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Spectrum and frequency of use of statistical techniques in psychiatric journals.

Educators in psychiatry face an important challenge in deciding what quantitative skills to teach and where in the educational agenda to teach them. One strategy is to focus the quantitative training of psychiatrists on techniques they need to be effective consumers of their literature. The authors catalogued the statistical methods described in 15 major psychiatric journals during 1983 and 1984. A dozen procedures, typically encountered in intermediate-level statistics courses, accounted for approximately 95% of all the statistical methods reported. Readers of psychiatric journals also routinely encounter multivariate, nonparametric, and categorization techniques. Educators might apply these results in designing exposure to statistical skills for future psychiatrists.

Humans↗

Statistics: a time accounting system.

This article outlines a system of statistics currently used by the Occupational Therapy Department at the Montreal Childrens Hospital. This method was one of the results of a Health Systems Engineering Project conducted in the Occupational Therapy Department by the Montreal Joint Hospital Institute in 1975. The article outlines the problems in maintaining statistics which led to the evolution of the current method. A basic description of the procedure is given, samples of the forms used are included, and 3 sample days are calculated to illustrate the method. However, it is felt that the principles may be useful as a guideline to any type of Occupational Therapy Department. This method adheres to the recording requirements of the Dominion Bureau of Statistics, but also provides a careful breakdown of time and effort in all areas of the department's functioning. Some benefits of maintaining complete, standard statistics are also outlined.

Child↗

Research designs and statistical techniques used in the Journal of Learning Disabilities, 1989-1993.

One hundred seventy-four research articles published in the Journal of Learning Disabilities from 1989 through 1993 were analyzed and coded by the type of research design and statistical technique used. Eighty percent of the research designs employed were identified as nonintervention methods. Fifty-five percent of all statistical techniques in the research articles reviewed were coded as primary, 32% were found to be intermediate, and the remaining 14% were considered advanced. The most frequently reported designs and analyses were those that are typically taught in most introductory and intermediate courses in research methods and statistics. Thus, the study indicates that readers would need at least a strong conceptual understanding of basic and intermediate statistical procedures to interpret research reported in the Journal of Learning Disabilities.

Humans↗

Complex sampling designs and statistical issues in secondary analysis.

Conducting secondary analysis using large national survey data sets to answer pressing research questions is gaining acceptance in the nursing science community. There are, however, challenges confronted by researchers who wish to apply secondary analysis to large data sets due to the incorporation of complex sampling designs. This article presents sampling design issues inherent in many large national surveys and explains the rationale for applying sample and variance estimation weights when conducting statistical analyses. In addition, the rationale for using statistical software packages capable of analyzing data derived from complex sampling designs is described. Examples of differences in statistical outcomes with and without weights using Stata and SPSS are provided using data from the Medical Expenditure Panel Survey (MEPS). Based on the example analyses, the implications of the statistical outcome differences for study findings are discussed.

Data Collection↗

Reducing the influence of anecdotal reasoning on people's health care decisions: is a picture worth a thousand statistics?

BACKGROUND: People's treatment decisions are often influenced by anecdotal rather than statistical information. This can lead to patients making decisions based on others' experiences rather than on evidence-based medicine. OBJECTIVE: . To test whether the use of a quiz or pictograph decreases people's reliance on anecdotal information. DESIGN: . Two cross-sectional survey studies using hypothetical scenarios. Participants read a scenario describing angina and indicated a preference for either bypass surgery or balloon angioplasty. The cure rate of both treatments was presented using prose, a pictograph, a quiz, or a pictograph and quiz combination. Participants read anecdotes from hypothetical patients who described the outcome of their treatment; the number of successful anecdotes was either representative or unrepresentative of the cure rates. Setting and Participants. Prospective jurors at the Philadelphia County Courthouse and travelers at the Detroit-Wayne County Metropolitan Airport. Measurements. Proportion of respondents preferring bypass over balloon angioplasty. RESULTS: . In study 1, when statistical information was presented in prose, treatment choices were influenced by anecdotes, with 41% of participants choosing bypass when the anecdotes were representative and only 20% choosing it when the anecdotes were unrepresentative (x(2) = 14.40, P < 0.001). When statistics were reinforced with the pictograph and quiz, anecdotes had no significant influence on treatment decisions (38% choosing bypass when anecdotes were representative v. 44% when unrepresentative, x(2) = 1.08, P > 0.20). In study 2, the tradeoff quiz did not reduce the impact of the anecdotes (27% v. 28% choosing bypass after receiving or not receiving the quiz, x(2) < 1, P > 0.20). However, the pictograph significantly reduced the impact of anecdotes, with 27% choosing bypass after receiving no pictograph and 40% choosing bypass after receiving a pictograph (x(2) = 6.44, P < 0.001). CONCLUSIONS: . Presenting statistical information using a pictograph can reduce the undue influence of anecdotal reasoning on treatment choices.

