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[Age and sex dependent distribution pattern and normal range of blood cell parameters obtained by automated blood cell analyzer].

Distribution and normal value of 23 blood cell parameters in healthy 2509 males and 1658 females (20-69 year of age) who are the visitors of our health examination clinic or workers of the hospital were studied. These parameters were obtained by automated cell analyzer (Sysmex NE-8000, Toa Med. Electronics). Distribution pattern and normal range of 23 parameters were studied in different groups of the sex and the age (decade). Distribution of the parameters in each groups was classified into 5 patterns such as Gaussian (G), log-Gaussian (L), skewed toward lower values (P1), skewed toward higher values with shorter tail than of log-Gaussian (P2), skewed toward higher values with longer tail than of log-Gaussian (P3). Normal range of parameters in each groups was calculated by mean +/- 1.96SD of normal distribution curve obtained by power transformation procedure in L, P1, P2 and P3 distribution. Parameters concerning leukocytes and platelets showed rarely G distribution in each groups. Significant sex difference was observed in leukocyte count (male > female, p < 0.001) and platelet count (female > male, p < 0.01) in each age group. Normal values of newly analysed parameters as volume distribution curve of erythrocytes and platelets, mean platelet volume and large platelet ratio were established.

Adult↗

Caffeine as a probe for CYP1A2 activity: potential influence of renal factors on urinary phenotypic trait measurements.

Two established caffeine-based urinary methods for measuring CYP1A2 activity were compared with each other, and also with the systemic clearance of caffeine which served as a standard of reference for such activity. Following a standardized dose, caffeine (137X) and its metabolites were measured in urine and plasma of 39 healthy subjects. The measurements allowed determinations of: (1) systemic caffeine clearance (CL(caff)); (2) the caffeine metabolite ratio (AFMU + 1X + 1U)/17U determined in an overnight-urine specimen and referred to as CMR, and (3) the ratio (17X + 17U)/137X measured in urine collected between 4 and 5 h after caffeine intake and referred to as PCUR for 'paraxanthine-caffeine urinary ratio'. The PCUR showed a bimodal distribution and a relatively wide variation, CL(caff) and CMR were both normally distributed. The correlation between CL(caff) and CMR was r = 0.77 (p < 0.001), between CLcaff and PCUR r = 0.46 (p < 0.01), and between CMR and PCUR r = 0.40 (p < 0.02). The difference between the correlation coefficients 0.77 and 0.46 was statistically significant (z-test; p < 0.05). The well established decrease of caffeine metabolism by oral contraceptive use was observed with both CL(caff) and CMR but not with PCUR. Examination of possible explanations for the differences between PCUR and CMR led to the finding of a correlation between PCUR and the renal clearance of caffeine (CLr) with r = -0.47 (p < 0.01). Further scrutiny demonstrated that a bimodal or non-normal frequency distribution as shown by PCUR was also shown by CLr and by urine flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biometric evaluation of gastric urease activity in man.

The 14C-urea breath test is claimed to be the best test for detection of Helicobacter pylori infection. We present a procedure for estimating its cutoff value on the basis of biometric evaluation only, without involving other diagnostic methods. Cumulative gastric urease activity (CA) was determined during the first 30 min after oral administration of 14C-urea (92.5 kBq) in 56 random volunteers and 49 consecutive patients with peptic ulcer disease. The distribution of CA in random volunteers was positively skewed. Logarithmic transformation yielded two separate populations, each normally distributed. Their normal probability density functions intercepted at log cutoff value. A bimodal distribution of log CA was confirmed in patients with peptic ulcer disease before and after treatment aimed at H. pylori eradication. Cutoff values were determined for both random volunteers and patients with peptic ulcer disease. By application of the present procedure for determination of cutoff value, the 14C-urea breath test distinguishes between individuals who have an increased gastric urease activity and individuals who do not, with the smallest possible arbitrariness.

Adult↗

Red cell and white cell counts in adult female guinea-pigs.

