestational diabetes was associated with a larger fetal size that started at week 20 and became significant at gestational week 28. Efforts to mitigate gestational diabetes-related fetal overgrowth should start before 24–28 gestational weeks, when gestational diabetes is typically screened for in the USA. Funding National Institutes of Health.

Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with impaired clearance of hepatitis C virus (HCV) infection. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we analyzed episodes of malaria, gastrointestinal and respiratory infections using information for 30,626 clinic visits from birth through up to 5 years of follow-up. Genetic polymorphisms IFNL4-rs368234815 and IFNL3-rs4803217 that functionally affect type III interferons were genotyped with TaqMan assays. For both genetic variants and each infection, we evaluated time-to-first episode and calculated odds ratios (ORs) for the risk of an infection episode during follow-up, controlling for relevant covariates. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), each copy of the rs368234815-dG allele was associated with an earlier first episode of a gastrointestinal infection (p=0.003) and respiratory infection (p=0.045). The risk of experiencing an infection episode during the follow-up was also significantly increased with each copy of the rs368234815-dG allele – for gastrointestinal infections (OR=1.53, 95%CI (1.13-2.07), p=0.005) and malaria (OR=1.30, 95%CI (1.02-1.65), p=0.033). IFNL4-rs368234815 and IFNL3-rs4803217 were in moderate linkage disequilibrium in this population (r2=0.78), and all the associations for rs4803217 were weaker and lost significance after adjusting for rs368234815, implicating IFN-λ4 and not IFN-λ3 as the primary cause of these associations. We conclude that the ability to produce IFN-λ4 may have broad health-related implications by negatively affecting the immune response and clinical outcomes of several common infections.

Background: Genetic polymorphisms within the IFNL3 / IFNL4 genomic region, which encodes type III interferons, have been strongly associated with impaired clearance of hepatitis C virus (HCV) infection. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. Methods: In a cohort of 914 Malian children, we analyzed episodes of malaria, gastrointestinal and respiratory infections using information for 30,626 clinic visits from birth through 1-5 years of follow-up. Genetic polymorphisms IFNL4 -rs368234815 and IFNL3-rs4803217 that functionally affect type III interferons were genotyped with TaqMan assays. For both genetic variants and each infection, we evaluated time-to-first episode and calculated odds ratios (ORs) for the risk of an infection episode during follow-up. Results: Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), each copy of the rs368234815-dG allele was associated with an earlier first episode of a gastrointestinal infection (p=0.003) and respiratory infection (p=0.045). The risk of experiencing an infection episode during the follow-up was also significantly increased with each copy of the rs368234815-dG allele – for gastrointestinal infections (OR=1.53, 95%CI (1.13-2.07), p=0.005) and malaria (OR=1.30, 95%CI (1.02-1.65), p=0.033). IFNL4 -rs368234815 and IFNL3 -rs4803217 were in moderate linkage disequilibrium in this population (r2 =0.78), and all the associations for rs4803217 were weaker and lost significance after adjusting for rs368234815, implicating IFN-λ4 and not IFN-λ3 as the primary cause of these associations. Interpretation: Our results provide support for the role of IFN-λ4 in common gastrointestinal infections, and possibly in other infections as well. Trial Registration: NCT01168271 Funding Statement: The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), the Intramural Research Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, US Department of Health and Human Services. Declaration of Interests: L.P.-O. is a co-inventor on IFN-λ4-related patents issued to NCI/NIH, and receives royalties for monoclonal antibodies for IFN-λ4 detection. Other authors have no conflict of interest to declare. Ethics Approval Statement: The protocol and study procedures were approved by the institutional review board of the National Institute of Allergy and Infectious Diseases (NIAID) at the US National Institutes of Health (ClinicalTrials.gov ID NCT01168271), and the Ethics Committee of the Faculty of Medicine, Pharmacy and Dentistry at the University of Bamako, Mali.

In analysis of diagnostic data with multiple tests, it is often the case that these tests are correlated. Modeling the correlation explicitly not only produces valid inference results but also enables borrowing of information. Motivated by the Physician Reliability Study (PRS) that investigated the diagnostic performance of physicians in diagnosing endometriosis, we construct a correlated modeling framework to estimate ROC curves and the associated area under the curves. This correlated approach is quite appealing for the PRS data set that suffers from the problem of small sample sizes, as it enables information borrowing between physician groups and sessions. Given that the test scores appear to be non-normal even after logarithm transformation, we use the ranks of the data to conduct likelihood estimation and inference. We use the deviance information criterion to select competing models and conduct simulation studies to assess model performances. In application to the PRS data set, we found that the physicians are not significantly different in their diagnostic performance between groups; however, they are different between the sessions. This suggests that clinical information may play a more important role in physicians' diagnostic performance than their experiences. Our empirical evidence also demonstrates that when using both woman- and physician-specific random effects, the model parameter estimates are much smoother.

