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Within and between field variability of residue data and sampling implications.

Information on the variability of residues in individual fruits and vegetables is required to estimate the acute dietary exposure to pesticides. The distribution of residues in apples, kiwi fruits, potatoes and butter beans was studied in field experiments representing commercial farming practice. No correlation was found between the residue concentration or surface residue and the mass of apples. The relative frequency distributions of residues in crop units were continuous and skew positive. The log-normal transformation did not result in a normal distribution in any of the trials. Consequently, 299, 120 and 59 random samples should be analysed to estimate 99th, 97.5th and 95th percentile of the residues at 95% confidence level. The distribution of residues is not significantly influenced by the mean residue, pre-harvest interval, chemical and physical properties of the active ingredient, formulation of pesticide or, on top fruit, the foliar application method. However, the residue distribution is likely to be influenced by the size, shape and density of the plants, and mode of application of pesticides. The variability factor should be defined as the ratio of the highest value at a specified percentile of residues occurring in unit crops and the population mean. Generic variability factors may be determined for various groups of commodities. Variability factors of 5 and 9 are recommended for medium size fruits, and potato following granular application of pesticides, respectively.

Agriculture↗

Validity of the relative-dose-response test and the modified-relative-dose-response test as indicators of vitamin A stores in liver.

BACKGROUND: Our group and many others have used the relative-dose-response (RDR) test and the modified-RDR (MRDR) test as proxy indicators of liver stores of vitamin A. However, we have become concerned about the validity of these indicators. OBJECTIVE: Simulation models were used to assess effects of random variations in serum retinol concentration on the RDR and to assess effects of group differences in serum retinol concentration on the distribution of RDR and MRDR values. DESIGN: Random and independent samples were drawn from normally distributed, computer-generated numbers whose distributions simulated serum concentrations of retinol and 3,4-didehydroretinol as obtained from published reports. The resulting data sets were used to compute surrogate RDR or MRDR values. In model 1, the relation between serum concentrations of retinol and RDR was examined within a fictitious population. In models 2 and 3, fictitious populations with different distributions of serum retinol concentration were compared with respect to their RDR and MRDR values. RESULTS: Simulated RDR values and serum retinol concentrations were negatively related. Models 2 and 3 showed that group differences in serum retinol concentrations necessarily produced group differences in mean RDR or MRDR values. A mathematical artifact may explain the negative relation reported between MRDR and serum retinol concentration, and it dictates that this relation will necessarily vary between populations with different degrees of vitamin A deficiency. CONCLUSION: A continued search for alternative blood indicators of liver stores of vitamin A is needed.

Computer Simulation↗

Parasternal lymphoscintigraphy using 99Tcm-dextran.

99Tcm-dextran was evaluated as a lymphoscintigraphic agent in 10 normal volunteers and 24 patients with breast cancer. 99Tcm-dextran (0.5-1 mCi) in a volume of 0.1-0.2 ml was injected into the posterior rectus sheath in the subcostal site on one side. Scintigrams were obtained at 2-2.5 h after injection and the injection was repeated on the other side. The final image was taken at 4.5-5 h after the first injection. The normal distribution of lymph nodes and anatomical variations in scintigraphic images were first determined in normal subjects. In the patient group, eight scintigrams were evaluated as pathological and the rest as normal. In the 25 women whose lymphoscintigrams were normal the mean number of parasternal nodes visualized was six (range: 3-11). Bilateral symmetrical or asymmetrical chain was observed in 20 subjects (80%) and unilateral chain in five subjects (20%). There was cross-drainage in five subjects (20%). Supraclavicular lymph nodes were visualized in 11 subjects (44%). Varying abnormal images were obtained in eight patients. Our results are in good agreement with those reported in the literature, using radiocolloids. It is concluded that 99Tcm-dextran is a promising agent and may well replace radiocolloids because of the simplicity of the labelling procedure, stability of the label, easy availability and low cost.

Adult↗

Anisometropia and changes in anisometropia in school myopia.

Human anisometropia and changes in it were followed over a 3-year period in 238 schoolchildren who had uncomplicated school myopia in both eyes. Anisometropia of the spherical equivalent (ASFE) type increased in 27%, decreased in 6%, and remained unchanged in 67% of these children. When mean myopia increased from -1.43 to -3.06 D, mean ASFE increased from 0.30 to 0.51 D and the anisometropia of astigmatism (AAST) from 0.15 to 0.23 D. The faster the increase in myopia the greater was the increase in ASFE (r = 0.133, N = 238, p = 0.020). The higher the spherical equivalent at the end of the study the higher was the ASFE (r = 0.135, N = 238, p = 0.019). The initial refractive error or the amount or the axis of astigmatism did not have any prognostic value for the changes in ASFE. The higher the ASFE at the end of the study the higher also was the AAST (r = 0.136, N = 238, p = 0.018). The change in ASFE was independent of the wearing of spectacles. The distribution of the anisometropia of the spherical equivalent and its change followed a nearly normal distribution with the peak of eyes at about +/- 0 refraction.

