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PubMed1990

Correlations between numbers of microflora in plaque and saliva.

An epidemiologic investigation to reliably identify caries-susceptible subjects by microbiological and chemical assessment of plaque and saliva is currently in progress. As part of that study, the numerical relationships of mutans streptococci, lactobacilli and total viable microflora in plaque and saliva among 12- to 15-year-old children in a fluoridated community were determined. Paraffin-stimulated whole saliva and pooled dental plaque were collected. Each sample was suspended in reduced transport fluid, chilled on ice, and assayed. The bivariate normal distribution was found to be a suitable model for the distribution of the pairs [numbers of bacteria in plaque (log10), numbers of bacteria in saliva (log10)]. Statistically significant positive correlations were found between numbers of mutans streptococci in plaque and saliva, and between lactobacilli in plaque and saliva.

Adolescent↗

PubMed1998

British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood.

To update the British growth reference, anthropometric data for weight, height, body mass index (weight/height2) and head circumference from 17 distinct surveys representative of England, Scotland and Wales (37,700 children, age range 23 weeks gestation to 23 years) were analysed by maximum penalized likelihood using the LMS method. This estimates the measurement centiles in terms of three age-sex-specific cubic spline curves: the L curve (Box-Cox power to remove skewness), M curve (median) and S curve (coefficient of variation). A two-stage fitting procedure was developed to model the age trends in median weight and height, and simulation was used to estimate confidence intervals for the fitted centiles. The reference converts measurements to standard deviation scores (SDS) that are very close to Normally distributed - the means, medians and skewness for the four measurements are effectively zero overall, with standard deviations very close to one and only slight evidence of positive kurtosis beyond+/-2 SDS. The ability to express anthropometry as SDS greatly simplifies growth assessment.

Adolescent↗

PubMedDate not supplied

Measures of body mass and of obesity from infancy to adulthood and their appropriate transformation.

In this paper we investigate first the choice of an appropriate index of body mass. The traditional indices weight/height (W/H), W/H2 and W/H3 are compared, as well as an approach due to Cole (1986) making the index W/Hp age-dependent, i.e. by allowing the power p to depend on age. While there may be no perfect index reflecting over- and underweight--irrespective of height and width--the Quetelet index W/H2 turned out to be a reasonable index from childhood to adulthood. Second, we study the development of the body mass index W/H2 longitudinally from birth onwards, based on structural average distance, velocity and acceleration curves. As a third topic, transformations for obtaining an approximate normal distribution for W/H2, weight and skinfolds are compared. The usual log-transformation turned out to be unsatisfactory. While for height and arm skinfolds a transformation -1/square root of x performs rather well across age and sex, a transformation -1/x is more appropriate for trunk skinfolds and W/H2.

Age Factors↗

PubMed1999

Approximate sample sizes for testing hypotheses about the ratio and difference of two means.

This article deals with a unifying approach to approximate sample size determination for different types of hypotheses formulated in terms of two means of normally distributed data. A simple approximation is given to the sample size required for testing hypotheses about the ratio of the means. The formula includes the situations of testing noninferiority, superiority, or equivalence. We present a more general formula that also covers hypotheses formulated in terms of the difference of means. We show that over a wide range of parameter values the approximation provides reliable sample sizes.

Controlled Clinical Trials as Topic↗

PubMed1997

Treatment-patient interactions for diagnostics of cross-over trials.

In cross-over trials, various types of responses may be recorded, not all of which can be appropriately modelled by a Normal distribution. Widening the class of models to the generalized linear model family has a number of advantages. An important one is that certain interactions, especially that between patients and treatments, can easily be fitted for frequency and count data. These can be used as diagnostics for the fit of the model used. One handicap has been the frequentist difficulty of comparing the fit of different non-nested models in this family. This can be overcome by the use of a model selection criterion such as the Akaike or Bayesian information criterion. This approach to modelling and diagnostics for cross-over trials is applied to two studies involving small counts of anginal attacks, previously analysed in the literature using classical Normal techniques.

Clinical Trials as Topic↗

PubMed2004

Effects of censoring on parameter estimates and power in genetic modeling.

