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PubMed1992

Pantomime, praxis, and aphasia.

The production and comprehension of pantomimed movements by asphasic subjects were studied with respect to their relationship to the aphasic deficit on one hand and apraxia on the other. At issue was whether impaired use of pantomime is a manifestation of reduced symbolic capacity or purely a manifestation of an apraxic impairment of purposeful movement or both. Tests of pantomime included a Pantomime Recognition Test, a nonverbal Transitive Pantomime Production Test, and an Intransitive Pantomime Production Test (to oral command). Imitation of Nonmeaningful Movements served as a measure of apraxia, uncontaminated by symbolic or linguistic factors. Imitation of Meaningful Movements taken from the pantomime tasks was also tested. Independent measures of auditory comprehension, picture naming, and reading comprehension were used as indices of language impairment. Intellectual function was measured by the Performance scale of the WAIS. Thirty aphasic subjects were examined. Twenty healthy age-matched normals served to establish scoring standards for the pantomime tests. Multiple regression analysis revealed significant, independent contributions from both auditory comprehension and imitation of Nonmeaningful Movements to all of the tests of pantomime production and pantomime recognition. All measures of pantomime production and pantomime recognition were strongly intercorrelated. While the three language measures were strongly correlated with each other, auditory comprehension was the only one of them that was significantly and consistently related to the pantomime tests. None was related to the imitation of nonmeaningful movement. The results are taken as indicating (1) that pantomime production and imitation share common factors with both praxis and auditory comprehension; (2) apraxia entails impairment of both production and interpretation of purposeful movements. Possible theoretical accounts for these results are offered.

Aged↗

PubMed2006

Developing methods for assessing neurotoxic effects in Hispanic non-English speaking children.

Many factors affect the growth and development of children, including chemicals in the environment. Children have greater exposure to toxicants than adults due to both behavior and their increased food: body-mass ratio. Furthermore, the developing brain and organ systems of infants and children and their immature metabolism also make them more vulnerable to environmental toxins. Children from all cultures and backgrounds are at risk. However, minorities may be at greatest risk. In order to evaluate the impact of environmental exposures on neurodevelopment it is necessary to have effective methods that will allow accurate conclusions to be drawn. We have developed a battery to assess neurobehavioral performance in non-English speaking Hispanic children ages 4 years and older. This paper will examine the associations between age and performance and present test-retest correlations. Two hundred and forty one Hispanic children between the ages of 4 and 9 years completed a neurobehavioral test battery twice, approximately 1 month apart. The battery consists of computerized tests from the Behavioral Assessment and Research System, tests selected from the Pediatric Environmental Neurobehavioral Test Battery, and the Object Memory Test. Multiple regression was used to examine the association between age, gender and mother's education on performance. All of the tests, except for Continuous Performance, showed that performance improved as the child gets older. Gender differences were found on several tests with females generally performing worse than males. Correlation coefficients on performance retest measures ranged from .51 to .88. This study has demonstrated the utility of using this test battery to assess cognitive and motor performance in non-English speaking Hispanic children. Tests in the battery assess a range of functions and the measures are sensitive to differences in ages. Test-retest correlations show the reliability of the battery. These support the use of this battery in both cross-sectional and longitudinal studies.

Child↗

PubMed2004

A longitudinal study of implicit and explicit memory in old persons.

Decline in explicit memory with advancing age is a common finding, but it is unclear whether implicit memory (repetition priming) declines or remains stable. Meta-analyses of studies that examined differences between extreme groups (young-old), typically at a single point in time and on a single test, suggest that a mild reduction in priming occurs with advancing age. The authors examined explicit memory and priming, on multiple tests over 4 annual data-collection waves, in a large group of older persons without dementia at baseline. Explicit memory declined significantly, but priming remained stable. Findings indicate that explicit memory and priming are dissociable on the basis of age-related change and that mildly reduced priming is not an inevitable consequence of growing older.

Aged↗

PubMed2006

A tutorial on statistical methods for population association studies.

