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PubMed1988

Nephrotoxicity screening in rats; general approach and establishment of test criteria.

The concept of a nephrotoxicity screening test that is based on quantitative assessment of urine collected under standardized conditions for 15.5 h is presented. One to eight urine collections were performed in large numbers of untreated female Sprague-Dawley rats. Normal values for water consumption, urine volume, pH, and excretion of protein, gamma-glutamyltranspeptidase, malate dehydrogenase, electrolytes, glucose, amino acids, leukocytes, erythrocytes, epithelia, unspecified cells and cylinders were determined. Test criteria were established based on the statistical distribution of these measurements. In rats repeatedly placed in metabolism cages, a statistically significant decrease in leukocyte excretion and an increase in excretion of epithelia and unspecified cells were observed. All other variables did not change with time.

Animals↗

PubMed1989

Preventive distinction of patients with primary or secondary hypertension by discriminant analysis of chronobiologic parameters estimated on 24-hour blood pressure patterns.

This investigation deals with a statistical probatory that patients with primary (PH) or secondary (SH) hypertension may be correctly diagnosed by a discriminant analysis of the chronobiologic characteristics computed on the 24-hour blood pressure (BP) patterns. The methodology concerning non-invasive 24-h BP monitoring, chronobiologic analysis and the discrimination process is detailed. Substantial dissimilarities were found in the statistical distribution for systolic and diastolic BP rhythmometric parameters (mesor, amplitude and acrophase) by a retrospective assessment of two groups, consisting of 54 patients with PH and 16 patients with SH. The group-related distribution for rhythmometric parameters was found to be significantly different to generate a statistically significant intergroup discriminatory boundary. The discriminant analysis correctly diagnosed patients with PH and SH in a percentage of about 91% and 63%, respectively. The high incidence of success is convincing that the combination of 24-h BP monitoring/chronobiologic analysis/discrimination process cna be a practical tool for confidently selecting patients with a presumable PH or SH.

Adolescent↗

PubMed1975

Dangers and problems in calculating coefficients of a sum of exponential functions.

The use of the computer in making calculations has led increasingly to the estimation of parameters of exponential functions from point experimental measurements. This involves the use of techniques such as logarithmic transformations and criteria (especially that of the least squares), of which the use is not always justified. Radioactivity measurements raise special problems as they are subject to a statistical distribution of the Poisson type. The authors propose a method based on the statistical criterion of "maximum likelihood" which permits tests of the number of exponentials from point measurements (in practice, this method is valid for one or two exponentials), and also the calculation of parameters more satisfactorily than customary methods.

Mathematics↗

PubMed1982

[Distribution of 5-methylcytosine in phage lambda genome methylated by DNA methylase Eco RII].

The distribution of 5-methylcytosine in Eco RI-Bam HI fragments of phage lambda DNA in vitro methylated by Eco RII methylase has been studied. The general picture of distribution of methylated sites in phage lambda DNA is slightly different from the statistical distribution. However, the sites have been found, where the distribution of 5-methylcytosine is not accidental. A complete absence of 5-methylcytosine in the J-fragment, a genome lambda area essential for site-specific recombination, has been found. The absence of Eco RII is supposed to be the best protection of this area of phage genome from the increased mutagenesis, characteristic for nucleotide sequences methylated by DNA-methylated Eco RII and Eco RII type.

5-Methylcytosine↗

PubMed1992

Specificity of auditory brainstem response audiometry criteria in acoustic neuroma screening as a function of deviations of reference values in patients with cochlear hearing loss.

On the basis of 79 patients with cochlear hearing loss, the statistical distribution of two criteria commonly used in auditory brainstem response audiometry (ABR) was analyzed: the interaural V latency difference (ILD V) and the interaural difference of I-V interpeak interval (ID I-V). The distribution of both criteria was Gaussian. By evaluating their standard deviations the percentages of statistical false-positives were estimated. The estimated results were 24% false-positive findings using the decision criterion ILD V greater than 0.2 ms and 5.4% false-positive findings using ID I-V greater than 0.3 ms. This corresponds closely to the actual false-positive ABR rates obtained in this sample: 21.5% and 6.3%, respectively. In a separate series of 301 unselected cases with asymmetric sensorineural hearing loss, 29 ABRs were suspect for retrocochlear pathology. In 20 patients, ABRs were absent due to severe hearing loss. Retrocochlear pathology could be confirmed in only 2 cases (both from the group with ABR present). Thus, 47 ABRs (15.7% of 299) were false-positive.

Cochlear Diseases↗

PubMed1978

On the statistical validity of standards used in profile monitoring of health care.

