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Results for “Statistics, Nonparametric”

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PubMed1996

Serum erythropoietin and blood lead concentrations.

The aim of the study was to test the hypothesis that high blood lead levels are associated with depressed serum erythropoietin concentrations in workers occupationally exposed to lead. The results in exposed workers and in a control group of unexposed subjects were compared. Blood lead values were < or = 20 micrograms/dl in unexposed subjects and > or = 30 micrograms/dl in exposed subjects. The two groups of exposed workers and the control population were matched for sex and age. Hemoglobin levels were not affected by blood lead values and did not differ significantly between the three groups. The two-tailed, nonparametric Mann-Whitney U-test was used to compare unpaired groups. The Spearman rank correlation test was used to evaluate the dose-effect relationship between Pb and EPO. The analysis of the data indicate that erythropoietin values are significantly lower in exposed subjects than a controls. However no correlation was demonstrated between blood lead concentrations and erythropoietin in any group.

Adult↗

PubMed2001

Bayesian nonparametric modeling using mixtures of triangular distributions.

Nonparametric modeling is an indispensable tool in many applications and its formulation in an hierarchical Bayesian context, using the entire posterior distribution rather than particular expectations, increases its flexibility. In this article, the focus is on nonparametric estimation through a mixture of triangular distributions. The optimality of this methodology is addressed and bounds on the accuracy of this approximation are derived. Although our approach is more widely applicable, we focus for simplicity on estimation of a monotone nondecreasing regression on [0, 1] with additive error, effectively approximating the function of interest by a function having a piecewise linear derivative. Computationally accessible methods of estimation are described through an amalgamation of existing Markov chain Monte Carlo algorithms. Simulations and examples illustrate the approach.

Algorithms↗

PubMed2004

Centile charts II: alternative nonparametric approach for establishing time-specific reference centiles and assessment of the sample size required.

BACKGROUND: Reference intervals, and more generally centile estimates, are used to characterize a reference population for the purposes of interpreting an individual patient's clinical measurement. We describe methods of calculating reference intervals where these centiles vary with a covariate, usually age or time. METHODS: The US Food and Drug Administration and the IFCC have made recommendations on two approaches: the parametric approach, which models the structural characteristics of the data set with a theoretical distribution, and the nonparametric approach, which makes no particular assumption about this structure. In this report we propose a nonparametric procedure that relies on the principles of regression and show how sample size determination can be assessed. We also show how the sample size calculation is influenced by the distribution of the times measured. RESULTS: We illustrated our method on three data sets and compared the results for our proposed nonparametric method with parametric estimates. We showed that the bias is reduced and that the nonparametric method is less likely to produce fluctuating profiles. CONCLUSIONS: To achieve adequate precision the sample size needs to be larger than 120, as has often been recommended. If there is doubt about the parametric model, then threshold sample sizes may need to be as high as 500.

Adolescent↗

PubMed1999

Linkage analysis in alcohol dependence.

Alcohol dependence often is a familial disorder and has a genetic component. Research in causative factors of alcoholism is coordinated by a multi-center program, COGA [The Collaborative Study on the Genetics of Alcoholism, Begleiter et al., 1995]. We analyzed a subset of the COGA family sample, 84 pedigrees of Caucasian ancestry comprising 745 persons, 339 of whom are affected according to DSM-III-R and Feighner criteria. Using parametric and nonparametric methods, evidence for linkage was found on chromosome 1 (near markers D1S532, D1S1588, and D1S534), as well as on chromosome 15 (near marker D15S642). Other regions of the genome showed suggestive evidence for contributing loci. Related findings are discussed in recent publications investigating linkage in humans [Reich et al., 1998] and mice [Melo et al., 1996].

Alcoholism↗

PubMed2001

Model-free linkage analysis: performance under real-world conditions.

The simulated data of the Genetic Analysis Workshop 12 problem set affords an ideal environment for testing real-world performance of model-free linkage analysis methods. To this end, we applied three different methods of model-free linkage analysis: mod scores [Hodge and Elston, Genet Epidemiol 11:329-42, 1994], maximized maximum lod score (MMLS) [Greenberg et al., Am J Hum Genet 63:870-9, 1998], and nonparametric linkage (NPL) scores [Whittemore and Halpern, Biometrics 50:118-27, 1994], as well as standard parametric linkage analysis to the detection of major gene 6 (MG6) using only the qualitative disease status data. Our results indicate that both mod scores and NPL scores perform well, even in the presence of an extremely complicated disease model. MMLS analysis did not perform well, except at the disease locus itself.

Chromosome Mapping↗

PubMed2002

Nonparametric methods for identifying differentially expressed genes in microarray data.