We made red cell and white cell counts in an homogeneous sample of more than 250 healthy, non gravid, adult, female guinea-pigs. Up to the present it is the highest number of guinea-pigs on which systematic blood counts have been taken. Each category of cells was studied statistically. Our mean of the red cells (5.03 X 106/mm3) is close to most of the means reported in the literature for both sexes; the distribution apparently follows the Gauss normal distribution. The mean of the white cells that we obtained (11.800/mm3) is greater than those of many authors in both sexes. The total number of lymphocytes and monocytes (6.180/mm3) is larger than that of the granulocytes (4.970/mm3). The mean Kurloff cells is 422/mm3. The distribution curves of the aggregate of white cells and those of the granulocytes, the lymphocytes and monocytes, the Kurloff cells are asymmetrical and spread towards the right; the normality hypothesis is rejected for each of them.

Animals↗

Planning and revising the sample size for a trial.

The sample size for a trial depends on the type I and type II error rates and on the minimum relevant clinical difference, all of which are known, and on the anticipated, but unknown, value of a measure of variation for the key response. This measure is the overall response rate when the key response is binomially distributed, or the residual variance in each treatment group when the key response is continuous and normally distributed. Since the true value of the measure is unknown, it must be guessed or estimated from previous trials. We describe approaches to determine an appropriate value for it, both before the trial begins and after it has begun, for use in calculating the final sample size. These approaches differ from previously described 'internal pilot' methods in not requiring unblinding of the treatment assignments in the trial. They preserve the power and do not affect the type I error rate materially. The approaches can be applied to longitudinal studies where the rate of change over time is the response of interest, and to group sequential trials.

Algorithms↗

Distribution and possible function of lysosomal enzymes in the inner ear under normal and pathophysiological conditions.

The normal distribution of several lysosomal enzymes was studied in 20 guinea pigs. In the outer hair cells lysosomal enzymes are mainly localized at the apical cell pole, while in inner hair cells the distribution was uniform. Nonlysosomal enzymes like alcaline phosphatase are of predominantly basal localization. The concentration of some lysosomal enzymes like N-acetyl-beta-glucosaminidase was higher in outer than in inner hair cells while others like acid phosphatase, beta-glucuronidase and sulfatase showed a stronger reaction in the inner hair cells. After 10 days of sound overstimulation with 120 dB for 1 h a day, there was an increase of lysosomal enzyme content namely in the outer hair cells. There was no change of non-lysosomal enzymes. Under these conditions there might be a partial destruction of cellular organelles eliminated by lysosomal activity without loss of a total cell. In addition the distribution and possible function of lysosomal enzymes in other labyrinthine tissues was discussed.

Acetylglucosaminidase↗

[Predictive equations and analysis of influence factors of lung ventilation based on a large occupational population in North China].

OBJECTIVE: To establish suitable predictive equations of lung function for occupational population in North China. METHODS: A total of 5 002 on the job or retired healthy adults from five enterprises in North China with category of mild or moderate work intensity underwent spirometry using a Chest HI-198 spirometer and the procedures recommended by the American Thoracic Society, were a sample. RESULTS: The data of 3 913 subjects were used. A normal distribution of our data was shown using the normality test and distribution curve. Univariate analysis showed that both age and height were significantly correlated with FVC, FEV(1), FEV(1)/FVC (%) and MMF. Further multiple linear stepwise regression analysis indicated that the levels of FVC, FEV(1), FEV(1)/FVC (%) and MMF were highly influenced by age, height, and weight rather than chest circumference. Thus, only age, height, and weight were introduced into our regression equations. Data from the studied subjects and other source were utilised to examine the validity of the equations and a high accordance rate (> 90%) was obtained. No significant difference (P > 0.05) was found in the predictive values between the simplified equations and equations in which more variables were included. CONCLUSION: The studied predictive equations for male non-smokers, female non-smokers, and male smokers were established based on data from a large occupational population. These equations should be more applicable for evaluating lung ventilatory function of occupational populations in North China.

Adolescent↗

Bone strength statistical distribution functions for broilers.

Shear and three-point bending tests were conducted on the femur and tibia bones from Hubbard broilers to establish the type of statistical distribution function that best fits bone strength data. In the past it was assumed that these types of data followed a normal distribution. The results of this investigation indicate that a log-normal function best describes the mechanical properties of the tibia and a normal function describes the properties of the femur. Overall the results of the distribution analysis indicate that the mechanical properties of bone tend to follow a log-normal distribution.

