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PubMed2004

Evolutionarily stable transition rates in a stage-structured model. An application to the analysis of size distributions of badges of social status.

This paper deals with the adaptive dynamics associated to a hierarchical non-linear discrete population model with a general transition matrix. In the model, individuals are categorized into n dominance classes, newborns lie in the subordinate class, and it is considered as evolutionary trait a vector eta of probabilities of transition among classes. For this trait, we obtain the evolutionary singular strategy and prove its neutral evolutionary stability. Finally, we obtain conditions for the invading potential of such a strategy, which is sufficient for the convergence stability of the latter. With the help of the previous results, we provide an explanation for the bimodal distribution of badges of status observed in the Siskin (Carduelis spinus). In the Siskin, as in several bird species, patches of pigmented plumage signal the dominance status of the bearer to opponents, and central to the discussion on the evolution of status signalling is the understanding of which should be the frequency distribution of badge sizes. Though some simple verbal models predicted a bimodal distribution, up to now most species display normal distributions and bimodality has only been described for the Siskin. In this paper, we give conditions leading to one of these two distributions in terms of the survival, fecundity and aggression rates in each dominance class.

Animals↗

PubMed2006

Sampling properties of homozygosity-based statistics for linkage disequilibrium.

Homozygosity-based statistics such as Ohta's identity-in-state (IIS) excess offer the potential to measure linkage disequilibrium for multiallelic loci in small samples. However, previous observations have suggested that for independent loci, in small samples these statistics might produce values that more frequently lie on one side rather than on the other side of zero. Here we investigate the sampling properties of the IIS excess. We find that for any pair of independent polymorphic loci, as sample size n approaches infinity, the sampling distribution of the IIS excess approaches a normal distribution. For large samples, the IIS excess tends towards symmetry around zero, and the probabilities of positive and of negative IIS excess both approach 1/2. Surprisingly, however, we also find that for sufficiently large n, independent loci can be chosen so that the probability of a sample having positive IIS excess is arbitrarily close to either 0 or 1. The results are applied to interpretation of data from human populations, and we conclude that before employing homozygosity-based statistics to measure LD in a particular sample, especially for loci with either very small or very large homozygosities, it is useful to verify that loci with the observed homozygosity values are not likely to produce a large bias in IIS excess in samples of the given size.

Algorithms↗

PubMed2006

Mixture models of serum iron measures in population screening for hemochromatosis and iron overload.

Homozygosity for the C282Y mutation of the hemochromatosis gene on chromosome 6p (HFE) is a common genetic trait that increases susceptibility to iron overload. The authors describe and apply methodology developed for the analysis of phenotypic and genotypic data from 46,136 non-Hispanic Caucasians, a subset of the multi-ethnic cohort enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. For analysis of the distribution of transferrin saturation (TS), mixtures of normal distributions were considered and the expectation-maximization (EM) algorithm was applied for parameter estimation. Maximized log-likelihoods were compared, and significance was assessed by resampling. Sensitivity, specificity, and predictive values from the modeled subpopulations were compared with the actual observed genotypes for C282Y and H63D mutations in the HFE gene. A strong association between HFE genotype and TS subpopulations was found in these data collected from different geographic regions, confirming the external validity of the statistical approach when applied to population-based data. It was concluded that mixture modeling of phenotypic data may provide a clinical guide for screening with gender-specific thresholds to identify potential samples for genetic testing.

Adult↗

PubMed2005

Pupillary evaluation of retinal asymmetry: development and initial testing of a technique.

Glaucomatous damage to upper and lower retina is often unequal. We have developed a rapid, objective, quantitative measure of asymmetry of retinal sensitivity, using infrared pupillometry and pairs of large stimuli that are symmetric about the horizontal meridian. Results for a group of 11 young subjects free of eye disease indicate that the distribution of asymmetry is close to a normal distribution centered near upper/lower symmetry. Some subjects showed modest amounts of asymmetry, which was relatively uniform within each eye, and between the two eyes, of the subject. This approach to determination of asymmetry within an eye is potentially applicable to testing patients with glaucoma. The narrowness of the distribution should make it possible to detect asymmetries caused by disease.

Adult↗

PubMed1988

Red-cell-volume distribution curves in diagnosis of glomerular and non-glomerular haematuria.

