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PubMed1996

Interindividual variations in susceptibility and sensitivity: linking risk assessment and risk management.

In the past few years, our knowledge of mammalian genomes has increased enormously. Our understanding of the molecular basis of the normal cellular processes of DNA replication and repair and cell cycle control, together with how their fidelity malfunctions as part of tumor development, has increased in parallel. This has led to a clearer appreciation that there are subpopulations that have been generically described as being genetically or otherwise susceptible to the induction of cancer or birth defects. The term susceptibility is a default option, since there clearly will be a very broad range of sensitivities among the so-called susceptible populations, dependent upon the specific underlying mechanism. This could lead to the conduct of risk assessments for each specific situation, involving both genotypes of individuals and agents of concern. This would ideally take into account the effects on response of various modifying factors, genetic and other. One advantage to be gained from this approach is the ability to determine if a particular susceptibility places subpopulations at extreme risk as compared to the overall normal distribution of risk in the population, or whether such a susceptible population presents a slight extension of the upper bound of the risk distribution or lies within the normal distribution. In addition, the specific mechanism of the susceptibility as related to exposure scenarios and the magnitude and demographics of the susceptible populations need to be taken into account. Thus, the management of risk has to be linked to the specific risk assessment. For many of the so-called susceptible populations an uncertainty factor of less than 10, even including 1, would be predicted to bring the risk within the normal distribution. It is hoped that as more mechanistic information on susceptibility becomes available and a specific risk can be defined, the practice of risk management will be considerably improved.

Animals↗

PubMed1981

Examination of a lognormal distribution equation for describing distributions of diameters of bovine adipocytes.

Samples of subcutaneous, intermuscular and mesenteric adipose tissues from beef steers were fixed with osmium tetroxide, and freed adipocytes were counted with an automatic particle counter to determine whether a lognormal distribution function would describe adipocyte size distributions more accurately than a normal distribution function. Modes and medians of size distributions generally were larger than means for adipocyte size distributions modeled with a lognormal distribution function. Normalized third and fourth moments of predicted lognormal distributions often were close to 0 and 3, respectively, which are expected values for a normally distributed population. Considerable variation was observed in the skewness of adipocyte size distributions. Both normal and lognormal models for adipocyte size distribution yielded similar means. The lognormal model yielded a greater standard deviation than the normal model for adipocyte size distributions. Smaller chi-square values were found for size distributions modeled with a lognormal than with a normal distribution function. Results suggest that a lognormal distribution function more accurately models the size distributions of bovine adipocytes.

Adipose Tissue↗

PubMed2000

Induced sputum cellularity. Reference values and distribution in normal volunteers.

Sputum induction has recently been proposed as the only direct noninvasive method for measuring airway inflammatory indices. The reference values and the distribution of cells in induced sputum in a control population have not yet been well defined. We therefore evaluated data from a large number of healthy volunteers. One hundred fourteen healthy, nonatopic, nonsmoking volunteers without airway hyperreactivity were enrolled (age: 38 +/- 13 yr [mean +/- SD]; FEV(1): 105 +/- 10% predicted; provocative dose of methacholine inducing a 20% decrease FEV(1) > 3,200 microgram). Ninety-six subjects (84%) produced adequate analysis samples. The subjects had a normal age distribution. Their induced sputum was rich in macrophages (69.2 +/- 13%) and neutrophils (27.3 +/- 13%), and poor in eosinophils (0.6 +/- 0.8%), lymphocytes (1.0 +/- 1.2%), and epithelial cells (1.5 +/- 1.8%). Only macrophages and neutrophils showed a normal distribution; total and differential counts of other cells did not. We propose that these data be used in comparison of the induced sputum cells of normal subjects and those of patients with airway inflammation.

Adult↗

PubMed1996

Sonographic appearance and distribution of normal cervical lymph nodes in a Chinese population.

In 100 normal subjects who had a sonographic examination of the neck, 1211 lymph nodes were detected. In all the subjects, at least five lymph nodes were seen. The distribution, number, echogenicity, shape, presence or absence of echogenic hilus, and the sharpness of nodal borders of normal cervical lymph nodes were determined. The usefulness of these sonographic features in understanding the normal distribution and characteristics of the nodes in the Chinese population is discussed. The relationship between the shape and size of lymph node also was assessed.

Adolescent↗

PubMed1978

The correlation between relatives with assortative mating.

The equilibrium correlation between various close relatives is calculated for phenotypic assortative mating for a character determined by additive loci without dominance and an uncorrelated environment. It is supposed that the phenotypes of spouses have a bivariate normal distribution and environment and heredity are normally distributed. Heredity is Gaussian if either there are many alleles with approximately normally distributed effects at each of an arbitrary number of loci or the trait is controlled by many loci, each of which makes only a small contribution. It is also assumed that the regression of the phenotype or genotype of an individual on the phenotype or genotype of any one of his relatives is linear. The results show that with the above assumptions Fisher's formulae for the correlation between relatives hold with no restrictions on the linkage map.

