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PubMedDate not supplied

Estimating hydraulic properties using a moving-model approach and multiple aquifer tests.

A new method was developed for characterizing geohydrologic columns that extended >600 m deep at sites with as many as six discrete aquifers. This method was applied at 12 sites within the Southwest Florida Water Management District. Sites typically were equipped with multiple production wells, one for each aquifer and one or more observation wells per aquifer. The average hydraulic properties of the aquifers and confining units within radii of 30 to >300 m were characterized at each site. Aquifers were pumped individually and water levels were monitored in stressed and adjacent aquifers during each pumping event. Drawdowns at a site were interpreted using a radial numerical model that extended from land surface to the base of the geohydrologic column and simulated all pumping events. Conceptually, the radial model moves between stress periods and recenters on the production well during each test. Hydraulic conductivity was assumed homogeneous and isotropic within each aquifer and confining unit. Hydraulic property estimates for all of the aquifers and confining units were consistent and reasonable because results from multiple aquifers and pumping events were analyzed simultaneously.

Florida↗
PubMed2006

Longitudinal study of ELISA seroreactivity to Mycobacterium avium subsp. paratuberculosis in infected cattle and culture-negative herd mates.

Two thousand nine hundred fifty-two serum samples, collected once or twice annually from 545 cows of known fecal culture status were tested for antibodies to Mycobacterium avium subsp. paratuberculosis using a commercially available enzyme-linked immunosorbent assay (ELISA) test. Overall, 13.5% of the samples from 282 infected cows had positive ELISA results, but when tested multiple times, 38.3% of the cows had at least 1 serum sample with positive results. Among 263 fecal culture-negative cows, 98.1% of the serum samples had negative ELISA results, but when tested multiple times, 7.8% of the cows had at least 1 positive ELISA sample. Fecal culture was positive on a test before the first positive ELISA in 50 cows, ELISA was positive before fecal culture in 12 cows, and in 38 cows, both tests became positive at the same testing time. An additional 174 cows were positive on fecal culture and always negative on ELISA until culled. For cows that had ELISA sample:positive (S/P) ratios below the cutoff point, the change in S/P between sequential tests was evaluated to determine whether a rise in S/P could predict infection status. In this study, change in S/P was not a useful predictor of infection status in seronegative cows.

Animals↗
PubMed1983

The analysis of the red cell unsaturated fatty acid test for multiple sclerosis using laser cytopherometry.

Using a laser cytopherometer, the electrophoretic mobility of glutaraldehyde-fixed erythrocytes from patients with multiple sclerosis (MS) has been compared with that of cells from control subjects. The effect of incubating cells with different concentrations of linoleic acid (LA) has been tested. At a concentration of 20 micrograms LA per 2 x 10(7) cells, slower mobilities were observed, on average, than those of control subjects, but there was overlap between control and patient groups. At a higher concentration of LA (160 micrograms per 2 x 10(7) cells), many of the MS samples showed a slower mobility than the control samples, although overlap was still evident. The value of the application of laser cytopherometry compared with conventional cytopherometry to this type of test is discussed.

Adult↗
PubMed1995

Accuracy of diagnostic methods used for epidemiological studies of Helicobacter pylori.

