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PubMed2005

Photon-beam subsource sensitivity to the initial electron-beam parameters.

One limitation to the widespread implementation of Monte Carlo (MC) patient dose-calculation algorithms for radiotherapy is the lack of a general and accurate source model of the accelerator radiation source. Our aim in this work is to investigate the sensitivity of the photon-beam subsource distributions in a MC source model (with target, primary collimator, and flattening filter photon subsources and an electron subsource) for 6- and 18-MV photon beams when the energy and radial distributions of initial electrons striking a linac target change. For this purpose, phase-space data (PSD) was calculated for various mean electron energies striking the target, various normally distributed electron energy spread, and various normally distributed electron radial intensity distributions. All PSD was analyzed in terms of energy, fluence, and energy fluence distributions, which were compared between the different parameter sets. The energy spread was found to have a negligible influence on the subsource distributions. The mean energy and radial intensity significantly changed the target subsource distribution shapes and intensities. For the primary collimator and flattening filter subsources, the distribution shapes of the fluence and energy fluence changed little for different mean electron energies striking the target, however, their relative intensity compared with the target subsource change, which can be accounted for by a scaling factor. This study indicates that adjustments to MC source models can likely be limited to adjusting the target subsource in conjunction with scaling the relative intensity and energy spectrum of the primary collimator, flattening filter, and electron subsources when the energy and radial distributions of the initial electron-beam change.

Algorithms↗

PubMed1981

Isomyosin distribution in normal and pressure-overloaded rat ventricular myocardium. An immunohistochemical study.

We have used affinity-purified antibodies reacting with guinea pig soleus muscle and ventricular myosin heavy chains to analyze the distribution of specific isomyosin in the ventricular myocardium of normal and renal hypertensive rats. Immunofluorescent staining of cardiac tissue sections with the two antimyosins revealed striking variations in reactivity among ventricular muscle fibers, reactive fibers being more numerous in the left compared to the right ventricle and in subendocardial compared to subepicardial layers. The response of the ventricular myocardium changed during development: all fibers were stained in the newborn rat, whereas most fibers were unreactive in 1-month-old animals. The number of reactive fibers increased again in subsequent stages leading to a mixed pattern in adult animals. The normal mixed pattern of reactivity was transformed into a uniformly positive pattern in hypertensive rats 2 months after surgery. This complete transformation was observed in 20 out of 23 hypertensive animals examined. These findings indicate that the two antimyosins cross-react with a particular type of ventricular myosin heavy chain, whose distribution varies in different muscle cells and whose relative concentration changes during development and during cardiac hypertrophy induced by systemic hypertension. We suggest that differences in pressure load may be responsible for both regional variations in isomyosin distribution and for isomyosin changes in hypertensive animals.

Animals↗

PubMed1999

Inheritance of LDL peak particle diameter: results from a segregation analysis in Israeli families.

Genetic and environmental determinants of LDL peak particle diameter (LDL-PPD) were investigated in a sample of 80 kindreds residing in kibbutz settlements in Israel. The sample included 182 males and 191 females ages 15-93 years. LDL-PPD levels were first adjusted for variability in sex and age. Commingling analysis demonstrated that a mixture of two normal distributions fit the adjusted LDL-PPD levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex and age adjusted data but was not conclusive. However, when the regression model for sex and age allowed coefficients to be ousiotype (class) specific, the mixed environmental model was rejected while a major Mendelian model was not. These results suggest that the particular genotypes determined by the major gene, which are associated with different phenotypic variances, are likely to be more realistic, and that this analytic approach can contribute to improving our understanding of the genetics of LDL particle size.

Adolescent↗

PubMed2001

Allelochemicals in wheat (Triticum aestivum L.): variation of phenolic acids in shoot tissues.

