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At least 469 records · Page 26Linked to original sources
PubMed2005

Endoscopic treatment of sphincterotomy-associated distal common bile duct strictures by using sequential insertion of multiple plastic stents.

BACKGROUND: A rare, late complication of endoscopic biliary sphincterotomy is the occurrence of short strictures extending from the papillary orifice to the distal parts of the extraduodenal common bile duct. METHODS: We evaluated the efficacy of the sequential insertion of multiple stents in the treatment of endoscopic biliary sphincterotomy associated common bile duct strictures. The design of the study is a prospective, single-arm observational study at a university-affiliated teaching hospital of 20 patients with distal common bile duct strictures because of choledocholithiasis-related endoscopic biliary sphincterotomy. Endoscopic treatment consisted of the sequential insertion of an increasing number of plastic stents with ever-larger diameters in 3-month follow-up intervals until stricture resolution. The primary outcome of the study was the rate of resolution of the stricture. The parameters measured were the duration of placement of stents, the maximum diameter, the total number of stents, and the total number of endoscopic sessions required for dilation of the strictures. RESULTS: After a median of 9.0 months of stent placement (range 3-22 months) and a median of 20F maximum stent diameter (range 10F-30F), 18 patients (90%) remained stent-free for a median of 14.5 months (range 6-38 months). Two patients (10%) had stricture recurrences at 10 and 24 months. Multivariate regression analysis demonstrated that the time elapsed after endoscopic biliary sphincterotomy was significantly associated with the stent-placement time (however, significance was removed by correction for multiple testing) and the number of ERCPs required for dilation. The initial common bile duct size was significantly associated with the total stent number and diameter needed for stricture resolution (however, significance was removed by correction for multiple testing). Limitations are the low case number and the single-arm, noncontrolled study design. CONCLUSIONS: Sequential insertion of an increasing number of biliary stents affords effective treatment of the distal biliary strictures that develop as a late complication of endoscopic biliary sphincterotomy.

Adult↗
PubMed2005

The effect of polymorphisms in the enhancer of split gene complex on bristle number variation in a large wild-caught cohort of Drosophila melanogaster.

The Enhancer of split complex [E(spl)-C] in Drosophila encompasses a variety of functional elements controlling bristle patterning and on the basis of prior work is a strong candidate for harboring alleles having subtle effects on bristle number variation. Here we extend earlier studies identifying associations between complex phenotypes and polymorphisms segregating among inbred laboratory lines of Drosophila and test the influence of E(spl)-C on bristle number variation in a natural cohort. We describe results from an association mapping study using 203 polymorphisms spread throughout the E(spl)-C genotyped in 2000 wild-caught Drosophila melanogaster. Despite power to detect associations accounting for as little as 2% of segregating variation for bristle number, and saturating the region with single-nucleotide polymorphisms (SNPs), we identified no single SNP marker showing a significant (additive over loci) effect after correcting for multiple tests. Using a newly developed test we conservatively identify six regions of the E(spl)-C in which the insertion of transposable elements as a class contributes to variation in bristle number, apparently in a sex- or trait-limited fashion. Finally, we carry out all possible 20,503 two-way tests for epistasis and identify a slight excess of marginally significant interactions, although none survive multiple-testing correction. It may not be straightforward to extend the results of laboratory-based association studies to natural populations.

Animal Structures↗
PubMed2002

Assessing insulin secretion by modeling in multiple-meal tests: role of potentiation.