Animals↗

Creatine kinase activity in the detection of carriers of Duchenne muscular dystrophy: comparison of two methods.

Serum creatine kinase activity was estimated in 48 control women and 22 female carriers of Duchenne muscular dystrophy by two different methods. One method is based on the colorimetric determination of creatine liberated from creatine phosphate; the other, an N-acetyl cysteine activated UV system, was used in an automated mode. The two methods were equally efficient in carrier detection, and results were closely correlated over the range of values encountered in controls and carriers. Log creatine kinase values appeared to be normally distributed in controls, but the distribution in carriers appeared skewed towards its upper end. If both distributions are assumed to be Normal, the probability, together with its standard error, that a consultand is a carrier, can be calculated from her creatine kinase value, and if the latter is expressed in standard deviation units of the control log creatine kinase distribution, probability estimates can be compared between laboratories.

Adult↗

Improving the calculation of statistical significance in genome-wide scans.

Calculations of the significance of results from linkage analysis can be performed by simulation or by theoretical approximation, with or without the assumption of perfect marker information. Here we concentrate on theoretical approximation. Our starting point is the asymptotic approximation formula presented by Lander and Kruglyak (1995, Nature Genetics, 11, 241--247), incorporating the effect of finite marker spacing as suggested by Feingold et al. (1993, American Journal of Human Genetics, 53, 234--251). We consider two distinct ways in which this formula can be improved. Firstly, we present a formula for calculating the crossover rate rho for a pedigree of general structure. For a pedigree set, these values may then be weighted into an overall crossover rate which can be used as input to the original approximation formula. Secondly, the unadjusted p -value formula is based on the assumption of a Normally distributed nonparametric linkage (NPL) score. This leads to conservative or anti-conservative p -values of varying magnitude depending on the pedigree set structure. We adjust for non-Normality by calculating the marginal distribution of the NPL score under the null hypothesis of no linkage with an arbitrarily small error. The NPL score is then transformed to have a marginal standard Normal distribution and the transformed maximal NPL score, together with a slightly corrected value of the overall crossover rate, is inserted into the original formula in order to calculate the p -value. We use pedigrees of seven different structures to compare the performance of our suggested approximation formula to the original approximation formula, with and without skewness correction, and to results found by simulation. We also apply the suggested formula to two real pedigree set structure examples. Our method generally seems to provide improved behavior, especially for pedigree sets which show clear departure from Normality, in relation to the competing approximations.

Computer Simulation↗

Hydrogen peroxide-induced endothelial retraction is accompanied by a loss of the normal spatial organization of endothelial cell adhesion molecules.

Treatment of confluent monolayers of human umbilical vein endothelial cells with sublethal concentrations of hydrogen peroxide (H2O2) produces reversible cell retraction that opens gaps between adjacent cells. Despite the retraction, adjacent cells remain in contact through a network of dendrite-like processes. Retraction depends on cellular metabolism but not new protein synthesis or protein kinase C. Shape changes induced by H2O2 are accompanied by partial redistribution of actin filaments from the cell periphery in resting endothelial cells to a tangled network of centrally located filaments in H2O2-treated endothelial cells. This change in actin organization is associated with a loss of the normal distribution pattern of surface protein expression. Specifically, beta 1 and beta 3 integrins partly escape from focal adhesion plaques and migrate to the lateral and apical surface of the cell; PECAM-1 redistributes from the lateral borders to the basal surface; and ICAM-1 and ICAM-2 spread from apical caps to the basal surface and to the dendrite-like processes. The likely consequence of endothelial retraction accompanied by abnormal membrane protein distribution is a loss of normal endothelial cell functions. These changes are best considered manifestations of H2O2-induced sublethal injury that may cause endothelial dysfunction.

Actins↗

[Blood flow and oxidative metabolism of the brain in patients with dementia (author's transl)].