Although genetic association studies have been with us for many years, even for the simplest analyses there is little consensus on the most appropriate statistical procedures. Here I give an overview of statistical approaches to population association studies, including preliminary analyses (Hardy-Weinberg equilibrium testing, inference of phase and missing data, and SNP tagging), and single-SNP and multipoint tests for association. My goal is to outline the key methods with a brief discussion of problems (population structure and multiple testing), avenues for solutions and some ongoing developments.

Genetics, Medical↗

PubMed2003

Statistical evaluation of the Predictive Toxicology Challenge 2000-2001.

MOTIVATION: The development of in silico models to predict chemical carcinogenesis from molecular structure would help greatly to prevent environmentally caused cancers. The Predictive Toxicology Challenge (PTC) competition was organized to test the state-of-the-art in applying machine learning to form such predictive models. RESULTS: Fourteen machine learning groups generated 111 models. The use of Receiver Operating Characteristic (ROC) space allowed the models to be uniformly compared regardless of the error cost function. We developed a statistical method to test if a model performs significantly better than random in ROC space. Using this test as criteria five models performed better than random guessing at a significance level p of 0.05 (not corrected for multiple testing). Statistically the best predictor was the Viniti model for female mice, with p value below 0.002. The toxicologically most interesting models were Leuven2 for male mice, and Kwansei for female rats. These models performed well in the statistical analysis and they are in the middle of ROC space, i.e. distant from extreme cost assumptions. These predictive models were also independently judged by domain experts to be among the three most interesting, and are believed to include a small but significant amount of empirically learned toxicological knowledge. AVAILABILITY: PTC details and data can be found at: http://www.predictive-toxicology.org/ptc/.

Algorithms↗

PubMedDate not supplied

Microsatellite marker development and analysis in the eastern oyster (Crassostrea virginica): confirmation of null alleles and non-Mendelian segregation ratios.

Eighteen microsatellite markers were developed for the Crassostrea virginica nuclear genome, including di-, tri-, and tetranucleotide microsatellite repeat regions that included perfect, imperfect, and compound repeat sequences. A reference panel with DNA from the parents and four progeny of 10 full-sib families was used for a preliminary confirmation of polymorphism at these loci and indications of null alleles. Null alleles were discovered at three loci; in two instances, primer redesign enabled their amplification. Two to five representative alleles from each locus were sequenced to ensure that the targeted loci were amplifying. The sequence analysis revealed not only variation in the number of simple sequence repeat units, but also polymorphisms in the microsatellite flanking regions. A total of 3626 bp of combined microsatellite flanking region from the 18 loci was examined, revealing indels as well as nucleotide site substitutions. Overall, 16 indels and 146 substitutions were found with an average of 4.5% polymorphism across all loci. Eight markers were tested on the parents and 39-61 progeny from each of four families for examination of allelic inheritance patterns and genotypic ratios. Twenty-six tests of segregation ratios revealed eight significant departures from expected Mendelian ratios, three of which remained significant after correction for multiple tests. Deviations were observed in both the directions of heterozygote excess and deficiency.

Alleles↗

PubMed2003

A tree-based scan statistic for database disease surveillance.

Many databases exist with which it is possible to study the relationship between health events and various potential risk factors. Among these databases, some have variables that naturally form a hierarchical tree structure, such as pharmaceutical drugs and occupations. It is of great interest to use such databases for surveillance purposes in order to detect unsuspected relationships to disease risk. We propose a tree-based scan statistic, by which the surveillance can be conducted with a minimum of prior assumptions about the group of occupations/drugs that increase risk, and which adjusts for the multiple testing inherent in the many potential combinations. The method is illustrated using data from the National Center for Health Statistics Multiple Cause of Death Database, looking at the relationship between occupation and death from silicosis.

Databases, Factual↗

PubMed1980

Suppression of early rhesus sensitization by passive anti-D immunoglobulin: suppression of early rhesus sensitization.

Anti-D immunoglobulin is an effective prophylactic against rhesus isoimmunization. It is generally regarded as ineffective once antibody production has developed though there have been a number of inconclusive reports suggesting it may suppress early sensitization. Anti-D (100 micrograms) was given after delivery of a rhesus (D) positive child to a rhesus (D) negative mother who was shown to have anti-D antibodies at that time by five tests on two separate specimens in two different laboratories and by a weakly positive direct anti-globulin test on the cord blood. In a further pregnancy with a rhesus (D) positive child no antibody was detected by multiple tests including enzyme technique.