Many researchers in biology and medicine have focused on trying to understand biological rhythms and their potential impact on disease. A common biological rhythm is circadian, where the cycle repeats itself every 24 hours. However, a disturbance of the circadian pattern may be indicative of future disease. In this article, we develop new statistical methodology for assessing the degree of disturbance or irregularity in a circadian pattern for count sequences that are observed over time in a population of individuals. We develop a latent variable Poisson modeling approach with both circadian and stochastic short-term trend (autoregressive latent process) components that allow for individual variation in the degree of each component. A parameterization is proposed for modeling covariate dependence on the proportion of these two model components across individuals. In addition, we incorporate covariate dependence in the overall mean, the magnitude of the trend, and the phase-shift of the circadian pattern. Innovative Markov chain Monte Carlo sampling is used to carry out Bayesian posterior computation. Several variations of the proposed models are considered and compared using the deviance information criterion. We illustrate this methodology with longitudinal physical activity count data measured in a longitudinal cohort of adolescents.

Jun, K.; Jun, B.-H.; Lee, H.; Kim, S., and Tak, W., 2018. The study of utilization and precision based on the comparison and analysis of drone-based coastal hazard data and its application in the ocean environment. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 811–815. Coconut Creek (Florida), ISSN 0749-0208. As more economic activities are developing along the coast, many studies are performed within the area concerning biological, social, economic factors closely linked to human activities. As coastal hazards occur in various categories, consistent monitoring would establish effective countermeasures and management of the coastal hazard region. Many surveys concerning seashore disasters exist already, like the bathymetric survey, beach profile survey, and shoreline survey. However, some of their disadvantages include high price, the use of equipme...

Kim, S.; Lee, H.; Jun, K., and Jun, B.-H., 2018. The monitoring of topography change in the estuary of the Korean east coast using LiDAR. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 46–50. Coconut Creek (Florida), ISSN 0749-0208. Recently, due to abnormal climates caused by climate changes, important shorelines found in the east coast of Korea are facing many topographical changes. Especially within the estuary regions that meet the rivers, complex phenomenon due to artificial causes like topographical and stream character changes are occurring. In this study, GPS with RTK (Real Time Kinematic) application and above ground LiDAR (Light Detection And Ranging) were used to observe and the changing typography by season of Gagok River estuary region located in the east coast of Korea. Also the changes in water discharge from the Gagok River were measu...

Lee. H.; Kim, S., and Jun, K., 2018. The study for storm surge prediction using generalized regression neural networks. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 781–785. Coconut Creek (Florida), ISSN 0749-0208.Although the dangers of storm surge have recently garnered increasing awareness, studies on storm surge height predictions in accordance with regional characteristics are quite insufficient. However, accurate and prompt storm surge height prediction is necessary to promptly respond to disaster caused by storm surge. Currently, most storm surge height prediction figures are obtained from numerical modelling technique-based study, which has a number of analytical limitations. For example various meteorological data and complex physical factor analysis are lacking. Therefore, the Generalized Regression Neural Network(GRNN) is applied in this study in order to create a storm surge height prediction model through simplified data input and hidden layer and output layer. When the established GRNN was applied to the Tongyeong and Yeosu area, the obtained values were very similar to the actual surveyed data. When the model was applied to ungauged areas, the tendency of storm surge height was identified.

Summary Low-density lipoprotein cholesterol (LDL-C) has been identified as a causative factor for atherosclerosis and related coronary heart disease, and as the main target for cholesterol- and lipid-lowering therapy. Statin drugs inhibit cholesterol synthesis in the liver and are typically the first line of therapy to lower elevated levels of LDL-C. On the other hand, a different drug, Ezetimibe, inhibits the absorption of cholesterol by the small intestine and provides a different mechanism of action. Many clinical trials have been carried out on safety and efficacy evaluation of cholesterol lowering drugs. To synthesize the results from different clinical trials, we examine treatment level (aggregate) network meta-data from 29 double-blind, randomized, active, or placebo-controlled statins +/$-$ Ezetimibe clinical trials on adult treatment-naïve patients with primary hypercholesterolemia. In this article, we propose a new approach to carry out Bayesian inference for arm-based network meta-regression. Specifically, we develop a new strategy of grouping the variances of random effects, in which we first formulate possible sets of the groups of the treatments based on their clinical mechanisms of action and then use Bayesian model comparison criteria to select the best set of groups. The proposed approach is especially useful when some treatment arms are involved in only a single trial. In addition, a Markov chain Monte Carlo sampling algorithm is developed to carry out the posterior computations. In particular, the correlation matrix is generated from its full conditional distribution via partial correlations. The proposed methodology is further applied to analyze the network meta-data from 29 trials with 11 treatment arms.

