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PubMed1995

Chromosomal instability in multiple endocrine neoplasia type 1. Cytogenetic evaluation with DEB test.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant condition with high penetrance and variable expressivity, in which tumors or hyperplasia occur in two or more endocrine organs. Some authors have investigated chromosomal instability in MEN 1 and MEN 2; the results are controversial. Chromosome analyses were performed on lymphocytes from seven patients with MEN 1, four healthy first-degree relatives (three of whom were children), six phenotypically normal volunteers, and three patients with Fanconi's anemia. To evaluate chromosomal instability we analyzed phytohemagglutinin-stimulated lymphocyte cultures with and without diepoxibutane. We observed an increase in the frequency of spontaneous chromosomal alterations in four patients. After the DEB test we found an increase in chromatid breakages, gaps, and exchange figures. These findings support the inclusion of the MEN 1 syndrome among the disorders with "chromosomal instability."

Adult↗

PubMed1978

[Application of the multiple vocabulary test to assessing mental disorders].

The multiple vocabulary test has been used to investigate approaches to objectifying general mental deterioration. Compared to methods used to determine the actual level of intelligence, the premorbid levels of intelligence which were determined with the use of the multiple vocabulary test were roughly the same for patients with brain injuries that cannot be detected by means of specialized instruments. In the case of patients where brain injuries were detectable through the use of instruments, the premorbid level of intelligence was significantly higher than the actual intelligence level. Patients with general mental deterioration showed highly significant differences between premorbid and actual levels of intelligence. The results obtained indicate that the multiple vocabulary test is a useful means of diagnosing general mental deterioration due to organic or psychological factors. Also discussed by the authors in their present paper are hitherto unsolved problems that stand in the way of an objective diagnosis of dementia and loss of intelligence.

Humans↗

PubMed2005

Nonparametric tests of association of multiple genes with human disease.

The genetic basis of many common human diseases is expected to be highly heterogeneous, with multiple causative loci and multiple alleles at some of the causative loci. Analyzing the association of disease with one genetic marker at a time can have weak power, because of relatively small genetic effects and the need to correct for multiple testing. Testing the simultaneous effects of multiple markers by multivariate statistics might improve power, but they too will not be very powerful when there are many markers, because of the many degrees of freedom. To overcome some of the limitations of current statistical methods for case-control studies of candidate genes, we develop a new class of nonparametric statistics that can simultaneously test the association of multiple markers with disease, with only a single degree of freedom. Our approach, which is based on U-statistics, first measures a score over all markers for pairs of subjects and then compares the averages of these scores between cases and controls. Genetic scoring for a pair of subjects is measured by a "kernel" function, which we allow to be fairly general. However, we provide guidelines on how to choose a kernel for different types of genetic effects. Our global statistic has the advantage of having only one degree of freedom and achieves its greatest power advantage when the contrasts of average genotype scores between cases and controls are in the same direction across multiple markers. Simulations illustrate that our proposed methods have the anticipated type I-error rate and that they can be more powerful than standard methods. Application of our methods to a study of candidate genes for prostate cancer illustrates their potential merits, and offers guidelines for interpretation.

Case-Control Studies↗

PubMed1998

Writing cognitive educational objectives and multiple-choice test questions.

Guidelines for writing cognitive objectives and multiple-choice test questions for pharmacy educational programs are suggested. Cognitive educational objectives relate to intellectual skills and can usually be tested with multiple-choice questions. Pharmacy educators writing cognitive objectives should focus on the major, not minor, knowledge or skills that participants in an educational program are expected to acquire; ensure that the objectives are supported by instruction; define the desired performance of the learners; ensure that the objectives are observable and measurable; and define the learning level for each objective (i.e., knowledge, comprehension, application, analysis, synthesis, or evaluation). Each multiple-choice test question should be written with a view to assessing the learner's achievement of one of the stated objectives. Educators should write test questions that are clear and concise, are in the form of complete sentences, include one clearly correct or best response, are phrased positively rather than negatively, and give no clues as to the correct answer. The learning level of each question should match that of the objective the question is designed to test. Educators should weight tests fairly by including the same number of questions for each objective. It may be necessary to include some higher-level questions to ensure assessment of the competence level at which the program is aimed. Cognitive educational objectives should be observable and measurable; multiple-choice test questions should correspond to specific objectives and be based on the appropriate learning level.

