James A. Calvin

IDENTIFYING THE TIME OF A STEP-CHANGE WITH X 2 CONTROL CHARTS

A maximum likelihood estimator is proposed for the time of a step-change in a multivariate process mean when the observations follow a multivariate Normal distribution. The estimator can be used to identify the change point when a multivariate x(2) cont..

Nondietary ingestion of pesticides by children in an agricultural community on the US/Mexico border: preliminary results.

An environmental measurement and correlation study of nondietary ingestion of pesticides was carried out in a colonia in south Texas. The purpose of the study was to evaluate young childrens exposure to environmental levels of organophosphate (OP) pesticides in the household. Samples were collected to measure levels of OP pesticides in housedust and on childrens hands. These, in turn, were compared to levels of OP pesticide metabolites in urine. A total of 52 children, 25 boys and 27 girls, participated in the spring and summer of 2000. The children were 7–53 months of age at the time of recruitment. Univariate and multivariate regression analyses were carried out using SAS statistical software. Seventy-six percent of housedust samples and 50% of hand rinse samples contained OP pesticides. All urine samples had at least one metabolite and over 95% had at least two metabolites above the limit of detection (LOD). Total OP loadings in the housedust ranged from nondetectable (nd) to 78.03 nmol/100 cm2 (mean=0.15 nmol/100 cm2; median=0.07 nmol/100 cm2); total OP loadings on the childrens hands ranged from nd to 13.40 nmol/100 cm2 (mean=1.21 nmol/100 cm2; median=1.41 nmol/100 cm2), and creatinine corrected urinary levels (nmol/mol creatinine) of total OP metabolites ranged from 3.2 to 257 nmol/mol creatinine (mean=42.6; median 27.4 nmol/mol creatinine). Urinary metabolites were inversely associated with the age of the child (in months) with the parameter estimate (pe)=−2.11, P=0.0070, and 95% confidence interval −3.60 to −0.61. The multivariate analysis observed a weak association between concentrations of OP pesticides in housedust, loadings in housedust, and concentration on hands, hand surface area, and urinary levels of OP metabolites. However, hand loadings of OP pesticides were more strongly associated (r2=0.28; P=0.0156) with urinary levels of OP metabolites (pe=6.39; 95% CI 0.98–11.80). This studys preliminary findings suggest that surface loadings of pesticides, on hands, are more highly correlated with urinary bioassays and, therefore, may be more useful for estimation of exposure in epidemiologic studies than levels of pesticides in housedust.

IDENTIFYING THE TIME OF A STEP CHANGE IN A NORMAL PROCESS VARIANCE

Information concerning the time of a process change is valuable to process engineers since it can simplify their search for the special cause. In this article we propose an estimator of the time of a step change in the variance of the normal process. Th..

A Nonparametric Test for Spatial Isotropy Using Subsampling

A common requirement for spatial modeling is the development of an appropriate correlation structure. Although the assumption of isotropy is often made for this structure, it is not always appropriate. A conventional practice when checking for isotropy is to informally assess plots of direction-specific sample (semi)variograms. Although a useful diagnostic, these graphical techniques are difficult to assess and open to interpretation. Formal alternatives to graphical diagnostics are valuable, but have been applied to a limited class of models. In this article we propose a formal approach to test for isotropy that is both objective and valid for a wide class of models. This approach, which is based on the asymptotic joint normality of the sample variogram, can be used to compare sample variograms in multiple directions. An L2-consistent subsampling estimator for the asymptotic covariance matrix of the sample variogram is derived and used to construct a test statistic. A subsampling approach and a limiting chi-squared approach are developed to obtain p values of the test. Our testing approach is purely nonparametric in that no explicit knowledge of the marginal or joint distribution of the process is needed. In addition, the shape of the random field can be quite irregular. The results apply to regularly spaced data as well as to irregularly spaced data when the point locations are generated by a homogeneous Poisson process. A data example and simulation experiments demonstrate the efficacy of the approach.

Children's mouthing and food-handling behavior in an agricultural community on the US/Mexico border

Childrens mouthing and food-handling activities were measured during a study of nondietary ingestion of pesticides in a south Texas community. Mouthing data on 52 children, ranging in age from 7 to 53 months, were collected using questionnaires and videotaping. Data on childrens play and hand-washing habits were also collected. Children were grouped into four age categories: infants (7–12 months), 1-year-olds (13–24 months), 2-year-olds (25–36 months) and preschoolers (37–53 months). The frequency and type of events prompting hand washing did not vary by age category except for hand washing after using the bathroom; this increased with increasing age category. Reported contact with grass and dirt also increased with increasing age category. The median hourly hand-to-mouth frequency for the four age groups ranged from 9.9 to 19.4, with 2-year-olds having the lowest frequency and preschoolers having the highest. The median hourly object to mouth frequency ranged from 5.5 to 18.1 across the four age categories; the frequency decreased as age increased (adjusted R2=0.179; P=0.003). The median hourly hand-to-food frequency for the four age groups ranged from 10.0 to 16.1, with the highest frequency being observed in the 1-year-olds. Hand-to-mouth frequency was associated with food contact frequency, particularly for children over 12 months of age (adjusted R2=0.291; P=0.002). The frequency and duration of hand-to-mouth, object-to-mouth and food-handling behaviors were all greater indoors than outdoors. Infants were more likely to remain indoors than children in other age groups. The time children spent playing on the floor decreased with increasing age (adjusted R2=0.096; P=0.031). Parental assessment was correlated with hand-to-mouth activity but not with object-to-mouth activity. The highest combined (hand and object) mouthing rates were observed among infants, suggesting that this age group has the greatest potential for exposure to environmental toxins.