Epidemiological studies involve groups of individuals, or whole populations, many or most of whom are not ill. Clinical investigation has an individual perspective and precise statements need to be made about the individual alone. Serological methods are most commonly used for population-based epidemiological studies. Non-invasive epidemiological methods, using breath tests or the study of saliva or urine, are increasing in use. All methods depend on accuracy in identifying presently infected or non-infected persons, and accuracy in defining a previously infected person. The performance of serological methods varies with the antigens chosen, the population from which reference sera are drawn, age, ethnicity, and homologous and heterologous infection rates in the population being studied. Much of the standardization of epidemiological assays has been done in adults, which means that for children there is still uncertainty concerning standards and cut-off values. Because of differences in strains of H. pylori in different geographical areas, antigen selection is important when geographical comparisons are made. The sensitivity and specificity of a test is not strongly affected by the prevalence of infection. However, as the prevalence rises in the tested populations, the reported positive predictive value rises, and the negative predictive value falls. Depending on the patient population studied, accuracy varies with changes in the prevalence, and its magnitude depends both on the sensitivity and specificity. Accuracy is therefore not a very useful measure. It is better to look at the sensitivity and specificity, and the prevalence in the study, where they are measured. An alternative to separating test results into two or three categories is to report likelihood ratios, which report the probability of a person with a particular result being truly positive compared with the probability of a person with that result being truly negative. A receiver operating characteristic (ROC) curve, which describes the effect of varying the cut-off value on the performance of a test, can be useful in comparing the performance of two or more different tests. The use of multiple tests to augment positive culture as a 'gold standard', has been aided by use of polymerase chain reactions and other molecular biological methods. However, this augmentation has its limitations, since each of the additional methods may produce false positives. For example, polymerase chain reactions can be falsely positive if instruments are contaminated. There are people with more than one strain of Helicobacter pylori in the stomach, and, without molecular biological efforts, or serological typing tests, the 'gold standard' does not deal with multiple infections.

Helicobacter Infections↗
PubMed1981

[Glial migration inhibition test in multiple sclerosis patients and its changes during treatment with immunosuppressants].

Results of examining the blood serum of 90 patients with disseminated sclerosis, 94 patients with other nervous diseases, and 20 healthy subjects using the glia migration inhibition test are presented. It is shown that the index of the glia migration inhibition (IGMI) gets higher during exacerbation of the disseminated sclerosis and drops in cases of relative stabilization of the clinical manifestations and remission. In the course of treatment with immunodepressants, such as, prednisolone (alone, or in combination with cyclophosphan) and antilymphocytic immunoglobulin, the IGMI falls down. Possible use of the IGMI for determining the indications for the immunodepressant therapy and for solving differential diagnostic and therapy control problems is discussed.

Antilymphocyte Serum↗
PubMed1999

Effective use of polymerase chain reaction for diagnosis of central nervous system infections.

Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) specimens has become standard for confirmatory diagnosis of central nervous system (CNS) infections; however, these tests increase health care costs. We reviewed 3-year data from 974 consecutive CSF specimens submitted for detection of seven pathogens by PCR. In 1997, 237 of 367 specimens (64.6%) were submitted for multiple tests, compared with 203 of 522 (38.9%) in 1996 and 18 of 85 (21.2%) in 1995. In each year the arrival of new house officers coincided with a peak in multiple testing. Among 732 specimens submitted for herpesvirus detection, results were positive for 24 (4.6%) of 523 specimens with increased leukocyte counts or protein levels. None of 209 specimens with normal leukocyte and protein levels were positive for herpesviruses. None of 471 CSF specimens submitted for Borrelia burgdorferi detection were PCR-positive. Use of protein and leukocytes to screen CSF specimens before employing PCR for herpesvirus detection would save almost one-third of costs without reducing sensitivity.

Central Nervous System Infections↗
PubMed2005

The search for genenotype/phenotype associations and the phenome scan.

All the approaches to the search for genotype/phenotype associations have their share of problems. Comparing the genome scan and candidate gene approaches, the former makes fewer assumptions at the genetic level or about mechanism but has greater statistical difficulties while the latter partially solves the statistical problem but makes more assumptions at both genetic and mechanistic levels. Among current difficulties is a lack of information about the nature of gene variant/phenotype associations: the frequency with which different classes of gene or sequence are involved; the type of genetic variation most commonly involved; the appropriate genetic models to apply to analysis. The overarching problem is that of multiple testing, one solution to which is to integrate genetic information to create a smaller number of compound variables. At the other end of the scale, decisions about the level of complexity at which to pitch the identification of phenotypes also affect the multiple testing problem: whether to pitch them at the level of disease outcomes, or at any of the multiple levels of intermediate phenotypes or traits. The third issue is how best to deal with gene/gene or gene/environment interactions, or whether to ignore them. Only as more genotype/phenotype associations emerge, by whatever means, will the numbers of results allow these questions to be answered. We describe here a new approach to genotype/phenotype association studies, the phenome scan, in which dense phenotypic information in human cohorts is scanned for associations with individual genetic variants. We believe that this approach can generate data that will be useful in answering generic questions about genotype/phenotype associations as well as in discovering novel ones.

