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Comparison of a visual analogue scale and a numerical rating scale for assessment of lameness, using sheep as a model.

A study was designed to compare use of an numerical rating scale (NRS) and a visual analogue scale (VAS) for subjective assessment of lameness, using sheep as a model. The NRS consisted of 5 divisions, 0, 1, 2, 3, and 4; 4 of these divisions (1-4) described lameness. The VAS used a 100-mm horizontal line with vertical bars at either end; one end was labeled 'sound' and the other was labeled 'could not be more lame.' Two independent observers graded lameness in 62 sheep, and between- and within-observer differences were assessed for each scoring system to compare the NRS with the VAS. Results indicated no significant differences between the 2 observers scoring lameness, using either the VAS or the NRS. The scores obtained, using the VAS, were not normally distributed, although differences between scores for the 2 observers were. The NRS scores followed a normal distribution pattern. Investigation of repeated measurement for the same sheep, using both scales, revealed no significant difference between either. A comparison of the NRS and VAS scores made by each observer indicated that although correlation was good (observer 1; r = 0.94; observer 2; r = 0.95), there was not perfect agreement. The maximal NRS score of 4 was associated with VAS values > 68 mm, indicating that the NRS divisions did not reflect equal increases in lameness. The VAS and NRS scores for each observer were highly reproducible, although they were more variable for sheep that were regarded as moderately lame.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in flow velocity, resistance indices, and cerebral perfusion pressure in the maternal middle cerebral artery distribution during normal pregnancy.

BACKGROUND: There are few longitudinal data currently available detailing the normal changes in maternal cerebral hemodynamics during human pregnancy. This lack of information limits the study of pregnancy-associated cerebrovascular adjustments and, in particular, preeclampsia, where the brain appears to be especially susceptible to ischemic and encephalopathic injury. Our objective was to define the hemodynamic changes, specifically velocity, resistance indices, and cerebral perfusion pressure, in the middle cerebral artery (MCA) distribution of the brain during normal pregnancy. METHODS AND MATERIALS: Transcranial Doppler ultrasound was used to determine the systolic, diastolic and mean blood velocities in the middle cerebral arteries in non-laboring women studied longitudinally during normal gestation. The resistance index (RI), pulsatility index (PI), and cerebral perfusion pressure (CPP) were calculated using the velocity and blood pressure data. Data were analyzed using a longitudinal statistical model incorporating random patient effects and a homoscedastic (compound symmetric) variance-covariance structure over time (gestational age). The predicted mean value (Least Squares Mean), and the 5th and 95th percentiles, were defined for normal pregnancy. RESULTS: MCA systolic velocity decreased (24%) as did the mean velocity (17%). The diastolic velocity did not change significantly. The MCA RI decreased by 19% and the PI decreased by 25%. The MCA CPP increased by 52% between 12 and 40 weeks of gestation. CONCLUSIONS: The normative ranges for MCA velocity, RI, and CPP have been defined in normal human pregnancy using longitudinally collected data. By having a defined normal range, identification of abnormalities in cerebral hemodynamics during pregnancy is now possible, and this may help researchers and clinicians to elucidate etiologies and treatments for pregnancy-related pathophysiologic states such as preeclampsia

Adult↗

Bimodality of blood pressure levels.

I examine distribution of systolic blood pressure by means of maximum likelihood fitting of various statistical models to the extensive data of Bøe et al., and find evidence for a compound or mixed log-normal distribution, rather than the single log-normal distribution proposed by Pickering. I find a second distribution with a mean blood pressure above the ordinary range. I demonstrate further evidence for the existence of this subgroup in the abnormalities of regression to the mean found in the same data set.

Adolescent↗

Calcium, sulfur, and zinc distribution in normal and arthritic articular equine cartilage: a synchrotron radiation-induced X-ray emission (SRIXE) study.

Calcium, sulfur, and zinc content in normal and arthritic equine cartilage have been studied by synchrotron radiation-induced X-ray emission (SRIXE). Ranging from the superficial to the columnar zone of the normal tissue, calcium and zinc concentrations are increasingly higher, whereas sulfur is at its highest concentration in the transitional zone. In the arthritic tissue, calcium concentration is at its maximum in the transitional zone, whereas zinc and sulfur distributions are relatively homogeneous. Sulfur concentration in arthritic cartilage is reduced to about one-third with respect to that in normal tissue. The possibility that zinc concentration reflects the distribution of the zinc-containing enzyme alkaline phosphatase is presented.

Animals↗

Treating grouped data as continuous in alcohol consumption measures.