Antimicrobials including parabens, triclosan, and triclocarban have endocrine disrupting properties. Among 501 male partners of couples planning to become pregnant, preconception urinary biomarkers of parabens, triclosan and triclocarban exposure were quantified in spot urine samples. Men also provided two fresh semen samples collected approximately one month to undergo 24-hour semen quality analysis. Linear mixed-effects models, adjusted for creatinine, race, age and body mass index, were utilized to assess the relationship between log transformed chemical concentrations rescaled by their standard deviations and semen parameters. Methyl, ethyl and butyl parabens, were associated with diminished sperm count and several sperm motility parameters. Hydroxylated paraben metabolites and triclosan were significantly positively associated with select semen quality parameters. Overall, our findings suggest that specific urinary parabens found in consumer goods (methyl, ethyl and butyl parabens) may adversely impact sperm quality parameters among reproductive-age male partners of couples trying for pregnancy.

Objective This article aims to determine if the number of maternal ultrasound scans where the highest thermal (TI) or mechanical (MI) indices recorded during obstetrical ultrasound exceed 1.0 were associated with neonatal anthropometric measurements. Study Design A prospective cohort of 2,334 nonobese low-risk pregnant women from 12 U.S. clinical sites underwent a total of six ultrasound scans, for which the highest TI and MI values were recorded. Neonatal anthropometric measurements were obtained within 12 to 24 hours of delivery. Multiple linear regression models adjusted for maternal race/ethnicity, body mass index, weight gain, and gestational age were used to examine associations between the number of maternal ultrasounds during gestation with a TI or MI exceeding 1.0 and the mean change in neonatal anthropometry. Results Ultrasounds with TI or MI >1.0 were not associated with birth weight, neonatal length, nor head, chest, and abdominal circumferences. TI >1.0 was negatively associated with neonatal mid-upper arm and mid-upper thigh circumferences. MI >1.0 was negatively associated with neonatal skinfold measurements of the anterior thigh and triceps, and neonatal circumferences of the mid-upper thigh and umbilicus. Conclusion Prenatal ultrasound examinations in which TI or MI intermittently exceeded 1.0 did not identify a pattern of alterations of birth size.

Objectives To evaluate the frequency with which gestational weight gain and estimated fetal weight do not track across gestation and to assess the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) birth weight as a function of tracking. Methods This study included a pregnancy cohort (2009–2013) of 2438 women from 4 racial/ethnic groups in the United States. We calculated race- and trimester-specific gestational weight gain and estimated fetal weight z scores. The prevalence of how often gestational weight gain and estimated fetal weight did not or did directly track was examined by grouping z scores into measure-specific categories ( 1 SD) and then examining 2-measure combinations. Trimester-specific relative risks for SGA and LGA births were estimated with a gestational weight gain and estimated fetal weight z score interaction. We estimated coefficients for selected gestational weight gain and estimated fetal weight values (–1 SD, 0 SD, and +1 SD) compared with the referent of 0 SD for both measures. Small and large for gestational age were calculated as birth weight below the 10th and at or above the 90th percentiles, respectively. Results Gestational weight gain and estimated fetal weight were within 1 SD 55.5%, 51.5%, and 48.2% of the time in the first, second, and third trimesters, respectively. There was no significant interaction between gestational weight gain and estimated fetal weight on the risk of SGA in the first and second trimesters (interaction term P = .48; P = .79). In the third trimester, there was a significant interaction (P = .002), resulting in a 71% (95% confidence interval, 1.45–2.02) increased risk of SGA when estimated fetal weight was low and gestational weight gain was high. These relationships were similar for the risk of LGA. Conclusions Deviations in either measure, even in the presence of average gestational weight gain or estimated fetal weight, still suggest an increased risk of SGA and LGA.