Female↗

PubMed1982

A multi-stage Gaussian transformation algorithm for clinical laboratory data.

We have developed a multi-stage computer algorithm to transform non-normally distributed data to a normal distribution. This transformation is of value for calculation of laboratory reference intervals and for normalization of clinical laboratory variates before applying statistical procedures in which underlying data normality is assumed. The algorithm is able to normalize most laboratory data distributions with either negative or positive coefficients of skewness or kurtosis. Stepwise, a logarithmic transform removes asymmetry (skewness), then a Z-score transform and power function transform remove residual peakedness or flatness (kurtosis). Powerful statistical tests of data normality in the procedure help the user evaluate both the necessity for and the success of the data transformation. Erroneous assessments of data normality caused by rounded laboratory test values have been minimized by introducing computer-generated random noise into the data values. Reference interval endpoints that were estimated parametrically (mean +/- 2 SD) by using successfully transformed data were found to have a smaller root-mean-squared error than those estimated by the non-parametric percentile technique.

Adult↗

PubMed1986

Distributional expectations and the induction of category structure.

Previous research on how categories are learned from observation of exemplars has largely ignored the possible role of prior expectations concerning how exemplars will be distributed. The experiments reported here explored this issue by presenting subjects with category-learning tasks in which the distributions of exemplars defining the categories were varied. In Experiments 1 and 2 the distributional form of a category was found to affect speed of learning. Learning was faster when a category's distribution was normal than when it was multimodal. Also, subjects in the early stages of learning a multimodal category responded as if it were unimodal. These results suggested that subjects enter category-learning tasks with expectations of unimodal, possibly normal, distributions of exemplars. Experiments 3 and 4 attempted to manipulate subjects' prior expectations by varying the distribution of exemplars in the first of two consecutive category-learning tasks. Learning a multimodal category was influenced by the shape of a previously learned distribution and was facilitated when the earlier distribution was either multimodal or skewed, rather than normal. These results are interpreted as support for a dual-process model of category learning that incorporates the effects of prior expectations concerning exemplar distributions.

Adolescent↗

PubMed1994

Computing the central location of immunofluorescence distributions: logarithmic data transformations are not always appropriate.

The idea of the "average" intensity of immunofluorescence data is often poorly defined, with such terms as average, mean, and peak used interchangeably. In addition, the common use of logarithmic amplifiers with immunofluorescence data further complicates the problem. Log amplifiers permit the display of a wider range of fluorescence intensities. At the same time, they effect a log transformation of the data. This transformation decreases the variance resulting in narrower fluorescence distributions, which are assumed to approximate normal distributions. When the log transform is used, the distribution mean is the geometric mean of the untransformed data, which is computed simply as the mean of the channel values. This mean value serves as a simple indicator of the population center. Despite the prevalence of log transformations in flow cytometry, this transformation may not yield normally distributed immunofluorescence data, whereas the square root or other fractional power transformations can yield normal distributions.

Flow Cytometry↗

PubMed1976

Differential transglutaminase distribution in normal rat liver and rat hepatoma.

Distribution of transglutaminase activity was determined in normal rat liver, a 3'-methyl-4-dimethylaminoazobenzene-induced primary hepatoma, and the Novikoff hepatoma. Over 90% of the total enzyme activity was found in the 105,000 X g supernatant of normal liver, whereas only 30% was found in this fraction of the hepatomas, the remainder being found in the particulate fraction. The is distribution pattern did not correlate with protein distribution nor did it change during cellular proliferation, since regenerating liver and embryonic tissue had the same pattern as normal liver. Cell protein was a suitable acceptor substrate for the enzyme. Kinetic analyses showed that liver and hepatoma enzymes had a similar Km and Vmax for putrescine incorporation into cell protein. Hepatoma particulate enzyme was more stable than either liver or hepatoma supernatant enzyme. The enzyme may also act as the acceptor molecule.

Animals↗

PubMedDate not supplied

Dystrophin and dystrophin-related protein (utrophin) distribution in normal and dystrophin-deficient skeletal muscles.

