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PubMed1980

[Leukocyte migration inhibition test in multiple sclerosis - results of a migration technic according to Clausen using brain specific antigens].

The leukocyte migration inhibitory factor (LIF) was examined in 57 test persons--27 patients with multiple sclerosis (MS) and 30 normals--with the indirect and the direct leucocyte migration inhibition test in agarose (LMIAT). The stimulation of lymphocytes was carried out by the application of myelin basic protein (BP) and a membrane-associated antigen of normal brain (NTA). The mean value of controls +/- 2 s and the migration index less than or equal to 0,80 were used for limiting. In the indirect technique could be established significant group effects (NTA- and BP-values of MS cases compared to the controls) after 10 hours of incubation. The direct method showed in MS patients a significant lowered migration-index on an average after stimulation with the NTA; controls gave negative findings (except two cases). The valence of the test system and prospective modifications for further results were indicated.

Adult↗
PubMed2005

Multiplicity issues in microarray experiments.

OBJECTIVES: Discussion of different error concepts relevant to microarray experiments. Review of some commonly used multiple testing procedures. Comparison of different approaches as applied to gene expression data. METHODS: This article focuses on familywise error rate (FWER) and false discovery rate (FDR) controlling procedures. Methods under investigation include: Bonferroni-type methods and their improvements (including resampling approaches), modified Bonferroni methods, data-driven approaches, as well as the linear step-up method and its modifications. Particular emphasis lies on the description of the assumptions, advantages and limitations for the investigated methods. RESULTS: FWER controlling procedures are often too conservative in high dimensional screening studies. A better balance between the raw P-values and the stringent FWER-adjusted P-values may be required in many situations, as provided by FDR controlling and related procedures. CONCLUSIONS: The questions remain open, which error concept to apply and which multiple testing procedure to use. Although we believe that the FDR or one of its variants will be applied more often in the future, longterm experience with microarray technology is missing and thus the validity of appropriate multiple test procedures cannot yet be assessed for microarray data analysis.

Algorithms↗
PubMed2005

Analysis of single-locus tests to detect gene/disease associations.

A goal of association analysis is to determine whether variation in a particular candidate region or gene is associated with liability to complex disease. To evaluate such candidates, ubiquitous Single Nucleotide Polymorphisms (SNPs) are useful. It is critical, however, to select a set of SNPs that are in substantial linkage disequilibrium (LD) with all other polymorphisms in the region. Whether there is an ideal statistical framework to test such a set of 'tag SNPs' for association is unknown. Compared to tests for association based on frequencies of haplotypes, recent evidence suggests tests for association based on linear combinations of the tag SNPs (Hotelling T(2) test) are more powerful. Following this logical progression, we wondered if single-locus tests would prove generally more powerful than the regression-based tests? We answer this question by investigating four inferential procedures: the maximum of a series of test statistics corrected for multiple testing by the Bonferroni procedure, T(B), or by permutation of case-control status, T(P); a procedure that tests the maximum of a smoothed curve fitted to the series of of test statistics, T(S); and the Hotelling T(2) procedure, which we call T(R). These procedures are evaluated by simulating data like that from human populations, including realistic levels of LD and realistic effects of alleles conferring liability to disease. We find that power depends on the correlation structure of SNPs within a gene, the density of tag SNPs, and the placement of the liability allele. The clearest pattern emerges between power and the number of SNPs selected. When a large fraction of the SNPs within a gene are tested, and multiple SNPs are highly correlated with the liability allele, T(S) has better power. Using a SNP selection scheme that optimizes power but also requires a substantial number of SNPs to be genotyped (roughly 10-20 SNPs per gene), power of T(P) is generally superior to that for the other procedures, including T(R). Finally, when a SNP selection procedure that targets a minimal number of SNPs per gene is applied, the average performances of T(P) and T(R) are indistinguishable.

Computer Simulation↗
PubMed1998

The ebb and flow of infant attentional preferences: evidence for long-term recognition memory in 3-month-olds.