The endocrine-disrupting properties of paracetamol have been previously demonstrated in rodent studies of abnormal sperm morphology and diminished testosterone production, in addition to epidemiologic studies of diminished couple fecundity. In this study, we examined the relationship between paracetamol and its metabolite p-aminophenol quantified in a single spot urine and semen quality among 501 male partners of couples planning for pregnancy. Men provided a urine specimen and two fresh semen samples collected approximately one month apart and underwent 24-h analysis for 35 semen quality parameters. Paracetamol and p-aminophenol were quantified in urine by ultra-high-performance liquid chromatography coupled with an electrospray triple quadrupole mass spectrometry. The relationship between natural-log-transformed urinary paracetamol and p-aminophenol rescaled by their standard deviation and 21 Box-Cox-transformed, 14 non-transformed semen parameters was assessed using linear mixed-effects models. The median concentrations (IQR) of urinary paracetamol and p-aminophenol were 15.5 ng/mL (5.44, 73.5) and 978 ng/mL (500, 1596), respectively. Following adjustment for creatinine and age, a 1-standard deviation increase in log-transformed urinary paracetamol was associated with a reduction in beat cross-frequency and an increase in DNA fragmentation [β (95% CI): -0.59 Hz (-1.16, -0.03) and 0.05% (0.01, 0.09), respectively]. These findings were corroborated in models of categorical chemical concentrations; higher concentrations of paracetamol remained associated with reduced beat cross-frequency and increased DNA fragmentation. A 1-standard deviation increase in log-transformed urinary p-aminophenol was associated with a reduction in sperm head area [β (95% CI): -0.1 μm2 (-0.18, -0.02) and width -0.02 μm (-0.04, -0.01)]. However, only the association with sperm head area remained statistically significant in models of p-aminophenol quartiles. Our findings suggest that adult male urinary paracetamol is associated with sperm motility and DNA fragmentation, while the metabolite, p-aminophenol, is predominantly associated with sperm head morphometry.

Objectives To determine whether longitudinal fetal growth is altered among pregnant women reporting greater perceived stress or more symptoms of depression. Methods This analysis was based on a multicenter longitudinal study of fetal growth. Women were screened at gestational ages of 8 weeks to 13 weeks 6 days for low-risk status and underwent serial sonographic examinations. At each study visit during pregnancy, women were asked to complete the Cohen Perceived Stress Scale (PSS) and Edinburgh Postpartum Depression Survey (EPDS). Growth curves for estimated fetal weight and individual biometric parameters were created by using linear mixed models with cubic splines and compared on the basis of whether women scored 15 or higher on the PSS or 10 or higher on the EPDS either at the start of or at any time during pregnancy. Results Of the 2334 women enrolled in the study, 2088 (89%) and 2108 (90%) completed the PSS and EPDS, respectively, at least once in all trimesters. The longitudinal growth curves of estimated fetal weight as well as all individual biometric parameters were similar (P > .05) regardless of whether the participants reported PSS of 15 or higher or EPDS of 10 or higher in the first trimester or whether these scores persisted throughout the pregnancy. Similarly, effect modification by race/ethnicity was not statistically significant for the biometric parameters under study (P > .05 for all race/ethnicity interactions). Conclusions More depressive symptoms and greater perceived stress, as quantified by the EPDS and the PSS, respectively, are not associated with alterations in fetal growth throughout gestation.

The joint modeling of longitudinal and time-to-event data is an active area in biostatistics research. The focus of this article is on developing a modeling framework for these joint models when the longitudinal and time-to-event data do not have a meaningful time-zero. The motivating example is the study of a longitudinal assessment of station during child labor and it’s relationship to time-to-delivery. A good predictor of delivery type and timing would help obstetricians better manage the end of pregnancy and better facilitate delivery. One measure of labor progression is station, a measure of the position of the fetus’ head in relation to the pelvis of the pregnant women, may be a good marker for delivery time and type. However, women enter the hospital, where their station is closely monitored, at arbitrary points in their labor process, resulting in no clear time zero. In addition, since delivery may be of various types, the competing risks due to type need to be accounted for. We develop a joint model of longitudinal and time-to-event data for this situation. The model is formulated through shared random effects between the survival and longitudinal processes, and parameter estimation is conducted through a Bayesian approach. The model is illustrated with longitudinal data on station where the relationship between station and event-time is studied and the model is used to assess the ability of longitudinal measures of station to predict the type and timing of pregnancy. We illustrate the methodology with longitudinal data taken during labor.