Environmental Exposure↗
PubMed2006

Extensive linkage disequilibrium mapping at HTR2A and DRD3 for schizophrenia susceptibility genes in the Galician population.

The serotonin and dopamine neurotransmitter systems are candidate pathways in the development of schizophrenia because of the assumed causal relationship with the observed symptoms as well as effective targeting of the corresponding receptors by antipsychotic drugs. However, genetic association studies have systematically focused on a limited set of genes and single nucleotide polymorphisms (SNPs), including T102C at HTR2A and Ser9Gly at DRD3. Meta-analyses of the associations between these two markers and schizophrenia revealed a true increase in risk, the magnitude of the effect being very low. In the present study we analyzed 260 schizophrenic patients and 354 control subjects from a homogeneous population, the Galician population, using an extensive linkage disequilibrium (LD) mapping approach, genotyping a total of 47 SNPs to test for the existence of additional variants that confer higher risk. We detected nominal significant association with schizophrenia for several haplotype tag SNPs (htSNPs) at HTR2A, although the significance was lost after multiple test corrections. In addition, haplotype analyses involving a sliding window approach, with window size 2 to 4 SNPs, revealed significant differences in frequencies of the DRD3 haplotypes at the 3' half of the gene region. This difference, which remains clearly significant after multiple test corrections (p=0.002, 0.0001, and 0.0025, for window sizes 2, 3, and 4, respectively), was mainly due to over-representation of several rare haplotypes in patients, at the expense of a single common haplotype; this represents interesting evidence of rare haplotypes for susceptibility detected using common htSNPs due to their strong effect.

3' Flanking Region↗
PubMed2000

Multiple-changepoint testing for an alternating segments model of a binary sequence.

A binary sequence may give the appearance of being composed of alternating segments with relatively high and relatively low probability of success. Determining whether such an alternating pattern is significant is a multiple-changepoint problem where the number of segments and their success probabilities are unknown, with the added constraint of segment alternation. A dynamic programming method for determining the optimal segmentation into a given number of segments is provided. Given this, a variation on the simulation method of Venter and Steel (1996, Computational Statistics and Data Analysis 22, 481-504) may be employed to test the null hypothesis of a homogeneous sequence as well as to estimate the number and location of changepoints. A sample application, the assessment of the possibility of genetic recombination in HIV sequences, is presented.

Base Sequence↗
PubMed2003

Predisposition locus for major depression at chromosome 12q22-12q23.2.

Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component. As a first step toward identification of chromosomal loci contributing to genetic predisposition to major depression, we have conducted a genomewide scan by using 628 microsatellite markers on 1,890 individuals from 110 Utah pedigrees with a strong family history of major depression. We identified significant linkage to major depression in males at marker D12S1300 (multipoint heterogeneity LOD score 4.6; P=.00003 after adjustment for multiple testing). With additional markers, the linkage evidence became highly significant, with the multipoint heterogeneity LOD score at marker D12S1706 increasing to 6.1 (P=.0000007 after adjustment for multiple testing). This study confirms the presence of one or more genes involved in psychiatric diseases on the q arm of chromosome 12 and provides strong evidence for the existence of a sex-specific predisposition gene to major depression at 12q22-q23.2.

Chromosome Mapping↗
PubMed1997

Affected sibpair linkage tests for multiple linked susceptibility genes.

Genome-wide searches for susceptibility genes using pairs of affected siblings are being undertaken to dissect out individual polygenes that contribute to human multifactorial disease. Efficient identity-by-descent (IBD)-based sibpair linkage tests are available that test individual markers or maps of linked markers for linkage to a single putative susceptibility gene. In order to assess the support for linkage to a second putative susceptibility gene that happens to map close to an established susceptibility gene, it is necessary to use a method that correctly allows for the IBD distortion that directly results from the linkage between the two genes. A maximum likelihood-based, multilocus linkage test is proposed, which accounts for this interdependency and evaluates the support for an interaction between constituent susceptibility genes. The size and power of a test for a second linked susceptibility gene is investigated by simulation studies.