We developed a mathematical model of the glucose control of insulin secretion capable of quantifying beta-cell function from a physiological meal test. The model includes a static control, i.e., a secretion component that is a function of plasma glucose concentration (the dose-response function), and a dynamic control, i.e., a secretion component that is proportional to the positive values of the glucose concentration derivative. Furthermore, the dose-response function is assumed to be modulated by a time-varying potentiation factor. To test the model, nine nondiabetic control subjects and nine type 2 diabetic patients received three standardized mixed meals over a period of 14-15 h. Blood samples were drawn for the measurement of glucose, insulin, and C-peptide concentration. The dose-response function, the parameter of the dynamic control, and the potentiation factor were determined by fitting the model to glucose and C-peptide concentrations. In diabetic patients, the dose-response function was shifted to the right (glucose concentration at a reference insulin secretion of 300 pmol.min(-1).m(-2) was 11.7 +/- 1.1 vs. 7.2 +/- 0.7 mmol/l; P < 0.05), and decreased in slope (53 +/- 15 vs. 148 +/- 38 pmol.min(-1).m(-2).mmol(-1).l; P < 0.05) and the parameter of the dynamic control was decreased (220 +/- 67 vs. 908 +/- 276 pmol.m(-2).mmol(-1).l; P < 0.05) compared with the nondiabetic control subjects. Furthermore, potentiation was markedly blunted and delayed: maximum potentiation was observed at the first meal in normal subjects and at the second meal (about 4 h later) in diabetic subjects; the mean time for the potentiation factor was higher (7.1 +/- 0.2 vs. 5.9 +/- 0.2 h; P < 0.01), and the size of potentiation was reduced (2.6 +/- 0.5 vs. 7.2 +/- 1.5 fold increase; P < 0.005). In conclusion, our model of insulin secretion extracts multiple indexes of beta-cell function from a physiological meal test. Use of the model in patients with type 2 diabetes retrieves known defects in insulin secretion but also uncovers new facets of beta-cell dysfunction.

Adult↗
PubMed2002

Investigation of promoter variants of the histamine 1 and 2 receptors in schizophrenia and clozapine response.

We report the identification of four novel histamine 1 (H1-17-C/T, -974-C/A, -1023-A/G and -1536-G/C) and four novel histamine 2 promoter polymorphisms (H2-294-A/G, -592-A/G, -1018-G/A and -1077-G/A) which we have investigated for involvement in susceptibility to schizophrenia, and in clinical response to clozapine treatment. We identified a weak independent association between variants at the H1-1536-G/C locus and schizophrenia, where an excess of the H1-1536-C allele was observed amongst such patients (P = 0.036). However upon correction for multiple testing this relationship was no longer statistically significant. Similar investigation of the H2 receptor polymorphisms revealed association between genotype at the H2-1018-G/A locus and clinical response to clozapine treatment (P = 0.027), though upon correction for multiple testing this difference was no longer significant. We have concluded that the participation of these variants in the disorder is unlikely, particularly in view of their apparent lack of function and unlikely influence on receptor expression. However their nature alludes to the potential presence of other more important alterations further along these regions, where sequences encoding alternate promoters have recently been identified for each receptor that may yet be found to harbour such polymorphisms.

Antipsychotic Agents↗
PubMed2002

Large-scale, high-throughput screening for coagulation and hematologic phenotypes in mice.

The Mouse Phenome Project is an international effort to systematically gather phenotypic data for a defined set of inbred mouse strains. For such large-scale projects the development of high-throughput screening protocols that allow multiple tests to be performed on a single mouse is essential. Here we report hematologic and coagulation data for more than 30 inbred strains. Complete blood counts were performed using an Advia 120 analyzer. For coagulation testing, we successfully adapted the Dade Behring BCS automated coagulation analyzer for use in mice by lowering sample and reagent volume requirements. Seven automated assay procedures were developed. Small sample volume requirements make it possible to perform multiple tests on a single animal without euthanasia, while reductions in reagent volume requirements reduce costs. The data show that considerable variation in many basic hematological and coagulation parameters exists among the inbred strains. These data, freely available on the World Wide Web, allow investigators to knowledgeably select the most appropriate strain(s) to meet their individual study designs and goals.

Animals↗
PubMed2005

Genome-wide associations of gene expression variation in humans.

The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs) with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis-) to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I) HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

Chromosome Mapping↗
PubMed1997

Power studies for the transmission/disequilibrium tests with multiple alleles.

