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PubMed2006

Predicted effects of hemoglobin A1c assay precision on a patient population distribution of serial hemoglobin A1c difference values.

BACKGROUND: Interpretation of serial measurements of % hemoglobin A1c includes an assessment of differences from preceding values (DHbA1c). We examined predicted effects of different assay precisions on an observed population distribution for DHbA1c. METHODS: Primary data were 5260 DHbA1c values from sequential HbA1c measurement pairs obtained within 1 calendar year. Each DHbA1c was replaced by a distribution obtained from sampling each component HbA1c value according to a normal distribution characterized by a fixed coefficient of variation (CV) of either 1%, 3% or 5% (forming data sets A, B and C, respectively). Data sets B and C, with inferior precision, were compared with the reference data set A (highest precision). RESULTS: Using DHbA1c bin widths of 0.5% HbA1c, differences in assay precision caused significant redistribution of numbers within bins. For instance, for CV=5%, there was a 7.2% decrease in the number of results within the DHbA1c bin=(-0.5 to 0.5. CONCLUSION: Different HbA1c assay CVs can significantly affect the fraction of patients within different clinical categorizations for DHbA1c and consequently may differently influence patient care recommendations.

Female↗

PubMed1999

c-Kit immunoreactive interstitial cells in the human gastrointestinal tract.

c-Kit immunopositive cells are considered to be pacemakers and/or mediators of neurotransmission in the gastrointestinal tract. They also correspond to the interstitial cells of Cajal (ICs) in mice. The normal distribution of c-Kit positive cells and their relation to ICs in the human gastrointestinal tract remain unclear. In this study we examine the distribution of c-Kit positive cells and their ultrastructure in normal human tissue. We then classified them and examined their relationship to ICs. Thirty nine samples of gut from the esophagus to the sigmoid colon from humans (ranging in age from a 16 week old fetus to a 57 year old and without motility disorders), were processed for immunohistochemistry, electronmicroscopy and immuno-electronmicroscopy. c-Kit immunopositive cells were located in the external muscle from the lower esophagus to the sigmoid colon, wherever the external muscle was composed of smooth muscle cells, and they were classified morphologically into two groups. Cells in the first group were mainly spindle-shaped bipolar cells with few branches; these cells ran parallel to nearby smooth muscle. Ultrastructurally, they possessed many intermediate filaments and caveolae. The spindle-shaped cells were present in the esophagus, stomach and small intestine. The second group of cells were located only in the colon, and were multipolar or bipolar cells with numerous branches. Cells in the second group were also rich in caveolae and/or smooth endoplasmic reticulum, but intermediate filaments were not prominent. Although both groups of c-Kit immunopositive cells corresponded to ICs, some ICs in the human gut do not appear to express c-Kit immunoreactivity.

Adolescent↗

PubMed2001

Incidence of clinical mastitis in Danish dairy cattle and screening for non-reporting in a passively collected national surveillance system.

Dairy herds from three counties in Denmark (n=2144) were monitored for a 1-year period to measure the incidence rate (incidence-density) of clinical mastitis. Two different screening methods were evaluated to remove herds from the database for which the herdsman and veterinarian were suspected of under-reporting the mastitis cases which had occurred. One method was based upon agreement between clinical mastitis reports and measures of somatic cell counts of >1 million cells per ml. A second method was based upon agreement between cases reported through the regular disease-reporting system and cases reported on a management questionnaire. Depending upon the method of calculation and screening method used, rates of clinical mastitis varied between 36 and 48 cases per 100 cow-years at risk. The exclusion of herds because of documented non-reporting behavior (screening) resulted in a preponderance of herds with zero or very low incidence of mastitis being removed from the database. Following screening, the frequency distribution of herd mastitis incidence rates became decidedly more symmetrically and normally distributed.

Animals↗

PubMed2000

Direct identification of pure Penicillium species using image analysis.