MOTIVATION: Gene expression experiments provide a fast and systematic way to identify disease markers relevant to clinical care. In this study, we address the problem of robust identification of differentially expressed genes from microarray data. Differentially expressed genes, or discriminator genes, are genes with significantly different expression in two user-defined groups of microarray experiments. We compare three model-free approaches: (1). nonparametric t-test, (2). Wilcoxon (or Mann-Whitney) rank sum test, and (3). a heuristic method based on high Pearson correlation to a perfectly differentiating gene ('ideal discriminator method'). We systematically assess the performance of each method based on simulated and biological data under varying noise levels and p-value cutoffs. RESULTS: All methods exhibit very low false positive rates and identify a large fraction of the differentially expressed genes in simulated data sets with noise level similar to that of actual data. Overall, the rank sum test appears most conservative, which may be advantageous when the computationally identified genes need to be tested biologically. However, if a more inclusive list of markers is desired, a higher p-value cutoff or the nonparametric t-test may be appropriate. When applied to data from lung tumor and lymphoma data sets, the methods identify biologically relevant differentially expressed genes that allow clear separation of groups in question. Thus the methods described and evaluated here provide a convenient and robust way to identify differentially expressed genes for further biological and clinical analysis.

Carcinoma, Squamous Cell↗

PubMed2003

Genome scan of the fifty-six bipolar pedigrees from the NIMH genetics initiative replication sample: chromosomes 4, 7, 9, 18, 19, 20, and 21.

The NIMH genetics initiative on bipolar disorder was established to collect uniformly ascertained bipolar pedigrees for genetic studies. In 1997, the four participating sites published a genome scan on the initial set of 97 bipolar pedigrees. Fifty-six additional bipolar pedigrees have now been ascertained and evaluated. This replication pedigree set contains 354 genotyped subjects, including 139 bipolar I (BPI) subjects, five schizoaffective bipolar type SA/BP subjects, 41 bipolar II (BPII) subjects, and 43 recurrent unipolar (RUP) depression subjects. Our site has recently genotyped the replication study bipolar pedigrees using 107 microsatellite markers from chromosomes 4, 7, 9, 18, 19, 20, and 21. We are now reporting parametric and nonparametric linkage results from this effort. Multipoint nonparametric linkage analysis produced three candidate regions with allele sharing LOD scores >/= 1.0. The linkage signal on 4q35 peaked between markers D4S3335 and D4S2390 with an allele sharing LOD score of 2.49. This finding exceeds standard criteria for suggestive linkage. Two additional loci approach suggestive linkage levels: the 4q32 finding had its maximum near marker D4S1629 with an allele sharing LOD score of 2.16, and the 20p12 finding peaked at D20S162 with an allele sharing LOD score of 1.82. Multipoint parametric linkage analysis produced similar findings. When we combined the genotype data from the original and the replication pedigree sets, 20p12 yielded a nonparametric LOD score of 2.38, which exceeds standard criteria for suggestive linkage, and a corresponding parametric HLOD score of 2.98. The combined analysis did not provide further support for linkage to 4q32 and 4q35.

Bipolar Disorder↗

PubMed1997

Comparison of parametric and nonparametric methods to map oligogenes by linkage.

A sample of 95 sib pairs affected with insulin-dependent diabetes and typed with their normal parents for 28 markers on chromosome 6 has been analyzed by several methods. When appropriate parameters are efficiently estimated, a parametric model is equivalent to the beta model, which is superior to nonparametric alternatives both in single point tests (as found previously) and in multipoint tests. Theory is given for meta-analysis combined with allelic association, and problems that may be associated with errors of map location and/or marker typing are identified. Reducing by multipoint analysis the number of association tests in a dense map can give a 3-fold reduction in the critical lod, and therefore in the cost of positional cloning.

Adult↗

PubMed1983

Roles of stress and adaptation in the elicitation of face-immersion bradycardia.

Thirteen young healthy human volunteers immersed their faces in warm or cold water on one day while breathing through a snorkel and on another day while breath holding. The magnitude of the elicited bradycardia was most prominently due to water temperature, with apnea playing a less important role. Perceived stress could affect the magnitude of the response, but it was less important than the other variables. Thus statistically significant nonparametric correlations were found for the group but not for most individuals between a scoring technique that assessed perceived stress and heart rate. In contrast to animals, these data indicate that bradycardia may be reliably elicited in humans by face immersion in cold water and that stress is neither necessary nor sufficient to produce this phenomenon. Adaptation did not seem to play a role in the development of this physiological response.

Adaptation, Physiological↗

PubMed2004

Mammographic breast glandularity in Malaysian women: data derived from radiography.