Adult↗

Nosology and statistical classification.

There is a fundamental difference between nosology and a statistical classification, and the two should not be confused. The discipline of nosology uses scientific methods to arrive at a classification of psychiatric disorders and is concerned with the validity of its entities. A statistical classification aims to attain the widest compliance in spite of differences in the theoretical orientation of its users. It must therefore be atheoretical, and must represent a widely negotiated agreement between its future users. The most important statistical classification is the "International Classification of Diseases, Injuries and Causes of Death" (ICD-9) endorsed by the member states of the World Health Organization. The DSM III (Diagnostic and Statistical Manual), a newly accepted classification of the American Psychiatric Association, departs in many ways from the ICD-9, and Canada will have to decide whether adherence to ICD-9 should continue, or be replaced by the adoption of DSM III. Advantages and disadvantages of the DSM III are briefly discussed.

Diagnosis, Differential↗

Statistical model building and model criticism for human circadian data.

Mathematical models have played an important role in the analysis of circadian systems. The models include simulation of differential equation systems to assess the dynamic properties of a circadian system and the use of statistical models, primarily harmonic regression methods, to assess the static properties of the system. The dynamical behaviors characterized by the simulation studies are the response of the circadian pacemaker to light, its rate of decay to its limit cycle, and its response to the rest-activity cycle. The static properties are phase, amplitude, and period of the intrinsic oscillator. Formal statistical methods are not routinely employed in simulation studies, and therefore the uncertainty in inferences based on the differential equation models and their sensitivity to model specification and parameter estimation error cannot be evaluated. The harmonic regression models allow formal statistical analysis of static but not dynamical features of the circadian pacemaker. The authors present a paradigm for analyzing circadian data based on the Box iterative scheme for statistical model building. The paradigm unifies the differential equation-based simulations (direct problem) and the model fitting approach using harmonic regression techniques (inverse problem) under a single schema. The framework is illustrated with the analysis of a core-temperature data series collected under a forced desynchrony protocol. The Box iterative paradigm provides a framework for systematically constructing and analyzing models of circadian data.

Adult↗

Dynamic statistical parametric mapping for analyzing the magnetoencephalographic epileptiform activity in patients with epilepsy.

Our current purpose is to evaluate the applicability of dynamic statistical parametric mapping, a novel method for localizing epileptiform activity recorded with magnetoencephalography in patients with epilepsy. We report four pediatric patients with focal epilepsies. Magnetoencephalographic data were collected with a 306-channel whole-head helmet-shaped sensor array. We calculated equivalent current dipoles and dynamic statistical parametric mapping movies of the interictal epileptiform discharges that were based in the minimum-L2 norm estimate, minimizing the square sum of the dipole element amplitudes. The dynamic statistical parametric mapping analysis of interictal epileptiform discharges can demonstrate the rapid change and propagation of interical epileptiform discharges. According to these findings, specific epileptogenic lesion-focal cortical dysplasia could be found and patients could be operated on successfully. The presurgical analysis of interictal epileptiform discharges using dynamic statistical parametric mapping seems to be promising in patients with a possible underlying focal cortical dysplasia and might help to guide the placement of invasive electrodes.

Adolescent↗

Improved statistical methods for hit selection in high-throughput screening.