OBJECTIVES: Gestational diabetes (GDM) is associated with increased risk for large-for-gestational-age birth. Yet, longitudinal fetal growth trajectories in women with GDM and the timing of alterations related to GDM is not well understood, particularly in early pregnancy. This study aims to investigate these critical data gaps. METHODS: The NICHD Fetal Growth Studies–Singleton Cohort enrolled women at 8w0d to 13w6d gestation from 12 U.S. clinical centers and randomized them among four ultrasonology schedules for longitudinal fetal measurement. Fetal biparietal diameter, head circumference (HC), abdominal circumference (AC), femurs length and humerus length were measured. Estimated fetal weight (EFW) was calculated using the Hadlock formula. GDM was defined using the Carpenter-Coustan Criteria, impaired glucose tolerance (IGT) was defined as 2-hour plasma glucose in the 75 g or 100 g oral glucose tolerance test (OGTT) 140–199 mg/dL, and normal glucose tolerance (NGT) was defined by no elevated values on either the OGTT or 50 g glucose challenge test. The fetal growth trajectories were modeled using linear mixed models with cubic spline adjusting for race, age, parity, pre-pregnancy BMI and infant sex. RESULTS: One hundred and seven women developed GDM, 118 developed IGT, and 2,020 had NGT. Most fetal growth measures were larger at 10–12 weeks and became smaller at 14–16 weeks in GDM than NGT group. At 28 weeks, AC and EFW became larger in GDM group, and the differences persisted through 40 weeks (at 40 weeks: AC: 368 vs. 355 mm, P = 0.03; EFW: 3866 vs. 3558 g, P = 0.003). The HC to AC ratio was smaller in GDM group 19–36 weeks. The associations were modified by the family history of diabetes (p-interaction

Background: Alcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver. Methods: A cohort of patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model. Findings: Obesity was common amongst patients with AH, seen in 19% of individuals. cBMI correlated with volume AT (r2= 0.623, p

The circadian system influences virtually all biological functions. Understanding the impact of circadian variation on metabolism may provide insight into mechanisms of circadian-associated disorders and guide the implementation of chrono-therapy. Previous research has reported circadian variation in 7-20% of metabolites in human blood. In this study, untargeted metabolomics profiles were measured using blood of two healthy men and one healthy woman, collected every two hours for up to 48 hours under carefully controlled conditions. The pattern of variation of each metabolite over time was examined on each participant separately, using both one- and two-order harmonic models. One hundred of 663 metabolites, representing all metabolite categories, showed diurnal rhythmic concentrations that exceeded the Bonferroni threshold (P

Background Amniotic fluid is essential to normal fetal development and is estimated clinically with ultrasound scanning to identify pregnancies that are at risk for poor perinatal outcome. Objective Our goal was to develop a United States standard for amniotic fluid volume that is estimated by the amniotic fluid index and single deepest pocket. Study Design We performed a planned secondary analysis of a multicenter observational study of 2334 low-risk women with normal singleton gestations from 1 of 4 self-reported racial/ethnic groups. Eligible women had confirmed first-trimester dating criteria with health status, lifestyles, and medical and obstetric histories that were associated with normal fetal growth. Consenting women underwent serial (up to 5) sonographic evaluations of amniotic fluid between 15 and 40 weeks of gestation after being assigned randomly to 1 of 4 gestational age observation schedules. Twelve United States perinatal centers participated, and all sonograms were performed by credentialed sonographers who used identical, high-resolution equipment; caregivers were unaware of results but were notified for oligohydramnios. Women (n=597) who were subsequently found to have clinically significant antepartum complications were excluded. Racial/ethnic–specific nomograms for amniotic fluid index and single deepest pocket across gestation were developed with the use of linear mixed models with cubic splines; racial/ethnic differences were evaluated both with global and between-group tests. Median, 3rd, 5th, 10th, 90th, 95th and 97th percentile values were also estimated. We further considered the possible confounding effects of selected maternal characteristics and the estimated fetal weight at each sonogram. Results A total of 1719 pregnant women met inclusion criteria and had available data. These included 480 non-Hispanic white women, 418 non-Hispanic black women, 485 Hispanic women, and 336 Asian women. Both the amniotic fluid index and the single deepest pocket varied across gestation with maximal values at 26 and 33 weeks of gestation, respectively. Statistically significant differences were observed by maternal race/ethnicity. The between-group differences that were observed at 17–22 and 35–40 weeks of gestation remained statistically significant after adjustment for maternal characteristics and estimated fetal weight. These between-group racial/ethnic differences were most prominent after 35 weeks of gestation and at the extremes of dispersion (3rd and 97th percentiles). All 3rd and 97th percentile amniotic fluid index values were within the range of commonly used cutoffs to define oligohydramnios (≤5 cm) and polyhydramnios (≥25 cm). However, the 3rd percentile values ranged between 5.9 cm at 40 weeks of gestation and 10.1 cm at 25–27 weeks of gestation; the 97th percentile values ranged between 24.8 cm at 38 weeks of gestation and 15.7 cm at 15 weeks of gestation. Conclusion Sonographic amniotic fluid volume estimates vary by racial/ethnic group, but the absolute differences appear to be small and may not be clinically significant. Selected maternal characteristics and estimated fetal weight did not affect the racial/ethnic differences. Between-group differences are maximal after 35 weeks of gestation and at the extremes of the upper and lower dispersion estimates. Given the observed variability in extreme (3rd and 97th percentile) dispersion values over the gestation, use of single cutoffs to define out-of-range measurements may not be appropriate clinically. These data might form a contemporary United States standard for amniotic fluid estimation that uses the amniotic fluid index and the single deepest pocket.