Seven known phenolic acids implicated in wheat allelopathy were analyzed in a worldwide collection of 58 wheat accessions by gas chromatography and tandem mass spectrometry (GC-MS-MS). Chemical analysis showed that accessions differed significantly in the production of p-hydroxybenzoic, vanillic, syringic, trans-p-coumaric, cis-p-coumaric, trans-ferulic, and cis-ferulic acids in the shoots of 17-day-old wheat seedlings. The concentrations of p-hydroxybenzoic, vanillic, cis-p-coumaric, and cis-ferulic acids were normally distributed in the 58 accessions. A binormal distribution was found for syringic and trans-ferulic acids and a skewed normal distribution for trans-p-coumaric acid. The concentration of each compound also varied with phenolic acids. The relative abundance of each phenolic acid was ordered decreasingly as trans-ferulic, vanillic, trans-p-coumaric, p-hydroxybenzoic, syringic, cis-ferulic, and cis-p-coumaric acids. The concentration of total identified phenolic acids varied from 93.2 to 453.8 mg/kg in the shoots of 58 accessions. The content of each phenolic acid or group was highly associated with others in the shoots of wheat seedlings. Wheat accessions with high levels of total identified phenolic acids in the shoots are generally strongly allelopathic to the growth of annual ryegrass.

Gas Chromatography-Mass Spectrometry↗

PubMed1981

Probability paper analysis of flow cytofluorometric measurements of cellular deoxyribonucleic acid content.

A graphic analysis of cellular deoxyribonucleic acid (DNA) histograms obtained by flow cytofluorometry is described. This technique utilizes probability paper that graphs data in cumulative percentile form. From this graphic representation, individual normal distributions contributing to the histogram may be isolated and statistically describe. G0G1 and G2M distributions are independently described and S phase is fit to 1--5 overlapping normal distributions as dictated by the analysis results. This technique offers several advantages, including relatively simple mathematical calculations and few assumptions or restraints placed on the analysis. It has proved to be useful in analyzing proliferating and nonproliferating populations as well as distributions with unusual findings such as debris or aberrant DNA contents.

Bone Marrow Cells↗

PubMed1989

Uniform elimination pattern for glibenclamide in healthy Caucasian males.

It has been shown, that the elimination rate of intravenously administered tolbutamide shows considerable interindividual variation, due to strong genetic influence. These pharmacogenetic differences in the metabolic clearance rate of tolbutamide may result in drug failure in fast-eliminators, and it may cause an increased incidence of side effects in slow-eliminators. It is not known whether different "pharmacogenetics" exist for other sulfonylurea drugs. Therefore, we have injected glibenclamide (0.02 mg/kg body weight) intravenously in 52 male, normal weight, healthy volunteers. Serum glibenclamide levels were followed for up to 24 h. The terminal phase half-life of glibenclamide was 2.46 +/- 0.67 h (mean +/- SD), total drug clearance was 48.7 +/- 11.0 ml.min-1 and the slow disposition phase rate constant was 0.30 +/- 0.08 h-1. From the individual data of each subject frequency histograms were developed for these and other kinetic parameters and tested with a Kolmogoroff-Smirnoff-test for unimodal normal distribution. There was no significant (p greater than 0.05) deviation from the unimodal normal distribution for these parameters. In contrast to the pharmacogenetics of tolbutamide metabolism the present data indicate that glibenclamide follows an uniform elimination pattern in healthy caucasian males.

Adolescent↗

PubMed1994

[Assessment of nucleolar organizer regions (Ag-NORs) in primary lung cancer--correlation between Ag-NORs and tumor doubling time].

A total of 86 resected cases with primary lung cancer were examined on relationships between argyrophil nucleolar organizer regions (Ag-NORs) and other prognostic factors and correlation between Ag-NORs and tumor doubling time (DT). Survival rates were compared between patients with low Ag-NOR counts and patients with high Ag-NOR counts. 1) After logarithmic conversion of mean Ag-NOR counts in lung cancer, a small skewness (0.00486) and a small kurtosis (-0.7859) showed a normal distribution. Mean Ag-NOR counts was found to have a log-normal distribution. 2) There was a significantly inverse correlation between mean Ag-NOR counts and DT (correlation coefficient -0.705, p < 0.001). By plotting log (DT) on X axis and log (Ag-NORs) on Y axis, a formula representing a linear correlation was obtained: Y = 1.17-0.312 X, correlation coefficient -0.886. 3) The five-year survival rate (35%) of 46 patients with mean Ag-NOR counts which were more than or equal to 3.0 significantly lower than that (74%) of 40 patients with mean Ag-NOR counts of less than 3.0.

Adult↗

PubMed1993

[The distribution of normal oral flora in 49 healthy children and juvenile].