In quantity-frequency methods used for self-report measurement of alcohol intake (or other exposures), respondents mark the appropriate ranges, e.g. '5 to 8 drinks', '5 or 6 times per week'. To calculate average consumption only single values, not ranges, can be multiplied, and midpoints are commonly used. This results in bias if the range lies in the tail of a distribution, as often happens with drinks per occasion. The same bias occurs when risk, for example, is plotted against consumption levels, which inevitable are grouped into ranges. Consequently, estimates of aggregate consumption can be exaggerated and curves of risk against exposure level can be misleading. A method is described to calculate a relatively unbiased representative value for a range, requiring only knowledge of the normal distribution table, the log-normal distribution, and basic arithmetic. Part of the procedure is also useful for estimating percentile points in data that have been grouped differently, such as income in dollar groups.

Alcohol Drinking↗

Theory of hapten binding to IgM: the question of repulsive interactions between binding sites.

Various workers in their studies of the binding of haptens to IgM have observed that at low hapten concentration IgM has an apparent valence of five or near five, while at high hapten concentration IgM has a valence of ten. A possible explanation for this is that there is an interaction between binding sites on the same F(ab')2 region of the IgM molecule. In this paper the theory for such an interaction is presented and an expression for the apparent valence is derived. It is shown that the apparent valence depends on both the interaction between binding sites on the IgM molecule and on the width of the affinity distribution which characterizes the antiserum. A broad affinity distribution can give an apparent valence of five even when there is no interaction between sites, i.e., even when the ten binding sites on the IgM molecule are identical and independent. The general properties of a Scatchard plot are also discussed. When there is no interaction between sites it is shown that the average affinity and the variance of the affinity distribution can be obtained from a Scatchard plot. To illustrate the theory, an antiserum with affinities characterized by a normal distribution is considered and a simple method is presented for determining alpha, the parameter which measures the width of the normal distribution.

Animals↗

Quantitative changes in macrophage distribution in normal mouse ovary over the course of the estrous cycle examined with an image analysis system.

PROBLEM: The current study considered the distribution of macrophages within the major ovarian structures throughout the estrous cycle. METHODS: Immunohistochemical analyses were carried out using an avidin-biotin-peroxidase staining method and the rat anti-mouse macrophage monoclonal antibody anti-Mac-l was applied to stain macrophages. A computer-assisted image analysis system was used to quantify and compare the distribution of macrophages within individual ovarian structures during the estrous cycle. The following morphological structures were analyzed: primordial, preantral, antral, pre-Graafian, and atretic follicles; first-, second-, and third-generation corpora lutea; and the interstitium. The analysis included follicular and corpus luteum substructures: theca, granulosa cells, and interstitium. The system allows the estimation of macrophage distribution as a macrophage density per microns2 of the defined area. RESULTS: Primordial and preantral follicles did not contain macrophages during all stages of the estrous cycle. In antral, pre-graafian, and graafian follicles, macrophages were located and quantified only in the theca and were not detected in the granulosa cell layer. In contrast, atretic follicles showed macrophage localization in both thecal and granulosa cell layers. Macrophages were present in small numbers in the granulosa luteal cell layer and in high numbers in the thecal layer of newly developing corpora lutea. In the second generation of corpus luteum, macrophages followed the same pattern of distribution, while old corpora lutea contained significantly higher numbers of macrophages in both thecal and luteal cell layers. Surprisingly, significant quantitative changes in the macrophages distribution were detected over the course of the estrous cycle. Macrophage density was significantly higher in proestrus and metestrus when compared with the density in diestrus and estrus in most of the studied substructures with the exception of atretic follicles. Atretic follicles showed high macrophage density throughout the cycle with a two-fold higher density at metestrus. CONCLUSION: Macrophages were present in the mouse ovary over the course of the estrous cycle. The greatest numbers of macrophages appearing in corpora lutea and in atretic follicles suggest a role for macrophages in corpus luteum differentiation and follicular atresia. Their patterns of distribution at proestrus and metestrus within microenvironmental compartments suggests a functional correlation with the events of ovarian development.

Animals↗

Bimodal distribution of angiographic measures of restenosis six months after coronary stent placement.