Using paired-comparisons, 3-month-olds' (n = 148) recognition of dynamic visual events was investigated after retention intervals of 1 minute, 1 day, and 1 and 3 months (Experiment 1) and 1 minute, 1 day, and 1 week (Experiment 2). Participants were either tested at each retention interval (Multiple Tests) or tested at one interval (Single Test). The proportion of total looking time to the novel event and the length of the longest look to novel and familiar events in the first 15 s of the retention test revealed significant novelty preferences at 1 minute and 1 day and a null preference at 1 week for Multiple- and Single-Test groups. At 1 month, Multiple- (Proportion of Total Looking Time and Longest Look) and Single-Test groups (Longest Look only) preferred the familiar event. The 3-month test revealed a familiarity preference (both measures) for Single- and a null preference for Multiple-Tests groups. This changing pattern of attentional preferences is consistent with models of infant recognition memory in which novelty, familiarity, and null preferences are considered conjointly and hypothesized to reflect the accessibility of novel and familiar event representations in memory.

Analysis of Variance↗
PubMed1999

Nonparametric step-down test procedures for finding minimum effective dose.

Nonparametric versions of normal theory step-down multiple-test procedures for inferring minimum effective dose (see Tamhane et al. (1)) were developed and studied by Monte Carlo simulation. Two types of step-down testing procedures were examined. For both procedures, pairwise, linear, or Helmert contrasts of mean ranks were studied. All nonparametric step-down procedures controlled familywise error rate under normal, double exponential, and exponential distributions. Specific recommendations based on power and bias comparisons of nonparametric methods among themselves, with Shirley's (2) test, and with parametric step-down multiple-test procedures are given.

Computer Simulation↗
PubMed1985

The hot bath test in multiple sclerosis: comparison with visual evoked responses and oligoclonal bands.

We studied 50 patients with definite, probable, and possible multiple sclerosis (MS), prospectively (20 patients) and retrospectively (30 patients), to determine the value of the hot bath test for diagnosing MS and to compare it to visual evoked responses and oligoclonal bands. The hot bath test was abnormal in 8 of the 23 patients with definite MS (35%), and 4 of the 27 patients with probable or possible MS (15%). Only one patient with an abnormal hot bath test did not also have other evidence of definite multiple sclerosis. Our results suggest that the hot bath test seldom adds diagnostic information, especially when tests for evoked responses and oligoclonal bands are available.

Adult↗
PubMed2005

Not all errors are created equal: metacognition and changing answers on multiple-choice tests.

Two experiments investigated the role of metacognition in changing answers to multiple-choice, general-knowledge questions. Both experiments revealed qualitatively different errors produced by speeded responding versus confusability amongst the alternatives; revision completely corrected the former, but had no effect on the latter. Experiment 2 also demonstrated that a pretest, designed to make participants' actual experience with answer changing either positive or negative, affected the tendency to correct errors. However, this effect was not apparent in the proportion of correct responses; it was only discovered when the metacognitive component to answer changing was isolated with a Type 2 signal-detection measure of discrimination. Overall, the results suggest that future research on answer changing should more closely consider the metacognitive factors underlying answer changing, using Type 2 signal-detection theory to isolate these aspects of performance.

Analysis of Variance↗
PubMed1970

Value of routine multiple blood tests in patients attending the general practitioner.

The paper describes the investigation of 296 patients selected at random from those attending the general practitioners' surgery and studied by means of multiple biochemical and haematological tests. The tests that would not normally have been requested led to a new diagnosis of clinical significance in 16.9% of patients, in most instances requiring an alteration of the patient's therapy. The effect of the profile tests on patient follow-up, referral of patients to hospital, and the need for subsequent investigations was studied by comparing the patients profiled with a control group of patients not having a blood profile. The place of such an investigation in general practice is considered.

Adolescent↗
PubMed1979

Analysis of answer changes by dental students on multiple choice tests in pathology: attack on an educational myth.

The outcome of answer changes on multiple choice examination questions was studied in four groups. Roughly 80 percent of changes profited students or left final numbers of errors unaffected. The ratio of number of wrong to right changes/right to wrong changes ranged from 2.5:1 to 6.2:1. These changes deviated very significantly from chance expectations. The ratio of percent of changers profiting to losing ranged from 3.2:1 to 11.7:1. Revisions resulted in clearly significant decreases in prechange numbers of errors, leading to a mean gain per answer changer of 2.4 to 5.3 percent in test score. Findings were consistent with those of others gathered from different populations and disciplines. Together, they dispel the myth that changing initial responses more often is detrimental than beneficial. Students should be encouraged to review their examinations, and to change answers if they have reason.