Genetic and environmental influences on variance in phenotypic traits may be estimated with normal theory Maximum Likelihood (ML). However, when the assumption of multivariate normality is not met, this method may result in biased parameter estimates and incorrect likelihood ratio tests. We simulated multivariate normal distributed twin data under the assumption of three different genetic models. Genetic model fitting was performed in six data sets: multivariate normal data, discrete uncensored data, censored data, square root transformed censored data, normal scores of censored data, and categorical data. Estimates were obtained with normal theory ML (data sets 1-5) and with categorical data analysis (data set 6). Statistical power was examined by fitting reduced models to the data. When fitting an ACE model to censored data, an unbiased estimate of the additive genetic effect was obtained. However, the common environmental effect was underestimated and the unique environmental effect was overestimated. Transformations did not remove this bias. When fitting an ADE model, the additive genetic effect was underestimated while the dominant and unique environmental effects were overestimated. In all models, the correct parameter estimates were recovered with categorical data analysis. However, with categorical data analysis, the statistical power decreased. The analysis of L-shaped distributed data with normal theory ML results in biased parameter estimates. Unbiased parameter estimates are obtained with categorical data analysis, but the power decreases.

Computer Simulation↗

PubMed1992

A quantitative and qualitative description of electromyographic linear envelopes for synergy analysis.

The muscular synergy patterns of human locomotion can be described by the phasic activity of electromyographic linear envelopes (LE) and the interphasic spatio-temporal relations. To represent the phasic activity, the LE is modeled as the summation of Gaussian pulses of various lengths. The parameters of interest are the temporal features: time, duration, and amplitude of the phases of activity. A maximum likelihood approach to the parameter estimation for a mixture of normal distributions is adopted for extracting the temporal features. Based on the derived temporal features, a set of relational descriptors can be defined to describe the spatio-temporal relations between the multichannel phasic activities. The strength of this approach is not only that the phasic activity of LE can be quantitatively represented accurately, but also that the resulting synergy patterns can be easily interpreted by observers.

Algorithms↗

PubMedDate not supplied

Receiver operator characteristic (ROC) analysis without truth.

Receiver operator characteristic (ROC) analysis, the preferred method of evaluating diagnostic imaging tests, requires an independent assessment of the true state of disease, which can be difficult to obtain and is often of questionable accuracy. A new method of analysis is described which does not require independent truth data and which can be used when several accurate tests are being compared. This method uses correlative information to estimate the underlying model of multivariate normal distributions of disease-positive and disease-negative patients. The method is shown to give results equivalent to conventional ROC analysis in a comparison of computed tomography, radionuclide scintigraphy, and magnetic resonance imaging for liver metastasis. When independent truth is available, the method can be extended to incorporate truth data or to evaluate the consistency of the truth data with the imaging data.

Calibration↗

PubMed2002

A decision theoretic approach to sample size determination in clinical trials.

In this paper, we discuss a Behavioral Bayes approach to the determination of sample size in phase III clinical trials for which the data are assumed to come from a normal distribution for which the mean and variance are both unknown. Software is described which minimizes the expected net cost as a function of the sample size, thereby establishing the optimal sample size. This methodology extends previous work by the assumption of unknown variance. Numerical examples show that the more general model can have a large effect on the optimal sample size, compared with a procedure which uses the known variance model with an estimate of the variance.

Algorithms↗

PubMed1992

The Elston-Stewart algorithm for continuous genotypes and environmental factors.

The Elston-Stewart algorithm for a normally distributed trait under a polygenic model is explained in detail and extended to allow for other continuous environmental variables. This formulation is especially useful for large pedigrees, as it avoids the need to invert matrices. Whereas it may not be feasible by this method to estimate all the various components of previously suggested models for polygenic inheritance, it can allow for a reasonably flexible pedigree correlational structure under which valid tests can be performed for fixed effects that may affect the phenotype.

Algorithms↗

PubMed1999

Applying Bayesian ideas to the development of medical guidelines.

