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PubMed1976

An assessment of hypothesis testing in mentally retarded adolescents.

Groups of educable and trainable institutionalised retarded adolescents were tested on a discrimination learning problem with a modified blank trials procedure in an attempt to measure their hierarchy of hypotheses. Results indicated that the hierarchy and size of initial hypothesis sets varied as a function of degree of retardation. Trainable retarded subjects had fewer hypotheses, and initially chose position hypotheses predominantly. Under discriminate reinforcement, most of these were readily switched to stimulus dimension hypotheses, which they retained during additional non-discriminate (100 per cent) reinforcement trials. Educable retarded subjects predominantly chose stimulus dimension hypotheses initially, and most of these switched to position hypotheses during either discriminate or non-discriminate reinforcement trials.

Adolescent↗
PubMed2005

Hypothesis testing and the choice of the dose-response model.

The shape of the dose-response curve for exposure to ionising radiation is probably one of the most contentious issues in toxicology. The initial assumption was that there was a threshold to the appearance of a health detriment, including cancer, with the so-called linear-no-threshold (LNT) hypothesis first being introduced in the early 1960s. Since that time a number of models have been suggested, and present work in health physics, toxicology and epidemiology is concerned with questions about both the shape of the dose-response curve and whether or not a threshold exists. This paper presents an analysis of the robustness of the LNT hypothesis from a philosophy of science standpoint-arguing that claims about dose-response curve need to pay more attention to the assumptions and auxillary hypotheses behind choices, and that further mechanistic studies are required to unravel the effects of exposure to ionising radiation. It suggests that whereas LNT falls short of the requirements for a good scientific hypothesis, it is a reasonable model for regulating the carcinogenic and hereditary effects of radiation exposure.

Animals↗
PubMed2000

Multiple data sets, congruence, and hypothesis testing for the phylogeny of basal groups of the lizard genus Sceloporus (Squamata, Phrynosomatidae).

Several data partitions, including nuclear and mitochondrial gene sequences, chromosomes, isoenzymes, and morphological characters, were used to propose a new phylogeny and to test previously published hypotheses about the phylogenetic positions of basal clades of the lizard genus Sceloporus and the relationship of Sceloporus to the former genus "Sator". In accord with earlier studies, our results grouped "Sator" as internal to Sceloporus, and both support a hypothesis of transgulfian vicariance for the origin of the former genus "Sator" on islands in the Sea of Cortez. Robustness of support for internal nodes in our best tree was established though widely used indices (bootstrap proportions, decay values) but also through congruence among independent data partitions. Several deep nodes in the tree recovered by several methods, including equally weighted and differentially weighted parsimony and maximum likelihood models, are only weakly supported by the traditional indices. This methodological concordance is taken as evidence for insensitivity of the deep structure of the topology to alternative assumptions.

Animals↗
PubMedDate not supplied

A strategy for introducing diagnostic reasoning: hypothesis testing using a simulation approach.

The ability to generate a number of hypotheses, so all possibilities in a situation are recognized, is a vital component in arriving at a correct nursing diagnosis. Students need learning experiences in this aspect of the diagnostic reasoning process. The authors discuss the four phase simulation method of teaching, which provides a useful model for developing beginning skills in hypothesis generation.

Clinical Competence↗
PubMedDate not supplied

Hypothesis testing in the polychotomous logistic model with an application to detecting gastrointestinal cancer.

We discuss the use of the trichotomous logistic model to discriminate between patients with gastrointestinal (GI) cancer, patients with benign GI disease and 'normal' subjects, using symptoms and the concentrations of some serum proteins that are potentially indicative of malignancy as covariates. A parsimonious model can be obtained by invoking an indistinguishability hypothesis which is appropriate when a covariate is considered to have no predictive value between categories. It is shown that the polychotomous model can be re-parameterised under the null hypothesis to give a 'reduced form', which can be fitted by maximum likelihood. The validity of the use of the same methods for retrospective sampling is discussed. The approach is illustrated by the development of a logistic model to identify symptomatic and asymptomatic subjects with a high risk of GI cancer.

C-Reactive Protein↗
PubMed1998

A neglected window on hypothesis testing in adolescence: explicit standard order conditional selection tasks.