In current methods of profile monitoring, standards of acceptability (cut-offs) are set either by consulting panels of experts, or by selecting an arbitrary point (e.g., the 75th percentile) on the profile (statistical distribution). However, experts have only vague ideas of what outcome rates ought to be, while profile statistics stem from samples for which unknown percentages of cases have received acceptable care. Poorly chosen standards could cause profile monitoring to be ineffective, inefficient, or unnecessarily disruptive. A new method proposes to set standards by using statistics for which the percentage of adequate care has been predetermined by examining the process of care. Plans to circumvent the pitfalls involved are described, as are two approaches to estimating the degree of process adequacy from routinely produced outcome rates.

Hospitals↗

PubMed1986

Endocytosis via galactose receptors in vivo. Ligand size directs uptake by hepatocytes and/or liver macrophages.

We followed the intrahepatic binding and uptake of variously sized ligands with terminal galactosyl residues in rat livers. The ligands were administered to prefixed livers in binding studies and in vivo and in situ (serum-free perfused livers) in uptake studies. Gold sols with different particle diameters were prepared: 5 nm (Au5), 17 nm (Au17), 50 nm (Au50) and coated with galactose exposing glycoproteins (asialofetuin (ASF) or lactosylated BSA (LacBSA)). Electron microscopy of mildly prefixed livers perfused with LacBSA-Au5 in serum-free medium showed ligand binding to liver macrophages, hepatocytes and endothelial cells. Ligands bound to prefixed cell surfaces reflect the initial distribution of receptor activity: pre-aggregated clusters of ligands are found on liver macrophages, single particles statistically distributed on hepatocytes and pre-aggregated clusters of particles restricted to coated pits on endothelial cells. Ligand binding is prevented in the presence of 80 mM N-acetylgalactosamine (GalNAc), while N-acetylglucosamine (GlcNAc) is without effect. Electron microscopy of livers after ligand injection into the tail vein shows that in vivo uptake of electron-dense galactose particles by liver cells is size-dependent. Using a LacBSA-Au preparation with heterogeneous particle diameter (2.2-11.7 nm) we found that hepatocytes take up only ligands up to the size of 7.8 nm, whereas particles of all sizes available in this experiment are found in liver macrophages and endothelial cells. ASF-Au17 and LacBSA-Au17 are endocytosed by liver macrophages and endothelial cells, but not by hepatocytes. ASF-Au50 is taken up by liver macrophages only. In vivo uptake by liver macrophages is mediated by galactose-specific recognition as shown by inhibition with GalNAc. Some 52-65% inhibition was measured in in vivo experiments and 78% inhibition in in situ experiments. GlNAc showed no inhibitory effect. Furthermore, we measured uptake of [125J]ASF and of [125J]ASF adsorbed to Au17 by the different cell populations of rat livers in vivo. While the bulk of the molecular ligand is found in the hepatocyte fraction, the particulate ligand is located in the sinusoidal fraction.

Animals↗

PubMed1989

Statistical methods for short-term projections of AIDS incidence.

Short-term projections of AIDS incidence are critical for assessing future health care needs. This paper focuses on the method of back-calculation for obtaining short-term projections. The approach consists of back-calculating from AIDS incidence data through use of the incubation period distribution to obtain estimates of the numbers previously infected. The numbers previously infected are then projected forward to obtain short-term projections. An approach is suggested for accounting for new infections in short-term projections of AIDS incidence. Back-calculation requires accurate AIDS incidence data. A method which is computationally easy to implement is proposed for estimating the distribution of the delays in reporting AIDS cases. It was found that the reporting delay distribution in the United States varies by geographic region of diagnosis. Back-calculation also requires a reliable estimate of the incubation period distribution. Statistical issues associated with estimating the incubation period distribution are considered. The methods are applied to obtain short-term projections of AIDS incidence in the United States. The projected cumulative AIDS incidence in the U.S. by the end of 1992 was 287,100 under the assumption that there are no new infections after 1 July 1987, and 330,600 under the assumption that the infection rate remains constant. These projections do not account for the new broadened AIDS surveillance definitions or the underreporting of AIDS cases to the Centers for Disease Control.

Acquired Immunodeficiency Syndrome↗

PubMed1984

Guidelines for the statistical evaluation of SCE.

