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At least 1,621 records · Page 90Linked to original sources
PubMed1985

Statistical age-period-cohort analysis: a review and critique.

Descriptive and statistical age-period-cohort (APC) analysis methods have received considerable attention in the literature. The statistical modeling of APC data often involves the popular multiple classification model, a model containing the effects of age groups (rows), periods of observation (columns), and birth cohorts (diagonals of the age-by-period table). The identifiability problem inherent to this model is discussed, and its adverse effects on the results of APC modeling exercises are illustrated numerically. Potential problems attendant with the use of two-factor models are described, and other possible modeling approaches currently in use are discussed. Interpretational limitations due to certain innate characteristics of typical APC data sets are also detailed. Given all the documented potential sources for error, the current state-of-the-art regarding the statistical modeling of APC data should be considered to be at an early stage of development.

Adult↗
PubMed1987

Limiting dilution assays. Experimental design and statistical analysis.

Two issues in limiting dilution analysis are considered. The first concerns the experimental design: a mathematical algorithm has been developed which calculates the number of replicate culture groups, and the (mean) number of cells per well to be used on the basis of the experimenter's a priori information about the unknown frequency. The procedure guarantees useful data if the a priori interval estimate of the frequency to be determined is correct and the cells are willing to grow. The second issue concerns the statistical method to be used for estimation of the unknown frequency. Several methods (minimum chi-square, maximum likelihood and the jackknife version of the maximum likelihood method) have been evaluated with artificial data from extensive Monte Carlo experiments. All three methods were useful in the statistical analysis of data. As a result of these experiments and theoretical considerations the jackknife version of the maximum likelihood estimation procedure is proposed as the statistical procedure of choice. The next best method is the maximum likelihood procedure.

Algorithms↗
PubMed1987

Selection of DNA binding sites by regulatory proteins. Statistical-mechanical theory and application to operators and promoters.

We present a statistical-mechanical selection theory for the sequence analysis of a set of specific DNA regulatory sites that makes it possible to predict the relationship between individual base-pair choices in the site and specific activity (affinity). The theory is based on the assumption that specific DNA sequences have been selected to conform to some requirement for protein binding (or activity), and that all sequences that can fulfil this requirement are equally likely to occur. In most cases, the number of specific DNA sequences that are known for a certain DNA-binding protein is very small, and we discuss in detail the small-sample uncertainties that this leads to. When applied to the binding sites for cro repressor in phage lambda, the theory can predict, from the sequence statistics alone, their rank order binding affinities in reasonable agreement with measured values. However, the statistical uncertainty generated by such a small sample (only 6 sites known) limits the result to order-of-magnitude comparisons. When applied to the much larger sample of Escherichia coli promoter sequences, the theory predicts the correlation between in vitro activity (k2KB values) and homology score (closeness to the consensus sequence) observed by Mulligan et al. (1984). The analysis of base-pair frequencies in the promoter sample is consistent with the assumption that base-pairs at different positions in the sites contribute independently to the specific activity, except in a few marginal cases that are discussed. When the promoter sites are ordered according to predicted activities, they seem to conform to the Gaussian distribution that results from a requirement for maximal sequence variability within the constraint of providing a certain average activity. The theory allows us to compare the number of specific sites with a certain activity to the number that would be expected from random occurrence in the genome. While strong promoters are "overspecified", in the sense that their probability of random occurrence is very low, random sequences with weak promoter-like properties are expected to occur in very large numbers. This leads to the conclusion that functional specificity is based on other properties in addition to primary sequence recognition; some possibilities are discussed. Finally, we show that the sequence information, as defined by Schneider et al. (1986), can be used directly (at least in the case of equilibrium binding sites) to estimate the number of protein molecules that are specifically bound at random "pseudosites" in the genome.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Composition↗
PubMed1989

Statistical analysis of drug-drug and site-site interactions with isobolograms.

The use of more than one drug to achieve a desired effect has been a common practice in pharmacologic testing and in clinical practice. For example, combinations of analgesics are frequently prescribed with a view to enhancing pain relief and reducing adverse effects. It is also well established that administration of more than one drug may give effects that are greater than, or less than, the additive effect of each drug given individually. A non-mechanistic method of characterizing the effect resulting from the administration of two compounds is the isobologram. It is relatively simple to draw and interpret isobolograms. However, this graphical technique, which employs equieffective concentrations of individual drugs and combinations of these, obtains the concentrations as random variables from concentration-effect data, usually transformed to a parallel line assay. Thus, statistical confidence limits from such assays, as well as from non-parallel designs, must be expressed on the isobologram if this diagram is to establish superadditive, subadditive, or merely additive effects. We now present a detailed statistical analysis of the isobolographic method illustrated with examples of the statistical procedures, a rational basis for selecting proportions of each drug in the combination, and a relatively novel application of the isobolographic concept, i.e., interactions involving different anatomical sites.