The purpose of this retrospective study was to investigate how the blood flow and oxidative metabolism of the brain was changed in dementia and the influence of the age factor. Cerebral blood flow (CBF) was measured in 115 patients aged from 40 to 83 years by means of the Kety-Schmidt technique with the modification of Bernsmeier and Siemons. The cerebral metabolic rates of oxygen and CO2 were determined by the van Slyke method and by gaschromatography respectively and of glucose and lactate by standard enzymatic methods. All cases of dementia due to head injuries, cerebral infections, cerebral infarctions, exogenous or endogenous intoxications or circulatory diseases were excluded from this study, but no classification of the dementias was made. Statistical calculations were carried out by means of the analysis of variance for a two-way design. Cerebral blood flow did not show a normal distribution curve but was at least triphasic; CBF in demented patients was either lower than normal, normal or higher than normal. The distribution curves showed further that a low cerebral blood flow of mean 32.5 ml/100 g min coincided with a low CMR oxygen of 2.50 ml/100 g min; however, CMR glucose was either low (2.50 mg/100 g min), or nearly normal (4.50 mg/100 g min) or elevated (7.50 mg/100 g min). A normal (45.0 ml/100 g min) or enhanced (62.5 ml/100 g min) CBF correlated with a CMR oxygen which was either decreased to 2.75 ml/100 g min or increased to 4.75 ml/100 g min; CMR glucose was either decreased to 1.50 mg/100 g min, or nearly normal (4.50 mg/100 g min), or was elevated to 6.50 and 10.50 mg/100 g min with respect to the peaks of the distribution curves. It is assumed that the variability of the findings with respect to the blood flow and oxidative metabolism of the brain in dementia is due to different pathophysiological and pathobiochemical disturbances in the brain. A significant influence of age on CBF and metabolism in patients with dementia was not found.

Adult↗

The logistic transform for bounded outcome scores.

The logistic transformation, originally suggested by Johnson (1949), is applied to analyze responses that are restricted to a finite interval (e.g. (0,1)), so-called bounded outcome scores. Bounded outcome scores often have a non-standard distribution, e.g. J- or U-shaped, precluding classical parametric statistical approaches for analysis. Applying the logistic transformation on a normally distributed random variable, gives rise to a logit-normal (LN) distribution. This distribution can take a variety of shapes on (0,1). Further, the model can be extended to correct for (baseline) covariates. Therefore, the method could be useful for comparative clinical trials. Bounded outcomes can be found in many research areas, e.g. drug compliance research, quality-of-life studies, and pain (and pain relief) studies using visual analog scores, but all these scores can attain the boundary values 0 or 1. A natural extension of the above approach is therefore to assume a latent score on 0,1) having a LN distribution. Two cases are considered: (a) the bounded outcome score is a proportion where the true probabilities have a LN distribution on (0,1) and (b) the bounded outcome score on [0,1] is a coarsened version of a latent score with a LN distribution on (0,1). We also allow the variance (on the transformed scale) to depend on treatment. The usefulness of our approach for comparative clinical trials will be assessed in this paper. It turns out to be important to distinguish the case of equal and unequal variances. For a bounded outcome score of the second type and with equal variances, our approach comes close to ordinal probit (OP) regression. However, ignoring the inequality of variances can lead to highly biased parameter estimates. A simulation study compares the performance of our approach with the two-sample Wilcoxon test and with OP regression. Finally, the different methods are illustrated on two data sets.

Anticholesteremic Agents↗

A simplified model for the disruption of Escherichia coli: the effect of cell septation.

A new model for the disruption of Escherichia coli by high-pressure homogenization has been previously presented. Initial model development assumed a bimodal distribution of effective cell strengths to allow for a possible difference in strength between septated and nonseptated cells. A considerably simpler model is obtained when any difference in strength is neglected and a normal distribution is employed. In this article, the disruption of a culture with an abnormally high septated fraction is examined. Disruption versus pressure curves are predicted using both the bimodal and normal approximations to the strength distribution. An examination of disrupted cultures by optical and electron microscopy suggests that septated cells are indeed weaker, thus implying that a bimodal approximation is strictly correct. However, comparison of the model predictions with the experimental results suggests that the simple normal distribution provides sufficient predictive accuracy even for cultures with a high septated fraction.