Measurements of the quality of health care, in particular the underuse and overuse of medical therapies and diagnostic tests, often involve employment of medical practice guidelines to assess the appropriateness of treatments. This paper presents a case study of a Bayesian analysis for the development of medical guidelines based on expert opinion, using ordinal categorical rater data. We develop guidelines for the use of coronary angiography following an acute myocardial infarction (AMI) for 890 clinical indications using statistical models fit to appropriateness ratings obtained from a nine-member expert panel. The main foci of our analyses were on the estimation of an appropriateness score for each of the clinical indications, an associated measure of precision, and functions of the underlying score. We considered two classes of models that assume the ratings are either in the form of grouped normal data or are ungrouped variables arising from a normal distribution, while permitting rater effects and indication heterogeneity in both. We estimated models using Markov chain Monte Carlo methods and constructed indices quantifying appropriateness based on posterior probabilities of selected model parameters. We compared our model-based approach to the standard approach currently employed in medical guideline development and found that the standard approach correctly identified 99 per cent of the appropriate indications while overestimating appropriateness 18 per cent of the time compared to our model-based approach.

Bayes Theorem↗

PubMed1995

Population characteristics of hepatic dihydropyrimidine dehydrogenase activity, a key metabolic enzyme in 5-fluorouracil chemotherapy.

Dihydropyrimidine dehydrogenase is the initial rate-limiting enzyme in catabolism of 5-fluorouracil, one of the most widely used cancer chemotherapeutic agents. Previous studies have shown the clinical importance of determination of dihydropyrimidine dehydrogenase in patients with cancer, particularly in those with deficiency of this enzyme who experience severe 5-fluorouracil-associated toxicity (including death) after 5-fluorouracil treatment. In the present study, dihydropyrimidine dehydrogenase activity was determined in 138 donor liver samples. A normal distribution of human liver dihydropyrimidine dehydrogenase activity was shown. The mean enzyme activity was compared across different groups by age, gender, and race, with no significant differences observed except that the mean enzyme activity in women was slightly higher than that observed in men. With use of a polyclonal antibody generated against human liver dihydropyrimidine dehydrogenase, Western blot analysis showed that dihydropyrimidine dehydrogenase protein in the liver cytosol correlated with the activity of this enzyme.

Adult↗

PubMed1995

Model inconsistency, illustrated by the Cox proportional hazards model.

We consider problems involving the comparison of two or more treatments where we have the opportunity to adjust for relevant covariates either conditionally in a regression model or implicitly in repeated measures data, for example, in crossover trials. It is seen that for data arising from non-Normal distributions there is the possibility that models adjusting for covariates and those not adjusting for covariates will be inconsistent, that is, at most one of the models can be valid. Alternatively, even if conditional and unconditional models are valid, parameters in each model may have different interpretations. We note that this presents difficulties for the specification and interpretation of the analysis. It is also clear that model validation is critical. Specific attention is paid to survival data analysed by the Cox proportional hazards model.

Analysis of Variance↗

PubMed2005

An update on the analysis of agreement for orthodontic indices.

The training of clinicians in the correct use of commonly used orthodontic indices involves calibration. The level of agreement between the trainee and a standard is assessed both as a measure of reproducibility and the success of training programmes. For the Peer Assessment Rating (PAR) index and the Index of Complexity, Outcome and Need (ICON), the recommended level of acceptable inter-rater agreement is no more than +/-12 and +/-18, respectively. Many commonly used methods of analysing this type of agreement are inappropriate. The method used in this investigation allows the calculation of limits of agreement, which easily demonstrate any major departures in agreement between trainee scores and standard scores. The basic method assumes that the differences between trainee and standard scores are normally distributed and that there is no relationship between these differences and the magnitude of the index. An extension to this approach is required when the assumptions of the basic method are not upheld. This extension provides a regression-based approach to calculating limits of agreement. The results of this study demonstrate that the assumptions of the basic approach need to be checked for each comparison of trainee versus standard. In addition, regression-based methods are a more accurate means of calculating limits of agreement when these assumptions are not upheld. They also provide more information about bias and the range of disagreement between raters.

Algorithms↗

PubMed1997

Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias.