BACKGROUND: Restenosis has been perceived as the tail end of a normal distribution of the response of the vessel to the intervention. However, recent studies have described a bimodal distribution for de novo lesions after percutaneous transluminal coronary angioplasty. This finding suggests that some lesions may be more susceptible for restenosis. Whether this holds true for a wider spectrum of lesions undergoing stent placement is not yet known. The present study analyzes the frequency distribution of angiographic indexes of restenosis 6 months after coronary stent implantation. METHODS AND RESULTS: Quantitative angiographic evaluation was performed in 1084 lesions of 1084 patients before, immediately after, and 6 months after successful Palmaz-Schatz stent placement; this represented 80.4% of patients eligible for follow-up angiography. Principal end points of the analysis were angiographic indexes of restenosis at 6 months. Twenty-two lesions that became totally occluded at follow-up were excluded from most parts of the analysis. Diameter stenosis, minimal luminal diameter (MLD), and lumen loss at 6 months did not follow a normal pattern; the bimodal pattern was demonstrated through deconvolution that yielded two separate normal components delineating two lesion populations, which developed distinctively different degrees of lumen renarrowing. The first and larger subgroup of lesions, which was less prone to restenosis, was centered around a mean value of 27% for diameter stenosis and 2.19 mm for MLD, whereas the second subgroup, with a greater tendency for restenosis, was situated around a mean value of 68% for diameter stenosis and 0.76 mm for MLD. The intersection point between the two theoretical normal distribution components was 53.5% for diameter stenosis and 1.09 mm for MLD at follow-up. CONCLUSIONS: Frequency-distribution curves of angiographic indexes of restenosis after coronary stent placement have a bimodal pattern, suggesting the existence of two distinct populations with different propensity to restenosis. These findings may encourage future efforts for the timely identification of the subset with a higher risk as the target of specific antirestenotic strategies.

Aged↗

Monte Carlo sampling and principal component analysis of flux distributions yield topological and modular information on metabolic networks.

The work presented here uses Monte Carlo random sampling combined with flux balance analysis and linear programming to analyse the steady-state flux distributions on the surface of the glucose-ammonia phenotypic phase plane of an Escherichia coli system grown on glucose-minimal medium. The distribution of allowable glucose and ammonia uptake rates showed a triangular shape, the apex corresponding to maximum growth rate. The exact shape, e.g. the diagonal boundary is determined by the relative amounts of nutrients required for growth. The logarithm of flux values has a normal distribution, e.g. there is a log normal distribution, and most of the reactions have an order of magnitude between 10(-1) and 1. The increase in the number of blocked reactions as growth switched from aerobic to micro-aerobic phase and the presence of alternate networks for a single optimal solution were both reflections of the variability of pathway utilization for survival and growth. Principal component analysis (PCA) provided us with significant clues on the correlations between individual reactions and correlations between sets of reactions. Furthermore, PCA identified the most influential reactions of the system. The PCA score plots clearly distinguish two different growth phases, micro-aerobic and aerobic. The loading plots for each growth phase showed both the impact of the reactions on the model and the clustering of reactions that are highly correlated. These results have proved that PCA is a promising way to analyse correlations in high-dimensional solution spaces and to detect modular patterns among reactions in a network.

Ammonia↗

Body mass index among Japanese inpatients with schizophrenia.

BACKGROUND: Many studies have emphasized the high frequency of obesity in schizophrenic patients. However, the characteristics of the Body Mass Index (BMI) distribution in Japanese schizophrenic patients remain unknown, and the aim of this study was to clarify these characteristics in a Japanese schizophrenic inpatient population. METHODS: The subjects were 273 inpatients (males: 141, females: 132) with schizophrenia. The patient BMI distribution was compared with normal control data obtained from the 2003 Japanese National Health and Nutrition Survey. RESULTS: The mean patient BMI was 23.0 +/- 4.3, and the BMI showed a normal distribution. The proportion of patients who were obese, of normal weight and underweight was 30.8%, 53.1%, and 16.1%, respectively. No statistical evidence of a higher frequency of obesity was found in male patients, compared to normal controls, but a higher frequency of underweight patients and a lower frequency of normal-weight patients were apparent in most decades of age. In female schizophrenia patients, a higher prevalence of obesity occurred in patients aged 50-59 years old, compared to controls. A higher rate of underweight elderly patients and a lower rate of normal-weight patients aged 40 to more than 70 years old were also apparent. CONCLUSIONS: The results suggest that not only obesity but also weight problems related to an underweight condition occur more frequently in Japanese schizophrenic inpatients than in normal controls. The deviation of the BMI distribution in Japanese schizophrenic inpatients may have a relationship with higher mortality and sudden death in schizophrenia.

Body Mass Index↗

Misclassification among methods used for multiple group discrimination--the effects of distributional properties.

