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Goal specificity effects on hypothesis testing in problem solving.

Previous research has found that having a nonspecific goal (NSG) leads to better problem solving and transfer than having a specific goal (SG). To distinguish between the various explanations of this effect requires direct evidence showing how a NSG affects a participant's behaviour. Therefore we collected verbal protocols from participants learning to control a linear system consisting of 3 outputs by manipulating 3 inputs. This system was simpler than the one we had used previously, so in Exp. 1 we generalized our earlier goal specificity findings to this system. In Exp. 2 protocol analysis confirmed our prediction (based on dual-space theories of problem solving) that NSG participants focused on hypothesis testing whereas SG participants focused on the goal. However, this difference only emerged over time. We also replicated the goal specificity effect on performance and showed that giving participants a hypothesis to test improved performance.

Goals↗

Feedback in hypothesis testing: an ERP study.

We used event-related potentials (ERPs) to probe the effects of feedback in a hypothesis testing (HT) paradigm. Thirteen college students serially tested hypotheses concerning a hidden rule by judging its presence or absence in triplets of digits and revised them on the basis of an exogenous performance feedback. ERPs time-locked to performance feedback were then examined. The results showed differences between responses to positive and negative feedback at all cortical sites. Negative feedback, indicating incorrect performance, was associated to a negative deflection preceding a P300-like wave. Spatiotemporal principal component analysis (PCA) showed the interplay between early frontal components and later central and posterior ones. Lateralization of activity was selectively detectable at frontal sites, with a left frontal dominance for both positive and negative feedback. These results are discussed in terms of a proposed computational model of trial-to-trial feedback in HT in which the cognitive and emotive aspects of feedback are explicitly linked to putative mediating brain mechanisms. The properties of different feedback types and feedback-related deficits in depression are also discussed.

Adult↗

Resampling-based multiple hypothesis testing procedures for genetic case-control association studies.

In case-control studies of unrelated subjects, gene-based hypothesis tests consider whether any tested feature in a candidate gene--single nucleotide polymorphisms (SNPs), haplotypes, or both--are associated with disease. Standard statistical tests are available that control the false-positive rate at the nominal level over all polymorphisms considered. However, more powerful tests can be constructed that use permutation resampling to account for correlations between polymorphisms and test statistics. A key question is whether the gain in power is large enough to justify the computational burden. We compared the computationally simple Simes Global Test to the min P test, which considers the permutation distribution of the minimum p-value from marginal tests of each SNP. In simulation studies incorporating empirical haplotype structures in 15 genes, the min P test controlled the type I error, and was modestly more powerful than the Simes test, by 2.1 percentage points on average. When disease susceptibility was conferred by a haplotype, the min P test sometimes, but not always, under-performed haplotype analysis. A resampling-based omnibus test combining the min P and haplotype frequency test controlled the type I error, and closely tracked the more powerful of the two component tests. This test achieved consistent gains in power (5.7 percentage points on average), compared to a simple Bonferroni test of Simes and haplotype analysis. Using data from the Shanghai Biliary Tract Cancer Study, the advantages of the newly proposed omnibus test were apparent in a population-based study of bile duct cancer and polymorphisms in the prostaglandin-endoperoxide synthase 2 (PTGS2) gene.

Algorithms↗

Hypothesis testing in a rule discovery problem: when a focused procedure is effective.

We investigated individuals' ability to use negative evidence in hypothesis testing. We compared performance in two versions of Wason's (1960) rule discovery problem. In the original version, a triple of numbers--(2, 4, 6)--was presented as an example of a rule that the experimenter had in mind (i.e., "increasing numbers"). Participants had to discover the rule by proposing new triples. In the other version, the same triple was presented as a counter-example to the experimenter's rule (i.e., "decreasing numbers"). We predicted that, in both conditions, participants would form hypotheses based on the features of the triple, and test only instances of the hypothesized rule. However, in the counter-example condition, such focused testing would invariably produce negative evidence. As a consequence, participants would be forced to revise their hypotheses. The reported results corroborated our predictions: Participants solved the counter-example version significantly better than the original problem.

Adult↗

Selecting protein targets for structural genomics of Pyrobaculum aerophilum: validating automated fold assignment methods by using binary hypothesis testing.