Objectives To report on the ultrasound quality assurance program for the National Institute of Child Health and Human Development Fetal Growth Studies and describe both its advantages and generalizability. Methods After training on an ultrasound system and software, research sonographers were expected to capture blank (unmeasured) images in triplicate for crown-rump length, biparietal diameter, head circumference, abdominal circumference, and femur length. A primary expert sonographer was designated and validated. A 5% sample (n = 740 of 14,785 scans) was randomly selected in 3 distinct rounds from within strata of maternal body mass index (round 1 only), gestational age, and research site. Unmeasured images were extracted from selected scans and measured with the ultrasound software by an expert sonographer. Correlations and coefficients of variation (CVs) were calculated, and the within-measurement standard deviation (ie, technical error of the measurement), was calculated. Results The reliability between the site sonographers and the expert was high, with correlations exceeding 0.99 for all dimensions in all rounds. The CV % values showed low variability, with the percentage differences being less than 2%, except for abdominal circumference in rounds 2 and 3, in which it averaged about 3%. Correlations remained high (>0.90) with increasing fetal size; there was a monotonic increase in technical errors of the measurement but without a corresponding increase in the CV %. Conclusions Using rigorous procedures for training sonographers, coupled with quality assurance oversight, we determined that the measurements acquired longitudinally for singletons are both accurate and reliable for establishment of an ultrasound standard for fetal growth.

Summary Published findings from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study regarding the relation between environmental chemicals and couple fecundity, as measured by time-to-pregnancy (TTP), are reviewed with a particular focus on role of the male partner. The LIFE Study recruited 501 couples from 16 counties in two U.S. states upon discontinuing contraception for purposes of becoming pregnant. Upon enrollment, couples provided a blood and urine sample for the quantification of persistent and non-persistent environmental chemicals, respectively, and then completed daily journals until pregnant or up to one year of trying. Female partners used fertility monitors to aid the timing of intercourse relative to ovulation, and digital home pregnancy test kits on the day of expected menses. Chemical classes included: metals, persistent organic pollutants, environmental phenols, and phthalates that were quantified using inductively coupled plasma mass spectrometry or isotope dilution high-resolution or tandem mass spectrometry. Time-to-pregnancy (TTP) was defined as the number of prospectively observed menstrual cycles required for pregnancy. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for each chemical and partner after adjusting for potential confounders and accounting for right censoring and time off contraception. FORs

Lee, H.; Kim, S.; Jun, K.W.; Park, H.K., and Park, J.S., 2016. The Effects of Groundwater Pumping and Infiltration on Seawater Intrusion in Coastal Aquifer. In: Vila-Concejo, A.; Bruce, E.; Kennedy, D.M., and McCarroll, R.J. (eds.), Proceedings of the 14th International Coastal Symposium (Sydney, Australia). Journal of Coastal Research, Special Issue, No. 75, pp. 652–656. Coconut Creek (Florida), ISSN 0749-0208. The purpose of this study is to identify the characteristics of seawater intrusion; an examination was carried out of the impacts of groundwater pumping and infiltration by precipitation on the seawater intrusion in coastal aquifers. To simulate seawater intrusion, three layers (layers 1, 2 and 3) were identified based on a drilling log. The infiltration rate of 30 years of rainfall data was calculated as 26.43%. The change of salt concentration was simulated using the FEMWATER model by considering the infiltration rate and assuming the pumping rate as 185m3/day for 300 days. The proporti...

Kim, S.;Lee, H., and Jun, K.W., 2016. The impacts of debris torrents in Caribbean coast of Honduras, Central America. In: Vila-Concejo, A.; Bruce, E.; Kennedy, D.M., and McCarroll, R.J. (eds.), Proceedings of the 14th International Coastal Symposium (Sydney, Australia). Journal of Coastal Research, Special Issue, No. 75, pp. 1347–1351. Coconut Creek (Florida), ISSN 0749-0208. One of the main contributing factors in creating debris torrents is heavy rainfall. Global climate changes have led to an increase in localized downpours, causing an increase in torrent occurrences as well. The purpose of this experiment is to utilize numerical simulation for the analysis of debris torrents in their behaviour and mechanism. The numerical simulation is comprised of equations calculating mass continuity and momentum in order to consider erosion, deposition, and the combination of them both. The Finite Difference Method is applied to analyze the debris torrents. The numerical model of present study was applied ...