Anisometropia↗

Rate and time of DNA synthesis of individual Chinese hamster cells.

The duration of DNA synthesis of a diploid cell line of Chinese hamster fibroblasts was determined in a comparative study by the FLM technique, and also by a new technique for measuring the rate of DNA synthesis of individual cells. These methods produced comparable results when applied during exponential growth of the cells. The rate of DNA synthesis was measured by means of quantitative autoradiography following a short-term incubation of the cells with 5 X 10(-6) M FUdR and 10(-5) M 14C-TdR. The choice of the medium for this purpose did not seem to be critical. The autoradiographic silver grains over cells and 14C-standard sources are counted by microphotometry using incident light bright-field. The direct measurements of DNA synthesis rate are 'compartment' statistics which have been converted into 'flux' parameters for comparison with the FLM method and applicability in cell-kinetic calculations. Frequency distributions of the rate of DNA synthesis of individual cells thus obtained may resemble normal distributions quite closely. They result from several factors: differences in the rate of synthesis in different parts of the S-phase, the density distribution of cells within the S-phase, the variation in the time of DNA synthesis among individual cells, and the experimental error. In the case of a pronounced partial synchronization as probably has been present in one experiment performed in the lag phase, an incorrect time of DNA synthesis may result from the rate values. Due to the variation in DNA synthesis rate in different parts of the S-phase it is not possible to determine the duration of DNA synthesis of an individual cell. However, the mean values of DNA synthesis time are reliable. The new method will be preferentially applied for determining the duration of DNA synthesis of human cells in as far as difficulties are encountered with the classical methods. In addition, it may be used to advantage for studying cells which make up low percentages in mixed populations. It finally permits a safer morphological classification of the cells under study than is possible with the classical methods.

Autoradiography↗

Feulgen microdensitometry and analysis of S-phase cells in cervical tumour biopsies.

Tissue specimens from the cervical tumours of 70 patients undergoing radiotherapy were examined by Feulgen microdensitometry. Twenty-five of the 70 specimens were also subjected to in-vitro tritiated thymidine autoradiography to determine the proportion of DNA synthesising cells they contained. A spectrum of frequency distributions of nuclear DNA content was obtained from Feulgen microdensitometry, but by inspecting the data the basic DNA content of malignant cells could be established in most cases. Fifty-nine per cent of the tumours were 'diploid', 10% 'tetraploid', 13% 'diploid to tetraploid', and the remaining 18% 'aneuploid'. Grafical analysis of DNA frequencies from 48 'diploid' or 'tetraploid' tumours enabled the proportion of DNA synthesising (S) cells to be estimated by frequency distribution analysis. Estimates of the S component ranged from nil to 30%, were log normally distributed, and comparable to direct measurements of cells in S determined by autoradiography for 25 cases (range 1.2-28.7%). For all paired data the mean difference was 1.2 +/- 1.45% (confidence limits), suggesting that overall Feulgen microdensitometry analysis may be an equally valid technique in providing cellular kinetic information with human tumour material.

Autoradiography↗

A proposed structure of chondroitin 6-sulfate proteoglycan of human normal and adjacent atherosclerotic plaque.

Chondroitin sulfate proteoglycan monomers were prepared from intima media minces of grossly normal human aorta and adjacent fatty fibrous atherosclerotic plaques. Glycosaminoglycan chains prepared from monomer from normal aorta displayed a normal distribution profile on Ultrogel ACA 54 with a Kav of 0.48, whereas those of atherosclerotic aorta displayed a bimodal distribution (major peak, Kav 0.35; minor peak, Kav 0.70). The Mr of glycosaminoglycans from normal aorta was estimated to be 1.5 X 10(4). For atherosclerotic aorta, the majority of chains were 2.0 X 10(4) while the smaller population was 1.2 X 10(4). All glycosaminoglycans were identified as chondroitin sulfate sulfated at the C-6 position. The amino acid compositions of both core proteins were similar with Mr of about 1.6 X 10(5). After beta-elimination in the presence of sodium borohydride prior to acid hydrolysis, chondroitin sulfate proteoglycan from normal aorta had reductions in serine from 109 to 68 and in threonine from 117 to 55. For the monomer from atherosclerotic plaque, reductions in serine and threonine, respectively, were from 103 to 81 and from 107 to 77 residues per 1000. The results suggested fewer chondroitin sulfate chains and oligosaccharides on the core protein in the proteoglycan of atherosclerotic plaque. Compared to normal aorta, substituted serines and threonines in the proteoglycan of atherosclerotic plaque were about half, respectively, 38% vs 21% for serine, 53% vs 28% for threonine. It is estimated that in atherosclerotic plaque there are fewer, but longer, chondroitin sulfate chains per core protein, translating into a smaller overall monomer size in atherosclerotic plaque.