Three-dimensional protein folds were assigned to all ORFs of the recently sequenced genome of the hyperthermophilic archaeon Pyrobaculum aerophilum. Binary hypothesis testing was used to estimate a confidence level for each assignment. A separate test was conducted to assign a probability for whether each sequence has a novel fold-i.e., one that is not yet represented in the experimental database of known structures. Of the 2,130 predicted nontransmembrane proteins in this organism, 916 matched a fold at a cumulative 90% confidence level, and 245 could be assigned at a 99% confidence level. Likewise, 286 proteins were predicted to have a previously unobserved fold with a 90% confidence level, and 14 at a 99% confidence level. These statistically based tools are combined with homology searches against the Online Mendelian Inheritance in Man (OMIM) human genetics database and other protein databases for the selection of attractive targets for crystallographic or NMR structure determination. Results of these studies have been collated and placed at http://www.doe-mbi.ucla.edu/people/parag/P A_HOME/, the University of California, Los Angeles-Department of Energy Pyrobaculum aerophilum web site.

Algorithms↗

Hypothesis tests for and against a simple order among proportions estimated by pooled testing.

The use of pooled testing as a means of estimating the prevalence of rare traits has received considerable attention in recent years, particularly in the areas of public health, genetics, animal-disease assessment, and plant pathology. In pooled-testing applications, observations are made on pools of individuals amalgamated together. In this paper, we examine order-restricted hypothesis tests involving k >2 binomial proportions estimated by pooled testing, extending the earlier work of Tebbs and Swallow (2003, Biometrika, 90, 471-477 and Biometrical Journal, 45, 618-630). In particular, we focus on (i) testing the equality of proportions versus an isotonic alternative and (ii) testing for a violation of isotonicity. We propose new tests for each scenario and provide results which characterize the small-sample performance of our procedures. We illustrate our methods using two data sets; one from an observational HIV study and one from an agricultural experiment.

Animals↗

Statistical inference for a linear function of medians: confidence intervals, hypothesis testing, and sample size requirements.

When the distribution of the response variable is skewed, the population median may be a more meaningful measure of centrality than the population mean, and when the population distribution of the response variable has heavy tails, the sample median may be a more efficient estimator of centrality than the sample mean. The authors propose a confidence interval for a general linear function of population medians. Linear functions have many important special cases including pairwise comparisons, main effects, interaction effects, simple main effects, curvature, and slope. The confidence interval can be used to test 2-sided directional hypotheses and finite interval hypotheses. Sample size formulas are given for both interval estimation and hypothesis testing problems.

Humans↗

Hypothesis testing and confidence interval construction in 2 x 2 tables of correlated proportions.

The 2 x 2 table is an invaluable tool for displaying bivariate binary data. It is easy to find examples of correlated binary response in biopharmaceutical experiments and clinical research and analysis of these data is a current research topic. The most common hypothesis tested for 2 x 2 tables of correlated proportions is that of homogeneity of the marginal proportions or, equivalently, the hypothesis of table symmetry. The 2 x 2 table of correlated proportions is rich with information and we present a survey of some of the analyses relevant for these data. Using asymptotic theory, we develop estimators of relevant parameters and associated test statistics that are of interest. We discuss interval estimation using arguments proposed by Quesenberry and Hurst (1) and Goodman (2). These interval estimators do not rely on estimation of the covariance matrix and are not necessarily equivalent to those obtained using modified chi-square statistics.

Analysis of Variance↗

Hypothesis testing in patients with chronic progressive multiple sclerosis.

Patients with chronic progressive MS (N = 38) were compared with an age and education matched medical control group (N = 19) on a visual discrimination task designed to evaluate hypothesis testing and focusing behavior. Thirty-three MS patients (85%) and all control patients were able to formulate and use hypotheses, but MS patients were less likely to employ strategies leading to a correct solution. Furthermore, MS patients were more likely to perseverate with one strategy despite negative verbal feedback. Five MS patients were unable to formulate hypotheses. These findings suggest that MS patients have impaired cognitive functioning in addition to previously reported problems with memory.

Adult↗

Smoking, lung cancer and hypothesis testing.