Education, Pharmacy↗

PubMed2003

Statistical analysis of microarray data: a Bayesian approach.

The potential of microarray data is enormous. It allows us to monitor the expression of thousands of genes simultaneously. A common task with microarray is to determine which genes are differentially expressed between two samples obtained under two different conditions. Recently, several statistical methods have been proposed to perform such a task when there are replicate samples under each condition. Two major problems arise with microarray data. The first one is that the number of replicates is very small (usually 2-10), leading to noisy point estimates. As a consequence, traditional statistics that are based on the means and standard deviations, e.g. t-statistic, are not suitable. The second problem is that the number of genes is usually very large (approximately 10,000), and one is faced with an extreme multiple testing problem. Most multiple testing adjustments are relatively conservative, especially when the number of replicates is small. In this paper we present an empirical Bayes analysis that handles both problems very well. Using different parametrizations, we develop four statistics that can be used to test hypotheses about the means and/or variances of the gene expression levels in both one- and two-sample problems. The methods are illustrated using experimental data with prior knowledge. In addition, we present the result of a simulation comparing our methods to well-known statistics and multiple testing adjustments.

Algorithms↗

PubMed2004

Total retrieval time and hypermnesia: investigating the benefits of multiple recall tests.

Hypermnesia is an increase in recall over repeated tests. A core issue is the role of repeated testing, per se, versus total retrieval time. Prior research implies an equivalence between multiple recall tests and a single test of equal total duration, but theoretical analyses indicate otherwise. Three experiments investigated this issue using various study materials (unrelated word lists, related word lists, and a short story). In the first experimental session, the study phase was followed by a series of short recall tests or by a single, long test of equal total duration. Two days later, participants took a final recall test. The multiple and single test conditions produced equivalent performance in the first session, but the multiple test group exhibited less forgetting and fewer item losses in the final test. In a fourth experiment, using a brief delay (15 min) between the recall sessions, the multiple recall condition produced greater hypermnesia as well as fewer item losses. In addition, final recall was significantly higher in the multiple than in the single test condition in three of the four experiments. Thus, single and repeated recall tests of equal total duration are not functionally equivalent, but rather produce differences observable in subsequent recall tests.

Analysis of Variance↗

PubMed1983

Multimodality evoked potentials and neurophysiological tests in multiple sclerosis. Effects of hyperthermia on test results.

Data on critical frequency of photic driving (CFPD), frequency following response (FFR), and visual, somatosensory (peroneal nerve), and brain-stem auditory evoked potentials (EPs) were obtained from 20 patients who had clinically definite multiple sclerosis and ten healthy normal subjects in a controlled, balanced study under normothermic and hyperthermic (+1 degrees C) conditions with a test-retest interval of one week. Normal subjects' test results showed no changes during hyperthermia. Patients' EP and CFPD data correlated well with history, clinical signs, and symptoms during both normothermia and hyperthermia. The FFR test data were equivocal and not fully analyzed. Data from the four other tests showed additional patient abnormalities during hyperthermia. Multimodality testing increased the number of patient abnormalities compared with single tests, and the number increased further during hyperthermia. Test-retest reproducibility was higher during hyperthermia.

Adult↗

PubMed2006

Clinical impact of 20% worsening on Timed 25-foot Walk and 9-hole Peg Test in multiple sclerosis.