Lee, H.; Kim, S., and Jun, K.W., 2016. The scour depth of the submarine pipeline area on the algorithm of the Radial Basis Function. In: Vila-Concejo, A.; Bruce, E.; Kennedy, D.M., and McCarroll, R.J. (eds.), Proceedings of the 14th International Coastal Symposium (Sydney, Australia). Journal of Coastal Research, Special Issue, No. 75, pp. 1382–1386. Coconut Creek (Florida), ISSN 0749-0208. The submarine pipeline is a facility that requires frequent usage for transporting substances like crude oil or gas. Failures in the submarine pipeline can cause marine pollution and the cost to restore the induced damage can be great. Therefore, it is important to consider several impact factors that can help secure the stability of the submarine pipeline during its installment. Scour is one of the factors that cause great damage to submarine pipelines. In this study, existing experimental data from previous experiments are analyzed in order to predict scour depth and deduce the main parameters affecting scou...

Predicting binary events such as newborns with large birthweight is important for obstetricians in their attempt to reduce both maternal and fetal morbidity and mortality. Such predictions have been a challenge in obstetric practice, where longitudinal ultrasound measurements taken at multiple gestational times during pregnancy may be useful for predicting various poor pregnancy outcomes. The focus of this article is on developing a flexible class of joint models for the multivariate longitudinal ultrasound measurements that can be used for predicting a binary event at birth. A skewed multivariate random effects model is proposed for the ultrasound measurements, and the skewed generalized t-link is assumed for the link function relating the binary event and the underlying longitudinal processes. We consider a shared random effect to link the two processes together. Markov chain Monte Carlo sampling is used to carry out Bayesian posterior computation. Several variations of the proposed model are considered and compared via the deviance information criterion, the logarithm of pseudomarginal likelihood, and with a training-test set prediction paradigm. The proposed methodology is illustrated with data from the NICHD Successive Small-for-Gestational-Age Births study, a large prospective fetal growth cohort conducted in Norway and Sweden.

Tak, W.J.; Jun, K.W., Kin, S.D., and Lee, H.J., 2020. Using drone and LiDAR to assess coastal erosion and shoreline change due to the construction of coastal structures. In: Malvarez, G. and Navas, F. (eds.), Global Coastal Issues of 2020. Journal of Coastal Research, Special Issue No. 95, pp. 674-678. Coconut Creek (Florida), ISSN 0749-0208.Recently, The construction of structures on the coastal zone near estuaries, which are the supply sources of sediments, causes a variation in the waterway; this induces a change in the surrounding coasts, and the resulting coastal erosion can adversely affect the lives of the local residents. In the case of a balanced sediment flow, the quantity of the sediment deposited on the coast is equal to the quantity of the released sediment. However, an increase in either of the quantities causes an imbalance in the sediment transport; consequently, the sand is either deposited or eroded in the coastal or proximate shore regions. In this study, the changes in the shoreline and Wolcheon Beach region located on the east coast of Korea was monitored between 2010 to 2019 investigate the phenomena of coastal erosion and beach deformation. The shorelines, beach width, and beach profile were primarily monitored by employing a drone and a terrestrial LiDAR. The results showed that the sediments were transported northward in summer and southward in winter until 2010 in Wolcheon Beach; however, this seasonal sediment transport was blocked during 2011–2012 by the construction of coastal structures such as breakwaters, leading to partial coastal erosion and sedimentation. Wolcheon Beach originally had the coastal characteristics of the Korean East Coast region (2010), but the sediment transport changed due to the variations in the waterway by the construction of coastal structures, leading to a significant change in the coast (2011). In addition, the northern beach volume increased with respect to estuary, while the southern beach volume decreased. When the offshore breakwater was constructed, the northward sediment occurred dominantly in the shield area. In particular, the planar layout of the harbor facilities concentrated the waves, which increased the quantity of the northward sediment.