The frequencies and proportions of predominant cultiv ableoral bacteria associated with 49 healthy children and juvenile (6-25 yr old) were studied. A total of 72 bacterial species belonging to 28 genus were detected in 195 samples of saliva, fissure plaque, supragingival plaque, and subgingival plaque. The predominant bacteria were Oral streptococci, Neisseria, Actinomyces, Capnocytophaga, Bacteroides and Fusobacterium in the normal oral cavity of healthy children and juvenile. There were differences in the distribution of the predominant flora, e.g. Fusobacterium and Bacteroides had higher incidence and proportion in the subgingival plaque than in the fissure plaque.

Adolescent↗

PubMed2005

Distribution of GFAP+ astrocytes in adult and neonatal rat brain.

Astrocytes can proliferate as a result of trauma to the brain, such as occurs in a variety of diseases. Understanding the normal distribution of astrocytes is necessary before the extent of astrogliosis can be clearly determined. However, little is known about the normal distribution of GFAP+ astrocytes especially during development. This study examined distribution of GFAP+ astrocytes in regions of the cortex, cerebellum, and brainstem of adult and rat pup brains by immunocytochemistry using antibodies against GFAP. The findings showed a differential distribution of GFAP+ astrocytes in the rat brain. A paucity of GFAP expression was found in most regions of the normal adult rat brainstem, whereas GFAP+ astrocytes were abundantly distributed in all areas of the cortex and cerebellum. A similar regional heterogeneity in the distribution of GFAP+ astrocytes was seen in the neonatal rat brain. These findings suggest that the development of the differential pattern of GFAP+ astrocytes seen in the rat brain does not occur postnatally, but instead is present at birth and appears to be determined during fetal development.

Aging↗

PubMed2000

Percentiles of the product of uncertainty factors for establishing probabilistic reference doses.

Exposure guidelines for potentially toxic substances are often based on a reference dose (RfD) that is determined by dividing a no-observed-adverse-effect-level (NOAEL), lowest-observed-adverse-effect-level (LOAEL), or benchmark dose (BD) corresponding to a low level of risk, by a product of uncertainty factors. The uncertainty factors for animal to human extrapolation, variable sensitivities among humans, extrapolation from measured subchronic effects to unknown results for chronic exposures, and extrapolation from a LOAEL to a NOAEL can be thought of as random variables that vary from chemical to chemical. Selected databases are examined that provide distributions across chemicals of inter- and intraspecies effects, ratios of LOAELs to NOAELs, and differences in acute and chronic effects, to illustrate the determination of percentiles for uncertainty factors. The distributions of uncertainty factors tend to be approximately lognormally distributed. The logarithm of the product of independent uncertainty factors is approximately distributed as the sum of normally distributed variables, making it possible to estimate percentiles for the product. Hence, the size of the products of uncertainty factors can be selected to provide adequate safety for a large percentage (e.g., approximately 95%) of RfDs. For the databases used to describe the distributions of uncertainty factors, using values of 10 appear to be reasonable and conservative. For the databases examined the following simple "Rule of 3s" is suggested that exceeds the estimated 95th percentile of the product of uncertainty factors: If only a single uncertainty factor is required use 33, for any two uncertainty factors use 3 x 33 approximately 100, for any three uncertainty factors use a combined factor of 3 x 100 = 300, and if all four uncertainty factors are needed use a total factor of 3 x 300 = 900. If near the 99th percentile is desired use another factor of 3. An additional factor may be needed for inadequate data or a modifying factor for other uncertainties (e.g., different routes of exposure) not covered above.

Algorithms↗

PubMed1997

Group sequential monitoring of distribution-free analyses of repeated measures.

In many clinical trials the principal analysis consists of a 1 degree of freedom test based on an aggregate summary statistic for a set of repeated measures. Various methods have been proposed for the marginal analysis of such repeated measures that entail estimates of a measure of treatment group difference (the treatment effect) at each of K repeated measures and a consistent estimate of the covariance matrix, where asymptotically these estimates are normally distributed. One can then obtain an overall large sample 1-d.f. test of group differences, such as by taking the average of these K estimates. These methods include the Wei-Lachin family of multivariate rank tests and a corresponding multivariate analysis using the Mann-Whitney difference estimator as a measure of treatment group differences. Other methods, such as O'Brien's non-parametric test, are based on a single summary score for each patient, such as the within-patient mean value. These, and other such methods, allow for some observations to be missing at random. Herein I employ sequential data augmentation to conduct group sequential analyses using a 1 degree of freedom test from a multivariate Mann-Whitney analysis and for the O'Brien rank test. Su and Lachin used this method to perform group sequential analyses of a vector of Hodges-Lehmann estimators. By augmentating the data from the sequential looks in a single analysis, one obtains an estimate of the covariance of the estimates at each look, from which one obtains an estimate of the correlations among the sequential 1-d.f. test statistics. I describe a simple secant algorithm to determine the group sequential boundaries based on recursive integration of the standard multivariate normal distribution with the estimated correlation matrix. Although the boundary obtains readily using the method of Slud and Wei, the more flexible method of Lan and DeMets may be preferred. The true information fraction at each look, needed to apply the spending function method of Lan and DeMets, however, is unknown. Thus, I also describe the use of a surrogate measure of information.