It has been shown previously that the precipitator hypothesis of causation is able to account for certain key features of the epidemiological evidence that conflict with initiator and promoter hypotheses. The precipitator hypothesis states that the carcinogenic risk depends linearly in the average rate of smoking at an interval of tau years before death and that the 'doubling dose-rate', of D cigarettes per yr, is constant with respect to age from 35yr and above. In an earlier paper this hypothesis was tested by analysing secular trends in sex- and age-specific mortality from lung cancer recorded in England and Wales in relation to secular trends in cigarette consumption. The periods considered extended from 1950 up to 1975. The great majority of data failed to support the precipitator hypothesis but the well known errors in death certification were undoubtedly responsible for many anomalies. There were some indications of improved diagnostic accuracy towards the end of the period and hence it was considered important to update the analysis. This paper considers the trends over the recent period, 1974-5 to 1977-8. Unfortunately these newer data also appear to contain anomalies and they fail to support the precipitator hypothesis. In view of the difficulties confronting initiator and promoter hypotheses we have little alternative but to adopt Oldham's agnostic attitude "...we still do not know how cigarettes cause lung cancer, nor even, if we are particularly rigorous in our use of scientific logic, whether they do."

Age Factors↗

GeneMerge--post-genomic analysis, data mining, and hypothesis testing.

SUMMARY: GeneMerge is a web-based and standalone program written in PERL that returns a range of functional and genomic data for a given set of study genes and provides statistical rank scores for over-representation of particular functions or categories in the data set. Functional or categorical data of all kinds can be analyzed with GeneMerge, facilitating regulatory and metabolic pathway analysis, tests of population genetic hypotheses, cross-experiment comparisons, and tests of chromosomal clustering, among others. GeneMerge can perform analyses on a wide variety of genomic data quickly and easily and facilitates both data mining and hypothesis testing. AVAILABILITY: GeneMerge is available free of charge for academic use over the web and for download from: http://www.oeb.harvard.edu/hartl/lab/publications/GeneMerge.html.

Algorithms↗

Confidence regions and hypothesis tests for topologies using generalized least squares.

A confidence region for topologies is a data-dependent set of topologies that, with high probability, can be expected to contain the true topology. Because of the connection between confidence regions and hypothesis tests, implicitly or explicitly, the construction of confidence regions for topologies is a component of many phylogenetic studies. Existing methods for constructing confidence regions, however, often give conflicting results. The Shimodaira-Hasegawa test seems too conservative, including too many topologies, whereas the other commonly used method, the Swofford-Olsen-Waddell-Hillis test, tends to give confidence regions with too few topologies. Confidence regions are constructed here based on a generalized least squares test statistic. The methodology described is computationally inexpensive and broadly applicable to maximum likelihood distances. Assuming the model used to construct the distances is correct, the coverage probabilities are correct with large numbers of sites.

Animals↗

Bootstrap hypothesis testing and power analysis at low dose levels.

This study demonstrates the variability in dose estimates using the nonparametric bootstrap to estimate the variability in the mean dose when mean values from environmental data are used in the dose calculation. Bootstrap hypothesis testing and power analysis are demonstrated. For the data set shown here, the normal assumption works well if the environmental data can be considered fixed, known constants. However, when there exists a good deal of variability in the environmental data, as is most often the case, or where scarce data are available, making a normal assumption leads to gross underestimation of the variability in the mean dose.

Animals↗

Nonparametric analysis of covariance for hypothesis testing with logrank and Wilcoxon scores and survival-rate estimation in a randomized clinical trial.

Many clinical trials have time-to-event variables as principal response criteria. When adjustment for covariates is of some importance, the relative role of methods for such analysis may be of some concern. For the Wilcoxon and logrank tests, there is an issue of how covariance adjustment can be nonparametric in the sense of not involving any further assumptions beyond those of the logrank and Wilcoxon test. Also of particular interest in a clinical trial is the estimation of the difference between survival probabilities for the treatment groups at several points in time. As with the Wilcoxon and logrank tests, there is no well known nonparametric way to incorporate covariate adjustment into such estimation of treatment effects for survival rates. We propose a method that enables covariate adjustment for hypothesis testing with logrank or Wilcoxon scores. Related extensions for applying covariate adjustment to estimation of treatment effects are provided for differences in survival-rate counterparts to Kaplan-Meier survival rates. The results represent differences in population average survival rates with adjustment for random imbalance of covariates between treatment groups. The methods are illustrated with a clinical trial example.