Adult↗

PubMed1981

Quality control limits for ampicillin, carbenicillin, mezlocillin, and piperacillin disk diffusion susceptibility tests: a collaborative study.

A multilaboratory in vitro study was carried out to determine disk diffusion susceptibility testing quality control limits for two new semisynthetic penicillins, mezlocillin and piperacillin. Existing limits for carbenicillin and ampicillin were reevaluated. Multiple tests (which followed standards set by the National Committee for Clinical Laboratory Standards ASM-2 revised) were performed in nine laboratories by different technologists using disks and Mueller-Hinton agar from different manufacturers. Clinically significant differences between disks produced by different manufacturers were not noted. Inhibitory zone diameter measurements from all laboratories were analyzed, and upper and lower control limits were established by using the overall median +/-0.5 the median range of the individual laboratory measurements as determining parameters. Close agreement of the data in this study with the results of national proficiency testing and quality control programs for ampicillin and carbenicillin supports the validity of our approach to making initial recommendations for quality control guidelines for new antimicrobial agents.

Ampicillin↗

PubMed2004

Statistical models to optimize production of probiotic characteristics.

The use of probiotic microorganisms has been widely promoted in the last 20 years. Probiotics have applied to the gastrointestinal tract as capsules or as fermented milks. The characteristics of the strains proposed as probiotics have been published or patented after elaboration of the product. The first step in designing a probiotic product is to isolate and characterize strains with beneficial properties. Our group has reported the isolation and characterization of 134 strains of lactobacilli from the vagina of women from our city. Surface properties and the production of antagonistic substances has also been published. From these studies, certain strains were selected because they shared probiotic characteristics. The second step in the design of a pharmaceutical product is to determine the optimal conditions for obtaining the highest amount of viable microorganisms, as well as the best conditions to produce antagonistic substances. To perform these types of experiments, laboratory assays can be carried out to determine the optimum conditions in which the microorganisms can be cultured. Growth parameters and optimal growth conditions can be studied by the classical methodology or by the application of alternative methodologies. Alternative methods have been widely used in the food industry, including experimental designs to test multiple conditions at the same time, complemented by the use of statistical models to evaluate and compare all the conditions tested. The object of this chapter is to describe the experimental designs used to study the technological characteristics of vaginal probiotic lactobacilli as well as the application of statistical models for evaluation of the different conditions tested for the production of biomass and antagonistic substances in these bacteria. With this objective in mind, in the present chapter, the following areas are explored: 1. Growth experiments performed to study the effect of temperature, pH, agitation, and culture media on the growth and production of antagonistic substances by vaginal lactobacilli. 2. Fractional and complete factorial experimental designs used to perform the growth experiments. 3. Statistical models applied to evaluate the growth parameters and their modifications under the conditions assayed.

Bacteriological Techniques↗

PubMed2004

Assessment of acute thermal nociception in laboratory animals.

Models of acute nociception using a thermal stimulus are widely employed as screening methods for nociceptive properties of new drug compounds. In this chapter, detailed descriptions for conducting of two of the most commonly used models; the hot plate test and the "Hargreaves test," are described. These models are applicable to both rats and mice and have the advantage of allowing repeated and multiple testing using a single animal because the stimulus is transitory and produces no tissue damage. Additionally, a modification of these models using a skin-twitch reflex that is applicable to large laboratory animals such a dogs or sheep is described. Guidance concerning potential confounding variable are discussed, as are tips for reducing variably among testing sessions.

Animals↗

PubMed2000

Proficiency-testing issues relating to sirolimus.