The purpose of this article is to demonstrate how adaptive changes in myocardial microstructure provide mechanisms for emergent new conduction disturbances that initiate reentrant arrhythmias. The mechanisms are based on discontinuous conduction phenomena produced by increases in cellular loading; these increases result from changes in the normal distribution of the gap junctions. Recent studies that at a microscopic level propagation in normal mature cardiac muscle is stochastic. For example, the nonuniform and irregular distribution of the gap junctions in such normal muscle produces load variations that are associated with changes in Vmax inside individual cells during both longitudinal and transverse propagation. The stochastic nature of normal propagation at a microscopic level offers considerable protection against arrhythmias by reestablishing the general trend of wavefront movement after small variations in excitation events occur. If such microscopic diversity is decreased, large fluctuations in load develop that are distributed over more cells than usual. The decrease in diversity may be caused by loss of side-to-side coupling between fibers, which produces relatively isolated groups of cells with microfibrosis. With loss of side-to-side fiber coupling, the myocardial architecture may fail to reestablish a smoothed wavefront at the macroscopic level. Spatial nonuniformities of electrical loading then give rise to conduction block and reentry.

Animals↗

PubMed1991

Parental data used to predict growth of craniofacial form.

The sample for this study consisted of 250 families. From 850 lateral and posteroanterior cephalograms, 81 variables from the X, Y coordinates of 67 landmarks were calculated and matched with the normal distribution. Principal component analysis was used to summarize these 81 variables in proper factor scores. The craniofacial patterns of 500 adults were classified by cluster analysis on the basis of those factor scores. This study introduced the concept of "similar parent" and "dissimilar parent" instead of the father and mother equally. Finally, the following model for predicting the individual growth of craniofacial characters was obtained. The predicted value Y(t) [formula: see text] is the logistic curve used in growth studies, C1X(s) is for the similar parent of a child, and C2X(d) is for the dissimilar parent. Multiple regression functions were calculated for both sexes in each of four craniofacial patterns. The errors of prediction at the average age of 18 years from the data at the average age of 11.6 years were 1.12, 2.88, 2.87, 3.14, and 1.93 mm for the respective distances S-N, N-Me, S-Me, Gn-Cd, and G-G'. These errors in our growth prediction are much smaller than in ordinary normal facial diagrams and may be considered negligible for orthodontic clinical application.

Adolescent↗

PubMed2004

Local polynomial regression modeling of human plasma melatonin levels.

Accurate characterization of features of the melatonin production curve is important for research in chronobiology. Local polynomial regression is used to model the plasma melatonin concentration curve and obtain consistent and asymptotically normally distributed estimates of synthesis onset and offset times, duration, peak concentration, and area under the curve. A simple production-clearance model for melatonin kinetics provides the connection between plasma concentrations and the melatonin production curve. This model identifies onset and offset times with critical points of derivatives of the concentration curve. The method proposed has the advantage of flexibility and ease of implementation. Local polynomial regression can be shown to produce consistent estimates of the regression curve and parameters of interest. Furthermore, the method can be implemented in any software package with weighted least squares routines.

Area Under Curve↗

PubMed2001

Passive permeability and outward active transport of fluorescein across the blood-retinal barrier in early ARM.

AIM: To study the passive and active transport of fluorescein across the blood-retina barrier in early age related maculopathy (ARM) (soft drusen > 63 microm, hyperpigmentation and/or hypopigmentation in patients above 50 years of age). METHODS: 15 patients and 10 healthy subjects were included. Morphological changes were graded from 30 degrees fundus photographs using a simplified version of the epidemiological ARM study group classification system. Differential vitreous spectrofluorophotometry was used to assess the transport properties of the blood-retina barrier (that is, passive permeability and unidirectional permeability caused by outward active transport from the vitreous to the blood). RESULTS: The passive permeability of the patient group was not significantly different from that of the control group. Four patients with passive permeability more than 3 SD above the mean of the control group (mean 1.8 (SD 0.7) nm/s, range 1.0-3.0 nm/s, data normally distributed) all had centrally located drusen > 500 microm and superjacent pigment clumps of 63-500 microm in diameter. There was no significant difference between the unidirectional permeabilities for the patient group and for the control group (mean 47.4 (29.3) nm/s, range 12.7-91.1 nm/s). CONCLUSION: There was no significant difference in the passive permeability and in the unidirectional permeability of fluorescein. However, the study may indicate that the combination of very large drusen and superjacent pigment clumps in ARM may be associated with a deterioration of the blood-retina barrier.

Aged↗