This paper presents a method for direct identification of fungal species solely by means of digital image analysis of colonies as seen after growth on a standard medium. The method described is completely automated and hence objective once digital images of the reference fungi have been established. Using a digital image it is possible to extract precise information from the surface of the fungal colony. This includes color distribution, colony dimensions and texture measurements. For fungal identification, this is normally done by visual observation that often results in a very subjective data recording. Isolates of nine different species of the genus Penicillium have been selected for the purpose. After incubation for 7 days, the fungal colonies are digitized using a very accurate digital camera. Prior to the image analysis each image is corrected for self-illumination, thereby gaining a set of directly corresponding images with respect to illumination. A Windows application has been developed to locate the position and size of up to three colonies in the digitized image. Using the estimated positions and sizes of the colonies, a number of relevant features can be extracted for further analysis. The method used to determine the position of the colonies will be covered as well as the feature selection. The texture measurements of colonies of the nine species were analyzed and a clustering of the data into the correct species was confirmed. This indicates that it is indeed possible to identify a given colony merely by macromorphological features. A classifier (in the normal distribution) based on measurements of 151 colonies incubated on yeast extract sucrose agar (YES) was used to discriminate between the species. This resulted in a correct classification rate of 100% when used on the training set and 96% using cross-validation. The same methods applied to 194 colonies incubated on Czapek yeast extract agar (CYA) resulted in a correct classification rate of 98% on the training set and 71% using cross-validation.

Color↗

PubMed2001

Evaluation of airborne gamma-ray spectrometric data for the Missikat uranium deposit, Eastern Desert, Egypt.

The examination of gamma-ray spectrometric data of the Missikat area was found to be useful in locating areas worth exploring for uranium occurrence. The statistical treatment of these data shows that the uranium threshold level is 13 ppm. Such a value represents indirectly the presence of uranium mineralization and identifies anomalous areas on the eU contour map in the northern border of the Missikat-Ria El Gerra granitic plutons. This area should be of prime concern in uranium exploration of these plutons. The interpretation of the variation in the eU/eTh ratio with eU and eTh suggests that uranium redistribution has occurred within the Missikat-Ria El Gerra granitic plutons. Uranium may be reconcentrated in silicification, sericitization and kaolinization alterations which are geologically evident. eU, eTh and their ratio eU/eTh for the Missikat-Ria El Gerra granites exhibit a lognormal distribution which is in agreement with the general distribution of trace elements, whereas the K content tends towards a normal distribution.

Journal Article↗

PubMed2003

Some steps toward a central theory of ecosystem dynamics.

Ecology is said by many to suffer for want of a central theory, such as Newton's laws of motion provide for classical mechanics or Schroedinger's wave equation provides for quantum physics. From among a plurality of contending laws to govern ecosystem behavior, the principle of increasing ascendency shows some early promise of being able to address the major questions asked of a theory of ecosystems, including, "How do organisms come to be distributed in time and space?, what accounts for the log-normal distribution of species numbers?, and how is the diversity of ecosystems related to their stability, resilience and persistence?" While some progress has been made in applying the concept of ascendency to the first issue, more work is needed to articulate exactly how it relates to the latter two. Accordingly, seven theoretical tasks are suggested that could help to establish these connections and to promote further consideration of the ascendency principle as the kernel of a theory of ecosystems.

Animals↗

PubMed2003

The use of sedimentation field flow fractionation and photon correlation spectroscopy in the characterization of casein micelles.

Sedimentation Field Flow Fractionation (SdFFF) was combined with Photon Correlation Spectroscopy (PCS), to characterize changes in the structure of the colloidal particles of reconstituted skim milk of diameter >50 nm (aggregates of casein and calcium phosphate known as casein micelles) with the changes in partitioning (with the addition of salt) of calcium (Ca), inorganic phosphate (Pi) and casein between the serum and colloidal phases of the milk. The number weighted particle size distributions are determined. These are well represented by a log-normal distribution. Methods are presented for estimating the relative contributions of scattering and absorbance to the SdFFF detector signal and for taking both into account when analysing SdFFF data. The values found for the effective density of the casein micelles were in good agreement with the literature and ranged from (1.06-1.08 g cm(-3)) according to the composition of micelles. The changes in the scattering intensity as determined by PCS correlated with the changes in the particle composition. Although the concentrations of colloidal calcium phosphate (CCP) (1.1-3.5 g/kg milk) and micellar casein (18.1-27.2 g/kg milk) varied considerably only small changes in the size distribution of particles >50 nm diameter were observed except for milk to which 30 mmol Pi+10 mmol Ca/kg milk had been added where the particle size distribution shows a swelling of the particles consistent with a lower than expected value for the particle density. These observations suggest that the micelles have the ability to both lose (depleted micelles) and accommodate (enriched micelles) more casein, calcium and inorganic phosphate in their interior, thus confirming the model of the micelles which postulates an open structure allowing freedom of movement of casein and small ions.

Animals↗

PubMed2004

Dynamic response of Permian brachiopod communities to long-term environmental change.

