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PubMed1994

Immune promotion of central nervous system remyelination.

Remyelination by oligodendrocytes is the normal response to injury of the central nervous system following experimental demyelination by toxins and viruses in rodents. By contrast, in immune-mediated myelin disorders such as human MS, Theiler's virus-induced demyelination or EAE, remyelination is incomplete. We have considered two hypotheses to explain why myelin repair is incomplete in these disorders. Hypothesis I is that myelin repair is the normal consequence of primary myelin injury but there are immune factors which prevent its full expression. To test hypothesis I, we depleted T cells in Theiler's virus infected mice with cyclophosphamide or with monoclonal antibodies to CD4, CD8, or immune response gene products (Ia). Enhanced remyelination and proliferation of glial cells was observed in mice depleted of CD4+ or CD8+ T cells. Hypothesis II is that there are immune factors within some demyelinated lesions which, when present, promote new myelin synthesis. We envision these factors to be present in those lesions showing remyelination but absent in those lesions that remain demyelinated. To test hypothesis II, we generated polyclonal immunoglobulins directed against normal CNS antigens. Transfer of immunoglobulins from mice immunized repeatedly with spinal cord homogenate resulted in 4-5-fold enhancement of remyelination in Theiler's virus infected mice. We have also generated a series of monoclonal antibodies directed against normal autoantigens which also promote CNS remyelination. These experiments support the concept that full CNS remyelination is possible in human demyelinating diseases such as MS. Manipulation of the immune response either by inhibiting the function of T cells or by treatment with immunoglobulins (possibly normal autoantibodies) appears to promote remyelination. These experiments provide hope for patients with fixed neurological deficits for whom there are currently no available therapies.

Adjuvants, Immunologic↗
PubMed1999

Multinomial processing tree models: an implementation.

Multinomial processing tree (MPT) models have been widely used by researchers in cognitive psychology. This paper introduces MBT.EXE, a computer program that makes MPT easy to use for researchers. MBT.EXE implements the statistical theory developed by Hu and Batchelder (1994). This user-friendly software can be used to construct MPT models and conduct statistical inferences, including point and interval estimation, hypothesis testing, and goodness of fit. Furthermore, this program can be used to examine the robustness of MPT models. Algorithms for parameter estimation, hypothesis testing, and Monte Carlo simulation are presented.

Algorithms↗
PubMed2003

Early stage Parkinson's disease patients and normal volunteers: comparative mechanisms of sequence learning.

Early-stage nondemented Parkinson's disease (PD(es)) patients can learn short but not long sequences as well as controls. We have previously shown that to achieve normal performance, PD(es) patients activated the same right-sided cortical regions as controls plus the homologous left sided cortex and bilateral cerebellum. In this study, we evaluated two related hypotheses to explain the behavioral abnormalities and the increased bilateral brain activation observed in the PD(es) group. Hypothesis 1 proposed that PD(es) patients recruit regions from a normal bilateral network specialized for sequence learning that healthy controls would activate if performing difficult tasks. Thus, PD(es) patients can learn short sequences as well as controls. Hypothesis 2 proposed that information processing within the network in the PD(es) group is impaired. Thus, PD(es) patients cannot learn as difficult a sequence as controls. To test hypothesis 1, we increased task difficulty and statistical power in the control group and showed that the control and the PD(es) groups activated the same regions. To test hypothesis 2, we analyzed the equal performance data using two partial least squares (PLS) multivariate analyses. The task-PLS analysis showed that to perform equally with controls, the PD(es) group expressed the normal bilateral network more than the control group. The behavior-PLS analysis showed that the correlation between learning performance and regional activation was significantly different between the groups. We conclude that PD(es) patients have near normal learning if task difficulty is moderate because they can recruit additional regions from a normal bilateral network specialized for sequence learning. However, when a difficult task would normally require bilateral activation, PD(es) patients fail to learn because information processing within the network is impaired. Hum. Brain Mapp. 20:246-258, 2003.

Aged↗
PubMedDate not supplied

[Body mass index and its relationship to nutritional and socioeconomic variables: a linear regression approach to a Brazilian adult sub-population].