The paper reported four experiments on explicit standard order conditional selection tasks, which permit more direct inference of subjects' strategies than do other conditional selection tasks. The experiments allowed plausible rational support-seeking strategies to be reduced from nine to three, disproof strategies from six to three. The main strategy in early adolescence was either (1) models-based deduction, as suggested by Johnson-Laird and Byrne in 1991 or (2) rules-based deduction, as suggested by Rips in 1994, with a factual attitude to hypothesis and offered information. In late adolescence a substantial minority adopt a hypothetical attitude to both these things, which may be applied with either of these strategies or with (3) the nondeductive strategy suggested by Langford and Hunting in 1994. This general picture of developmental possibilities can be extended to Inhelder's and Piaget's problems requiring information search to test conditional and biconditional hypotheses, in particular their chemicals, pendulum, and rods problems. This extension is obtained by assuming that adolescents acquire a range of strategies for problems requiring more or less focussed information search, conditional selection tasks requiring the former, Piagetian formal operations tasks tending towards the latter. Current evidence does not indicate whether strategies (1) or (2) are dominant in younger adolescents or whether strategies (1) or (2) or (3) are dominant in older adolescents. Thus, the Piagetian argument that formal operations thinking passes from factual rules-based deduction to hypothetical rules-based deduction is only one of several styles of theory that can readily accommodate current evidence in this area.

Adolescent↗
PubMedDate not supplied

Hypothesis testing in evolutionary developmental biology: a case study from insect wings.

Developmental data have the potential to give novel insights into morphological evolution. Because developmental data are time-consuming to obtain, support for hypotheses often rests on data from only a few distantly related species. Similarities between these distantly related species are parsimoniously inferred to represent ancestral aspects of development. However, with limited taxon sampling, ancestral similarities in developmental patterning can be difficult to distinguish from similarities that result from convergent co-option of developmental networks, which appears to be common in developmental evolution. Using a case study from insect wings, we discuss how these competing explanations for similarity can be evaluated. Two kinds of developmental data have recently been used to support the hypothesis that insect wings evolved by modification of limb branches that were present in ancestral arthropods. This support rests on the assumption that aspects of wing development in Drosophila, including similarities to crustacean epipod patterning, are ancestral for winged insects. Testing this assumption requires comparisons of wing development in Drosophila and other winged insects. Here we review data that bear on this assumption, including new data on the functions of wingless and decapentaplegic during appendage allocation in the red flour beetle Tribolium castaneum.

Animals↗
PubMed2006

Hypothesis testing and Bayesian estimation using a sigmoid Emax model applied to sparse dose-response designs.

Application of a sigmoid Emax model is described for the assessment of dose-response with designs containing a small number of doses (typically, three to six). The expanded model is a common Emax model with a power (Hill) parameter applied to dose and the ED50 parameter. The model will be evaluated following a strategy proposed by Bretz et al. (2005). The sigmoid Emax model is used to create several contrasts that have high power to detect an increasing trend from placebo. Alpha level for the hypothesis of no dose-response is controlled using multiple comparison methods applied to the p-values obtained from the contrasts. Subsequent to establishing drug activity, Bayesian methods are used to estimate the dose-response curve from the sparse dosing design. Bayesian estimation applied to the sigmoid model represents uncertainty in model selection that is missed when a single simpler model is selected from a collection of non-nested models. The goal is to base model selection on substantive knowledge and broad experience with dose-response relationships rather than criteria selected to ensure convergence of estimators. Bayesian estimation also addresses deficiencies in confidence intervals and tests derived from asymptotic-based maximum likelihood estimation when some parameters are poorly determined, which is typical for data from common dose-response designs.

Algorithms↗
PubMed2006

Coalescent-based hypothesis testing supports multiple Pleistocene refugia in the Pacific Northwest for the Pacific giant salamander (Dicamptodon tenebrosus).

Phylogeographic patterns of many taxa are explained by Pleistocene glaciation. The temperate rainforests within the Pacific Northwest of North America provide an excellent example of this phenomenon, and competing phylogenetic hypotheses exist regarding the number of Pleistocene refugia influencing genetic variation of endemic organisms. One such endemic is the Pacific giant salamander, Dicamptodon tenebrosus. In this study, we estimate this species' phylogeny and use a coalescent modeling approach to test five hypotheses concerning the number, location and divergence times of purported Pleistocene refugia. Single refugium hypotheses include: a northern refugium in the Columbia River Valley and a southern refugium in the Klamath-Siskiyou Mountains. Dual refugia hypotheses include these same refugia but separated at varying times: last glacial maximum (20,000 years ago), mid-Pleistocene (800,000 years ago) and early Pleistocene (1.7 million years ago). Phylogenetic analyses and inferences from nested clade analysis reveal distinct northern and southern lineages expanding from the Columbia River Valley and the Klamath-Siskiyou Mountains, respectively. Results of coalescent simulations reject both single refugium hypotheses and the hypothesis of dual refugia with a separation date in the late Pleistocene but not hypotheses predicting dual refugia with separation in early or mid-Pleistocene. Estimates of time since divergence between northern and southern lineages also indicate separation since early to mid-Pleistocene. Tests for expanding populations using mismatch distributions and 'g' distributions reveal demographic growth in the northern and southern lineages. The combination of these results provides strong evidence that this species was restricted into, and subsequently expanded from, at least two Pleistocene refugia in the Pacific Northwest.

