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Power for detecting genetic divergence: differences between statistical methods and marker loci.

Information on statistical power is critical when planning investigations and evaluating empirical data, but actual power estimates are rarely presented in population genetic studies. We used computer simulations to assess and evaluate power when testing for genetic differentiation at multiple loci through combining test statistics or P values obtained by four different statistical approaches, viz. Pearson's chi-square, the log-likelihood ratio G-test, Fisher's exact test, and an F(ST)-based permutation test. Factors considered in the comparisons include the number of samples, their size, and the number and type of genetic marker loci. It is shown that power for detecting divergence may be substantial for frequently used sample sizes and sets of markers, also at quite low levels of differentiation. The choice of statistical method may be critical, though. For multi-allelic loci such as microsatellites, combining exact P values using Fisher's method is robust and generally provides a high resolving power. In contrast, for few-allele loci (e.g. allozymes and single nucleotide polymorphisms) and when making pairwise sample comparisons, this approach may yield a remarkably low power. In such situations chi-square typically represents a better alternative. The G-test without Williams's correction frequently tends to provide an unduly high proportion of false significances, and results from this test should be interpreted with great care. Our results are not confined to population genetic analyses but applicable to contingency testing in general.

Alleles↗

A comparison of three statistical models for IDDM associations with HLA.

The association between HLA-DQ haplotypes and insulin-dependent diabetes mellitus (IDDM) was studied in 48 children from 44 families ascertained from the high incidence area around Umeå, Sweden. Numerous hypotheses have been proposed to explain associations between HLA and IDDM, but comparisons of statistical models based on these hypotheses have not been attempted. The aim of the present study was to compare the goodness-of-fit and predictive abilities among different statistical models. A likelihood-based analysis rather than a conventional analysis based on contingency tables was therefore adopted. We first used parental haplotype information in a conditional likelihood analysis (1) and then compared this analysis with that of an unaffected control group which used information on geographically matched controls. Under the analysis conditional on parental haplotype, a statistical model motivated by the hypothesis that the entire DQ heterodimer is involved in IDDM pathogenesis fit the data significantly better and had greater predictive ability than either a model motivated by the explanation that an IDDM gene is linked to DQB1 or that the DQB1 chain itself is involved in IDDM pathogenesis, or a model arising from the hypothesis that single amino acids at codon 57 of DQB1 and codon 52 of DQA1, respectively, confer susceptibility. Under the case-control analysis, the identity of the best-fitting or more predictive statistical model was not as clear, although both approaches to analyzing risk suggested that the single-amino-acids model had significantly poorer fit compared to the remaining two models.

Diabetes Mellitus, Type 1↗

How to make clinical decisions from statistics.

Best practice health care depends on clinicians understanding and applying the results of trials in clinical practice. These results are most often presented in the language of statistics, which can be bewildering and even misleading for those of us who have only a limited understanding of the terms used in reporting statistics. This communication provides a simple explanation of some of the more common types of trials and their descriptors, presented in a way that should allow clinicians to understand, assess and apply the results. Confidence intervals are increasingly used in clinical research reports. They can be gold mines of information because they not only provide an estimate of statistical significance but also define the limits of the measured parameters within which the true estimate lies, the clinical importance of the findings and the power of the study to make possible these estimates. The 'number needed' to treat is a readily understood descriptor and if not described in the report it can be calculated simply from the figures already published. These and other statistical descriptors are explained with simple formulae, from which they may be calculated.

Clinical Trials as Topic↗

Issues in biomedical statistics: analysing 2 x 2 tables of frequencies.