This paper focuses on the relationship between body mass index (BMI) and family energy intake, occupational energy expenditure, per capita family expenditure, sex, age, and left arm circumference for a group of Brazilian adults randomly selected among those interviewed for a survey on food consumption and family budgets, called the National Family Expenditure Survey. The authors discuss linear regression methodological issues related to treatment of outliers and influential cases, multicollinearity, model specification, heteroscedasticity, as well as the use of two-level variables derived from samples with complex design. The results indicate that the model is not affected by outliers and that there are no significant specification errors. They also show a significant linear relationship between BMI and the variables listed above. Although the hypothesis tests indicate significant heteroscedasticity, its corrections did not significantly change the model's parameters, probably due to the sample size (14,000 adults), making hypothesis tests more rigorous than desired.

Adult↗
PubMed2001

The adaptive bleaching hypothesis: experimental tests of critical assumptions.

Coral bleaching, the loss of color due to loss of symbiotic zooxanthellae or their pigment, appears to be increasing in intensity and geographic extent, perhaps related to increasing sea surface temperatures. The adaptive bleaching hypothesis (ABH) posits that when environmental circumstances change, the loss of one or more kinds of zooxanthellae is rapidly, sometimes unnoticeably, followed by formation of a new symbiotic consortium with different zooxanthellae that are more suited to the new conditions in the host's habitat. Fundamental assumptions of the ABH include (1) different types of zooxanthellae respond differently to environmental conditions, specifically temperature, and (2) bleached adults can secondarily acquire zooxanthellae from the environment. We present simple tests of these assumptions and show that (1) genetically different strains of zooxanthellae exhibit different responses to elevated temperature, (2) bleached adult hosts can acquire algal symbionts with an apparently dose-dependent relationship between the concentration of zooxanthellae and the rate of establishment of the symbiosis, (3) and finally, bleached adult hosts can acquire symbionts from the water column.

Adaptation, Physiological↗
PubMed2003

Functional anatomy of the null hypothesis and of tests of it.

The author compared simulations of the "true" null hypothesis (zeta) test, in which sigma was known and fixed, with the t test, in which s, an estimate of sigma, was calculated from the sample because the t test was used to emulate the "true" test. The true null hypothesis test bears exclusively on calculating the probability that a sample distance (mean) is larger than a specified value. The results showed that the value of t was sensitive to sampling fluctuations in both distance and standard error. Large values of t reflect small standard errors when n is small. The value of t achieves sensitivity primarily to distance only when the sample sizes are large. One cannot make a definitive statement about the probability or "significance" of a distance solely on the basis of the value of t.

Humans↗
PubMed2002

Commentary on Meehl and Waller's (2002) path analysis and verisimilitude.

P. E. Meehl and N. G. Waller's (2002) proposed method may not yield unique solutions for model parameters nor unique solutions for model lack of fit. The author argues from a naturalistic-cognitive philosophy of science that science seeks objective knowledge and that hypothesis testing is central to achieving that goal. It is also argued that P. E. Meehl and N. G. Waller's proposal blurs the distinction between hypothesis testing and explorations of the data seeking an optimal model to serve as a prospective inductive generalization. But it is noted that inductive generalizations are never unique and must be tested to eliminate those that reflect subjective aspects of the researcher's methods and points of view.

Humans↗
PubMed1989

Sensible reasoning in two tasks: rule discovery and hypothesis evaluation.

The hypothesis testing skills of undergraduates were measured in two tasks: the 2-4-6 rule discovery task in which students generate and assess hypotheses, and a hypothesis evaluation task, which requires only the assessment of hypotheses. The results of Experiments 1 and 2 show that the students consistently employed a disconfirmation strategy when assessing hypotheses, but employed a counterfactual inference strategy when they also were required to generate the hypotheses. The results of Experiment 3 suggest that the selection of the hypothesis testing strategy reflected a balance between the logical requirements of the task and the desirability of possible outcomes. Taken together, the findings support a more consistent picture of human rationality across tasks, and suggest alternatives to accounts of confirmation bias.

Adult↗
PubMed1982

The relationship between classification and questioning strategies among adults.

Adults ranging from 30 to 90 were administered the Twenty Questions Task to evaluate questioning strategies and the Picture Pairing Test to assess classification preferences. With respect to the Twenty Questions Task, the results indicated that the percentage of constraint-seeking questions decreased while the percentage of hypothesis-testing questions increased across age. With respect to classification, the results indicated that the use of similarity-based classifications decreased while the use of complementary-based classification increased across age. Further, there was significant relationship between questioning strategy and classification preference. Individuals who asked constraint-seeking questions tended to use similarity-based classifications and those who asked hypothesis-testing questions tended to use complementary-based classifications.