Adult↗

Dopamine-beta-hydroxylase activity after acute myocardial infarction.

Serum dopamine-beta-hydroxylase (DBH) activities of 74 apparently healthy adults were not distributed normally, but skewed to the right. There were at least 2 subgroups in the distribution of DBH activity. Accordingly, 27 serial serum DBH activities following acute myocardial infarction were divided into 2 subgroups according to their activities on the 10th day or/and thereafter. The DBH activity was significantly elevated on the 1st day with average of 157% of the 10th day (p less than 0.015) in high DBH subgroup and also significantly elevated on the 1st and 2nd day with the average of 182% and 155%, respectively, of the 10th day (p=0.025 and p less than 0.05) in low DBH subgroup. There was no significant difference between the DBH activity of patients with anterior myocardial infarction and that of patients with inferior myocardial infarction. No significant correlation between the DBH activity and the coronary prognostic index was found. The observed elevation of the DBH activity on the 1st and 2nd day suggests an augmentation in the sympathetic nervous activity after acute myocardial infarction.

Acute Disease↗

Assessment of the maximum voluntary arm muscle contraction in sign language for the deaf.

OBJECTIVE: The purpose of this study was to investigate the levels of upper member muscles' activation of deaf individuals, who use the Brazilian sign language - LIBRAS, comparing these findings to volunteers with no postural deviations and normal hearing METHODS: Forty eight volunteers divided into two groups comprising healthy and deaf subjects (24 volunteers for each group). The signs of rest were obtained with the volunteer maintaining the upper member in an anatomical position, but with the forearm flexed and sustained by the lower member. Maximum voluntary isometric contractions (MVIC) of the biceps, triceps, deltoid, and trapezius muscles were performed in the position of muscular function testing. Statistical analysis was performed using the SPSS-10.0. Continuous data with normal distribution were analyzed by ANOVA with the significance level of p < 0.01. RESULTS: The normalized electromyographic muscle data obtained in muscular rest do not show statistically significant differences among the studies muscles, in both groups. In the comparison of normalized RMS values obtained in MVIC, the mean values for the trapezius muscle of deaf group were statistically lower than control group. CONCLUSIONS: This study's results indicate there are no differences between the levels of muscular activation for arm biceps, arm triceps, and the anterior portion of the deltoid muscle between the mean normalized RMS values of deaf and healthy individuals.

Adolescent↗

Erythroid progenitor cell numbers in human marrow - implications for regulation.

Marrow specimens were obtained from 34 different individuals (mainly stage I or II Hodgkins or Lymphomas) and evaluated for their content of erythropoietic and granulopoietic progenitor cells using conventional colony assay procedures and a standardized set of re-agents. Frequency distributions showed that the data for all types of progenitors appeared to be log normally distributed. Estimates of compartment size (i.e. no. of progenitors per 2 X 10(5) buffy coat cells) were 107 CFU-E, 70 BFU-E (37 classified as mature, 12 classified as primitive) and 64 CFU-C. The ratio's of CFU-E: mature BFU-E: primitive BFU-E numbers in vivo correspond well to those predicted by their proliferative capacity in vitro. Interestingly the spread of values obtained for each erythropoietic compartment was not the same but decreased with progressive differentiation, suggesting that stringent regulation of red cell output may not occur until the latter stages of erythroid cell maturation. The ratio of total BFU-E: CFU-C numbers was 1.25 +/- 0.15 suggesting that on average the probability of stem cell commitment to either the erythropoietic or granulopoietic pathway may be roughly equal.

Bone Marrow Cells↗

Major gene determination of liability to spontaneous cleft lip in the mouse.