Organophosphates and carbamates have been among the most commonly used insecticides, with both agricultural and residential uses. Previous studies have suggested associations of non-Hodgkin lymphoma (NHL) with some of these chemicals; however, many studies have been limited in their ability to evaluate associations with lymphoma subtypes. We evaluated the use of eleven organophosphate and two carbamate insecticides in association with NHL in the North American Pooled Project, which includes data from case-control studies in the United States and Canada (1690 cases/5131 controls). We used unconditional logistic regression adjusting for potential confounders, including use of other pesticides, to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between these chemicals and NHL overall, and NHL subtypes, i.e., follicular (FL), diffuse large B-cell (DLBCL), small lymphocytic lymphoma (SLL) and others. Ever use of malathion was associated with increased risk of NHL overall (OR = 1.43; 95% CI: 1.14–1.81) compared with never users. Categories using tertiles of duration (< 4 yrs., 4–12 yrs., and > 12yrs) also showed a significant exposure-response for increasing years of use of malathion and risk of NHL (OR < 4vsUnex = 1.33 (0.88, 2.03), OR4–12vsUnex = 1.42 (1.02, 1.96), OR > 12vsUnex = 1.55 (1.05, 2.28, p-trend < 0.01)). In addition, malathion use was statistically significantly associated with FL (OR = 1.58; 95% CI: 1.11–2.27) and DLBCL (OR = 1.61; 95% CI: 1.16–2.22) while there were no apparent associations with SLL or other subtypes, the p-value for heterogeneity across subtypes, however, was not significant. These results support previous studies suggesting an association between insecticide use and NHL overall, and provide new information on associations with NHL subtypes.

Fetal growth patterns in pregnancy-associated hypertensive disorders is poorly understood because prospective longitudinal data are lacking.The objective of the study was to compare longitudinal fetal growth trajectories between normotensive women and those with pregnancy-associated hypertensive disorders.This is a study based on data from a prospective longitudinal cohort study of fetal growth performed at 12 US sites (2009-2013). Project gestational age was confirmed by ultrasound between 8 weeks 0 days and 13 weels 6 days, and up to 6 ultrasounds were performed across gestation. Hypertensive disorders were diagnosed based on 2002 American College of Obstetricians and Gynecologists guidelines and grouped hierarchically as severe preeclampsia (including eclampsia or HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome), mild preeclampsia, severe gestational hypertension, mild gestational hypertension, or unspecified hypertension. Women without any hypertensive disorder constituted the normotensive group. Growth curves for estimated fetal weight and individual biometric parameters including biparietal diameter, head circumference, abdominal circumference, and femur and humerus length were calculated for each group using linear mixed models with cubic splines. Global and weekly pairwise comparisons were performed between women with a hypertensive disorder compared with normotensive women to analyze differences while adjusting for confounding variables. Delivery gestational age and birthweights were compared among groups.Of 2462 women analyzed, 2296 (93.3%) were normotensive, 63 (2.6%) had mild gestational hypertension, 54 (2.2%) mild preeclampsia, 32 (1.3%) severe preeclampsia, and 17 (0.7%) unspecified hypertension. Compared with normotensive women, those with severe preeclampsia had estimated fetal weights that were reduced between 22 and 38 weeks (all weekly pairwise values of P.008). Women with severe preeclampsia compared with those without hypertension also had significantly smaller fetal abdominal circumference between 23-31 and 33-37 weeks' gestation (weekly pairwise values of P.04). Scattered weekly growth differences were noted on other biometric parameters between these 2 groups. The consistent differences in estimated fetal weight and abdominal circumference were not observed between women with other hypertensive disorders and those who were normotensive. Women with severe preeclampsia delivered significantly earlier (mean gestational age 35.9 ± 3.2 weeks) than the other groups (global P.0001). Birthweights in the severe preeclampsia group were also significantly lower (mean -949.5 g [95% confidence interval, -1117.7 to -781.2 g]; P.0001) than in the normotensive group.Among women with pregnancy-associated hypertensive disorders, only those destined to develop severe preeclampsia demonstrated a significant and consistent difference in fetal growth (ie, smaller estimated fetal weight and abdominal circumference) when compared with normotensive women.

OBJECTIVE To assess the relationship between first-trimester vaginal bleeding and fetal growth patterns. METHODS We conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons, a prospective cohort study of low-risk, nonobese women with healthy lifestyles. Duration of bleeding was self-reported at enrollment (10 0/7 to 13 6/7 weeks of gestation) and categorized as 0, 1, or more than 1 day. Longitudinal measures of fetal biometrics were obtained in up to six study visits, and estimated fetal weight was computed. Growth trajectories were created for biometrics and estimated fetal weight. When global tests among groups was significant (P

Supplemental material for Bayesian multivariate skew meta-regression models for individual patient data by Joseph G Ibrahim, Sungduk Kim, Ming-Hui Chen, Arvind K Shah and Jianxin Lin in Statistical Methods in Medical Research