Animals↗
PubMed1996

A new approach to studying modern human origins: hypothesis testing with coalescence time distributions.

A new approach for testing hypotheses about modern human origins using molecular divergence dates is presented. Coalescence times from many unlinked loci are needed to test the alternative models. Hypotheses are evaluated on the basis of their differing predicted distribution patterns of coalescence times from multiple genes. No single coalescence time from one genetic system is sufficient to reject any of the three alternative models. Several nuclear datasets give recent dates for human genetic ancestors, at approximately the mitochondrial coalescence time, while some nuclear datasets support older dates. Given the overall distribution of available mitochondrial and nuclear coalescence times, the rapid replacement hypothesis is the likeliest model for modern human origins. The unusual nature of the human mitochondrial pattern is highlighted by comparative data from nonhuman hominoids. To understand the pattern of modern human genetic variability better, more nuclear data from all hominoid species are needed.

Animals↗
PubMed2001

Hypothesis testing of the aging male gonadal axis via a biomathematical construct.

Neuroendocrine axes are feedback- and feedforward-coupled dynamic ensembles. Disruption of selected pathways in such networklike organizations may explicate loss of orderly hormonal output as observed in aging. To test this notion more explicitly, we implemented an earlier computer-assisted biomathematical model of the interlinked male hypothalamo [gonadotropin-releasing hormone (GnRH)]-pituitary [luteinizing hormone, (LH)]-testicular [Leydig cell testosterone (Te)] axis (Am J Physiol Endocrinol Metab Physiol 275: E157--E176, 1988; Keenan D., W. Sun, and J. D. Veldhuis, SIAM J Appl Math 61: 934--965, 2000). Thereby, we appraise mechanistic hypotheses for more disorderly LH and Te secretion in aging men. We compare model predictions with monitored abnormalities in the older male, namely, irregular patterns of individual and synchronous LH and Te release, reduced 24-h rhythmic Te output, and variably elevated LH secretion. Among the mechanisms examined, the most parsimonious aging hypothesis would entail impaired LH feedforward on Te without or with attenuated Te feedback on GnRH/LH secretion. This investigative strategy should aid in exploring new postulates of disrupted feedback networks in pathophysiology.

Adult↗
PubMed2000

Anticipation of oxidative damage decelerates aging in virgin female medflies: hypothesis tested by statistical modeling.

Empirical analysis of survival data obtained from large samples of Mediterranean fruit flies shows that the trajectory of the mortality rate for virgin females departs from that for females maintained in mixed sex cages. It increases, decelerates, reaches its maximum, declines and then increases again within the reproductive interval. Non-virgin females, however, display an early-age plateau instead of this dip. We assume that these deviations are produced by the interplay between changes in oxygen consumption associated with reproductive behavior and the antioxidant defense that acts against anticipated oxidative damage caused by reproduction. Since there are no data on antioxidant mechanisms in medflies available that explain the observed patterns of mortality, we develop a model of physiological aging based on oxidative stress theory, which describes age-related changes in oxygen consumption and in antioxidative capacity during the reproductive period. Using this model, we simulate virtual populations of 25,000 virgin and non-virgin flies, calculate the respective mortality rates and show that they practically coincide with those of experimental populations. We show that the hypothesis about the biological support of reproduction used in our model does not contradict experimental data. The model explains how the early-age dip and plateau might arise in the mortality rates of female medflies and why the male mortality pattern does not exhibit such deviations.

Aging↗
PubMed1998

Pedigree analysis package (PAP) vs. MORGAN: model selection and hypothesis testing on a large pedigree.