The respective localizations of dystrophin and dystrophin-related protein (DRP or utrophin) along the sarcolemmal membrane and at the neuromuscular junctions (NMJs) in normal and dystrophin-deficient skeletal muscles, were determined using confocal laser microscopy. The analysis was prompted by the recent availability of a new anti-utrophin mAb [Bewick et al. NeuroReport 1992; 3:857-860] and different mAbs that react with dystrphin or both dystrophin and utrophin. In dystrophin-deficient muscles, utrophin was expressed and detectable over large subcellular areas normally occupied by dystrophin along the sarcolemmal membranes and at the NMJs. Utrophin was expressed in a non-uniform, discontinuous way on the sarcolemmal membrane in dystrophin-deficient skeletal muscles, similar to dystrophin in normal muscle fibres. The respective distributions of both related muscle proteins and their positions relative to the alpha-bungarotoxin acetylcholine (ACh) receptor marker were determined. Double-staining experiments and superimposition of the confocal images showed that utrophin was more closely associated with ACh receptors than dystrophin at the NMJs in normal muscles. Utrophin distribution consequently differed from that of dystrophin.

Adolescent↗

PubMed1995

Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).

The discovery that the epsilon 4 allele of the apolipoprotein E (apoE) gene is a putative risk factor for Alzheimer disease (AD) in the general population has highlighted the role of genetic influences in this extremely common and disabling illness. It has long been recognized that another genetic abnormality, trisomy 21 (Down syndrome), is associated with early and severe development of AD neuropathological lesions. It remains a challenge, however, to understand how these facts relate to the pathological changes in the brains of AD patients. We used computerized image analysis to examine the size distribution of one of the characteristic neuropathological lesions in AD, deposits of A beta peptide in senile plaques (SPs). Surprisingly, we find that a log-normal distribution fits the SP size distribution quite well, motivating a porous model of SP morphogenesis. We then analyzed SP size distribution curves in genotypically defined subgroups of AD patients. The data demonstrate that both apoE epsilon 4/AD and trisomy 21/AD lead to increased amyloid deposition, but by apparently different mechanisms. The size distribution curve is shifted toward larger plaques in trisomy 21/AD, probably reflecting increased A beta production. In apoE epsilon 4/AD, the size distribution is unchanged but the number of SP is increased compared to apoE epsilon 3, suggesting increased probability of SP initiation. These results demonstrate that subgroups of AD patients defined on the basis of molecular characteristics have quantitatively different neuropathological phenotypes.

Aged↗

PubMed1987

Glandular elements around the intrahepatic bile ducts in man; their morphology and distribution in normal livers.

The morphology and distribution of the glandular elements around the intrahepatic bile ducts, hitherto poorly described, were examined in autopsied human livers with the aid of postmortem cholangiographs. The glands could be divided into intramural and extramural. The former were small in number, scattered within the bile duct walls, and were simple tubular mucous glands. The latter were more abundant, located in the periductal connective tissue, and were branched tubuloalveolar seromucous glands. Serial section observations revealed that neither gland communicated with the hepatic parenchyma, and the extramural glands drained into the large bile duct lumina via the conduits. The mucous cells of both glands contained neutral, carboxylated and sulfated glycoproteins. The extramural glands were distributed from the hepatic to the segment ducts in almost all livers, and were also discerned around the area ducts in two-fifths of the livers. The glands seemed to decrease in number as the bile ducts became more branched.

Aged↗

PubMed1978

Coenzyme A and carnitine distribution in normal and ischemic hearts.

The distribution of coenzyme A and carnitine between the mitochondrial and cytosolic compartments was determined in rat heart ventricular muscle. The CoA and carnitine levels of homogenate, mitochondrial, and postmitochondrial fractions were determined in nonperfused hearts and in hearts that were perfused under control and ischemic conditions. Using the mitochondrial marker enzymes, citrate synthase and cytochrome c oxidase, the cellular content of mitochondrial protein was determined to be 53 +/- 1.0 (nonperfused), 53.5 +/- 1.5 (control), and 58.1 +/- 2.2 (ischemic) mg/g of wet heart muscle. These values were used to calculate the contribution of the CoA and carnitine located in the mitochondrial compartment to the total cellular levels of CoA and carnitine. Under both control and ischemic conditions, approximately 95% of the cellular CoA was mitochondrial. The percentage of the total cellular carnitine associated with the mitochondria increased from 8 to 9% in nonperfused and control hearts to 25% during ischemia, indicating that a net transfer of carnitine occurred from the cytosol to the mitochondrial matrix.

Animals↗

PubMed1999

A Dynamic Model of Cognitive Growth in a Population: Spatial Tasks and Conservation.