OBJECTIVE: This study was undertaken to estimate mammographic breast glandularity in Malaysian women from radiographic data. MATERIALS AND METHODS: A mammography X-ray unit was used to expose different thicknesses of phantom material of varying glandular and adipose composition at 27 kV. A least squares method was then used to fit the combined data of phantom glandularity, thickness, and milliampere-seconds. The subsequent fitted equation was then applied to calculate breast glandularity for 705 women who underwent diagnostic mammography, who were drawn equally from the three major ethnic groups of Malaysia: Malay, Chinese, and Indian. The difference in breast glandularity among ethnic groups was tested for significance using the nonparametric Kruskal-Wallis test. RESULTS: The fitted equation gave an absolute error of less than or equal to +/- 8% when applied to the data from phantom exposure. The average breast glandularity of the study sample was 48.9% +/- 18.7%. Breast glandularity was found to decrease with breast thickness and age. CONCLUSION: No significant difference was seen in breast glandularity among the ethnic groups (p > 0.05, Kruskal-Wallis test).

Adipose Tissue↗

PubMed2006

A nonparametric test reveals selection for rapid flowering in the Arabidopsis genome.

The detection of footprints of natural selection in genetic polymorphism data is fundamental to understanding the genetic basis of adaptation, and has important implications for human health. The standard approach has been to reject neutrality in favor of selection if the pattern of variation at a candidate locus was significantly different from the predictions of the standard neutral model. The problem is that the standard neutral model assumes more than just neutrality, and it is almost always possible to explain the data using an alternative neutral model with more complex demography. Today's wealth of genomic polymorphism data, however, makes it possible to dispense with models altogether by simply comparing the pattern observed at a candidate locus to the genomic pattern, and rejecting neutrality if the pattern is extreme. Here, we utilize this approach on a truly genomic scale, comparing a candidate locus to thousands of alleles throughout the Arabidopsis thaliana genome. We demonstrate that selection has acted to increase the frequency of early-flowering alleles at the vernalization requirement locus FRIGIDA. Selection seems to have occurred during the last several thousand years, possibly in response to the spread of agriculture. We introduce a novel test statistic based on haplotype sharing that embraces the problem of population structure, and so should be widely applicable.

Alleles↗

PubMed2004

Updating reference values for placental weights in Northern Alberta.

OBJECTIVE: The purpose of this study was to establish normal parameters for placental weights and fetal/placental weight ratios. STUDY DESIGN: Placentas (2402) from uncomplicated singleton deliveries at the Royal Alexandra Hospital (Edmonton, Alberta) were collected from 1997 to 1998 and weighed after fixation. The nonparametric Mann-Whitney test was applied. RESULTS: New reference values were developed for fixed placental weights. Placentas at the 90th percentile were 50 to 100 g heavier than previously reported. Fetal/placental weight ratios at term were similar to published values. CONCLUSION: The new placental weight reference values from our institution represent a recent and local population. New values may partly reflect parallel increases in term birth weights.

Alberta↗

PubMedDate not supplied

Relationship between sports drinks and dental erosion in 304 university athletes in Columbus, Ohio, USA.

Acidic soft drinks, including sports drinks, have been implicated in dental erosion with limited supporting data in scarce erosion studies worldwide. The purpose of this study was to determine the prevalence of dental erosion in a sample of athletes at a large Midwestern state university in the USA, and to evaluate whether regular consumption of sports drinks was associated with dental erosion. A cross-sectional, observational study was done using a convenience sample of 304 athletes, selected irrespective of sports drinks usage. The Lussi Index was used in a blinded clinical examination to grade the frequency and severity of erosion of all tooth surfaces excluding third molars and incisal surfaces of anterior teeth. A self-administered questionnaire was used to gather details on sports drink usage, lifestyle, health problems, dietary and oral health habits. Intraoral color slides were taken of all teeth with erosion. Sports drinks usage was found in 91.8% athletes and the total prevalence of erosion was 36.5%. Nonparametric tests and stepwise regression analysis using history variables showed no association between dental erosion and the use of sports drinks, quantity and frequency of consumption, years of usage and nonsport usage of sports drinks. The most significant predictor of erosion was found to be not belonging to the African race (p < 0.0001). The results of this study reveal no relationship between consumption of sports drinks and dental erosion.

Adolescent↗

PubMed1999

Nonparametric linkage and family-based association studies of a simulated complex disorder.

Affected sibling pairs are widely used to identify chromosomal regions harboring genetic loci underlying common disease. We explore the utility of nonparametric sibling pair and family-based association methods to search for disease susceptibility loci in simulated pedigree data for a qualitative disease trait. Logistic regression was used to model gene x gene and gene x environment interactions when significant linkage and association were detected. Using these methods, we were able to detect three of the four susceptibility loci underlying the disease trait with multipoint lod scores of 1.0 or greater.