BACKGROUND: A need exists to document laboratory proficiency to (1) compare results produced by different analytical techniques and (2) ensure consistency of results from multiple testing sites. OBJECTIVES: To enable concentration-controlled studies of sirolimus to proceed with confidence, proficiency-testing schemes were put in place at laboratories selected to act as reference laboratories. The feasibility of establishing an ongoing proficiency-testing scheme was addressed with respect to sample stability. The scheme was then used to test proficiency for the measurement of sirolimus in 3 blinded samples each month. METHODS: The method chosen for measurement of sirolimus was a prototype microparticle enzyme immunoassay. Initially, 15 laboratories were asked to analyze a series of 85 blinded samples that tested their inaccuracy, repeatability, and reproducibility for the measurement and their ability to dilute over-range samples competently. Both blood samples spiked with sirolimus and pooled blood samples from patients receiving the drug were circulated to a maximum of 50 laboratories. RESULTS: Overall, both inaccuracy and imprecision were acceptable by predefined criteria. Inaccuracy for the immunoassay (percentage difference of the measured value against the nominal value) averaged -5% (95% CI, -9% to -1%). The mean percentage difference between the immunoassay and a high-performance liquid chromatographic assay with mass-spectrometric detection for the measurement of sirolimus in pooled samples (n = 5) from patients receiving the drug was 29% (95% CI, 24% to 34%). CONCLUSION: The techniques documented here as part of the International Sirolimus Proficiency Testing Scheme could be applied to other clinical studies requiring protocol-driven dosing adjustments based on sirolimus measurements, irrespective of analytical technique used.

Chromatography, High Pressure Liquid↗

PubMed2006

Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese.

Several linkage studies have predicted that human chromosome 20q is closely related to type 2 diabetes, but there is no clear evidence that certain variant(s) or gene(s) have strong effects on the disease within this region. To examine disease susceptibility variant in Japanese, verified SNPs from the databases, with a minor allele frequency larger than 0.15, were selected at 10-kb intervals across a 19.31-Mb region (20q11.21-13.13), which contained 291 genes, including hepatocyte nuclear factor 4alpha (HNF4alpha). As a result, a total of 1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples. By searching for HNF4alpha as a representative disease-susceptible gene, no variants of HNF4alpha were strongly associated with disease. To identify other genetic variant related with disease, we designed an extensive two-stage association study (725 first and 1,093 second test samples). Although SNP1146 (rs220076) was selected as a landmark within the 19.31 Mb region, the magnitude of the nominal P value (P = 0.0023) was rather weak. Subsequently, a haplotype-based association study showed that two common haplotypes were weakly associated with disease. All of these tests resulted in non-significance after adjusting for Bonferroni's correction and the false discovery rate to control for the impact of multiple testing. Contrary to the initial expectations, we could not conclude that certain SNPs had a major effect on this promising locus within the framework presented here. As a way to extend our observations, we emphasize the importance of a subsequent association study including replication and/or meta-analysis in multiple populations.

Aged↗

PubMed2004

A statistical method for the quantification of the learning index by means of multiple answer tests-Graduated Response Test.

In the fields of didactics and continuous professional development (CPD) plans, the increasing use of multiple answer tests for the evaluation of the level of knowledge in various kinds of subjects makes it increasingly important to have reliable and effective tools for data processing and for the evaluation of the results. The aim of the present work is to explore a new methodological approach based on a widely tested statistical analysis able to yield more information content when compared with the traditional methods. With this purpose we suggest a Graduated Response Test and the relative operating characteristic curve (ROC) for the evaluation of the results. A short description of a computerized procedure, written in Visual Basic Pro (v.6.0), which automatically performs the statistical analysis, the ROC curves plot and the calculation of a learning index is given as well.

Computer-Assisted Instruction↗

PubMed2002

An instrumented, dynamic test for anterior laxity of the ankle joint complex.