How best to analyse statistically experimental results that are set out as a 2 x 2 table of frequencies has been debated by statisticians for more than 50 years. The main issue is what framework of statistical inference should be adopted. The design of most biomedical experiments that result in 2 x 2 tables of independent observations is compatible with the randomization model of inference and with the Fisher exact test. It is rare that the Neyman-Pearson population model is applicable and that a case can be made for using the Pearson chi 2 test, or others that refer a test statistic to the chi-squared distribution. Even then, the adjustments for the mismatch between the test statistic and the chi-squared distribution so as to control the risk of Type I error are complex that the Fisher test is probably a safer option (or Yates' correction to the Pearson test if there is no access to a computer). When the 2 x 2 table results from two sets of measurements having been made on the same group, the population model of inference is inapplicable and the exact form of the McNemar test should be used. Confidence intervals for differences in proportions, the likelihood ratio, or the odds ratio, refer to randomly sampled populations and are not compatible with the randomization model of inference.

Animals↗

Assumptions and validations of statistical tests for functional neuroimaging.

We contrast two statistical methods: three-dimensional cluster analysis and statistical parametric mapping. We show that three-dimensional cluster analysis is based on a neurobiological theory of the regulation of blood flow and, unlike statistical parametric mapping, carries a minimum of assumptions that are tested. Statistical parametric mapping is a formal approach, which is based on a multitude of assumptions of which the majority have not been validated. We also demonstrate that in practice three-dimensional cluster analysis has a reasonable balance between sensitivity and the probability of false positives, giving high reproducibility with data on e.g. colour discrimination.

Brain↗

Basic concepts in statistics for veterinary ophthalmologists.

Abstract This review article provides a comprehensive coverage of basic statistical procedures commonly used in biologic experiments and is intended to be a basic guide to the selection of appropriate tests and also to aid the reader in the evaluation of published studies. The focus is on the use, interpretation and presentation of the main statistical tests and their key concepts for the practicing veterinary ophthalmologist. Several examples derived from actual ophthalmic research are presented in the text. Lastly, the article discusses computer-based statistical analysis, provides a list of different software available and gives a practical example of a 'real life' statistical analysis.

Animals↗

Statistical issues in the study of temporal data: daily experiences.

This article reviews statistical issues that arise in temporal data, particularly with respect to daily experience data. Issues related to nonindependence of observations, the nature of data structures, and claims of causality are considered. Through the analysis of data from a single subject, we illustrate concomitant time-series analysis, a general method of examining relationships between two or more series having 50 or more observations. We also discuss detection of and remedies for the problems of trend, cycles, and serial dependency that frequently plague temporal data, and present methods of combining the results of concomitant time series across subjects. Issues that arise in pooling cross-sectional and time-series data and statistical models for addressing these issues are considered for the case in which there are appreciably fewer than 50 observations and a moderate number of subjects. We discuss the possibility of using structural equation modeling to analyze data structures in which there are a large number (e.g., 200) of subjects, but relatively few time points, emphasizing the different causal status of synchronous and lagged effects and the types of models that can be specified for longitudinal data structures. Our conclusion highlights some of the issues raised by temporal data for statistical models, notably the important roles of substantive theory, the question being addressed, the properties of the data, and the assumptions underlying each technique in determining the optimal approach to statistical analysis.

Adaptation, Psychological↗

Statistical inference on mean dioptric power: hypothesis testing and confidence regions.

It has not hitherto been possible to apply formal methods of statistical analysis to data on dioptric powers. The solution to the basic statistical problem is now provided in this paper. Recognition of the matric-variate nature of dioptric power allows calculation of sample means and variance-covariances. These in turn can be used to calculate a statistic for testing hypotheses on population means and for obtaining confidence regions for those means. In a graphical representation of dioptric power the confidence region turns out to be an ellipsoid centred on the mean of the sample of dioptric powers. The theory is illustrated by means of numerical examples. Singularity of the variance-covariance matrix may occur especially when the sample is small. When it does occur it is the cause of some difficulty in applying the statistics. Nevertheless singularity is rare in practical situations and can usually be avoided simply by increasing the size of the sample. Singularity, therefore, is not treated fully in this paper. Dioptric power is essentially four-dimensional in character but in practice a three-dimensional subspace is almost always sufficient. To avoid the difficulty of having to represent four-dimensional shapes and to avoid the complication of singularity (which is the rule rather than the exception in practice in four-space) only the common three-dimensional problem is considered in detail.