Methods of multiple group discriminant analysis have not been fully studied with respect to classification into more than two populations when the covariate distributions are normal or non-normal. The present study examines the classification performance of several multiple discrimination methods under a variety of simulated continuous normal and non-normal covariate distributions. The methods include polychotomous logistic regression, multiple group linear discriminant analysis, kernel density estimation, and rank transformations of the data as input into the linear function. The parameters of interest were distance among populations, configuration of population mean vectors (collinear or forming the vertices of a regular simplex), skewness, kurtosis and bimodality. Simulation of the last three parameters was by log-normal, sinh-1 normal and a two-component mixture of normal distributions, respectively. Results with three trivariate populations show that for all distributions, logistic discrimination classifies close to the optimal under Neyman-Pearson allocation. These results suggest that logistic discrimination is preferable to other widely-used methods for multiple group classification with non-normal data, and is comparable to classification by multiple linear discrimination with normal data.

Discriminant Analysis↗

The "unisex phantom," sexual dimorphism, and proportional growth assessment.

The "unisex phantom" tactic of Ross and associates attempts to examine proportional growth, expressing body measurements relative to a phantom created from arbitrary mean dimensions and the observed coefficients of variation for an arbitrary sample of adult men and women. Fundamental assumptions of the model are (1) that data treated in unisex fashion have the normal distribution required of Z-type statistics throughout the period of growth, and (2) that it is reasonable to consider anthropometric measurements in all populations (regardless of ultimate size) as growing toward the common height chosen for the phantom. The validity and possible usefulness of this approach has been tested using anthropometric data collected on 546 francophone primary school children from the Trois Rivières district who had been measured repeatedly from 6 to 12 years of age. Over this age range, the mixing of data for girls and boys does not create a bimodal distribution, and has only a marginal effect upon skewing and kurtosis; however, the requirement of a normal distribution is not satisfied by quite a number of common anthropometric measurements even at this age. Moreover, application of the unisex phantom procedure to the Trois Rivières sample does little to clarify anticipated sex-related differences in regional growth, and it is argued that univariate standardization against a power function of an arbitrary adult height may not provide the best method of examining the multivariate problem of growth. Comparison of results with data from Saskatoon, previously treated by unisex phantom methodology, reveals puzzling inconsistencies; it is suggested that interlaboratory differences of methodology rather than ethnic differences are responsible for apparent discrepancies in growth patterns. It is urged that interlaboratory validation of techniques and landmarks should precede the ascription of apparent differences in body build to constitutional factors.

Anthropometry↗

Statistical criteria for using short-term measurements as an index of 24-hour mean arterial pressure in unanesthetized unrestrained dogs.

This study assessed the statistical validity of short time-interval measurements as estimators of true 24 hour mean arterial pressure in unanesthetized, unrestrained dogs. 24 hour intra-arterial pressure recordings were obtained using a stable FM telemetry system. The 24 hour pressure measurements approximated a normal distribution whose variance was inversely related to the selected averaging interval. Given the variance of a normal distribution one can calculate the 95% confidence interval for any single random measurement. Conversely the number of random samples necessary to be within a prescribed confidence interval can be determined. In this study, the 95% confidence interval for a single, random 30 minute arterial pressure average was calculated to be 11.2 mmHg. Only 4.8 +/- 1.4% of 480 individual 30 minute arterial pressure measurements fell beyond this confidence interval. These outlying values were distributed throughout the 24 hour period. The data suggest that randomly chosen short time-interval measurements may be a valid index of true 24 hour mean pressure if the average variance of a population is known and confidence intervals are defined.

Animals↗

Statistics: curse of the writing class.

Research projects and reports may fail because of investigators' misunderstandings about the principles underlying basic data analysis. Such errors may taint otherwise valid conclusions; related mistakes may serve to falsely support incorrect results. This article explains some of the principles underlying the use of statistical analysis for normally distributed interval data and explores the potential ramifications of misusing summary statistical tests on non-normal distributions. A discussion of the meaning of the statement of probability concerning hypothesis testing and a suggested attitude for researchers toward significance testing is also included.

Data Interpretation, Statistical↗

Properties of NMDA receptor channels in neurons acutely isolated from epileptic (kindled) rats.