Adult↗
PubMed2002

Knowledge is not everything: analysis of children's performance on a haptic comparison task.

The relative effects of developmental level and domain-specific knowledge on children's ability to identify and make similarity decisions about object concepts based only on haptic (touch) information were investigated. Children aged 4-9 years with varying levels of dinosaur knowledge completed a cross-comparison task in which they haptically explored pairs of familiar (dinosaur) and unfamiliar (sea creature) models that varied in terms of their degree of differentiability. Older children explored models more exhaustively, found more differentiating features and consequently made fewer errors than younger children did. High knowledge enabled children to identify models correctly, but was also associated with the use of a hypothesis testing strategy, which led children to make greater numbers of "miss" errors on the cross-comparison task. Performance in the control domain illustrated that the hypothesis testing strategy was specific to the high knowledge domain. Potential explanations for the role of knowledge and development in haptic exploration are considered.

Child↗
PubMed2005

Robust detection of periodic time series measured from biological systems.

BACKGROUND: Periodic phenomena are widespread in biology. The problem of finding periodicity in biological time series can be viewed as a multiple hypothesis testing of the spectral content of a given time series. The exact noise characteristics are unknown in many bioinformatics applications. Furthermore, the observed time series can exhibit other non-idealities, such as outliers, short length and distortion from the original wave form. Hence, the computational methods should preferably be robust against such anomalies in the data. RESULTS: We propose a general-purpose robust testing procedure for finding periodic sequences in multiple time series data. The proposed method is based on a robust spectral estimator which is incorporated into the hypothesis testing framework using a so-called g-statistic together with correction for multiple testing. This results in a robust testing procedure which is insensitive to heavy contamination of outliers, missing-values, short time series, nonlinear distortions, and is completely insensitive to any monotone nonlinear distortions. The performance of the methods is evaluated by performing extensive simulations. In addition, we compare the proposed method with another recent statistical signal detection estimator that uses Fisher's test, based on the Gaussian noise assumption. The results demonstrate that the proposed robust method provides remarkably better robustness properties. Moreover, the performance of the proposed method is preferable also in the standard Gaussian case. We validate the performance of the proposed method on real data on which the method performs very favorably. CONCLUSION: As the time series measured from biological systems are usually short and prone to contain different kinds of non-idealities, we are very optimistic about the multitude of possible applications for our proposed robust statistical periodicity detection method.

Algorithms↗
PubMed2002

Analyzing refractive data.

PURPOSE: To provide a general approach to the analysis of refractive data that overcomes the shortcomings of traditional treatments and can be easily adapted to most spreadsheets. SETTING: Corneal Service, Royal Liverpool Hospital, Liverpool United Kingdom, and Optometric Science Group, Rand Afrikaans University, Auckland Park, South Africa. METHOD: The basis of the analyses is the dioptric power matrix. Using a hypothetical sample of data on pre-event and post-event refractions, the calculation of the mean pre-event and post-event refractions and the effect of an event on the refractive outcome, for example the refractive surgical effect, are illustrated. The most important statistics, the mean and the variance-covariance of refractions, and the formal testing of hypotheses on the mean are provided. RESULTS: The method of analysis demonstrated how an event such as cataract surgery, occlusion treatment of amblyopia, or anisometropia can be evaluated in terms of refractive outcome. Hypothesis testing showed how the significance of this effect may be demonstrated. CONCLUSIONS: This standardized method of analyzing and reporting refractive data enables a quantitative analysis and statistical hypothesis testing of the complete refractive data. This approach has generalized applicability in a range of commonly encountered contexts such as the refractive change after cataract and refractive surgery, corneal transplantation, and treatment for amblyopia or the significance of anisometropia. The method is relatively straightforward and can be adapted to most conventional spreadsheets.

Amblyopia↗
PubMed1986

Cardiovascular responses in type A and type B men to a series of stressors.