Analysis of Variance↗

Impact of criticism of null-hypothesis significance testing on statistical reporting practices in conservation biology.

Over the last decade, criticisms of null-hypothesis significance testing have grown dramatically, and several alternative practices, such as confidence intervals, information theoretic, and Bayesian methods, have been advocated. Have these calls for change had an impact on the statistical reporting practices in conservation biology? In 2000 and 2001, 92% of sampled articles in Conservation Biology and Biological Conservation reported results of null-hypothesis tests. In 2005 this figure dropped to 78%. There were corresponding increases in the use of confidence intervals, information theoretic, and Bayesian techniques. Of those articles reporting null-hypothesis testing--which still easily constitute the majority--very few report statistical power (8%) and many misinterpret statistical nonsignificance as evidence for no effect (63%). Overall, results of our survey show some improvements in statistical practice, but further efforts are clearly required to move the discipline toward improved practices.

Conservation of Natural Resources↗

Statistical approaches in alcohol research: a comparative survey of two major alcohol journals with four major psychiatric journals.

This study surveyed and compared the statistical methods used in two major alcohol journals with those used in four major psychiatric journals. The alcohol specialty journals were Alcoholism: Clinical and Experimental Research and Journal of Studies on Alcohol. The psychiatry journals studied were the American Journal of Psychiatry, British Journal of Psychiatry, Archives of General Psychiatry, and Acta Psychiatrica Scandinavica. The aim of this study was to examine the extent to which alcohol researchers use statistical methods and their level of statistical sophistication. A second aim focused on the extent to which alcohol researchers are attentive to design and sample size issues. Comparisons between papers published in the four psychiatry journals and the two alcohol specialty journals published in 1990 revealed that the percentage of articles without any numerical results was substantially different among the journals: 21% of the psychiatry journals and 7% in the alcohol journals. There was a significant difference in favor of the alcohol journals with respect to frequency of intermediate statistical techniques. The number of papers published in the two alcohol journals using 20 or fewer subjects was similar to the four psychiatric journals. However, the alcohol journals contained more articles in which > 400 subjects were studied.

Alcoholism↗

The reporting of statistical inferences in selected prosthodontic journals.

Dental periodicals are the fundamental source of prosthodontic research. The ability to understand and contribute to dental literature is basic to the prosthodontic profession. The purpose of this study is to tally relative frequency with which various descriptive (n = 18), graphical (n = 7), and inferential statistical procedures (n = 68) are used in the prosthodontic literature. Our method consists of four procedures: journal selection, choice of 1987 through 1988 articles with inferential statistical content, tally of the statistical procedures in those articles, and quality control procedures used in obtaining these data. At least 50% of 10 prosthodontists selected 17 of 100 journals most likely to be read by prosthodontists. In the 17 journals, 1,320 articles were screened of which 406 were selected and evaluated for their statistical procedures. The bar and line plots were the most common graphical procedures occurring in over one fourth of the 406 articles. Percentages, means, and standard deviations occurred in more than 40%. Although 58% used the .05 significance level, only 0.3% mentioned power. Analysis of variance was used more often than the t tests (42% v 29%), whereas correlation/regression (21%) and chi-square tests (14%) were used less often. The t tests, analysis of variance (Duncan, Tukey, and Student-Newman-Keuls multiple comparison procedures), chi-square tests, correlation and regression, and the Wilcoxon tests occurred in at least 5% of the 406 articles.

Analysis of Variance↗

The power of a statistical test. What does insignificance mean?