Escherichia coli↗

Parameter estimation in the magnitude-only and complex-valued fMRI data models.

In functional magnetic resonance imaging, voxel time courses are complex-valued data but are traditionally converted to real magnitude-only data ones. At a large signal-to-noise ratio (SNR), the magnitude-only data Ricean distribution is approximated by a normal distribution that has been suggested as reasonable in magnitude-only data magnetic resonance images for an SNR of 5 and potentially as low as 3. A complex activation model has been recently introduced by Rowe and Logan [Rowe, D.B., and Logan, B.R. (2004). A complex way to compute fMRI activation. NeuroImage, 23 (3):1078-1092] that is valid for all SNRs. The properties of the parameter estimators and activation statistic for these two models and a more accurate Ricean approximation based on a Taylor series expansion are characterized in terms of bias, variance, and Cramer-Rao lower bound. It was found that the unbiased estimators in the complex model continued to be unbiased for lower SNRs while those of the normal magnitude-only data model became biased as the SNR decreased and at differing levels for the regression coefficients. The unbiased parameter estimators from the approximate magnitude-only Ricean Taylor model were unbiased to lower SNRs than the magnitude-only normal ones. Further, the variances of the parameter estimators achieved their minimum value in the complex data model regardless of SNR while the magnitude-only data normal model and Ricean approximation using a Taylor series did not as the SNR decreased. Finally, the mean activation statistic for the complex data model was higher and not SNR dependent while it decreased with SNR in the magnitude-only data models but less so for the approximate Ricean model. These results indicate that using the complex data model and not approximations to the true magnitude-only Ricean data model is more appropriate at lower SNRs. Therefore, since the computational cost is relatively low for the complex data model and since the SNR is not inherently known a priori for all voxels, the complex data model is recommended at all SNRs.

Algorithms↗

Reporting measurement uncertainty and coverage intervals near natural limits.

Different methods of treating data which lie close to a natural limit in a feasible range, such as zero or 100% mass or mole fraction, are discussed and recommendations made concerning the most appropriate. The methods considered include discarding observations beyond the limit, shifting observations to the limit, truncation of a classical confidence interval based on Student's t (coupled with shifting the result to the limit if outside the feasible range), truncation and renormalisation of an assumed normal distribution, and the maximum density interval of a Bayesian estimate based on a normal measurement distribution and a uniform prior within the feasible range. Based on consideration of bias and simulation to assess coverage, it is recommended that for most purposes, a confidence interval near a natural limit should be constructed by first calculating the usual confidence interval based on Student's t, then truncating the out-of-range portion to leave an asymmetric interval and adjusting the reported value to within the resulting interval if required. It is suggested that the original standard uncertainty is retained for uncertainty propagation purposes.

Journal Article↗

Commingling in the distributions of fat-related measures in Punjabi families.

The distribution of anthropometric measurements related to fatness levels is examined to determine if skewness alone accounts for the nonnormality of such measures. A mixture of two normal distributions or a single skewed distribution fit the data significantly better than a single normal in all cases. For maximum hip width, knee diameter, and weight, two skewed distributions give a better fit than one skewed distribution, rejecting the null hypothesis of a single distribution even when skewness is considered. There is evidence for three skewed component distributions for biceps skinfold. Abdomen circumference, upper arm circumference, triceps skinfold, and calf skinfold are best approximated by a one component log-normal distribution. Children and parents show slightly different patterns in skewness and kurtosis when considered separately, but differences between them do not account for the commingling found in the combined distributions.

Adipose Tissue↗

Psychology of syndromes. IQ and micropenis.

In 20 patients with a micropenis, IQs ranged from 81 to 137, with a mean of 117 +/- 14 and a median of 116. The distribution of IQs approximated a normal distribution except that the entire curve was skewed, with the majority (75%) of scores higher than 109. There was no clustering related to diagnosis, age, sex of rearing, or serial testing to account for the skew, which was stronger for verbal than for performance IQ. These findings negated the probability of an adverse intellectual prognosis for patients born with a micropenis.

Adolescent↗