Case-control studies compare marker-allele distributions in affected and unaffected individuals, and significant results suggest linkage but may simply reflect population structure. For markers with m alleles (m > or = 2), a McNemar-like statistic, I, estimates the level of population association between marker and disease loci. To test for linkage after significant case-control tests, within-family tests are performed. These operate on the contingency table, with i, jth element equal to the number of parents that transmit marker allele Mi and do not transmit marker allele Mi to an affected offspring. The dimension of the table is the number of alleles at the marker locus. Three test statistics have recently been proposed in the literature: Tc compares symmetric pairs of cells (i, j) and (j, i), Tm compares row and column totals for the same marker allele, and a likelihood ratio statistic Tl uses all the cells in the table. In addition, we consider a new statistic, Tmhet, that uses only the heterozygous parents and is approximately chi2 with (m - 1) df. We use a Monte Carlo test to guarantee valid tests and to demonstrate the inferiority of Tc and the equality of Tm and Tl in terms of power. The power of the Tmhet test is close but not always equal to the power of the Tm test. We also show that under the alternative hypothesis of linkage, Tm is approximately noncentral chi2 with (m - 1) df and noncentrality parameter 2NT(1 - 2theta)2I*, when data on single affecteds in NT families are used. If the disease has a low population frequency, then I* is estimated using the case-control statistic I. This offers a basis for choosing sample size, or choosing a marker system.

Alleles↗
PubMed1985

Serial delayed cutaneous hypersensitivity skin testing with multiple recall antigens in healthy volunteers: booster effect study.

Booster effects on delayed cutaneous hypersensitivity (DCH) responses have been demonstrated for various antigens when DCH is measured by the Mantoux technique. In the present study, we investigated this possibility when assessing DCH responses using the Multitest CMI multipuncture technique with simultaneous injections of seven test antigens and a control. The DCH responses were quantified for each antigen and for the overall DCH response expressed as a DCH score. In a group of healthy volunteers, DCH was repeatedly tested either 1 month apart or 2 months apart at least six times. When volunteers remained healthy, DCH variations were observed with only two of seven tested antigens: streptococcus which slowly decreased (P = .012) and proteus which slowly increased (P = .04). Responses to the other antigens and the DCH score remained stable. In contrast, greater DCH variations were observed when infections occurred. The results with the Multitest CMI multipuncture show that repeated application had minimal booster effect on DCH responses and may be used to evaluate and follow immunocompetence of patients.

Arm↗
PubMed1990

Intrathecal synthesis of virus antibodies: a diagnostic test for multiple sclerosis.

Intrathecally synthesized antibodies against measles and rubella were determined in 221 patients with multiple sclerosis (MS) and in 476 control cases. A local production was detectable in more than 80% of the MS cases but in none of the control group. These results show that the demonstration of intrathecally synthesized antibodies against neurotropic viruses not related with respective infections may serve as helpful test in the diagnosis of MS.

Antibodies, Viral↗
PubMed1992

k-ratio t tests for multiple comparisons involving several treatments and a control.

We consider the problem of simultaneously comparing several treatment means with a control mean and also with one another. Following an elementary decision-theoretic Bayesian approach requiring the choice of a type-I to type-II error-seriousness ratio k, a posteriori t tests are derived for testing both treatment versus control (TvC) and treatment versus treatment (TvT) differences. These k-ratio t tests are strictly comparisonwise in nature. That is, the test applied to any TvC or TvT difference d, depends in no way at all on whether the other differences are being tested. The test for d, however, does depend on the sizes of the other differences through tG, the standardized average of the observed TvC differences, and through FT, the observed between-treatments F ratio. From these adaptive dependences on tG and FT, the critical t values can be large or small, thus avoiding the intuitive objections of under- or over-conservatism in classical comparisonwise or experimentwise level testing rules.

Bayes Theorem↗
PubMed2004

Statistical significance threshold criteria for analysis of microarray gene expression data.