Fifty-six healthy adult males were administered the Type A Structured Interview and assessed as exhibiting either Type A (N = 42) or Type B (N = 14) behavior pattern. They were monitored for systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) responses during a series of six challenging tasks: Mental Arithmetic, Hypothesis Testing, Reaction Time, Video Game, Handgrip, and Cold Pressor. The results indicated that Type A subjects exhibited greater cardiovascular responses than did Type B subjects during some (Hypothesis Testing, Reaction Time, Video Game and Mental Arithmetic) but not all (Handgrip and Cold Pressor) of the tasks. These results are discussed in terms of previously reported findings on conditions that do and do not produce differences in Type A/B cardiovascular stress responses.

Adult↗
PubMed1985

On statistical comparison of two diagnostic tests.

A one-sample hypothesis testing method is presented for comparing the accuracy of two diagnostic tests. Costs and inconveniences related to the false positive and false negative diagnostic test results, to the extent that they are quantifiable, are considered as measures of the importance of avoiding misclassification. The use of the proposed method is illustrated by comparing the effectiveness of aspiration biopsy cytology and frozen section in detecting malignant thyroid disease.

Biopsy, Needle↗
PubMed1998

A longitudinal study of the relationship between attributional style, life events, and depression in Japanese undergraduates.

A longitudinal design was used to investigate the relationship between attributional style, life events, and depression in Japanese undergraduates. The 1st hypothesis tested was that among those experiencing negative events, the students with a depressogenic attributional style would be more depressed than those with a nondepressogenic attributional style. The 2nd hypothesis tested was that among those experiencing positive events, the students with an enhancing attributional style would be less depressed than those with a nonenhancing attributional style. A total of 143 undergraduates responded to a depression scale, a life event questionnaire, and an attributional style questionnaire. The results, which generally supported the hypotheses, may reflect cultural differences between Japan and the United States.

Adult↗
PubMed2003

Characterization of angiosperm nrDNA polymorphism, paralogy, and pseudogenes.

Many early reports of ITS region (ITS 1, 5.8S, and ITS 2) variation in flowering plants indicated that nrDNA arrays within individuals are homogeneous. However, both older and more recent studies have found intra-individual nrDNA polymorphism across a range of plant taxa including presumed non-hybrid diploids. In addition, polymorphic individuals often contain potentially non-functional nrDNA copies (pseudogenes). These findings suggest that complete concerted evolution should not be assumed when embarking on phylogenetic studies using nrDNA sequences. Here we (1). discuss paralogy in relation to species tree reconstruction and conclude that a priori determinations of orthology and paralogy of nrDNA sequences should not be made based on the functionality or lack of functionality of those sequences; (2). discuss why systematists might be particularly interested in identifying and including pseudogene sequences as a test of gene tree sampling; (3). examine the various definitions and characterizations of nrDNA pseudogenes as well as the relative merits and limitations of a subset of pseudogene detection methods and conclude that nucleotide substitution patterns are particularly appropriate for the identification of putative nrDNA pseudogenes; and (4). present and discuss the advantages of a tree-based approach to identifying pseudogenes based on comparisons of sequence substitution patterns from putatively conserved (e.g., 5.8S) and less constrained (e.g., ITS 1 and ITS 2) regions. Application of this approach, through a method employing bootstrap hypothesis testing, and the issues discussed in the paper are illustrated through reanalysis of two previously published matrices. Given the apparent robustness of the test developed and the ease of carrying out percentile bootstrap hypothesis tests, we urge researchers to employ this statistical tool. While our discussion and examples concern the literature on plant systematics, the issues addressed are relevant to studies of nrDNA and other multicopy genes in other taxa.

DNA, Ribosomal↗
PubMed1989

Statistical and graphical methods for testing the hypothesis that quanta are made up of subunits.

It has been proposed that at the neuromuscular junction quanta are made up of subunits, because regularly spaced peaks appear in some histograms of miniature end-plate potential (MEPP) amplitudes. Many sets of MEPP sizes fit lognormal probability distribution functions. I compared sets of MEPP amplitudes from the literature to lognormal distributions, using cumulative plots and a robust test for significance. Some data sets fit a single lognormal distribution, but most required two lognormal subpopulations. This bimodal model is a parsimonious alternative to the subunits hypothesis. I also used graphs in which cumulative MEPP sizes were plotted on the ordinate against probability on the abscissa. Model data sets, generated on the subunit assumptions, produced concave plots. End-plate potential sizes at low quantal outputs--in which we know there are subunits--show the same concave shape. Most of the tested data from the subunit literature produced convex curves.

Animals↗