In statistical testing of data, the p value is a standard measure for reporting quantitative results. When a significant difference is reported, (e.g., P less than .05), most readers understand that there is less than a 5% chance that the authors have made a type I error (false positive or alpha) with their conclusion. In contrast, when nonsignificant differences between treatments, groups, or parameters of interest are reported (e.g., P greater than .05), many investigators and readers incorrectly interpret the 95% confidence interval for this conclusion as a 95% chance of making the correct decision. In fact, the alpha level of significance (in this example, .05) is only one of the parameters that determines the probability of committing a type II error (false negative or beta) when concluding statistical insignificance. Statistical power is the probability of having made a correct decision when the statistical tests reveal insignificance (P greater than .05) and the null hypothesis is true. The higher the power, the greater the chance that the decision is correct. Power depends on the alpha level of significance, the sample size, the standard deviation of the population or the sample, and the magnitude of the difference the investigators are trying to demonstrate.

Probability↗

Intraventricular electrogram analysis for ventricular tachycardia detection: statistical validation.

Time-domain analysis of intraventricular electrogram morphology during ventricular tachycardia (VT) and sinus rhythm or atrial fibrillation (SR/AF) has been proposed as a method for increasing the specificity of pathological tachycardia detection by antitachycardia devices. However, few studies have validated the use of such analysis with statistical methods. When statistical methods have been utilized, it has been assumed that the distribution of the values derived from analysis of the intracardiac electrograms have had a normal (gaussian) distribution. In this study, we sought to determine whether: (1) the distribution of values derived from analysis of intracardiac electrogram during SR/AF and VT is gaussian or nongaussian; and (2) the discrimination of monomorphic VT from SR/AF using SR/AF templates can be validated statistically. Two previously proposed time-domain methods--correlation waveform analysis (CWA) and area of difference (AD)--were selected for evaluation of 29 patients with 33 distinct, sustained monomorphic VTs. An initial SR/AF template was used to analyze subsequent SR/AF and VT passages with a minimum of 50 consecutive depolarizations using a "best-fit" alignment. The values derived from each analysis were examined subsequently for skewness (asymmetry) and kurtosis (shape) using two-tailed tests (P less than 0.02). For passages of SR/AF, a normal (gaussian) distribution was present in only 24% (CWA), and 45% (AD); for passages of VT, normal distribution was present in only 58% for both CWA and AD. Using appropriate statistical testing with nonparametric tolerance intervals, CWA and AD discriminated VT from SR/AF in 29 out of 33 (88%), and 30 out of 33 (91%) instances, respectively, with 95% confidence.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗

Statistical methodology: VI. Mathematical modeling of the electrocardiogram using factor analysis.

UNLABELLED: The ECG is a 12-lead-vector system and is known to contain redundant information. Factor analysis (FA) is a statistical technique that improves measured data and eliminates redundancy by identifying a minimum number of factors accounting for variance in the data set. OBJECTIVE: To identify the minimum number of lead-vectors required to predict the 12-lead ECG. METHODS: A total of 104 ECGs were obtained from 24 normal men, 22 normal women, and 28 men and 30 women with variable pathologies. Each ECG lead was simultaneously acquired and digitized, resulting in a voltage-time data array stored for mathematical analysis. Each array was factor-analyzed to identify the minimum number of lead-vectors spanning the ECG data space. The 12-lead ECG was then predicted from this minimum lead-vector set. ANOVA was used to test for statistical significance between normal and pathologic data groups. RESULTS: FA revealed that 3 lead-vectors accounted for 99.12%+/-0.92% (95% CI+/-0.18%) of the variance contained in the 12-lead ECG voltage-time data for all 104 cases. There were no statistically significant differences between men and women (99.25%+/-0.66% vs 98.98+/-1.11%; p=0.139). Statistically significant differences were noted between normal and acute myocardial infarction ECGs (99.5%+/-0.27% vs 98.66+/-1.25%; p=0.00003). The measured and predicted leads were almost identical. A 3-dimensional spatial ECG derived from the 3-lead-vector set resulted in variable curved surfaces that differed by pathology. CONCLUSIONS: The 12-lead ECG can be derived from only 3 measured leads and graphed as a 3-D spatial ECG. This type of data processing may lead to instantaneous acquisition and may enhance the diagnostic capability of the ECG from routine bedside telemetry equipment.