High-throughput screening (HTS) plays a central role in modern drug discovery, allowing the rapid screening of large compound collections against a variety of putative drug targets. HTS is an industrial-scale process, relying on sophisticated automation, control, and state-of-the art detection technologies to organize, test, and measure hundreds of thousands to millions of compounds in nano- to microliter volumes. Despite this high technology, hit selection for HTS is still typically done using simple data analysis and basic statistical methods. The authors discuss in this article some shortcomings of these methods and present alternatives based on modern methods of statistical data analysis. Most important, they describe and show numerous real examples from the biologist-friendly Stat Server HTS application (SHS), a custom-developed software tool built on the commercially available S-PLUS and StatServer statistical analysis and server software. This system remotely processes HTS data using powerful and sophisticated statistical methodology but insulates users from the technical details by outputting results in a variety of readily interpretable graphs and tables.

Algorithms↗

Statistical power for detecting epistasis QTL effects under the F-2 design.

Epistasis refers to gene interaction effect involving two or more genes. Statistical methods for mapping quantitative trait loci (QTL) with epistasis effects have become available recently. However, little is known about the statistical power and sample size requirements for mapping epistatic QTL using genetic markers. In this study, we developed analytical formulae to calculate the statistical power and sample requirement for detecting each epistasis effect under the F-2 design based on crossing inbred lines. Assuming two unlinked interactive QTL and the same absolute value for all epistasis effects, the heritability of additive x additive (a x a) effect is twice as large as that of additive x dominance (a x d) or dominance x additive (d x a) effect, and is four times as large as that of dominance x dominance (d x d) effect. Consequently, among the four types of epistasis effects involving two loci, ;a x a' effect is the easiest to detect whereas ;d x d' effect is the most difficult to detect. The statistical power for detecting ;a x a' effect is similar to that for detecting dominance effect of a single QTL. The sample size requirements for detecting ;a x d', ;d x a' and ;d x d' are highly sensitive to increased distance between the markers and the interacting QTLs. Therefore, using dense marker coverage is critical to detecting those effects.

Chromosome Mapping↗

Statistical implications of pooling RNA samples for microarray experiments.

BACKGROUND: Microarray technology has become a very important tool for studying gene expression profiles under various conditions. Biologists often pool RNA samples extracted from different subjects onto a single microarray chip to help defray the cost of microarray experiments as well as to correct for the technical difficulty in getting sufficient RNA from a single subject. However, the statistical, technical and financial implications of pooling have not been explicitly investigated. RESULTS: Modeling the resulting gene expression from sample pooling as a mixture of individual responses, we derived expressions for the experimental error and provided both upper and lower bounds for its value in terms of the variability among individuals and the number of RNA samples pooled. Using "virtual" pooling of data from real experiments and computer simulations, we investigated the statistical properties of RNA sample pooling. Our study reveals that pooling biological samples appropriately is statistically valid and efficient for microarray experiments. Furthermore, optimal pooling design(s) can be found to meet statistical requirements while minimizing total cost. CONCLUSIONS: Appropriate RNA pooling can provide equivalent power and improve efficiency and cost-effectiveness for microarray experiments with a modest increase in total number of subjects. Pooling schemes in terms of replicates of subjects and arrays can be compared before experiments are conducted.

Computational Biology↗

Statistical significance for hierarchical clustering in genetic association and microarray expression studies.

BACKGROUND: With the increasing amount of data generated in molecular genetics laboratories, it is often difficult to make sense of results because of the vast number of different outcomes or variables studied. Examples include expression levels for large numbers of genes and haplotypes at large numbers of loci. It is then natural to group observations into smaller numbers of classes that allow for an easier overview and interpretation of the data. This grouping is often carried out in multiple steps with the aid of hierarchical cluster analysis, each step leading to a smaller number of classes by combining similar observations or classes. At each step, either implicitly or explicitly, researchers tend to interpret results and eventually focus on that set of classes providing the "best" (most significant) result. While this approach makes sense, the overall statistical significance of the experiment must include the clustering process, which modifies the grouping structure of the data and often removes variation. RESULTS: For hierarchically clustered data, we propose considering the strongest result or, equivalently, the smallest p-value as the experiment-wise statistic of interest and evaluating its significance level for a global assessment of statistical significance. We apply our approach to datasets from haplotype association and microarray expression studies where hierarchical clustering has been used. CONCLUSION: In all of the cases we examine, we find that relying on one set of classes in the course of clustering leads to significance levels that are too small when compared with the significance level associated with an overall statistic that incorporates the process of clustering. In other words, relying on one step of clustering may furnish a formally significant result while the overall experiment is not significant.