The fossil record preserves numerous natural experiments that can shed light on the response of ecological communities to environmental change. However, directly observing the community dynamics of extinct organisms is not possible. As an alternative, neutral ecological models suggest that species abundance distributions reflect dynamical processes like migration, competition, recruitment, and extinction. Live-dead comparisons suggest that such distributions can be faithfully preserved in the rock record. Here we use a maximum-likelihood approach to show that brachiopod (lamp shell) abundance distributions from four temporally distinct ecological landscapes from the Glass Mountains, Texas (of the Permian period), exhibit significant differences. Further, all four are better fitted by zero-sum multinomial distributions, characteristic of Hubbell's neutral model, than by log-normal distributions, as predicted by the traditional ecological null hypothesis. Using the neutral model as a guide, we suggest that sea level fluctuations spanning about 10 Myr altered the degrees of isolation and exchange among local communities within these ecological landscapes. Neither these long-term environmental changes nor higher-frequency sea level fluctuations resulted in wholesale extinction or major innovation within evolutionary lineages.

Animals↗

PubMed1989

Probability and sampling.

The concept of probability is introduced, and the role of probability distributions in statistical theory is discussed, with particular reference to the Normal distribution and its characteristics. Sampling and sampling variation are described, together with sampling error, the standard error of the mean, and confidence intervals for determining the likely magnitude of a population mean.

Child↗

PubMed2000

Composition profiling of seized ecstasy tablets by Raman spectroscopy.

Raman spectroscopy with far-red excitation has been investigated as a simple and rapid technique for composition profiling of seized ecstasy (MDMA, N-methyl-3,4-methylenedioxyamphetamine) tablets. The spectra obtained are rich in vibrational bands and allow the active drug and excipient used to bulk the tablets to be identified. Relative band heights can be used to determine drug/excipient ratios and the degree of hydration of the drug while the fact that 50 tablets per hour can be analysed allows large numbers of spectra to be recorded. The ability of Raman spectroscopy to distinguish between ecstasy tablets on the basis of their chemical composition is illustrated here by a sample set of 400 tablets taken from a large seizure of > 50,000 tablets that were found in eight large bags. The tablets are all similar in appearance and carry the same logo. Conventional analysis by GC-MS showed they contained MDMA. Initial Raman studies of samples from each of the eight bags showed that despite some tablet-to-tablet variation within each bag the contents could be classified on the basis of the excipients used. The tablets in five of the bags were sorbitol-based, two were cellulose-based and one bag contained tablets with a glucose excipient. More extensive analysis of 50 tablets from each of a representative series of sample bags have distribution profiles that showed the contents of each bag were approximately normally distributed about a mean value, rather than being mixtures of several discrete types. Two of the sorbitol-containing sample sets were indistinguishable while a third was similar but not identical to these, in that it contained the same excipient and MDMA with the same degree of hydration but had a slightly different MDMA/sorbitol ratio. The cellulose-based samples were badly manufactured and showed considerable tablet-to-tablet variation in their drug/excipient ratio while the glucose-based tablets had a tight distribution in their drug/excipient ratios. The degree of hydration in the MDMA feedstocks used to manufacture the cellulose-, glucose- and sorbitol-based tablets were all different from each other. This study, because it centres on a single seizure of physically similar tablets with the same active drug, highlights the fact that simple physical descriptions coupled with active drug content do not in themselves fully characterize the nature of the seized materials. There is considerable variation in the composition of the tablets within this single seizure and the fact that this variation can be detected from Raman spectra demonstrates that the potential benefits of obtaining highly detailed spectra can indeed translate into information that is not readily available from other methods but would be useful for tracing of drug distribution networks.

Hallucinogens↗

PubMed1976

Triacylglycerol biosynthesis in rat adipose-tissue homogenates.

The optimum cofactor requirements for triacylglycerol biosynthesis in rat adipose-tissue homogenates containing mitochondrial, microsomal and cytosolic fractions were investigated. In general the optimum concentrations of cofactors for triacylglycerol biosynthesis were found to differ from those for total fatty acid esterification. The results provided further evidence for the key role of phosphatidate phosphohydrolase in the regulation of triacylglycerol biosynthesis. Albumin was included in the incubation medium to permit the use of concentrations of added fatty acids that would swamp the effects of endogenous fatty acids. The addition of albumin had little effect on the incorporation of palmitic acid and stearic acid into lipids including triacylglycerols. By contrast, a critical concentration of albumin (about 60 muM) was required before incorporation of oleic acid or linoleic acid into triacylglycerols occurred. The system was used to study the incorporation of different 1-14C-labelled fatty acids from a mixture of unesterified fatty acids [palmitic acid 30%; stearic acid 10%; oleic acid 40%; linoleic acid 20% (molar percentages)] separately into the positions 1,2 and 3 of triacyl-sn-glycerols. In general the stereo-specific distribution of the labelled fatty acids incorporated into triacylglycerols paralleled the normal distribution of fatty acids within rat adipose-tissue triacylglycerols, suggesting that the specificities of the relevant acyltrasferases have the major role in determining the positional distribution of fatty acids within triacylglycerols.