Humans↗

Protein sequence-structure compatibility criteria in terms of statistical hypothesis testing.

The assignment of query protein sequences to probable folds in a threading approach is based on the statistical analysis (learning) of structural properties of amino acids in known protein structures. We formalize the recognition problem in terms of mathematical statistics, namely statistical hypothesis testing. Our general formulation leads to various mathematical forms of a decision rule function for evaluation of the quality of a sequence-structure fit. Three criteria were derived according to a likelihood ratio approach. Two of them have new functional forms while the third happens to coincide with the mean force potential function previously derived under the additional assumption of the Boltzmann law. New decision rule functions employ (i) the Parzen estimator of a probability density and (ii) the newly introduced non-parametric statistic with known asymptotic distribution. We compared criteria efficiency by a 'structure seeks sequence' search for three highly populated template folds through a query library of non-homologous sequences of proteins with known 3D structure using residue accessibility as an environmental variable. Various criteria reflect different underlying statistical propositions and thus often recognize diverse correct sequence-structure matches. On the other hand, if an amino acid sequence is recognized as compatible with a template by each of three decision rules it appears that one can make a more reliable inference of sequence-structure relationship since almost all false positives obtained by the three criteria differ.

Algorithms↗

Robust analysis of biomarker data with informative missingness using a two-stage hypothesis test in an HIV treatment interruption trial: AIEDRP AIN503/ACTG A5217.

Clinical trial AIN503/A5217 investigates whether a period of early treatment with antiretroviral therapy might lower the viral setpoint in subjects recently infected with HIV-1. We consider two statistical issues. First, even under the null hypothesis control arm subjects are more likely than treatment arm subjects to be missing final outcome data because of disease progression. The analysis must adjust for this missing data, or it may be unacceptably biased. Second, comparing outcomes between treatment and control arms at identical times post-randomization gives different information than comparing outcomes at the same amount of time off-therapy, as measured post-randomization. This may make interpretation of results problematic. We formulate the null hypothesis of the study as exchangeability under a time-shift between arms, which we call "time delay" between the study arms. This captures clinically relevant information, and allows us to formalize a two-stage hypothesis test in which stage one is a comparison between arms at identical times post-randomization, and stage two is a comparison between arms at identical times off-therapy, as measured post-randomization. Importantly, within this framework we can show that the two-stage test can be adjusted for the missing data using a simple worst-rank substitution.

Acquired Immunodeficiency Syndrome↗

Time-frequency intracranial source localization of feedback-related EEG activity in hypothesis testing.

The neural correlates of the response to performance feedback have been the object of numerous neuroimaging studies. However, the precise timing and functional meaning of the resulting activations are poorly understood. We studied the electroencephalographic response time locked to positive and negative performance feedback in a hypothesis testing paradigm. The signal was convoluted with a family of complex wavelets. Intracranial sources of activity at various narrow-band frequencies were estimated in the 100- to 400-ms time window following feedback onset. Positive and negative feedback were associated to 1) early parahippocampo-cingular sources of alpha oscillations, more posteriorly located and long lasting for negative feedback and to 2) late partially overlapping neural circuits comprising regions in prefrontal, cingular, and temporal cortices but operating at feedback-specific latencies and frequencies. The results were interpreted in the light of neurophysiological models of feedback and were used to discuss methodological issues in the study of high-level cognitive functions, including reasoning and decision making.

Adult↗

Bayesian hypothesis testing of four-taxon topologies using molecular sequence data.

The reconstruction of phylogenetic trees from molecular sequences presents unusual problems for statistical inference. For example, three possible alternatives must be considered for four taxa when inferring the correct unrooted tree (referred to as a topology). In our view, classical hypothesis testing is poorly suited to this triangular set of alternative hypotheses. In this article, we develop Bayesian inference to determine the posterior probability that a four-taxon topology is correct given the sequence data and the evolutionary parsimony algorithm for phylogenetic reconstruction. We assess the frequency properties of our models in a large simulation study. Bayesian inference under the principles of evolutionary parsimony is shown to be well calibrated with reasonable discriminating power for a wide range of realistic conditions, including conditions that violate the assumptions of evolutionary parsimony.

Base Sequence↗