INTRODUCTION: Quantitative tests of motor function, like the Timed 25-foot Walk (T25FW) and 9-hole Peg Test (9HPT), are increasingly being applied as outcome measures in multiple sclerosis (MS) clinical trials. The quantitative nature of the data has a favorable impact on responsiveness, but the clinical impact of the changes is uncertain. The goal of this study was to assess whether a change on T25FW and 9HPT does indeed have a clinical meaning. This was accomplished by comparing 20% changes on these quantitative measurements to concomitant changes on the Guy's Neurological Disability Scale (GNDS), a scale which measures patient-perceived daily life disability. METHODS: From a longitudinal database, we selected patients with at least two measurements of T25FW, 9HPT and GNDS with a minimal time interval of 350 days. In those patients who experienced at least a 20% change on T25FW or 9HPT, GNDS score changes were examined more closely. RESULTS: Of 527 patients, 143 experienced a >20% worsening on their T25FW and 71 on their 9HPT, respectively. Patients with a 20% increase in T25FW or 9HPT had more GNDS worsening than patients without such an increase. GNDS worsening associated with an increase in T25FW was mainly due to an increase in perceived disability related to lower extremity function and fatigue; GNDS worsening associated with an increase in 9HPT was more diffuse with respect to domains involved. CONCLUSION: Worsening on T25FW or 9HPT has a clinical impact on disability, as perceived by MS patients during daily life functioning.

Adult↗

PubMed1997

The latent class model for multiple binary screening tests.

Given multiple binary tests, such as repeated application of a blind screening test to each individual in a sample, we attempt to estimate the prevalence, sensitivity and specificity of the test without knowing the true disease status of those tested (gold standard). This problem is equivalent to finding the mixing distribution of a mixture of binomial distributions. We suggest a new method to determine the number of latent classes. Our simulations show that the coverage probabilities of the bootstrap confidence intervals of our estimates are correct. Our methods are illustrated by examples from published medical research.

Algorithms↗

PubMed2000

Evaluation of prostate cancer patients receiving multiple staging tests, including ProstaScint scintiscans.

BACKGROUND: Multiple serum tests were performed on archival samples from patients who participated in trials to assess the ProstaScint scan staging ability. Traditional statistical analysis as well as artificial neural network (ANN) analysis were employed to evaluate individual patients and the group as a whole. The results were evaluated so that each factor was tested for prognostic value. METHODS: Data obtained from serum tests, bone scans, and ProstaScint scans were evaluated by traditional statistical methods and ANN to determine the individual value in clinical staging of prostate cancer. RESULTS: Two hundred seventy-five patients (180 postprostatectomy, 95 intact prostate) with prostate cancer (14 with distant metastases) were available for analysis. Data available included: clinical state (remission or progression), most recent clinical TNM stage, bone scan, and ProstaScint scan. Serum was tested for prostate-specific membrane antigen(PSMA), prostate-specific antigen(PSA), free PSA (fPSA), and complexed PSA (cPSA). Additional calculations included percent free PSA, and percent complexed PSA. Spearman individual statistical assessment for traditional group evaluation revealed no significant factors for T-stage. The free PSA and complex PSA had a significant association with node (N)-status. The distant metastases (M) stage correlated well with the bone scan and clinical stage. ANN analysis revealed no significant T-stage factors. N-stage factors showed a 95% sensitivity and 49% specificity. These factors included the presence or absence of a prostate, PSA serum levels, bone scan, and ProstaScint scans as major associated indicators. ANN analysis of the important variables for M-stage included ProstaScint scan score, and PSA levels (total, percent complexed, percent free, and fPSA). These factors were associated with a 95% sensitivity and 15% specificity level. CONCLUSIONS: Two hundred seventy-five patients receiving treatment for prostate cancer were evaluated by ANN and traditional statistical analysis for factors related to stage of disease. ANN revealed that PSA levels, determined by a variety of ways, ProstaScint scan, and bone scan, were significant variables that had prognostic value in determining the likelihood of nodal disease, or distant disease in prostate cancer patients.

Bone and Bones↗

PubMed2006

Tests of multiplicative models in psychology: a case study using the unified theory of implicit attitudes, stereotypes, self-esteem, and self-concept.