Adipose Tissue↗

PubMed1997

13C-urea breath test for Helicobacter pylori: cut-off point determination by cluster analysis.

1. This study was performed on a large set of 13C-urea breath test results to determine the optimal cut-off point of the test for the diagnosis of Helicobacter pylori (Hp) infection. 2. The following steps were applied to three sets of urea breath test results obtained in three groups of subjects (696 adults before anti-Hp treatment, 1056 adults after anti-Hp treatment and 173 children under 17 years of age): (1) demonstrate the distribution of urea breath test results as a mix of two normal populations (Hp negative and Hp positive) by logarithmic transformation of the results in each group of subjects; (2) apply statistical cluster analysis to determine the separation point between Hp-negative and -positive populations; (3) calculate the mean and SD of each population, and use these parameters in the equation of the normal distribution to establish the frequency curves of Hp-negative and -positive populations; and (4) determine the cut-off point of the urea breath test as the intersection of the two curves, and the risks of error related to it. 3. The optimal cut-off point was found at +3.00 delta/1000, with a risk of false-negative or -positive response of the urea breath test of less than 3%. From this, a cut-off point of +3.00 delta/1000 for the 13C-urea breath test is recommended, with an indetermined zone between +2.5 and +3.5 delta/1000 to account for the spontaneous variation of 13CO2 in breath and the limits of GC-isotope ratio-MS analytical precision.

Adolescent↗

PubMed2003

Resistance of virus to extinction on bottleneck passages: study of a decaying and fluctuating pattern of fitness loss.

RNA viruses display high mutation rates and their populations replicate as dynamic and complex mutant distributions, termed viral quasispecies. Repeated genetic bottlenecks, which experimentally are carried out through serial plaque-to-plaque transfers of the virus, lead to fitness decrease (measured here as diminished capacity to produce infectious progeny). Here we report an analysis of fitness evolution of several low fitness foot-and-mouth disease virus clones subjected to 50 plaque-to-plaque transfers. Unexpectedly, fitness decrease, rather than being continuous and monotonic, displayed a fluctuating pattern, which was influenced by both the virus and the state of the host cell as shown by effects of recent cell passage history. The amplitude of the fluctuations increased as fitness decreased, resulting in a remarkable resistance of virus to extinction. Whereas the frequency distribution of fitness in control (independent) experiments follows a log-normal distribution, the probability of fitness values in the evolving bottlenecked populations fitted a Weibull distribution. We suggest that multiple functions of viral genomic RNA and its encoded proteins, subjected to high mutational pressure, interact with cellular components to produce this nontrivial, fluctuating pattern.

Animals↗

PubMed2026

Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a heterogenous disease with frequent late-stage diagnosis and high mortality rates, for which no reliable screening tests exist. In recent years, epigenetic biomarkers in the form of DNA methylation in CpG-rich regions have gained increased attention in the scientific community due to their robust nature and accessibility, allowing for diagnosis without the need for invasive surgery. In this study, we investigated the aberrant methylation of promoter regions in early stage EOC through non-parametric methods, with the purpose of characterizing candidate epigenetic biomarkers. The approach was used on a cohort of early stage EOC samples, and results were compared to existing programs for differential methylation. Significant regions were then used to construct a CpG panel for stratifying EOC histotypes through predictive classification in external data. Identified promoter regions were highly reproducible across cohorts, and the constructed CpG model stratified histotypes in external cohorts through predictive classification. Comparisons against other DMP and DMR callers showed a degree of homogeneity between results but also revealed promoter regions that were overlooked despite clear signs of aberrant methylation. Finally, EOC histotypes were found to differ in their methylation distribution types, and results indicate that methods sensitive to non-normally distributed data may be poorly suited to compare groups with different distribution types. The non-parametric approach identified aberrantly methylated promoter regions that were highly reproducible across cohorts. Results from predictive classification indicate that these regions may be useful for the purpose of EOC histotype stratification.

Humans↗

PubMed2002

Nonequivalent Loci and the distribution of mutant effects.