Attitude↗
PubMed1991

Comparing assessments of students' knowledge by computerized open-ended and multiple-choice tests.

At the State University of New York at Buffalo School of Medicine and Biomedical Sciences, interactive computerized tests that accept unrestricted natural-language input were used to assess the knowledge of medical students in a sophomore course on clinical biophysics in 1989. The course covered the physical bases, scopes, and limitations of the most widely used diagnostic, therapeutic, and prosthetic technologies. The test was composed of both open-ended sequential questions and multiple-choice questions on the same material. The scores for the two testing modes were correlated, paying special attention to answers that demonstrated a flagrant lack of knowledge, corroborated by subsequent answers. The correlation between the qualities of the answers for the two testing modalities was found to be significantly positive for the lower half of the class of students and negative for the upper half, suggesting that the two modes of testing measure different aspects of competence. The implications of the findings to medical education and accreditation are discussed.

Clinical Competence↗
PubMed1988

A multiple muscle strength testing protocol.

A quick test (QT) protocol was developed to allow for the rapid testing of multiple muscle groups in order to profile body strength. Maximum muscle strength was also obtained using a standard test (ST) protocol. The ST protocol consisted of three five-second trials with a one-minute rest between trials and no more than four muscle groups tested per day. The QT protocol allowed only a five-second rest between trials. Thirteen subjects were evaluated using both protocols. Subjects were positioned either sitting or supine, depending on the muscle groups being evaluated. Stabilization was provided to minimize substitution patterns. Measurements were obtained using a load cell and a computerized recording system. Using the QT protocol and testing 13 muscle groups in one session vs five sessions with the ST protocol resulted in an average reduction of 4% in strength values for the QT protocol. The results suggest that the clinical use of the QT protocol may not significantly reduce the accuracy of repeated measurements even though values obtained may be slightly lower than those obtained using the ST protocol.

Adult↗
PubMedDate not supplied

[Multiple latency test in a patient with episodes of sleep induced by pergolide].

OBJECTIVE: Recently, there have been report sleep attacks in parkinsonian patients as a side effect of pramipexole and ropinirole. We report a patient with similar episodes related with pergolide. CASE REPORT: A 64 year old man with rigid akinetic parkinsonism, treated with carbidopa/levodopa and pergolide, developed sudden, irresistible sleep episodes after increasing the dose of pergolide to 2.25 mg/day because of bad control of parkinsonian symptoms. These episodes started 30 minutes after each dose of pergolide and lasted 2 hours. Following reduction of the dose of pergolide to 1.5 mg/day the sleep episodes disappeared. Two double blind multiple sleep latency tests were performed, one after intaking pergolide and other after intaking placebo. RESULTS: The latencies to sleep onset were lower with pergolide than with placebo, but the differences did not reach statistical significance. There was no premature REM sleep onset. CONCLUSION: Sleep episodes are likely a not specific effect of dopamine agonists

Antiparkinson Agents↗
PubMed2006

Reliability of predictors of study success in medicine.

AIM: Examination of the reliability of predictors for study success found in a prospective study in the year 2002/03. We report the results of a retest in an unselected students' sample taken from the following academic year 2003/04. METHODS: In a comparison of successful and unsuccessful students in their first year at the Medical University of Vienna, four predictors for study success had been found (using a questionnaire in a prospective design). In a re-examination of this study, after testing for representativeness, all P values were first subjected to adjustment for multiple testing. Secondly, the items were retested in a student sample drawn in 2003/04 using the same procedures. RESULTS: After Finner's adjustment for multiple testing, the four predictors (male sex, German mother tongue, performance at school, learning capacity and learning style) were confirmed. In the students' sample of 2003/04, eighteen out of 22 items remained significant. CONCLUSION: The majority of the prognostic factors found are reliable.

Adult↗
PubMed2005

Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic laboratory.