Theories that posit multiplicative relationships between variables are common in psychology. A. G. Greenwald et al. recently presented a theory that explicated relationships between group identification, group attitudes, and self-esteem. Their theory posits a multiplicative relationship between concepts when predicting a criterion variable. Greenwald et al. suggested analytic strategies to test their multiplicative model that researchers might assume are appropriate for testing multiplicative models more generally. The theory and analytic strategies of Greenwald et al. are used as a case study to show the strong measurement assumptions that underlie certain tests of multiplicative models. It is shown that the approach used by Greenwald et al. can lead to declarations of theoretical support when the theory is wrong as well as rejection of the theory when the theory is correct. A simple strategy for testing multiplicative models that makes weaker measurement assumptions than the strategy proposed by Greenwald et al. is suggested and discussed.

Humans↗

PubMed2004

Comparative analysis of gene sets in the Gene Ontology space under the multiple hypothesis testing framework.

The Gene Ontology (GO) resource can be used as a powerful tool to uncover the properties shared among, and specific to, a list of genes produced by high-throughput functional genomics studies, such as microarray studies. In the comparative analysis of several gene lists, researchers maybe interested in knowing which GO terms are enriched in one list of genes but relatively depleted in another. Statistical tests such as Fisher's exact test or Chi-square test can be performed to search for such GO terms. However, because multiple GO terms are tested simultaneously, individual p-values from individual tests do not serve as good indicators for picking GO terms. Furthermore, these multiple tests are highly correlated, usual multiple testing procedures that work under an independence assumption are not applicable. In this paper we introduce a procedure, based on False Discovery Rate (FDR), to treat this correlated multiple testing problem. This procedure calculates a moderately conserved estimator of q-value for every GO term. We identify the GO terms with q-values that satisfy a desired level as the significant GO terms. This procedure has been implemented into the GoSurfer software. GoSurfer is a windows based graphical data mining tool. It is freely available at http://www.gosurfer.org.

Algorithms↗

PubMed1983

An exact linkage test for multiple case families.

A test of linkage that is exact even in small samples is developed for multiple case families, together with large-sample theory for estimation and supplementary tests. Hemochromatosis, insulin-dependent diabetes, and celiac disease are compatible with an intermediate model biased toward recessivity on the penetrance scale, whereas multiple sclerosis favors dominance and unlinked modifiers. Alternatives to the model are complex, and comparison of affected sib pairs with larger sets of relatives provides no critical evidence of epistasis. Problems of sampling and inference are discussed.

Epidemiologic Methods↗

PubMed1976

Utilisation of multiple biochemical tests in a large general hospital.

This report gives an account of the patterns of requesting of multiple biochemical tests in a large general hospital and the frequency of abnormal test results in different hospital departments. There are appreciable differences between some areas in the frequency of requests for multiple testing and in the proportions of abnormal results. If it is assumed that clinicians should be aware of abnormal values and their progress, facilities for multiple testing are desirable and economically justifiable.

Chemistry, Clinical↗

PubMed1992

The Multiple Sleep Latency Test: a paradoxical test?

The Multiple Sleep Latency Test (MSLT) has gradually gained acceptance as an objective equivalent of the complaint of sleepiness. The history of this test and questions considering the validity of the MSLT in different situations are discussed.

Arousal↗

PubMed2002

[Precision and economy of skin prick tests].

Due to a rise in the number of cases of allergic disease and a need to increase financial resources for the diagnosis of these conditions, the possibility of reducing costs of skin pricks tests (SPT) was very welcome. In an attempt to reduce costs some practitioners use one lancet for several pricks in one patient. The purpose of this study was to determine whether this way of performing SPT influences the results. 52 subjects with (39) and without (13) atopy were tested with histamine, codeine and standard allergen extracts. SPT were applied to the volar surface of a randomly assigned forearm using two methods: one lancet-one prick on one forearm (single test method) and one lancet-multiple pricks ("multiple test" method) on the other. The false positive tests at the placebo site following allergen were recorded only in multiple test method, in 41 out of 72 pricks (p < 0.00001) when all reactions above baseline were considered and in 26 out of 72 (p = 0.00001) when a 3 mm cut-off was considered. The size of the false positive reaction depends on the intensity of the reaction to the preceding allergen (rang Spearman factor R = 0.706, p < 0.000001) and decreases in the second consecutive placebo test. Our data show that one lancet for multiple test method cannot be used to diagnose factors responsible for allergy, particularly in patients qualified for immunotherapy and in scientific studies. For financial reasons multiple test method can be used in screening and epidemiological studies where atopy is studied and there is no need to identify the specific allergen.