Animals↗
PubMed1994

Determination of hprt mutant frequencies in T-lymphocytes from a healthy pediatric population: statistical comparison between newborn, children and adult mutant frequencies, cloning efficiency and age.

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning assay in a healthy pediatric population. Assays were performed on 49 subjects (29 males and 20 females) ranging in age from 0.08 to 15.2 years. A statistical analysis of the thioguanine-resistant (TGr) mutant frequency (MF), unselected cloning efficiency (CE) and age was performed using data obtained in this study and those previously obtained in our laboratory on 66 newborn umbilical cord blood samples and 230 adult blood samples. For statistical comparisons pediatric subjects were divided into 4 groups. Group I included cord blood samples (age 0 years); Group II were subjects between 0 and 5 years; Group III were between 6 and 11 years and Group IV were between 12 and 17 years. The ln MF of Groups I and II were significantly lower than Groups III and IV (p < 0.05). The mean ln MF for each of Groups I-IV was significantly lower than the adult value. The cloning efficiency for Group I was significantly lower than that for Groups II-IV and adults. The relationships among the ln MF, unselected CE and age were expressed by the equations: ln (MF) = 0.945 -2.453 CE (p < 0.001) and ln (MF) = 0.114 + 0.063 age (p 0.004). The slope coefficients for unselected CE and age were significantly different from adults (p < 0.05). Regression analysis of combined data from Groups I-IV and adults were performed using both age and unselected CE as well as terms to reflect differences in their relationships with ln MF in adults and children. The results showed that the intercept and the age coefficients differ significantly for children and adults after adjustment for CE and yielded the following equations: ln (MF) = 0.548 -1.676 CE + 0.075 age, (Groups I-IV) and ln (MF) = 2.263 -1.676 CE + 0.014 age (adults). An alternative statistical model using ln (age ), ln (MF) = 0.381 -1.767 CE + 0.673 ln (age + 1), (p < 0.001), describes the rapid increase in MF with age that levels off in late adolescence. These findings demonstrate the changing influence of age on mutant frequency in the pediatric population as compared to the adult populations. These studies also illustrate that the increase in background somatic mutant frequencies at the hprt locus in T-lymphocytes is not linear from birth to adolescence and is significantly different from that seen in the adult population.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

The problem of the type II statistical error.

OBJECTIVE: To determine if type II statistical errors (also known as beta errors) are a common problem in published clinical research. METHODS: Type II statistical errors occur when sample sizes are too small to show an effect of treatment, even when an effect truly exists. Searching the Medline data base, we identified ten meta-analyses published during 1986-1994 in the American Journal of Obstetrics and Gynecology, Obstetrics and Gynecology, and The Journal of Reproductive Medicine. Meta-analyses were used as sources of component or individual studies for the following reason: When small component studies have negative findings that differ from the overall conclusions of the meta-analysis, the component studies may have type II statistical errors. RESULTS: We found that only 6.5% (15 of 231) of component studies provided any documentation that power calculations to determine sample sizes had been done a priori (before) the research began. Thus, many of these component studies with findings of no treatment effect may have had type II errors because of too-small sample sizes. When stratifying the component studies by year of publication, we found that 7.9% (14 of 178) of studies published in the 1980s and 1990s had any documented evidence of a priori power calculations. In the 1960s and 1970s, only one of 53 component studies had documented evidence of power calculations. CONCLUSION: To ensure that truly effective treatments are introduced into clinical practice as quickly as possible, we believe that a priori power calculations should always be done in quantitative clinical research.

Meta-Analysis as Topic↗
PubMed1982

Energy metabolism and body size. I. Is the 0.75 mass exponent of Kleiber's equation a statistical artifact?

The statistical derivation of Kleiber's 0.75 interspecific mass exponent 'b' is based on an assumption that the mass coefficient 'a' is constant irrespective of a mammal's size and/or species. Analysis of covariance, a statistical technique not based on this assumption, reveals that the mass coefficient is not constant in a series of 7 species (Peromyscus m., mice, rats, cats, dogs, sheep, and cattle) but increases threefold with the size of the animal. THe mass coefficient is a power x mass-2/3, the power being expressed in watts and the mass in kg. (Peromyscus m.: a = 1.91 +/- 0.09; cattle: a = 6.06 +/- 0.14). The intragroup mass exponent is equal to 0.67 +/- 0.03 and is significantly different from 0.75. This study shows that the 0.75 interspecific mass exponent in Kleiber's equation is a statistical artifact and suggests that the data from literature are consistent with the theory of biological similitude of Lambert and Teissier.