The methodological advancement in microarray data analysis on the basis of false discovery rate (FDR) control, such as the q-value plots, allows the investigator to examine the FDR from several perspectives. However, when FDR control at the "customary" levels 0.01, 0.05, or 0.1 does not provide fruitful findings, there is little guidance for making the trade off between the significance threshold and the FDR level by sound statistical or biological considerations. Thus, meaningful statistical significance criteria that complement the existing FDR methods for large-scale multiple tests are desirable. Three statistical significance criteria, the profile information criterion, the total error proportion, and the guide-gene driven selection, are developed in this research. The first two are general significance threshold criteria for large-scale multiple tests; the profile information criterion is related to the recent theoretical studies of the connection between FDR control and minimax estimation, and the total error proportion is closely related to the asymptotic properties of FDR control in terms of the total error risk. The guide-gene driven selection is an approach to combining statistical significance and the existing biological knowledge of the study at hand. Error properties of these criteria are investigated theoretically and by simulation. The proposed methods are illustrated and compared using an example of genomic screening for novel Arf gene targets. Operating characteristics of q-value and the proposed significance threshold criteria are investigated and compared in a simulation study that employs a model mimicking a gene regulatory pathway. A guideline for using these criteria is provided. Splus/R code is available from the corresponding author upon request.

Journal Article↗
PubMed1996

Multiple susceptibility testing: is it helpful?

This study explored whether or not the use of combined group and individually administered susceptibility tests improve the predictive power over the use of a singly administered test. Two hundred and eighty undergraduates were assigned to one of five groups: Group 1 received the HGSHS: A and then the SHSS:C; Group 2 the CIS and SHSS:C; Group 3 the HGSHS: A and the SHCS:A; Group 4 received the CIS and the SHCS:A; and Group 5 was tested on the SHSS:C alone. After the susceptibility screening the subjects were hypnotized and tested on four types of target hypnotic behaviors. From the RSPSHS:I&II the following four factors were chosen (1) cognitive distortion, (2) positive hallucination, (3) negative hallucination, (4) dreams and regression. The items were matched on difficulty level. The data were subjected to a series of stepwise multiple regression and logistic regression analyses. The results confirmed previous research; i.e., (1) The SHSS:C is the best single measure, (2) the SHCS:A is a poor substitute for the SHSS:C; (3) the HGSHS:A is not adequate substitute for SHSS:C; (4) the CIS is weak in predictive power compared to the HGSHS:A; (5) Only for a weak measure such as SHCS:A does combined testing produce an advantage; (6) There appear to be no warm-up effects for SHSS:C when preceded by HGSHS:A.

Adolescent↗
PubMed2005

Serotonin 2A receptor gene polymorphism and personality traits: no evidence for significant association.

A number of studies have observed associations between the serotonin 2A (5-HT2A) receptor and mental disorders. Here, we investigated correlations between polymorphisms (-1438G/A and 102T/C) of the 5-HT2A gene and personality traits in healthy Japanese volunteers (n = 239). The personality traits were evaluated using the Revised NEO Personality Inventory (NEO PI-R). The -1438G/A and 102T/C were in complete linkage disequilibrium. There was a tendency for associations between the genotype and the scores for Agreeableness, Conscientiousness and Neuroticism of the NEO PI-R (P = 0.028, 0.039 and 0.062, respectively; analysis of variance, uncorrected for multiple testing). Subjects with the A/A of -1438G/A (or T/T of 102T/C) appeared to be lower in Neuroticism and higher in Conscientiousness than the rest of the subjects. However, the results were statistically non-significant after Bonferroni's correction for multiple testing of the five scales of the NEO PI-R. Thus, the present study provided no evidence for statistically significant associations between the 5-HT2A polymorphisms and the personality traits.

Adult↗
PubMed2004

On a hybrid method in dose finding studies.