Evaluation of anterior laxity of the ankle joint complex is a difficult clinical problem. Currently, the prime determinant for anterolateral ligament function is the subjective manual examination of anterior laxity of the ankle joint complex. An instrumented dynamic test was developed for objective measurement of anterior laxity of the ankle joint complex. The principle of the test was to apply a force-impulse to the calcaneus, within the muscle reflex time, and to measure anterior-posterior and mediolateral rotation. The test was performed on a cadaver specimen and on 15 volunteers of which five subjects suffered from chronic one-sided lateral ankle ligament instability. In the cadaver test, anterior translation values increased from 5 to 11 mm, after cutting the anterior talofibular ligament and subsequently cutting the calcaneofibular ligament. In the 10 normal subjects, the mean anterior translation value was 6.7 mm (+/-1.9 mm). The relative variation of the test result within a measurement session was 2.5% (+/-1.6%). Between the sessions the relative laxity variation was 2.6% (+/-2.6%). In the ten normal subjects the mean right-left difference was not significantly different from zero. In four out of the five patients it was more than 2mm. As in the cadaver test in all measurements, the mediolateral rotations were small (<2.5 degrees ). The volunteers complained about same pain at the heel after multiple test sessions. In conclusion the dynamic, functional test appears to be capable of objectively measuring a value for anterior laxity of the ankle joint complex reflecting the functional status of the anterolateral ankle ligaments.

Ankle Injuries↗

PubMed2005

Statistical analysis of microarray data.

Microarrays promise dynamic snapshots of cell activity, but microarray results are unfortunately not straightforward to interpret. This article aims to distill the most useful practical results from the vast body of literature available on microarray data analysis. Topics covered include: experimental design issues, normalization, quality control, exploratory analysis, and tests for differential expression. Special attention is paid to the peculiarities of low-level analysis of Affymetrix chips, and the multiple testing problem in determining differential expression. The aim of this article is to provide useful answers to the most common practical issues in microarray data analysis. The main topics are pre-processing (normalization), and detecting differential expression. Subsidiary topics include experimental design, and exploratory analysis. Further discussion is found at the author's web page (http://discover.nci.nih.gov --> Notes on Microarray Data Analysis).

Cluster Analysis↗

PubMed2002

Statistical significance of coincident spikes: count-based versus rate-based statistics.

Inspired by different conceptualizations of temporal neural coding schemes, there has been recent interest in the search for signs of precisely synchronized neural activity in the cortex. One method developed for this task is unitary-event analysis. This method tests multiple single neuron recordings for short epochs with significantly more coincident spikes than expected from independent neurons. We reformulated the statistical test underlying this method using a coincidence count distribution based on empirical spike counts rather than on estimated spike probabilities. In the case of two neurons, the requirement of stationary firing rates, originally imposed on both neurons, can be relaxed; only the rate of one neuron needs to be stationary, while the other may follow an arbitrary time course. By analytical calculations of the test power curves of the original and the revised method, we demonstrate that the test power can be increased by a factor of two or more in physiologically realistic regimes. In addition, we analyze the effective significance levels of both methods for neural firing rates ranging between 0.2 Hz and 30 Hz.

Action Potentials↗

PubMed2001

Persistent infection in Neotoma fuscipes (Muridae: Sigmodontinae) with Ehrlichia phagocytophila sensu lato.

Dusky-footed wood rats (Neotoma fuscipes Baird) and two species of Peromyscus mice (P. maniculatus Wagner and P. truei Shufeldt) were collected over a 16-month period from three sites in Sonoma County, California. Blood was collected from 93 wood rats and 177 mice and serum or plasma was tested for seroreactivity with Ehrlichia phagocytophila sensu lato (also known as the human granulocytic ehrlichiosis agent). Thirty-five (37.6%) wood rats and 15 (8.5%) mice were seropositive. Positive Neotoma serology by site ranged from 9.4% to 62.1%. Polymerase chain reaction (PCR) testing for the Ehrlichia groESL heat shock operon was performed on all the seropositive and selected seronegative wood rats; 24 (68.6%) seropositive animals were PCR positive. Two seroconversions and no seroreversions were detected among 18 of the seropositive wood rats that were recaptured and tested multiple times (range = 2-6). Fourteen (77.8%) of the 18 were also PCR positive with six of these positive at every testing point (range = 2-6). One wood rat remained serologically and PCR positive in six specimens collected over a 14-month period. One male of 84 questing adult Ixodes pacificus Cooley & Kohls collected was PCR-positive for E. phagocytophila. Borrelia burgdorferi, the agent of Lyme disease, was cultured from ear punch biopsies from six of seven E. phagocytophila seropositive and one of four seronegative wood rats.

Animals↗