The hyperexcitability accompanying chronic epileptiform activity may result from long-term alterations of ligand- and voltage-gated channels. Previous studies have indicated that NMDA responses and other electrophysiological characteristics of dentate gyrus granule cells are profoundly altered following chronic epilepsy (kindling). We have now investigated channels activated by NMDA using whole-cell patch-clamp and cell-attached single-channel recordings in granule cells acutely isolated from control and epileptic (kindled) rats. In control neurons, the amplitude of whole-cell NMDA currents was not sensitive to the presence of an intracellular ATP regeneration system, whereas NMDA currents in kindled cells showed a great variability, with larger amplitudes consistently recorded in the presence of intracellular high-energy phosphates. The ratio of peak to steady-state NMDA current (desensitization) was comparable (approximately 51%) in control and kindled neurons. Single-channel conductance determined from fluctuation analysis of whole-cell NMDA currents ranged between 21 and 35 pS in control and between 17 and 37 pS in kindled cells. Whole-cell NMDA channel noise power spectra yielded a single normal distribution of long channel lifetimes (mean, 4.3 msec) in control neurons, and the sum of two normal distributions (means, 4.6 and 7.1 msec) in kindled cells. The voltage-dependent Mg2+ block of NMDA channels was altered following kindling. From curves fitted to voltage-ramp-evoked currents in the presence of NMDA, the calculated affinity for Mg2+ of kindled channels at 0 mV was lower (12 mM) than that of controls (1.7 mM). Cell-attached recordings in the absence of Mg2+ have substantiated the lack of effect of kindling on single-channel conductance (approximately 50 pS), and have demonstrated large increases in mean open times (from 1.26 msec in control to 2.05 msec in kindled), burst lengths (from 1.91 msec to 4.18 msec), and cluster lengths (from 9.11 msec to 20.86 msec) of NMDA channels in kindled neurons. In summary, kindling, an NMDA receptor-dependent form of activity-dependent neuronal plasticity induced in vivo, results in lasting modifications in the function of single NMDA receptor channels that can be studied in acutely dissociated neurons. Kindling-induced epilepsy predominantly affects the mean open time, burst, and cluster duration of NMDA channels, their sensitivity to intracellular high-energy phosphates, and their block by Mg2+, but not the desensitization or single-channel conductance. Such alterations may reflect a change in the molecular structure of NMDA channels and may underlie the maintenance of the epileptic state.

Adenosine Triphosphate↗

A new method to explore the distribution of interindividual random effects in non-linear mixed effects models.

This article presents a new approach for exploring the distribution of interindividual random effects in nonlinear mixed effect models. The approach introduces a spline function, which transforms an assumed normally distributed interindividual random effect to an arbitrary distribution approximating that of the data. The performance of this tool is illustrated using simulated pharmacokinetic data with non-normally distributed random effects. Results of the analyses of two real kinetic data sets are also presented.

Biometry↗

The normal population distribution of PRNP codon 129 polymorphism.

OBJECTIVES: The common prion protein gene (PRNP) codon 129 polymorphism modifies the susceptibility to and the phenotype of prion diseases. However, no truly representative normal population-based data, or data stratified according to age or gender are available on the distribution of this polymorphism. MATERIAL AND METHODS: Allelic variation of codon 129 in three Finnish populations representing different age groups, and among Finnish, British and Irish blood donors were examined. RESULTS: The PRNP codon 129 genotype distribution in the total Finnish sample was 49% for methionine-methionine (MM), 42% for methionine-valine (MV) and 9% for valine-valine (VV), for the UK blood donors 42% for MM, 47% for MV and 11% for VV, and for the Irish blood donors 34% for MM, 56% for MV, and 10% for VV. CONCLUSIONS: The genotype frequencies were almost identical in all three Finnish populations of different ages, with no gender differences, and did not differ from corresponding figures for the Finnish blood donors. However, the PRNP codon 129 genotype distribution in Finland differed significantly from that of the British and the Irish blood donors and the previously published blood donor data on other Western Europeans and Americans.

Adolescent↗

Distribution of transferrin saturations in the African-American population.

To determine if transferrin saturations in African Americans may reflect the presence of a gene that influences iron metabolism, we analyzed the distribution of these values in 808 African Americans from the second National Health and Nutrition Survey. We tested for a mixture of three normal distributions consistent with population genetics for a major locus effect in which the proportion of normal homozygotes is p2; of heterozygotes, 2pq; of affected homozygotes, q2; and in which p+q = 1. Three subpopulations based on transferrin saturation were present (P < .0001) and the fit to a mixture of three normal distributions was good (P = .2). A proportion of .009 was included in a subpopulation with a mean +/- standard deviation transferrin saturation of 63.4% +/- 5.7% (postulated homozygotes for a gene that influences iron metabolism), while a proportion of .136 had an intermediate saturation of 38.0% +/- 5.7% (postulated heterozygotes) and .856 a saturation of 24.6% +/- 5.7% (postulated normal homozygotes). These proportions were consistent with population genetics because the sum of the square roots of the proportions with the lowest mean transferrin saturation (P = .925) and the highest (q = 0.093) was approximately 1 (1.018). The results are consistent with the presence in African Americans of a common locus that influences iron metabolism.

Adult↗