Cluster Analysis↗

Haplotype-sharing analysis for alcohol dependence based on quantitative traits and the Mantel statistic.

Haplotype-based methods have become increasingly popular in the last decade because shared lengths in haplotypes can be used for disease localization. In this contribution, we propose a novel linkage-based haplotype-sharing approach for quantitative traits based on the class of Mantel statistics which is closely related to the weighted pair-wise correlation statistic. Because these statistics are known to be liberal, we propose a permutation test to evaluate significance. We applied the Mantel statistic to the autosomal data from the genome-wide scan of the Collaborative Study on the Genetics of Alcoholism with the Affymetrix Genotype 10 K array that was provided for the Genetic Analysis Workshop 14. Four regions on chromosome 4, 8, 16, and 20 showed p-values less than 0.005 with a minimum p-value of < 0.0001 on chromosome 16 (tsc0520638 at 72.8 cM). Three of these four regions located on chromosome 4, 16, and 20 have been reported previously in the Genetic Analysis Workshop 11.

Alcoholism↗

Statistical model of natural stimuli predicts edge-like pooling of spatial frequency channels in V2.

BACKGROUND: It has been shown that the classical receptive fields of simple and complex cells in the primary visual cortex emerge from the statistical properties of natural images by forcing the cell responses to be maximally sparse or independent. We investigate how to learn features beyond the primary visual cortex from the statistical properties of modelled complex-cell outputs. In previous work, we showed that a new model, non-negative sparse coding, led to the emergence of features which code for contours of a given spatial frequency band. RESULTS: We applied ordinary independent component analysis to modelled outputs of complex cells that span different frequency bands. The analysis led to the emergence of features which pool spatially coherent across-frequency activity in the modelled primary visual cortex. Thus, the statistically optimal way of processing complex-cell outputs abandons separate frequency channels, while preserving and even enhancing orientation tuning and spatial localization. As a technical aside, we found that the non-negativity constraint is not necessary: ordinary independent component analysis produces essentially the same results as our previous work. CONCLUSION: We propose that the pooling that emerges allows the features to code for realistic low-level image features related to step edges. Further, the results prove the viability of statistical modelling of natural images as a framework that produces quantitative predictions of visual processing.

Models, Statistical↗

A simple method for statistical analysis of intensity differences in microarray-derived gene expression data.

BACKGROUND: Microarray experiments offer a potent solution to the problem of making and comparing large numbers of gene expression measurements either in different cell types or in the same cell type under different conditions. Inferences about the biological relevance of observed changes in expression depend on the statistical significance of the changes. In lieu of many replicates with which to determine accurate intensity means and variances, reliable estimates of statistical significance remain problematic. Without such estimates, overly conservative choices for significance must be enforced. RESULTS: A simple statistical method for estimating variances from microarray control data which does not require multiple replicates is presented. Comparison of datasets from two commercial entities using this difference-averaging method demonstrates that the standard deviation of the signal scales at a level intermediate between the signal intensity and its square root. Application of the method to a dataset related to the beta-catenin pathway yields a larger number of biologically reasonable genes whose expression is altered than the ratio method. CONCLUSIONS: The difference-averaging method enables determination of variances as a function of signal intensities by averaging over the entire dataset. The method also provides a platform-independent view of important statistical properties of microarray data.

Algorithms↗

Statistical methods for HIV dynamic studies in AIDS clinical trials.