Algorithms↗

PubMed1989

Doppler umbilical artery waveform indices--normal values from fourteen to forty-two weeks.

Normal values for Doppler waveform indices of the umbilical artery have been reported for gestational ages of 20 to 40 weeks in small numbers of normal patients. We evaluated 590 patients studies performed at 2-week intervals from 14 to 42 weeks' gestation on patients without medical or pregnancy complications. Readings were obtained during fetal quiet times (no fetal breathing or movements). Values for A (systolic) and B (diastolic) pressures were plotted as Pourcelot (A - B/A) and A/B ratios. Mean, SD, and 95% confidence limits were derived, and the skewness, kurtosis, and regression correlations were calculated. No diastolic flow was found in any pregnancy greater than 15 weeks' gestation (n = 25) or in 50% of the gestations between 15 to 17 weeks (n = 25). When diastolic pressure equals zero, the Pourcelot ratio value equals one and the A/B ratio approaches infinity and loses meaning. Recent work by Thompson et al. suggests that the Pourcelot ratio fits a normal distribution from 20 to 40 weeks' gestation and that the A/B ratio (which does not fit a normal curve) may be transformed to a normal distribution by conversion of the A/B ratio to 1/1 - Pourcelot ratio. Our data supports the normality of both indices from 18 to 42 weeks' gestation, but these assumptions are not applicable as the Pourcelot ratio approaches one or as the A/B ratio approaches infinity. Knowledge of normal umbilical flow ratios at gestational ages from 18 weeks may allow early detection and directed management of high-risk pregnancies.

Blood Flow Velocity↗

PubMedDate not supplied

Bite force and occlusal load distribution in normal complete dentitions of young adults.

The aim of this study was to investigate the bite force and its distribution over the maxillary dentition in completely dentate subjects. Twenty-three dental students (14 Danish, 9 Japanese) with complete dentitions, but without occlusal contact on the third molars participated and their maximal bite forces were measured using the Dental Prescale System close to intercuspation. The antero-posterior location of the occlusal load centre, i.e. the centre of balance of distributed occlusal load, was a little posterior of the centre of the upper first molar. These results could be used as a basic model for evaluation of occlusion.

Adult↗

PubMed2000

Is modelling dental caries a 'normal' thing to do?

OBJECTIVE: To introduce and encourage the use of generalised linear models (GLMs) in analysing caries data that do not require the response to be treated necessarily as a sample from a normal distribution. BASIC RESEARCH DESIGN: At the present time, it is most likely that the sampling distribution of dmf/DMF in industrialised countries will not approximate normality. Generalised linear modelling can be conducted assuming many underlying distributions which, in fact, includes the normal distribution. In this paper three GLMs are employed (normal, Poisson, negative binomial) for modelling an example caries data set. In addition, a binomial model is used to model the dichotomous outcome of caries-free/caries-present. CLINICAL SETTING: The data comprised 871 Old Trafford, Manchester primary school children aged between 4 years 0 months and 5 years 11 months. RESULTS: The effect of one study covariate was prominent in a normal model applied to all available dmf data but not in two non-normal models which used dmf > 0 data only. Furthermore, the same covariate was significant at the 5% level in a binomial model indicating that it influenced whether or not caries was present and not the level of dmf. CONCLUSION: A suitable modelling approach for caries data is to employ a Poisson or a negative binomial model for the dmf/DMF response and a binomial model for the caries-free/caries-present outcome. This allows separate estimation of those factors which influence the magnitude of caries and those factors which influence whether caries is actually present or not.

Binomial Distribution↗

PubMed1995

Genetic mapping of quantitative trait loci for traits with ordinal distributions.