Two genetic analyses suggested that the spontaneous and low frequency trait of cleft lip (primary palate) in the mouse is determined either by a recessive gene at one autosomal locus or by two loci with duplicate epistasis. The low frequency trait of open eyelids, which is characteristic of the A/J strain and sometimes reported to be associated with cleft lip as part of a "syndrome," has not been analyzed genetically. A backcross and test-mating study between A/J and C57BL/6J, done originally to define the genetic control of embryonic tolerance to cortisone-induced cleft palate (secondary palate), was reanalyzed for the cleft lip and open eyelids traits. Cleft lip frequencies in A/J did not change in dose-response studies of either cortisone- or 6-aminonicotinamide-induced cleft palate; for both teratogens the frequencies of open eyelids differed between doses but did not exhibit any obvious dose response. It appeared that the frequency of 7.6% cleft lip and 17.6% open eyelids in A/J in the genetic study, in which all pregnant A/J test-females were treated with a single dose of cortisone (100 mg/kg, day 12), did reflect the occurrence of the spontaneous traits. Within the A/J strain, the traits were not associated and, as expected on outcrossing to C57BL/6J (A.B6 F1 fetuses), both traits are recessive. Significant bimodality of the cleft lip scores of the BC1 sires (BC2 fetuses), test-mated with A/J, suggested that liability to cleft lip is determined by a single autosomal recessive gene. The distribution of open eyelids scores of the BC1 sires did not differ from one normal distribution, and this trait is, therefore, controlled by more than one genetic locus with additivity between loci. Cleft lip and open eyelids segregated independently and do not form a syndrome, in A/J, with one underlying genetic cause. There was no association between cleft lip and three autosomal marker genes, brown (b, chromosome 4), albinism (c, chromosome 7) and H-2 (chromosome 17), or the genetically independent tolerance traits of cortisone- and 6-aminonicotinamide-induced cleft palate. There was significant association between open eyelids and albinism (c) that is in a direction suggesting linkage or pleiotropy. Whether liability of the embryo to cleft lip is determined by one or two genes may be solved by a concerted effort to map the trait; a marker gene will be the key to further analysis of its cause.

Animals↗

A statistical method for determining normal ranges from laboratory data including values below the minimum detectable value.

Determination of normal ranges from laboratory data containing undectable values is a frequently encountered problem in the radioimmunoassay of peptide hormones. In the past, such determinations usually have been based on the mid-point method or the one-end Winsorized method. A graphic method involving the use of probability paper has also been reported. We propose that the maximum-likelihood estimation is a more appropriate statistical method for the determination of normal range from this type of data (Type I censored data). With this method, the mean and standard deviation, and hence the tolerance limits, can be estimated. We used the maximum-likelihood estimation method to determine the normal range of serum thyrotropin values obtained from 93 healthy subjects, based on a log normal distribution. Although the serum thyrotropin content was undetectable in 14% of the subjects, a normal range could be calculated. Using tolerance limits for 95% coverage of the population with 90% confidence, we calculated the normal range of thyrotropin to be 0.51-5.75 milliunits/L, with a mean value of 1.71 milliunits/L, and predicted that 91.4% of undetectable serum thyrotropin values will fall within the normal range.

Humans↗

[Dynamics of the distribution of variables in morphology].

This paper discusses examples of exponentially distributed, Poisson-distributed, and binomially distributed random variables from morphology and describes secular and historical processes as well as phenomena of aging as factors of the dynamics of such distributions, the major focus being on tests of morphometric variables for the existence of normal distributions. In those cases where hypotheses of the existence of particular distributions of random morphometric variables are established it is necessary that consideration be given to metrological and stereological factors pertaining to the process of measuring and the geometry of the structures being measured, respectively. Karyometric results are used to demonstrate the splitting of a single statistical population into several populations as a result of the process of aging of the human organism.

Aged↗

Distributions of long-term household exposure of different population groups to nitrogen dioxide.

Exposure distributions to nitrogen dioxide in living rooms during the summer and winter were calculated for four groups of Zagreb inhabitants (high school students, university students, employed, and retired persons) using Duan's Cartesianization method. Households were classified into three categories according to fuel used for cooking and heating--electricity (or no gas use), propane-butane, and natural gas. The results showed a seasonally dependent contribution to exposure in households from outdoor sources through ventilation, while type of fuel used for heating and cooking, representing indoor pollution sources, had a predominant influence on exposure levels. Exposure distribution functions could be represented by lognormal, or summation by proportion of lognormal and normal distributions. A comparison of the results and the proposed exposure guideline value suggests that either the guideline value is too large, or a nitrogen dioxide exposure problem exists only in a small percentage of homes and is caused by the high rate of air exchange between the kitchen and living room.

Air Pollution, Indoor↗

The mode ages of women with cervical dysplasia.