Alleles↗

PubMed2002

Probability-based construction of reference ranges for ratios of log-gaussian analytes: an example from automated leukocyte counts.

Reference ranges (RRs) are frequently used for interpreting laboratory values in clinical trials, assessing abnormality of laboratory results, and combining results from different laboratories. When a clinical laboratory measure must be derived from other tests, eg, the WBC differential percentage from the WBC count and WBC differential absolute count, a derivation of the RR may also be required. A naive method for determining RRs calculates the upper and lower limits of the derived test from the upper and lower limits of the measured values using the same algebraic formula used for the derived measure. This naive method and any others that do not use probability-based transformations do not maintain the distributional characteristics of the RRs. RRs derived in such a manner are deemed uninterpretable because they do not contain a specific proportion of the distribution. We propose a probability-based approach for the interconversion of RRs for ratios of 2 log-gaussian analytes. The proposed method gives a simple algebraic formula for calculating the RRs of the derived measures while preserving the probability relationships. The nonparametric method and a parametric method that takes the log transformation, estimates an RR, and then exponentiates are provided as comparators. An example that compares the commonly used naive method and the proposed method is provided on automated leukocyte count data. This provides evidence that the proposed method maintains the distributional characteristics of the transformed RR measures while the naive method does not.

Adolescent↗

PubMed2003

Decision-bound theory and the influence of familiarity.

In this article, we derive a nonparametric prediction from decision-bound theory (DBT). The crucial aspect that is tested is whether or not familiarity of a stimulus affects response time in categorization. We show that, for our design, DBT, extended with some reasonable and testable assumptions, predicts no familiarity effect. Our prediction is nonparametric in that, rather than fit a specific instantiation of general DBT, we posit only some general assumptions of this theory and derive the prediction from these assumptions. It is found that familiarity did have a strong impact on response time for at least half of our participants. We suggest that DBT is in itself incomplete and should be extended to account for the full range of available data.

Adolescent↗

PubMed1999

Circadian changes in blood ionized calcium, sodium, potassium, and chloride concentrations and pH in cattle.

OBJECTIVE: To explore diurnal variation in blood ionized calcium, sodium, potassium, and chloride concentrations and pH in pregnant dairy cows. ANIMALS: 14 dairy cows in their third or later pregnancy approximately 6 weeks before expected parturition. PROCEDURE: Throughout a 24-hour period, blood samples were taken at 2-hour intervals and analyzed for ionized calcium (iCa2+), potassium (K+), sodium (Na+), and chloride (Cl-) concentrations and pH. Paired t-tests were used to compare initial and final values. Circadian changes were tested by use of repeated-measures ANOVA. Additionally, a nonparametric analysis was performed for each animal to determine minimal and maximal values for the variables. RESULTS: Significant differences were not detected between initial and final values of any variable. Repeated-measures ANOVA indicated significant diurnal fluctuations in all variables. With the exception of Cl- concentration, nonparametric analysis of individual values also revealed significant changes over time. CONCLUSIONS AND CLINICAL RELEVANCE: The magnitude of daily fluctuations does not make it necessary to standardize time of sample collection for routine diagnostic examination of blood iCa2+, Na+, and Cl-concentrations and pH. However, it may be important to standardize time of sample collection in comparative studies in which more discrete differences may be identified.

Analysis of Variance↗

PubMed2002

Nonparametric AUC estimation in population studies with incomplete sampling: a Bayesian approach.

The estimation of the AUC in a population without frequent and/or fixed individual samplings is of interest because the number of plasma samples can often be limited due to technical, ethical and cost reasons. Non-linear mixed effect models can provide both population and individual estimates of AUC based on sparse sampling protocols; however, appropriate structural models for the description of the pharmacokinetics are required. Nonparametric solutions have also been proposed to estimate the population AUC and the associated error when particular sampling protocols are adopted. However, they do not estimate the individual AUCs and lack flexibility. Also a semiparametric method has been proposed for addressing the problem of sparse sampling in reasonably well designed studies. In this work, we propose and evaluate a nonparametric Bayesian scheme for AUC estimation in population studies with arbitrary sampling protocols. In the stochastic model representing the whole population, the individual plasma concentration curves and the "mean" population curve are described by random walk processes, allowing the application of the method to the reconstruction of any kind of "regular" curves. Population and individual AUC estimation are performed by numerically computing the posterior expectation through a Markov chain Monte Carlo algorithm.

Algorithms↗