Studies of HIV dynamics in AIDS research are very important for understanding pathogenesis of HIV infection and for assessing the potency of antiviral therapies. Since the viral dynamic results from clinical data were first published by Ho et al. and Wei et al., the study of HIV-1 dynamics in vivo has drawn a great attention from AIDS clinicians and researchers. Although the important findings from HIV dynamic studies have been published in many prestigious scientific journals, statistical methods for estimating viral dynamic parameters have not been paid enough attention by HIV dynamic investigators. The estimation methods in many viral dynamic studies are very crude and inefficient. In this paper, we review the statistical methods and mathematical models for HIV dynamic data analysis developed in recent years. We also address some practical issues and share our experiences in the design and analysis of viral dynamic studies. Some principles and guidelines for the design and analysis of viral dynamic studies are provided. The methodologies reviewed in this paper are also applicable to studies of other viruses such as hepatitis B virus or hepatitis C virus. We also pose some challenging statistical problems in this area in order to stimulate further study by the statistical research community.

Acquired Immunodeficiency Syndrome↗

Statistical evaluation of coincident prolactin and luteinizing hormone pulses during the normal menstrual cycle.

The purpose of this work was 2-fold. First, we sought to develop statistical criteria by which it could be established that the coincident occurrence of pulses of two different hormones exceeds that which would occur by chance alone, thereby suggesting that secretion of the two hormones is either coupled or controlled from a single source generator. Using computer simulations of uncoupled pulse generators operating at different frequencies, we were able to derive the appropriate statistical criteria and to apply them to achieve our second objective, to determine whether the occasional coincidence of plasma LH and serum PRL pulses that occurs throughout the menstrual cycle in normal women exceeds that which would happen by chance. The results of the computer simulations indicated that pulses emanating from two completely independent oscillators will occur coincidently at a predictable rate, despite the fact that the generator sources are not coupled; moreover, the rate of coincidence is increased when the pulse frequency of one of the source generators is increased. Using this knowledge and the statistical criteria we derived, we analyzed the coincidence of LH and PRL pulses in five normal women during their early follicular, late follicular, and midluteal phases and in another five women during their late luteal phase. We found that the number of PRL pulses that occurred coincidently with LH pulses consistently exceeded that which would be predicted if the two pulse generators were operating completely independently of one another; however, only during the late follicular and late luteal phases was the coincidence level between LH and PRL pulses sufficiently high in a sufficient number of women to conclude that there was coupling between the pulse sources. These studies suggest, first, that stringent and rigorous statistical criteria must be applied to the analysis of spontaneously coincident secretory phenomena before it can be deduced that two pulse generators are indeed coupled, and second, that the pulse generators governing the secretion of PRL and LH are probably coupled, at least during certain phases of the menstrual cycle.

Adult↗

Validation of statistical methods to compare cancellation rates on the day of surgery.

UNLABELLED: We investigated the validity of several statistical methods to monitor the cancellation of electively scheduled cases on the day of surgery: chi(2) test, Fisher's exact test, Rao and Scott test, Student's t-test, Clopper-Pearson confidence intervals, and Chen and Tipping modification of the Clopper-Pearson confidence intervals. Discrete-event computer simulation over many years was used to represent surgical suites with an unchanging cancellation rate. Because the true cancellation rate was fixed, the accuracy of the statistical methods could be determined. Cancellations caused by medical events, rare events, cases lasting longer than scheduled, and full postanesthesia or intensive care unit beds were modeled. We found that applying Student's two-sample t-test to the transformation of the numbers of cases and canceled cases from each of six 4-wk periods was valid for most conditions. We recommend that clinicians and managers use this method in their quality monitoring reports. The other methods gave inaccurate results. For example, using chi(2) or Fisher's exact test, hospitals may erroneously determine that cancellation rates have increased when they really are unchanged. Conversely, if inappropriate statistical methods are used, administrators may claim success at reducing cancellation rates when, in fact, the problem remains unresolved, affecting patients and clinicians. IMPLICATIONS: Operating room cancellation rates can be monitored statistically by considering the number of canceled and performed cases during each 4-week period, performing a transformation of each period's cancellation rate, and then applying Student's t-test. Methods such as the Fisher's exact test and {chi}2 test should be avoided for this application because they can give erroneous results.

Algorithms↗