OBJECTIVES: Combination of multiple testing and modeling techniques in dose-response studies. Use of hypotheses tests to assess the significance of the dose-response signal associated with a given candidate dose-response model. Estimation of target dose(s) following the previous model selection step. Illustration of the method with a real data example. METHODS: We assume a set of candidate models potentially reflecting the data generating process. The appropriateness of each individual model is evaluated in terms of contrast tests, where each set of contrast weights describes a specific dose-response shape. Optimum contrast weights are computed, which maximize the non-centrality parameters associated with the contrast tests. A reference set of appropriate candidate models is obtained while controlling the familywise error rate. A single model is then selected from this reference set using standard model selection criteria. The final step is devoted to dose finding by applying inverse regression techniques. This is illustrated for estimating the minimum effective dose. RESULTS: The method is as powerful as competing standard dose-response tests to detect an overall dose-related trend. In addition, the possibility is given to estimate one or more target doses of interest. The analysis of a real data example confirms the advantages of the proposed hybrid method. CONCLUSIONS: Combining multiple testing and modeling techniques leads to a powerful tool, which uses the advantages of both approaches: Rigid error control at the significance testing step and flexibility at the dose estimation step. The method can be extended to handle more general linear models including covariates and factorial treatment structures.

Clinical Trials as Topic↗
PubMed1998

A quantile plot for simultaneous representation of clinical and statistical attributes of probing change: application to early identification of the downhill patient.

When multiple periodontal sites are observed in patients over time there is an intention to identify those sites where there is important change, typically loss of attachment or increase in probing depth. A change may be declared if it: (a) exceeds a threshold level, and/or (b) is determined to be statistically significant (e.g. regression slope different from zero), perhaps after (c) that significance level has been corrected for multiple testing. These criteria are not often considered when clinical or research decisions are made and there is no universal protocol for their evaluation. A quantile (uniform probability) plot, modified to incorporate additional information, is proposed as a graphical method for the display of changes at multiple sites within a mouth. This plot identifies, for each site, clinical changes beyond a threshold, site-wise statistical significance and statistical significance adjusted for multiple testing. These alternative criteria for attachment change are, thereby, made explicit, providing a detailed evaluative context. In addition, this methodology permits incorporation of an estimation procedure for the number of sites for which the null hypothesis of no change is false. This statistic can provide evidence of progressive disease even when no site has significant clinical or statistical change and even if the average change is zero. Use of the quantile plot was elucidated by application to simulated data, and to a clinical dataset using a BASIC program to automate the computational process. In the clinical example presented, the approach appeared more effective in detecting periodontal change than traditional clinical and statistical criteria. Pending technical refinement, this graphical approach may represent a new tool for the early identification of the downhill patient.

Adult↗
PubMed1990

Biochemical heterozygosity and morphological variability: interpopulational versus intrapopulational analyses.

The literature is replete with articles suggesting the existence of a relationship between variability at biochemical loci and morphological variation in various animal populations, including humans. With few exceptions these previous studies have utilized an interpopulational approach by examining levels of heterozygosity between modal and extreme phenotypes, typically by use of analysis of variance. Here we consider these purported relationships in a midwestern Mennonite population (n = 890) by correlating individual biochemical heterozygosity and deviation from the mean for anthropometric traits. The results of this intrapopulational correlation indicate that (1) with protection for multiple tests, there are few significant correlations and these have low R2 values, and (2) males and females show different patterns of correlation (males negative, females positive). Based on these findings, the results of earlier studies are in question because nonprotected alpha values are used for multiple tests and heterozygosity is calculated on the basis of a few highly heterozygous blood group systems and is assumed to be representative of the heterozygosity for the entire genome. In general, no evidence is found to support the concept of a direct relationship between biochemical heterozygosity and morphological variability.

Adolescent↗
PubMed1995

Multivariate tests for multiple endpoints in clinical trials.

Clinical trials frequently lack a single definitive endpoint that completely describes treatment efficacy. When a treatment affects a disease in a multitude of ways, several endpoints are necessary to describe efficacy. There is a variety of statistical procedures to provide a single p-value when a treatment affects several endpoints. This paper reviews several procedures including Hotelling's T2 test, an approximate likelihood ratio test (Tang et al.), the weighted version of O'Brien's test, tests involving the maximum of several test statistics, and a test based on the average of the maximum of several endpoints (Wittes). I propose a risk score test whose rejection boundary corresponds to a contour of constant risk. Calculations and simulation studies help to compare the different tests with an emphasis on the effect of non-standard alternatives, and on identifying settings where some tests may lack clinical relevance.

Bias↗