Electrocardiography↗

Concepts determining statistical analysis of dental data.

This paper reviews some approaches to statistical analysis of dental data. Often dental data consist of more than one observation per patient which may not be independent, and consequently some standard statistical methods based on independence of all observations are inappropriate. This paper seeks to make the dental researcher and the consulting statistician aware of some of the efficient approaches that can be used to analyse the data successfully. No specialist statistical knowledge is assumed. Rather the goal is to increase awareness of what can be done. The statistical layman is introduced to some basic concepts, while references are given for the mathematically-minded reader. The data of Pack, Coxhead and McDonald is used as a springboard for this discussion.

Data Interpretation, Statistical↗

Statistical analysis of data derived from clinical variables of plaque and gingivitis.

Selection of suitable subjects and statistical analysis of data derived from clinical trials presents a number of problems. In this trial, clinical data were analysed separately for pooled whole mouth data and for data including positive scores only for the variables of dental plaque and gingivitis. It was demonstrated that comparable data sets and statistical analyses were obtained using both data sets. Furthermore, it was shown that in order to achieve the best possible results in a clinical trial, the variable of gingivitis should be used in preference to plaque scores, that only individuals of high and/or moderate susceptibility to inflammation should be selected for inclusion in the statistical analysis, and that sites which have positive signs of disease only, should be included in the statistical analysis.

Adult↗

Proper statistical analysis of transepidermal water loss (TEWL) measurements in bioengineering studies.

In irritancy studies, measurement of transepidermal water loss (TEWL) is a widely used technique to assess barrier function. Using inappropriate statistical methods, however, leads to loss of information and misinterpretation of results. In this paper, we discuss some problems and pitfalls when using a suitable statistical technique for most designs in bioengineering studies, analysis of variance (ANOVA): multiple comparisons, choice of sample size and violation of statistical assumptions. For clarification of these points, a practical example will be given. Using the proposed adequate statistical methods correctly will, although accompanied by increased complexity, increase the efficiency of bioengineering studies.

Analysis of Variance↗

Specific statistical considerations relevant to the design and analysis of gingivitis trials demonstrating product superiority or equivalence.

Simulation studies were conducted to address specific statistical issues which arise in the design and analysis of gingivitis studies whose principal aim is the demonstration of superiority or equivalence of one product to another. The effects of measurement scale, using differences or ratios of group means, particular statistical test produces and specific rules demonstrating superiority or equivalence were investigated. An alternative concept to equivalence--denoted "least as good"--was also defined and evaluated. For a wide class of possible distributions of gingivitis scores, characterized by specific gamma distributions, the student-t test applied to means of subject GI gingivitis scores proved to be the most powerful of the test produces considered, having statistical properties quite similar to the randomization or permutation test procedure. Transformations of subject GI mean gingivitis scores did not produce an advantage in demonstrating either superiority or equivalence, and in some cases made it more difficult. Little difference was observed in test results when using the difference in group means as compared with using the ratio of group means for demonstrating either equivalence or superiority. The clinically significant rule produced the lowest false-positive rates for products slightly better than the active control, and similar false-positive and -negative rates as the statistically significant rule for products clearly superior to the active control. Demonstration of product equivalence will require more subjects per group than demonstrating product superiority, the size of this difference being a function of the definition of superiority that is accepted. Showing that the 90% confidence interval for 100*R is completely contained within the [90%, 110%] interval is the preferred method of demonstrating equivalence today, although much more research needs to be done to improve methods for demonstrating product equivalence. The "least as good" alternative to "equivalence" makes it easier to demonstrate "equivalence" for products slightly better than the active control product, but both experience great difficulty in demonstrating equivalence for test products not quite as good as the active control.

Chlorhexidine↗