Animals↗
PubMed1986

Statistical aspects of the planning and analysis of collaborative studies on biological standards.

Statistical principles play a central role in the planning and analysis of collaborative studies on biological standards. These studies are carried out to assess the suitability of proposed biological standards, which should be demonstrated to provide valid and reproducible measurements of biological potency, and to assign units of activity (for example, by calibration against an existing standard). Guidelines have been published by the World Health Organization (WHO Tech Rep Ser 1978: 626: 101-141) describing the technical and general aspects of setting up biological standards and organizing collaborative studies. This paper, which is complementary to the WHO guidelines, expands on the statistical points which need to be considered. The general design of the study, the design of individual assays, the statistical analysis of the raw data, and the presentation of the results are described.

Biological Products↗
PubMed1995

A statistically based method to generate response maps objectively.

One scheme to classify the physiological response properties of single units in the cochlear nucleus is based on the average discharge rate of the unit and is reflected in the distribution of excitatory and inhibitory regions in a frequency-level map (response map) that spans the unit's receptive area (e.g., Evans and Nelson, 1973; Young and Brownell, 1976; Young and Voigt, 1982; Shofner and Young, 1985, Spirou and Young, 1991). Typically, discharge rate versus level curves are acquired at many frequencies and the investigator determines that a unit is excited or inhibited at a given level if the driven rate is above or below a spontaneous rate estimate by a specified criterion (for example, 20%). The investigator then encloses regions of excitation and inhibition where responses over adjacent frequencies and levels are consistent. In the present report, we describe an objective 3-step computer-based method to generate response maps: raw driven and spontaneous rate estimates are smoothed with a low-pass spatial filter; a unit is said to be excited or inhibited at a given level if the filtered driven rate is above or below the mean filtered spontaneous rate for that frequency by a specified criterion (percentage or statistical); and resultant response maps are median spatial filtered to eliminate spurious regions. The results shown here demonstrate that use of a statistical criterion provides a more reliable detection of excitation and inhibition than a 20% criterion, particularly when the variance of the rate estimates is high. Further, the statistically based method permits unit classification based on response map data that are more rapidly acquired with shorter duration stimuli (32 vs. 200 ms). Although this method is applied to units recorded in the dorsal cochlear nucleus, the technique may be applicable to studies of receptive fields and their plasticity in other systems.

Acoustic Stimulation↗
PubMed1982

An empirical approach to the statistical analysis of mutagenesis data from the Salmonella test.

A number of recent papers have suggested basing the statistical analysis of Salmonella (Ames) mutagenicity test results on a mathematical model of the complete dose-response curve. For most mutagens at low doses the curve increases linearly; then, as the dose increases, the curve may flatten and finally turn downwards due primarily to effects of toxicity. The exact mechanism underlying this shape is, however, not well understood and is likely to vary for different chemicals. A different approach is to assume that the initial part of the curve is linear and to base the statistical analysis solely on this region, reasoning that it contains most of the interpretable information about the mutagenesis dose response. In this paper a formal method of deciding which points are on the initial linear part of the curve is described, and a statistical method is proposed for analyzing these points. Computer simulations are used to examine the properties of the procedure and comparisons are made with a previously proposed mathematical model of the whole curve. It is concluded that the method suggested here provides a very satisfactory, robust method for the standard analysis of Salmonella data.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

A nonparametric approach to the statistical analysis of mutagenicity data.

A nonparametric statistical method for analysing count data from mutagenicity tests is proposed. This method does not make any stringent assumptions on the variation of the data. It requires only one ranking of the observations and the calculation of a resulting test statistic. The significance of this statistic can be assessed by approximation to the standard normal distribution or tables of critical values calculated by the authors. The method also includes a descriptive component through a series of K-1 estimates of a trend in a K group experiment. Several examples are discussed to illustrate the proposed method.

Dose-Response Relationship, Drug↗
PubMed1983

Inferential statistical methods for strengthening the interpretation of laboratory test results.

Laboratory test results for the diagnosis of psychiatric illness usually are reported descriptively despite the ready availability of appropriate inferential statistics. A test's sensitivity, specificity, and diagnostic confidence are conditional probabilities. Confidence intervals may be calculated for these probabilities in any given study. Statistical tests for comparing the results of several studies use techniques for planned and posterior comparisons applied to contingency tables. These established statistical methods aid in the interpretation of laboratory test findings.