Adult↗

PubMed2003

Experimental study of rapid versus slow sagittal sinus occlusion in dogs.

BACKGROUND: Clinical, radiological, postmortem and experimental studies are not enough for the definition of pathophysiological differences between rapid and slow-progressing cerebral venous system obstruction. AIMS: An experimental study was conducted to set some physiopathological differences between rapid and slow occlusion of the superior sagittal sinus. SETTINGS AND DESIGN: Eighteen dogs categorized into 3 groups were chosen as test subjects. The three groups were the rapid occlusion, slow occlusion and the control study groups and each group had six subjects. MATERIAL AND METHODS: Intracranial pressure values, histopathological findings, and the degree of cerebral edema formation, estimated by measuring the water content ratio of the brain and the angiographic results in the 2 different groups of subjects that underwent rapid and slow superior sagittal sinus obstruction were compared with that of the control subjects. STATISTICAL ANALYSIS: Statistical analysis was performed using GraphPad Prisma V.3 statistical software. Variables of the 3 groups were compared using non-parametric Kruskal Wallis ANOVA test and multiple comparisons were made using Dunn's multiple test. The comparison of initial and terminal intracranial pressure values obtained before and after the sinus occlusion, was made using the Wilcoxon test. A probability value of less than 0.05 was regarded as significant. RESULTS AND CONCLUSIONS: Comparison of the water content ratio of the brain in the 3 groups, the difference between the initial and terminal intracranial pressure values of the rapid occlusion study group, and the difference between the terminal intracranial pressure values of the 3 groups was statistically significant (P<0.05). Dunn's Multiple Comparison Test yielded significant differences in the water content ratio of the brain and in the intracranial pressure values between the rapid occlusion study group and the control group (P<0.05). Moreover, histopathological and radiological examination disclosed more prominent brain edema findings, and less apparent collateral venous flow in the rapid occlusion study group than in the slow occlusion one. To conclude, the clinical severity of sinus occlusion seems directly related to the quickness of the occlusion and the capacity of the collateral venous system.

Animals↗

PubMed2003

Intra-individual variation in lumbar bone mineral density as a measure of spondylotic deformity in the elderly.

In an attempt at quantitative assessment of spondylotic deformity, the intra-individual variation in L(1)-L(4) bone mineral density (BMD) was calculated, as the standard deviation (SD) and coefficient of variation (CV), obtained by dividing the SD by mean L(1)-L(4) BMD, in 463 subjects. The subjects ranged in age from their second to tenth decades. Dual-energy X-ray absorptiometry (DXA), using the Lunar DPX-L, was employed to assess the BMD. The SD of lumbar (L)BMD increased with advancing age in males, but not in females, whereas the CV of LBMD increased with age in both males and females, along with the radiographically assessed degree of severity of spondylosis deformans. Both the intra-individual SD and CV of L(1)-L(4) BMD showed a highly significant correlation with the radiological degree of severity of spondylosis deformans, and SD, but not CV, showed a strong dependence on the mean L(1)-L(4) BMD on a multiple regression test. Multiple regression test revealed no significant correlation between on body height, weight, fracture, and intra-individual variation in L(1)-L(4) projected area, reflecting compression fracture, one hand and SD or CV of L(1)-L(4) BMD on the other. Intra-individual variation in lumbar bone mineral density, expressed as a coefficient of variation, is suggested as an index of spondylotic deformity.

Adult↗