When planning studies by the sister chromatid exchange (SCE) test, it is necessary to calculate the size of the test groups, taking into consideration the variance of the test result and the statistical distribution of SCE frequencies. This paper deals with these problems. Recommendations are given for the preparation of slides under standardized conditions, for the subsequent counting of SCEs/cell in a random sample of 30 cells from each slide, and for the condensation of the information contained in the sample of 30 counts into a single statistic, that may be treated as a normally distributed variable. The adequacy of this transformation is shown for the data from 170 different subjects. Of these, 165 (58 nonsmokers and 107 cigarette smokers) had mean values of SCE/cell ranging from 6.5 to 13.5, while the remaining 5 subjects were on intermittent treatment with cytostatics every fourth wk, and exhibited a mean value of SCE/cell in the range 15-23. The variance associated with the recommended statistic has been decomposed into 4 variance components: variance within slides, variance between slides prepared from the same blood sample, variance within subjects, and variance between subjects. Based on a total of 680 SCE analyses in 218 persons, estimates of these variance components are given and used to calculate the necessary number of samples for the detection of a prescribed difference in SCEs/cell for selected values of Type I and Type II errors.

Analysis of Variance↗

PubMed1991

On cortical folds and neuromagnetic fields.

A folded cortical source of neuromagnetic fields, similar in configuration to the visual cortex, was simulated. Cortical activity was modelled by different distributions of independent current dipoles. The map of the summed fields of the dipoles of this cruciform model changed, depending upon the statistical distribution of the electrical activity of the dipoles and its geometry. Arrays of dipoles of random orientations and strengths produced field patterns that could be interpreted as due to moving neural currents, although the geometry of the neural tissue remained unchanged and the average activity remained approximately constant. The field topography at any instant was apparently unrelated to the depth or orientation of the underlying structure, thus raising questions about how to interpret topographic MEG and EEG displays. Furthermore, asynchronous activity (defined as independent directions and magnitudes of activity of the dipoles) did not result in less field power than when the dipoles were synchronized, i.e., when the direction of current flow was correlated across all of the dipoles within the cruciform structure. Therefore, in this model 'alpha blockage' cannot be mimicked by desynchronization. More generally, for the cruciform or any other symmetrically folded and active cortical sheet, 'blockage' cannot be attributed to desynchronization. The same is true for the EEG except that smooth unfolded sheets of radially oriented dipoles would result in enhancement of voltage due to synchronization. Such radial dipoles do not contribute to the MEG. Blockage was simulated by reducing the amount of activity within different portions of the synchronized cruciform model. This resulted in a dramatic increase in the net field because attenuation broke the symmetry of the synchronized cruciform structure. With asynchronous dipoles populating the structure, the attenuation of the same portion of the structure had no easily discerned effect on the net field. However, maps of average field power were consistently related to the position of the region of attenuated activity. The locations of regions of attenuated activity were determined by taking the difference between the mean square field pattern obtained when all portions of the cruciform structure were active and the pattern obtained when a portion of the structure was relatively inactive. When activity of the same portions were incremented rather than attenuated, the resulting plot of average power was essentially the same as that of the attenuated portion derived by taking these differences between power distributions. The major conclusions are that the concepts of synchronization and desynchronization have no explanatory power unless the physical conditions under which they occur are specified precisely.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗

PubMed1984

On the statistical significance of nucleic acid similarities.

When evaluating sequence similarities among nucleic acids by the usual methods, statistical significance is often found when the biological significance of the similarity is dubious. We demonstrate that the known statistical properties of nucleic acid sequences strongly affect the statistical distribution of similarity values when calculated by standard procedures. We propose a series of models which account for some of these known statistical properties. The utility of the method is demonstrated in evaluating high relative similarity scores in four specific cases in which there is little biological context by which to judge the similarities. In two of the cases we identify the statistical properties which are responsible for the apparent similarity. In the other two cases the statistical significance of the similarity persists even when the known statistical properties of sequences are modelled. For one of these cases biological significance is likely while the other case remains an enigma.

Base Sequence↗

PubMed1983

Analysis of gene duplication repeats in the myosin rod.

The helical coiled-coil region of the myosin rod in the nematode Caenorhabditis elegans is a repetitive sequence 1094 amino acids long which contains 39 repeats of a 28-residue pattern. The repeats are extremely significant when compared with the statistical distributions expected, first for random sequences, and then for sequences with a typical seven-residue coiled-coil periodicity. New and improved statistical tests are used. The repeats are stronger in the first 350 residues of the rod (fragment S-2) than in the remainder. The corresponding DNA sequence of the unc-54 gene shows the same features, but they are less significant when judged by the number of identical bases than are the amino acid similarities, as measured by Dayhoff scores. The rod sequence shows strong evidence for a longer repeat unit of 196 residues, which may be related to the cross-bridge spacing of 143 A in muscle.

Amino Acid Sequence↗

PubMed1982

Comparative pharmacokinetics of benzodiazepines in dog and man.

The pharmacokinetic parameters disposition half-life, metabolic clearance, volume of distribution, intrinsic clearance of unbound drug, and (distributive tissue volume/unbound fraction in tissue) were compared for 12 benzodiazepines in dog and man. With the exception of volume of distribution, statistically significant correlations were obtained when parameters were plotted on a double logarithmic grid. In general, benzodiazepines were metabolized more rapidly and exhibited greater tissue distribution in dog than in man. The variability in parameters was such, however, as to make extrapolations from one species to another subject to considerable error.