Depressive Disorder↗
PubMed1988

The power of analysis: statistical perspectives. Part 2.

A discussion of the importance of statistical power in research is presented accompanied by nomograms for determining sample size and statistical power for the Student's paired and unpaired t tests with a Type I error of 5%. A brief review of statistical inference is presented. Some findings from Part I are reviewed.

Clinical Trials as Topic↗
PubMed1994

Updates of bioequivalence programs (including statistical power approximated by Student's t)

Updates are given of the earlier published MS-DOS programs BIOEQV37, BIOPAR37 and BIOEQNEW for the statistical analysis of bioequivalence studies. The updates are named BIOEQV52, BIOPAR40 and BIOEQNEW, respectively. Modifications and improvements in the updated programs are discussed. Calculations of statistical power for two-period crossover studies are now based on Schuirmann's two one-sided tests procedure. It is demonstrated that good approximations of power can be obtained by Student's t-statistic. This not only applies to the equations published elsewhere for the 'additive model', but also to hitherto unpublished equations for the 'multiplicative model'.

Software↗
PubMed1988

The statistical analysis of graft patency data in a clinical trial of antiplatelet agents following coronary artery bypass grafting.

Because most coronary artery bypass patients receive more than one graft at surgery, it is most important to determine whether statistical analysis of graft patency should be performed on the premise that the multiple grafts within patients are dependent or independent experimental units. Veterans Administration Cooperative Study No. 207 was a multicenter clinical trial comparing four different antiplatelet regimens to placebo in the prevention of graft occlusion following coronary artery bypass grafting. Using the results from the 1-week postoperative angiograms from the Veterans Administration Cooperative Study No. 207, in which there were 3.2 distal anastomoses per patient, we have tested the hypothesis that grafts within patients tend to act dependently with respect to patency or occlusion by comparing the graft patency data to a binomial distribution (i.e., that distribution that would have been manifest if grafts were independent). Because the graft patency results in Study No. 207 significantly deviated from the binomial distribution (p = 0.0003), a more appropriate analysis for graft patency data was applied using a ratio estimate as applied to cluster sampling. The statistical methods used in 11 previous clinical trials of antithrombotic therapy after coronary artery bypass grafting were examined. Only one of the previous studies used such an analysis, and three additional reports attempted to correct for dependency of grafts within patients in their analyses using other statistical methods. In seven of the studies the investigators did not address the potential problem of a dependent relationship between multiple grafts within patients. We conclude that grafts within patients act as dependent experimental units and that the ratio estimate as applied to cluster sampling may be appropriately applied to these data.

Clinical Trials as Topic↗
PubMed1989

Making cancer statistics more informative: measures of the quality of recorded diagnosis in a population-based registry.

The quality of the recorded diagnosis is a major limit to the usefulness of Cancer Registry statistics that is easily overlooked by users of the data. With data from a large population-based cancer registry as an example, we demonstrate how Registry statistics could be improved by wider use of three simple indices, namely (1) the proportion histologically verified (adjusted for age), (2) the proportion of verified cases with an uninformative diagnosis, and (3) the proportion of cases that are staged. We believe that greater awareness of the deficiencies of Cancer Registry statistics will lead to a more critical interpretation of them, and help stimulate efforts to rectify matters.

Aged↗
PubMed1995

Statistical properties of DNA sequences.

We review evidence supporting the idea that the DNA sequence in genes containing non-coding regions is correlated, and that the correlation is remarkably long range--indeed, nucleotides thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationarity" feature of the sequence of base pairs by applying a new algorithm called detrended fluctuation analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and non-coding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to every DNA sequence (33301 coding and 29453 non-coding) in the entire GenBank database. Finally, we describe briefly some recent work showing that the non-coding sequences have certain statistical features in common with natural and artificial languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts. These statistical properties of non-coding sequences support the possibility that non-coding regions of DNA may carry biological information.

Algorithms↗
PubMed1991

Statistical significance and fragility criteria for assessing a difference of two proportions.

This paper compares the traditional methods of statistical inference on the data from biomedical studies with a proposed index of fragility in the results. In general, for any given study there are 8 possible combinations of conclusions regarding statistical significance, quantitative significance and fragility. The 8 possibilities are considered in turn with respect to how studies in each group might be interpreted. Numerical examples show that not all 8 possibilities need be attainable with a given study design, and that the relative likelihood of them occurring can vary widely. It is concluded that the fragility index may be a useful adjunct to conventional statistical inference, with certain intuitive appeal, but that more empirical experience is needed with the fragility method.

Analysis of Variance↗