Valproic Acid-Induced Changes in Gene Expression During Neurulation in a Mouse Model

The teratogenic potential of valproic acid has been well established both in experimental models and in human clinical studies. As with all human teratogens, there are genetically determined differences in individual susceptibility to the induction of congenital defects. Using a mouse model of valproate-induced neural tube defects, a study was undertaken to examine differential changes in gene expression for selected transcription factor (Pax-3, Emx-1, Emx-2, c-fos, c-jun, creb) and cell cycle checkpoint genes (bcl-2, p53, wee-1) during neural tube closure. In general, exposure to teratogenic concentrations of valproic acid elicited GD 9:12 control levels of transcription factor mRNA expression in GD 9:0 embryos of both strains. This accelerated developmental profile is marked by significant elevation of Emx-1, Emx-2, c-fos, c-jun, and creb expression. There was also a significant over expression of the cell cycle genes p53 and bcl-2 in the LM/Bc embryos in response to the teratogenic insult. Examination of the ratio of expression of these genes clearly favored bcl-2, which supports the hypothesis that altered neuroepithelial cell proliferation rates, rather than increased apoptosis, is the underlying mechanism by which valproic acid alters normal neural tube morphogenesis. An investigation into interactive effects of these genes on the molecular profile of GD 9:0 embryos further validated this observation. That is, the overall proliferative state among the control embryos was prematurely modified into a more differentiated state following teratogenic insult. These results suggest that alterations in the expression of multiple genes are most likely responsible for valproic acid-induced neural tube defects.

Phenytoin-Induced Teratogenesis: A Molecular Basis for the Observed Developmental Delay During Neurulation

Summary: Purpose: We wished to determine whether chronic phenytoin (PHT) exposure could impair neural development and if any morphological alterations could be linked to changes in gene expression.

ARSENIC-INDUCED ALTERATIONS IN EMBRYONIC TRANSCRIPTION FACTOR GENE EXPRESSION : IMPLICATIONS FOR ABNORMAL NEURAL DEVELOPMENT

We examined the morphological and molecular consequences of acute in utero exposure to teratogenic concentrations of arsenate. The treatment produced a dose-related increase in neural tube defects, along with a significant alteration in the pattern of gene expression for several transcription factors (creb, Hox 3.1, Pax3, and Emx-1) that were examined using in situ transcription and antisense RNA amplification procedures. On gestational day 9:0, there was a significant delay in the embryos progression through neural tube closure, accompanied by a significant downregulation of Hox 3.1 expression and a significant upregulation of Pax3, Emx-1, and creb. As both Hox 3.1 and Pax3 serve to regulate N-CAM expression, it is possible that abnormalities associated with N-CAM may compromise neural crest cell migration and normal neural tube closure.

Valproic acid-induced alterations in growth and neurotrophic factor

Abstract Although the teratogenicity of valproic acid (VPA) has been well established, the mechanism(s) by which this anticonvulsant drug induces malformations remains controversial. Using the combined molecular techniques of in situ-transcription (IST) and antisense RNA (aRNA) amplification we analyzed VPA-induced alterations in the gene expression for 10 genes within the neural tubes of embryos from two murine strains that have been shown to differ in their susceptibility to VPA-induce neural tube defects (NTD). Pregnant dams from both SWV (susceptible) and LM/Bc (resistant) strains were either treated with saline (control) or VPA (600 mg/kg) on gestational day (GD) 8:12 (day:hour). Neural tubes were isolated from control or VPA exposed embryos at three gestational time points, which represented the beginning (GD 8:18), middle (GD 9:00), and end (GD 9:12) of neural tube closure (NTC) in both of these murine strains. Using univariant statistics we demonstrated that in LM/Bc embryos with NTDs, the expression of bdnf , ngf , and trk , ngf-R were significantly elevated at all three time points, and the cytokine, cntf was significantly decreased at GD 9:00. In contrast, the major gene alterations observed in SWV embryos were a significant increase in tfgα and tgfβ1–3 at GD 9:00. In an effort to better define the more intricate interactions between VPA exposure and the expression of these genes, we analyzed our data using Principal Component Analysis. The results from this analysis demonstrated that embryos from these two stains behaved differently, not only in response to a VPA exposure, but also under control conditions, which may explain the multifactorial nature of NTDs in these mice.

Estimation of Fetal Growth and Gestation in Bowhead Whales

We address estimating fetal growth and gestation for bowhead whales of the Bering, Chukchi, and Beaufort seas stock. This population is subject to a subsistence hunt by Eskimo whale hunters, which is monitored via a quota system established by the International Whaling Commission. Quota determination is assisted by biological information, such as fetal growth and gestation, which is the basis of a population dynamics model used to estimate the annual replacement yield of the stock. We developed a Bayesian hierarchical nonlinear model for fetal growth with computation carried out via Markov chain Monte Carlo techniques. Our model allows for unique conception and parturition dates and provides predictive distributions for gestation length and conception dates. These results are used to propose estimates of geographic locations for conception and parturition. A sensitivity analysis indicated caution when specifying some hyperparameters related to growth rate, conception dates, and parturition dates.