It has been observed repeatedly that the distribution of new mutations of a quantitative trait has a kurtosis (a statistical measure of the distribution's shape) that is systematically larger than that of a normal distribution. Here we suggest that rather than being a property of individual loci that control the trait, the enhanced kurtosis is highly likely to be an emergent property that arises directly from the loci being mutationally nonequivalent. We present a method of incorporating nonequivalent loci into quantitative genetic modeling and give an approximate relation between the kurtosis of the mutant distribution and the degree of mutational nonequivalence of loci. We go on to ask whether incorporating the experimentally observed kurtosis through nonequivalent loci, rather than at locus level, affects any biologically important conclusions of quantitative genetic modeling. Concentrating on the maintenance of quantitative genetic variation by mutation-selection balance, we conclude that typically nonequivalent loci yield a genetic variance that is of order 10% smaller than that obtained from the previous approaches. For large populations, when the kurtosis is large, the genetic variance may be <50% of the result of equivalent loci, with Gaussian distributions of mutant effects.

Genetic Variation↗

PubMedDate not supplied

Allele frequencies in a cat population in Budapest.

Allelic frequencies were determined for the domestic cat population of Budapest, Hungary. Most of the frequencies are in the range of those of western European populations, but there are two unusual features. The first is the apparent absence of blotched tabby and a relatively high frequency of Abyssinian tabby. The second is in the distribution of frequencies of white spotting phenotypes. There is an approximately normal distribution around the most common pattern, which is 50 percent white fur, contrasted to western populations in which frequency is maximal between approximately 10-30 percent white fur and declines with increasing white fur.

Alleles↗

PubMed2000

Appropriate likelihood ratio tests and marginal distributions for evolutionary tree models with constraints on parameters.

We show how to make appropriate likelihood ratio tests for evolutionary tree models when parameters such as edge (internodes or branches) lengths have nonnegativity constraints. In such cases, under the null model of an edge length being zero, the marginal distribution of this parameter is proven to be a "half-normal", that is, 50% zero values and 50% the positive half of a normal distribution. Other constrained parameters, such as the proportion of invariant sites, give similar results. To make likelihood ratio tests between nested models, e.g., H(0): homogeneous site rates, and H(1): site rates follow a gamma distribution with variance 1/k, then asymptotically as sequence length increases, the distribution under H(0) becomes a mixture of chi distributions, in this case 50% chi(0), and 50% chi(1) (where the subscript denotes degrees of freedom, i.e. , not the usually assumed 100% chi(1); which leads to a conservative test). Such mixtures are sometimes called distributions. Simulations show that even with sequences as short as 125 sites, some parameters, including the proportion of invariant sites, fit asymptotic distributions closely.

Biological Evolution↗

PubMed2000

On variability in the density of corticocortical and thalamocortical connections.

Variability is an important but neglected aspect of connectional neuroanatomy. The quantitative density of the 'same' corticocortical or thalamocortical connection may vary by over two orders of magnitude between different injections of the same tracer. At present, however, the frequency distribution of connection densities is unknown. Therefore, it is unclear what kind of sampling strategies or statistical methods are appropriate for quantitative studies of connectivity. Nor is it clear if the measured variability represents differences between subjects, or if it is simply a consequence of intra-individual differences resulting from experimental technique and the exact placement of tracers relative to local spatial and laminar variation in connectivity. We used quantitative measurements of the density of a large number of corticocortical and thalamocortical connections from our own laboratories and from the literature. Variability in the density of given corticocortical and thalamocortical connections is high, with the standard deviation of density proportional to the mean. The frequency distribution is close to exponential. Therefore, analysis methods relying on the normal distribution are not appropriate. We provide an appendix that gives simple statistical guidance for samples drawn from exponentially distributed data. For a given corticocortical or thalamocortical connection density, between-individual standard deviation is 0.85 to 1.25 times the within-individual standard deviation. Therefore, much of the variability reported in conventional neuroanatomical studies (with one tracer deposited per animal) is due to within-individual factors. We also find that strong, but not weak, corticocortical connections are substantially more variable than thalamocortical connections. We propose that the near exponential distribution of connection densities is a simple consequence of 'patchy' connectivity. We anticipate that connection data will be well described by the negative binomial, a class of distribution that applies to events occurring in clumped or patchy substrates. Local patchiness may be a feature of all corticocortical connections and could explain why strong corticocortical connections are more variable than strong thalamocortical connections. This idea is supported by the columnar patterns of many corticocortical but few thalamocortical connections in the literature.

Animals↗