A dynamic model of cognitive growth is developed that is applicable to cross-sectional studies of growth in a population, and that predicts the distribution of scores as a function of age. This model modifies the theory of P. van Geert (1991, Psychological Review, 98, 3-53) for the cognitive growth of an individual under limited resources, by taking into account the effect of schooling or training. The modified theory provides an explanation for the puzzling effect reported by C. J. Brainerd (1977, Psychological Bulletin, 84, 919-939), that the gain in scores obtained in concept training experiments is independent of the initial state of the learner. In developing the modified theory, it was found that the assumption of delayed feedback is unnecessary. To apply the model to populations, it was assumed that the ability parameters that appear in the growth function are distributed normally in the population. A distribution function G(s; t) was derived that predicts the distributions of scores s at age t in terms of a small number of parameters. Although the abilities are assumed to be distributed normally, the score distributions are often bimodal. The model was applied to the studies of H. Thomas and A. Lohaus (1993, Monographs of the Society for Research in Child Development, 58, 1-169) on the growth of the concepts of verticality and horizontality, and to the study of P. M. Bentler (1970, Perceptual and Motor Skills, 31, 855-859) on the growth of the concept of conservation. In these applications the score distributions are clearly bimodal, but there is no evidence of abrupt transitions or catastrophes. This shows that the presence of a "catastrophe flag" (bimodal distributions) does not necessarily imply the presence of a catastrophe. Copyright 1999 Academic Press.

Journal Article↗

PubMed2000

Population dose due to natural radiation in Hong Kong.

In densely populated cities such as Hong Kong where people live and work in high-rise buildings that are all built with concrete, the indoor gamma dose rate and indoor radon concentration are not wide ranging. Indoor gamma dose rates (including cosmic rays) follow a normal distribution with an arithmetic mean of 0.22 +/- 0.04 microGy h(-1), whereas indoor radon concentrations follow a log-normal distribution with geometric means of 48 +/- 2 Bq m(-3) and 90 +/- 2 Bq m(-3) for the two main categories of buildings: residential and non-residential. Since different occupations result in different occupancy in different categories of buildings, the annual total dose [indoor and outdoor radon effective dose + indoor and outdoor gamma absorbed dose (including cosmic ray)] to the population in Hong Kong was estimated based on the number of people for each occupation; the occupancy of each occupation; indoor radon concentration distribution and indoor gamma dose rate distribution for each category of buildings; outdoor radon concentration and gamma dose rate; and indoor and outdoor cosmic ray dose rates. The result shows that the annual doses for every occupation follow a log-normal distribution. This is expected since the total dose is dominated by radon effective dose, which has a log-normal distribution. The annual dose to the population of Hong Kong is characterized by a log-normal distribution with a geometric mean of 2.4 mSv and a geometric standard deviation of 1.3 mSv.

Gamma Rays↗

PubMed1995

The influence on a 'normal' birthweight distribution of a minor population of growth retarded infants: a Monte Carlo simulation.

It is common practice to define babies below a certain birthweight as 'growth-retarded' or 'small-for-dates'. This presupposes that there is a specific subpopulation of babies who have not achieved their genetic growth potential. The presence of this subpopulation should result in a deviation from a normal distribution in the population as a whole. We have used a mathematical simulation, together with data from an actual sample of 1463 male Caucasian neonates delivered at 40 weeks, in order to define the characteristics of such a subpopulation which would yield deviations from the normal sufficient to be statistically significant. On the basis of this study, there was no evidence for such a subpopulation of low birthweight babies in the 1463 neonates observed.

Birth Weight↗

PubMed1980

Distribution of normal and abnormal forms among motile, non-motile, live and dead human spermatozoa.

The distribution of normal and abnormal forms among motile, non-motile live, and dead spermatozoa was investigated . For this purpose samples from each specimen of 100 fertile and infertile patients was photographed twice: once with the aid of the multiple exposure photography (MEP) technique and again by an ordinary high-speed phase-contrast photomicrography. From enlarged projected photographed images, percentage of abnormal forms in both, non motile fraction and in the while sperm population were determined. By using a simple formula the percentage of abnormal forms among motile spermatozoa has been easily calculated. An average of 42% abnormal forms among all 100 analyzed specimens was found. However, this rate was not distributed equally among the two sperm populations: only 22% abnormal forms were among motile spermatozoa, contrary to 59% among non-motile spermatozoa. In 30 specimens that have been further analyzed by the combined supravital staining and the MEP method, percentage of abnormal forms among non-motile-live spermatozoa was found to be 32, and 67 among the fraction of dead spermatozoa. The importance of studying the distribution of normal forms among motile spermatozoa, and the question of any relationship of this parameter to the fertilization capacity of the semen, is discussed.

Humans↗

PubMed1990

Distribution of age at menopause in two Danish samples.

We analyzed the distribution of reported age at natural menopause in two random samples of Danish women (n = 176 and n = 150) to determine the shape of the distribution and to disclose any possible trends in the distribution parameters. It was necessary to correct the frequencies of the reported ages for the effect of differing ages at reporting. The corrected distribution of age at menopause differs from the normal distribution in the same way in both samples. Both distributions could be described by a mixture of two normal distributions. It appears that most of the parameters of the normal distribution mixtures remain unchanged over a 50-year time lag. The position of the distribution, that is, the mean age at menopause, however, increases slightly but significantly.

Adult↗