Animals↗

PubMed1987

[Effect of new imaging procedures on conventional roentgen diagnostic methods].

The diagnostic radiology workload of a general hospital served as basis to assess the statistical distribution of various diagnostic radiology methods and the inroads made by new imaging methods on the conventional ones: CT, DAS, sonography and endoscopy. In particular, the statistical breakdown shows how these methods have been applied in examining the gastrointestinal tract, the kidneys, the gallbladder and biliary tract, and how they have influenced the frequency rate of special examination methods such as angiography and myelography. Statistic assessment of the results obtained during the past ten years shows an increasing predominance of less invasive examination methods and increasing use of endoscopic methods for examining the gastrointestinal tract, the sum total of examinations remaining approximately the same throughout.

Angiography↗

PubMed1988

Applications of statistical analysis in diagnostic histopathology and cytopathology.

Corresponding to the rapid increase in the amount of data available for use in clinical diagnoses, there is an increased need for procedures that can provide the diagnostician with meaningful statistical summaries of data and with statements concerning the statistical significance associated with a diagnostic evaluation. It has been demonstrated that multivariate statistical assessment of clinical material can provide consistent, reliable and highly sensitive diagnostic clues, even in instances in which trained personnel are unable to see any change. Several examples of applications of statistical analyses in diagnostic cytology and histopathology are given in this paper. The examples were chosen to be illustrative of the different types of problems for which statistical analyses have been found useful. These problems differ with respect to the extent of the statistical methods thus far developed and the difficulty involved in developing further analyses. For many problems, appropriate statistical analyses are readily available; other problems require definition of custom-made test statistics and, in some cases, also definition of new statistical distributions. The problems discussed here are only a small sample of the existing problems, but they provide at least an indication of the scope of the role that statistics plays in cytopathologic and histopathologic diagnosis.

Cytological Techniques↗

PubMed1986

Normative and reliability data for the Children's Depression Inventory.

The present study was undertaken to examine some of the psychometric properties of the Children's Depression Inventory (CDI), a self-report inventory devised by Kovacs and Beck (1977) to measure depression in children and adolescents. Normative and reliability data were obtained from three independent samples taken from eight public schools in central Pennsylvania. Age- and gender-related differences in reported characteristics of depression were also investigated. The subjects were 594 males and 658 females whose ages ranged from 8 to 16 years and whose combined mean age was 11.67 years (SD = 1.91). The CDI was group-administered to all 1,252 subjects; 155 fifth-grade subjects (77 males and 78 females) were retested after 3 weeks, and 107 seventh- and eight-grade subjects (45 males and 62 females) were retested after 1 year. The distribution statistics for the combined samples yielded an overall CDI mean of 9.09, a standard deviation of 7.04, and a cutoff score of 19 for the upper 10% of the distribution. Reliability assessed through coefficient alpha, item-total score product-moment correlations, and test-retest coefficients proved acceptable. Gender differences were obtained for several item-total score correlations and for test-retest reliability of CDI scores.

Adolescent↗

PubMed1979

Areawide fluctuations in hospital daily census.

The importance of variations in hospital census for planning bed requirements has long been recognized. Traditional models assume Poisson or normal distribution patterns accurately describe such variations in specific hospital units, entire facilities, and groups of hospitals serving the same area. A study of 20 groups of hospitals in five states indicates that these traditional statistical distributions are only occasionally accurate. Different services display different census variation patterns. The standard deviation of the daily census distribution becomes increasingly higher than the square root of the mean estimate as the size of the mean increases. Implications of this finding for regional planning and coordination of hospitals are discussed.

Bed Occupancy↗

PubMed1980

Influence of analytical quality on the diagnostic power of a single S-CK B test in patients with suspected acute myocardial infarction.

We have compared tow theoretical methods for assessing the effects of changing analytical quality of a clinical chemical test. The test considered was S-creatine kinase B subunit activity, used as the only diagnostic criterion for acute myocardial infarction. The two methods applied were based on (i) graphical analysis, and (ii) computer simulation. The results comprise the effects of changing analytical imprecision and bias on the weighted sum of misclassified cases on basis of the test results. The two methods yield comparable results at high analytical imprecision, but due to differences in assumptions about the error distribution of test results the difference increases with increased analytical imprecision. The graphical analysis is easily performed but is restricted in possible applications. The computer simulation is not a generally available methodology, but allows for mixing of different types of statistical distributions, which is not the case in conventional variance analysis.

Chemistry Techniques, Analytical↗