The MORGAN package of programs is compared to a commonly used package, PAP, with respect to model selection in segregation analysis of a quantitative trait. MORGAN uses Monte Carlo Markov chain (MCMC) methods to estimate the likelihood, whereas both versions of PAP used employ an approximation to the likelihood for the mixed model. Comparisons are done by using results obtained from simulated data. All simulations were done on the same 232-member pedigree using data generated under each of several variations of models, which included different combinations of environmental, polygenic, and major gene components. PAP, version 4.0, and MORGAN gave similar results with respect to model selection for the majority of situations, suggesting that MCMC methods provide a computationally tractable approach for analysis of more complex models that cannot be analyzed by more direct computational methods. PAP, version 3.0, gave somewhat more disparate results compared with either PAP version 4.0 or MORGAN. Both MORGAN and the two versions of PAP confirmed that the major gene component is much easier to detect in the presence of some dominance. All three packages frequently falsely accepted the polygenic model when there was high residual heritability.

Computer Simulation↗
PubMed2006

Stratified false discovery control for large-scale hypothesis testing with application to genome-wide association studies.

The multiplicity problem has become increasingly important in genetic studies as the capacity for high-throughput genotyping has increased. The control of False Discovery Rate (FDR) (Benjamini and Hochberg. [1995] J. R. Stat. Soc. Ser. B 57:289-300) has been adopted to address the problems of false positive control and low power inherent in high-volume genome-wide linkage and association studies. In many genetic studies, there is often a natural stratification of the m hypotheses to be tested. Given the FDR framework and the presence of such stratification, we investigate the performance of a stratified false discovery control approach (i.e. control or estimate FDR separately for each stratum) and compare it to the aggregated method (i.e. consider all hypotheses in a single stratum). Under the fixed rejection region framework (i.e. reject all hypotheses with unadjusted p-values less than a pre-specified level and then estimate FDR), we demonstrate that the aggregated FDR is a weighted average of the stratum-specific FDRs. Under the fixed FDR framework (i.e. reject as many hypotheses as possible and meanwhile control FDR at a pre-specified level), we specify a condition necessary for the expected total number of true positives under the stratified FDR method to be equal to or greater than that obtained from the aggregated FDR method. Application to a recent Genome-Wide Association (GWA) study by Maraganore et al. ([2005] Am. J. Hum. Genet. 77:685-693) illustrates the potential advantages of control or estimation of FDR by stratum. Our analyses also show that controlling FDR at a low rate, e.g. 5% or 10%, may not be feasible for some GWA studies.

Chromosome Mapping↗
PubMed1990

Statistical significance and statistical power in hypothesis testing.

Experimental design requires estimation of the sample size required to produce a meaningful conclusion. Often, experimental results are performed with sample sizes which are inappropriate to adequately support the conclusions made. In this paper, two factors which are involved in sample size estimation are detailed--namely type I (alpha) and type II (beta) error. Type I error can be considered a "false positive" result while type II error can be considered a "false negative" result. Obviously, both types of error should be avoided. The choice of values for alpha and beta is based on an investigator's understanding of the experimental system, not on arbitrary statistical rules. Examples relating to the choice of alpha and beta are presented, along with a series of suggestions for use in experimental design.

Research Design↗
PubMed2003

General linear contrasts on latent variable means: structural equation hypothesis tests for multivariate clinical trials.

Structural equation models articulate the assumed measurement and causal relations among variables, imposing discipline on otherwise unstructured and redundant associations that arise in correlational studies. Biomedical research has eschewed such methods, relying on the generally superior causal inference afforded by randomized controlled trials. Increasingly, however, clinical trials incorporate numerous covariates that are measured but unmanipulated. Most clinical trials now also include multiple correlated endpoints, which can generate ambiguous outcome patterns refractory to simple statistical analysis and interpretation. Modern clinical trials are really multivariate longitudinal studies with at best a component of randomized control; as such, structural equation approaches can add rigour and clarity. The analysis of latent variance (LANOVA) conception combines structural equation and experimental analysis of variance legacies. It allows, for any design that can be decomposed into between-group and within-person models, tests on latent means (that is, the means of the unobserved factors) that are directly analogous to their analysis of variance counterparts. LANOVA variables are either outcomes (which may have a time structure), varying covariates (which may have a time structure), or background covariates (which are static). Allowable causal relations are set-recursive: background covariates can affect all other variables; varying covariates can affect current outcomes and later outcomes and covariates; outcomes can affect only later outcomes. All standard ANOVA and ANCOVA hypotheses can then be tested by proper restrictions among the means and intercepts of these latent variables. Structural equation modelling programs can be used to estimate the models and test the hypotheses. I demonstrate the approach by expressing and testing hypotheses appropriate for two clinical studies that evaluate patient-reported outcomes in populations with solid and haematological malignancies.

Analysis of Variance↗