PURPOSE: Based on results of diagnostic MEN1 testing, we have attempted to further define the mutational spectrum of the MEN1 gene and the clinical features most frequently associated with MEN1 mutations. METHODS: Mutation testing was performed on blood samples by PCR amplification and sequencing of exons 2 to 10 of the MEN1 gene and the corresponding intron-exon junctions. Pedigree phenotypic information was obtained by written questionnaire. RESULTS: Among 288 presumably unrelated pedigrees, 73 independent mutations were found in 89 families. Five mutations were found in 2 pedigrees, and 4 mutations were seen in more than 2 pedigrees. There were 17 nonsense mutations (23.3%), 2 in-frame deletions (2.7%), 18 frameshift-deletion mutations (24.7%), 10 frameshift-insertion or -duplication mutations (13.7%), 13 splice-site mutations (17.8%), and 13 presumptive missense mutations (17.8%). Thirty-nine of 56 pedigrees with parathyroid and pancreatic islet neoplasia tested positive, compared with 4/24 and 8/32 pedigrees affected with hyperparathyroidism or hyperparathyroidism and pituitary tumors. MEN1 mutations were found in 6/20 sporadic patients, all of whom had both parathyroid and pancreatic neoplasms. Of 14 mutation-negative sporadic patients, 10 exhibited hyperparathyroidism and pituitary tumors without islet cell neoplasia. Somatic mosaicism was detected in 1 sporadic patient. CONCLUSION: Patients from pedigrees with hyperparathyroidism and pancreatic islet tumors are most likely to test positive for MEN1 mutations. Mutations are less often detected in patients from pedigrees with hyperparathyroidism alone or in combination with pituitary tumors without pancreatic islet neoplasia. Sporadic cases are less likely to test positive than familial cases, in part due to somatic mosaicism.

Adenoma, Islet Cell↗
PubMed2004

Using alpha wisely: improving power to detect multiple QTL.

The increase in the number of available markers for many experimental populations has led to QTL studies with ever increasing marker numbers and densities. The resulting conundrum is that as marker density increases, so does the multiple testing problem. It is important to re-examine the detection of multiple QTL in light of increasing marker density. We explore through simulation whether existing methods have achieved the maximum possible power for detecting multiple QTL and whether increasing the marker density is an effective strategy for locating multiple QTL. In addition to existing methods, such as the maximum, the CET, and the Benjamini-Hochberg and Benjamini-Yekutieli procedures, we propose and evaluate the complete set of order statistics with their corresponding empirical joint distribution. We examine these statistics in conjunction with a novel application of the alpha-spending approach, providing a less conservative solution to the problem of controlling the false discovery rate (FDR) in multiple tests. We conducted a simulation study to assess the relative power of these approaches as well as their ability to control FDR. We find that several of the new approaches have a reasonable FDR, and can substantially improve the experimenter's ability to detect multiple QTL compared to existing approaches in many cases; however, the Benjamini-Hochberg procedure remains a very reasonable choice. The methods are applied to a nine-trait Oat vernalization dataset.

Journal Article↗
PubMed1987

Antimicrobic susceptibility and plasmid profile analysis as identity tests for multiple blood isolates of coagulase-negative staphylococci.

We compared a disk diffusion antimicrobic susceptibility panel with plasmid DNA profiles as tests for identity of 106 isolates of coagulase-negative staphylococci cultured from the blood of 45 patients on multiple occasions. The antimicrobic panel included penicillin, oxacillin, clindamycin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, tobramycin, kanamycin, and gentamicin. Nineteen patterns of antimicrobic susceptibility were found. The most common pattern was present in 25% of the isolates, and at least one isolate from 31% of the patients had this pattern. Forty-seven distinct plasmid DNA profiles were found. The most common plasmid profile was present in 8.5% of the isolates, and at least one isolate from 15% of the patients had this profile. Twenty-eight patients had multiple isolates that were identical by plasmid profile analysis. Twenty-seven (96%) of these patients had isolates that were also identical by antimicrobic susceptibility. Nineteen patients had multiple isolates that were different by plasmid profile analysis. In 18 (95%) of these patients, the isolates were also different by antimicrobic susceptibility. Although plasmid DNA profile analysis is a more discriminating tool, these data confirm that a selected disk diffusion antimicrobic susceptibility panel may be used to screen multiple blood isolates of coagulase-negative staphylococci for identity or differences.

Anti-Bacterial Agents↗