Chromosome Mapping↗
PubMedDate not supplied

An fMRI version of the Farnsworth-Munsell 100-Hue test reveals multiple color-selective areas in human ventral occipitotemporal cortex.

Studies of patients with cerebral achromatopsia have suggested that ventral occipitotemporal cortex is important for color perception. We created a functional magnetic resonance imaging (fMRI) version of a clinical test commonly used to assess achromatopsia, the Farnsworth-Munsell 100-Hue test. The test required normal subjects to use color information in the visual stimulus to perform a color sequencing task. A modification of the test requiring ordering by luminance was used as a control task. Subjects were also imaged as they passively viewed colored stimuli. A limited number of areas responded more to chromatic than achromatic stimulation, including primary visual cortex. Most color-selective activity was concentrated in ventral occipitotemporal cortex. Several areas in ventral cortex were identified. The most posterior, located in posterior fusiform gyrus, corresponded to the area activated by passive viewing of colored stimuli. More anterior and medial color-selective areas were located in the collateral sulcus and fusiform gyrus. These more anterior areas were not identified in previous imaging studies which used passive viewing of colored stimuli, and were most active in our study when visual color information was behaviorally relevant, suggesting that attention influences activity in color-selective areas. The fMRI version of the Farnsworth-Munsell test may be useful in the study of achromatopsia.

Adaptation, Physiological↗
PubMed2000

Significant linkage for Tourette syndrome in a large French Canadian family.

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS.

Adult↗
PubMed2006

Stillbirths in multiple births: test of independence.

The stillbirth rate in twins is a more sensitive indicator of environmental hazards than the stillbirth rate in singletons. Medical care or other socioeconomic factors may be more influential for perinatal survival in twin than in single deliveries. Studies have indicated that stillbirths among children in a set of multiple maternities are not independent. Models were considered assuming independent outcomes within a set of multiple maternities. Analyses of the stillbirth rates confirm that the risk of stillbirth among males is almost constantly higher than among females. Any model introduced should assume different stillbirth rates for males and females. The models were tested with both maximum likelihood and minimum chi2 methods. Data was analyzed from Sweden, the Aland Islands, Saxony, England and Wales, and significant discrepancies obtained from the independence models. The same-sexed twin data contain both monozygotic and dizygotic twin sets with apparently different stillbirth rates. Consequently, for same-sexed twins the proposed model could be considered too simple. After improvement by splitting the same-sexed data into monozygotic and dizygotic twin sets, the dependence still remains. The proportion of both same-sexed and opposite-sexed twin pairs that contain two stillborn is greater than what the stillbirth rates and the independence should indicate. Consequently, stillbirth rate estimates based on the relative frequency of twin sets with two stillborn children have a positive bias. When the stillbirth rate decreases, the number of sets with two stillborn children decreases more slowly than would be indicated by independence.

Female↗
PubMed1985

A logistic regression analysis of multiple noninvasive tests for the prediction of the presence and extent of coronary artery disease in men.

The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy.

Adult↗
PubMed2006

Nonlinear tests for genomewide association studies.

As millions of single-nucleotide polymorphisms (SNPs) have been identified and high-throughput genotyping technologies have been rapidly developed, large-scale genomewide association studies are soon within reach. However, since a genomewide association study involves a large number of SNPs it is therefore nearly impossible to ensure a genomewide significance level of 0.05 using the available statistics, although the multiple-test problems can be alleviated, but not sufficiently, by the use of tagging SNPs. One strategy to circumvent the multiple-test problem associated with genome-wide association tests is to develop novel test statistics with high power. In this report, we introduce several nonlinear tests, which are based on nonlinear transformation of allele or haplotype frequencies. We investigate the power of the nonlinear test statistics and demonstrate that under certain conditions, some nonlinear test statistics have much higher power than the standard chi2-test statistic. Type I error rates of the nonlinear tests are validated using simulation studies. We also show that a class of similarity measure-based test statistics is based on the quadratic function of allele or haplotype frequencies, and thus they belong to nonlinear tests. To evaluate their performance, the nonlinear test statistics are also applied to three real data sets. Our study shows that nonlinear test statistics have great potential in association studies of complex diseases.

Acyltransferases↗