OBJECTIVE: To resolve the discrepancy that women seem to have Papanicolaou smears with dysplasia at younger ages than the reported mean ages. METHODS: Every other Papanicolaou smear diagnosed during a 5-year period at our institution was reviewed. There were 1947 cases with dysplasia or carcinoma. Dysplasia was defined as a lesion of disordered squamous epithelial differentiation and was graded by standard criteria. The mean, median, and mode ages of the women were determined by diagnosis. Normal (symmetrical) distribution was tested for each population, and significant differences were sought by diagnosis. RESULTS: Normal distribution was rejected for the ages of women with all grades of dysplasia and carcinoma in situ, but not for the ages of women with carcinoma. CONCLUSIONS: Because the ages of women with dysplasia are not distributed normally, but are asymmetrically skewed to younger women, we suggest that the mode better describes the central tendency for ages of women with dysplasia. The difference between the mean and mode ages of these women explains the apparent discrepancy between the reported mean ages and our clinical impression. Appropriate descriptive statistics like these help the clinician evaluate individual patients in the true context of the disease.

Adult↗

Statistical analysis of heterogeneous pharmacokinetic data from the literature.

To obtain the reliable pharmacokinetic quantities necessary for the adjustment of individual drug dosages, the pharmacokinetic data in the literature must be analysed by various appropriate statistical methods. Generally, pharmacokinetic quantities have been calculated from small sample sizes and published in different ways (the coefficient of variation of an estimated pharmacokinetic quantity is often higher than 40 percent). In the present study data were therefore structured and clustered according to the important influence variables. The important influence variables were obtained by known multivariate statistical methods. To obtain optimal estimators (uniformly minimum variance unbiased estimators) for the quantities inside the clusters, goodness of fit tests must be performed. Skewed distributions and samples with heterogeneous variances must be subjected to transformation procedures to obtain normally distributed values with homogeneous variances. The population-derived estimate of the a priori knowledge of pharmacokinetic quantities can be obtained by a statistical algorithm proposed in this paper. Information on the quantities half-life, total body clearance and volume of distribution of vancomycin were extracted from over 200 publications. These data were analysed with the proposed statistical algorithm, yielding population-based estimates for half-life, clearance and volume of vancomycin, taking into consideration the detected influence variables--renal function and the age of the patient. Important dependencies between different variables are discussed.

Age Factors↗

Breath-to-breath variability correlates with apnea-hypopnea index in obstructive sleep apnea.

BACKGROUND: Breathing in patients with obstructive sleep apnea (OSA) is frequently interrupted by periods of hypopnea and apnea. There is limited information regarding a possible disturbance of breathing outside these periods. STUDY OBJECTIVE: To analyze the degree of breathing disturbance during nonocclusion. DESIGN: Prospective determination of breathing variability during full polysomnographic sleep studies. PATIENTS: Breath-to-breath variation was monitored in 34 patients with OSA and in 9 healthy subjects. MEASUREMENTS AND RESULTS: All breath-to-breath intervals were automatically analyzed from flow signal, displayed, and manually corrected for artifacts. Distribution of all nonapneic breath intervals was analyzed for the extent of difference from a normal distribution pattern by specifying kurtosis. In untreated OSA patients, kurtosis was significantly reduced (0.0 +/- 0.5, mean +/- SD) compared to control subjects (0.8 +/- 0.5), indicating increased variability of nonoccluded breathing. This effect was present in all sleep stages, and the extent depended significantly on the degree of disease. Continuous positive airway pressure breathing was able to normalize kurtosis (1.0 +/- 0.9) immediately. CONCLUSIONS: Breathing in OSA is not only characterized by interruptions of breathing during occlusion, but by a greater variation in the pattern of normal-length breaths.

Adult↗

A method for adjusting the international growth curves for local use in the assessment of nutritional status of Saudi pre-school children.

The aim of this study is to illustrate a method for adjusting the internationally used National Center for Health Statistics (NCHS) growth curves for local use in the assessment of nutritional status of Saudi children. All children 1-60 months in three semiurban-rural communities in Asir region, Saudi Arabia (N = 1168) were subjected to weight and height (or length) measurements. These measurements were individually compared with those of the NCHS reference population. The distribution of the study population was found to be significantly shifted to the left of the normal distribution for reference population on the percentile growth curves (P < 0.001). This denoted the inappropriateness of the NCHS reference standards for local use. Accordingly, the lower limits for the expected normal on the growth curves has been shifted from the 3rd percentile line to -3 standard deviation line, to be suitable for the Saudi children. This led to 70% & 56% reductions in the estimation of undernutrition, based on wt/age and ht/age indicators respectively. It is recommended that this adjustment be supported by other studies locally and in other developing countries.

Anthropometry↗