Statistical methods for mapping quantitative trait loci relative to genetic markers are now well established for continuous traits with normal distributions. However, many traits of economic importance are recorded on a discrete, ordinal scale. Here we describe a model developed for the analysis of ordinal traits, such as degree of difficulty in calving or categories of plant disease resistance. The model estimates the distance from the quantitative trait locus to neighbouring genetic markers, and also genetic parameters, either as gene effects on an underlying continuous scale or as probabilities of the observed categories. The model is tested on simulated data and is compared with an analysis based on mixtures of normal distributions. The ordinal model is found to estimate the parameters more accurately, especially when the number of categories is small or when only one linked marker is available.

Animal Husbandry↗

PubMed2006

Minimum foot clearance during walking: strategies for the minimisation of trip-related falls.

This paper models minimum foot clearance (MFC) data during steady-state gait to investigate how the various descriptive statistics of the MFC distribution differ in healthy young and elderly females. A minimum of 20min of treadmill walking was analysed for 17 young and 16 elderly females using a Peak Motus motion analysis system. The results indicated that none of the 33 participants' MFC data sets were Normally distributed. The deviation from a Normal distribution was systematic (always skewness>0 and kurtosis>0). Skewness and kurtosis in MFC data was highly correlated (young: r=0.60, p=0.01; elderly: r=0.95, p<0.01). MFC descriptive statistics provide useful information about basic strategies used by individuals to minimize the likelihood of tripping. Possible strategies to minimize tripping include: (a) increasing MFC height central tendency, (b) reducing MFC variability, and/or (c) increasing right skewness. A low median MFC was often associated with a low IQR or high skewness to compensate. Further research is required to establish how, or if at all, these strategies are modified in populations that are more at risk of falling.

Accidental Falls↗

PubMed2001

Changes in quality of life after hormonal treatment of endometriosis.

BACKGROUND: To assess whether hormonal treatment of endometriosis improves quality of life for women with endometriosis. METHODS: In a prospective, randomized, double-blind, double-dummy study on 48 women with verified endometriosis, the pain pattern and quality of life were registered before, during and after treatment with nafarelin or medroxyprogesterone acetate. The distribution of the studied parameters were tested by means of a Skewness test. ANOVA analysis was used for normally distributed variables and Friedman's analysis and Mann-Whitney U-test for non normally distributed variables. RESULTS: There was a difference between the 30 women who participated all through the study and the 18 who dropped out. It was noticeable that anxiety-depression and sleep disturbances were significantly more common among the drop outs. There was a significant reduction in symptom score during the study, without any significant difference between the treatment groups. The sleep disturbances and anxiety-depression score improved significantly from before treatment to the end of the follow-up, but the anxiety-depression score increased during the nafarelin treatment period. There was a statistically significant improvement of paid working life in the nafarelin treated group. All the other psycho-social parameters as well as emotional balance improved during the study period without difference between groups. CONCLUSION: When hormonal treatment is planned it is very important to take into consideration previous psychosocial experiences of the patient. Factors of importance for quality of life such as sleep disturbances and anxiety-depression improved significantly after treatment with nafarelin or medroxyprogesterone acetate.

Adolescent↗

PubMed1990

Introduction to biostatistics: Part 6, Correlation and regression.

Correlation and regression analysis are applied to data to define and quantify the relationship between two variables. Correlation analysis is used to estimate the strength of a relationship between two variables. The correlation coefficient r is a dimensionless number ranging from -1 to +1. A value of -1 signifies a perfect negative, or indirect (inverse) relationship. A value of +1 signifies a perfect positive, or direct relationship. The r can be calculated as the Pearson-product r, using normally distributed interval or ratio data, or as the Spearman rank r, using non-normally distributed data that are not interval or ratio in nature. Linear regression analysis results in the formation of an equation of a line (Y = mX + b), which mathematically describes the line of best fit for a data relationship between X and Y variables. This equation can then be used to predict additional dependent variable values (Y), based on the value or the independent variable X, the slope m, and the Y-intercept b. Interpretation of the correlation coefficient r involves use of r2, which implies the degree of variability of Y due to X. Tests of significance for linear regression are similar conceptually to significance testing using analysis of variance. Multiple correlation and regression, more complex analytical methods that define relationships between three or more variables, are not covered in this article. Closing comments for this final installment of this introduction to biostatistics series are presented.

Biometry↗