The distribution curves of urinary red-blood-cell (RBC) size were obtained from automated blood-cell analysis in 146 patients with definite causes of haematuria. In 65 of 67 patients (97%) with haematuria and glomerulonephritis demonstrated by renal biopsy, urinary RBC had an irregular and asymmetrical distribution with RBC size showing a much smaller volume than that of venous RBC. This "glomerular" distribution contrasted with the "non-glomerular" normal distribution when the peak for RBC was at a larger volume than that for peripheral RBC. In 46 of 47 patients with haematuria who had lower urinary tract lesions other than infection, a non-glomerular distribution was obtained; 30 of these cases also showed glomerular distribution, and were classified as "mixed". All 32 patients with urinary tract infection had either a glomerular or mixed distribution, suggesting that they excreted distorted and dysmorphic urinary RBC. After excluding infections, this simple, rapid, reproducible, and non-invasive technique provides reliable information in distinguishing glomerular bleeding from other causes of haematuria.

Diagnosis, Differential↗

PubMed2002

Parametric receiver operating characteristic curve analysis using mathematica.

Several computer programs have been written to perform receiver operating characteristic (ROC) curve analysis, and are available in the public domain. Here, the author provides the theory and description for 'rocMath', a Mathematica program that performs parametric ROC curve analysis. The 'rocMath' program has some advantages over other ROC curve programs, including the ability to provide, through optional arguments: (a) user-specified pointwise confidence limits, as well as default 95% limits, on ROC curve area and on true-positive rates; (b) ROC curve plots with data points, a fitted curve, and user-specified pointwise confidence bands; and (c) ROC curve areas, tables, and plots based on a logistic distribution as well as on a standard normal distribution. In addition, the code of 'rocMath' can be modified to address additional ROC curve applications. The program uses Mathematica's ability to operate on purely symbolic as well as numeric data to achieve substantial coding efficiency. Limitations of the 'rocMath' program are also discussed.

Mathematical Computing↗

PubMedDate not supplied

[Metric characteristics of the Professional Quality of Life Questionnaire [QPL-35] in primary care professionals].

OBJECTIVE: To assess the internal consistency, discriminative capacity and factorial composition of the Professional Quality of Life Questionnaire (QPL-35) in a population of primary care professionals. METHODS: We performed a cross-sectional analytical study in a primary care area in Madrid from 2001 to 2003. Random sampling of 450 healthcare professionals was performed on 2 occasions. The sample was stratified into 3 groups: group I (clinicians, pharmacologists, psychologists), group II (nurses, midwives, physiotherapists, social workers) and group III (administrative staff, porters, auxiliary nurses). The self-administered questionnaire QPL-35 was sent in January 2001 and January 2003 and on each occasion the questionnaire was sent again 1 month later. The percentages of total responses and responses per item were studied. We also studied the distribution of each answer by examining the floor effect and ceiling effect, as well as the factorial composition based on a previous validation study. RESULTS: Five hundred sixty-three questionnaires (62.6%) were returned. All the questions had a response rate of more than 96%. At least one unanswered question was found in 22.0% of the questionnaires, and at least 2 were unanswered in 7.1%. The distribution of the answers did not fit normal distribution in any of the cases. The floor effect was present in questions related to management support and the ceiling effect was found in those related to motivation. The factorial analysis found 3 factors that explained 39.6% of the variance in the total number of questions. These factors were very similar to those of the previous validation study: management support, perception of workload and intrinsic motivation explained 17.0%, 13.2% and 9.4% of the variance, respectively. Internal consistency was high for each factor (Cronbach's alpha > 0.7) and for the total score (Cronbach's alpha = 0.81). CONCLUSIONS: The metric properties of the QPL-35 are maintained in different environments. This questionnaire can be recommended as a tool to measure and compare quality of professional life in primary care.

Adult↗

PubMed1997

Crystal size and properties of superparamagnetic iron oxide (SPIO) particles.

The properties of a superparamagnetic iron oxide (SPIO) model contrast agent have been studied. The test material, HEP-SPIO, contained iron oxide multicrystal agglomerates coated with heparin, polyanionic, naturally occurring glycosaminoglycan. Fractionation of the HEP-SPIO suspension showed the existence of colloidally stable particles ranging from approx. 100 nm down to single crystal sizes. The small (< 20 nm) particles represented the major number fraction of particles present, but only approx. 2% of the total iron oxide mass. The volume weighted average diameter of the individual iron oxide crystals forming the multicrystal agglomerates was found to be 11-12 nm using transmission electron microscopy and vibrating sample magnetometry (VSM) techniques. Comparable results were obtained with X-ray diffraction and Mössbauer spectroscopy. A number of additional SPIO properties could also be determined on a routine VSM, such as the distribution standard deviation for the log-normal distribution of crystal sizes, the magnetic susceptibility, the magnetic remanence, and the intrinsic magnetization (magnetic moment) of the iron oxide. These parameters are useful tools for evaluation of the magnetic characteristics and contrast efficacy of SPIO contrast agents.

Chemical Fractionation↗

PubMed2003

Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex.

BACKGROUND: Intellectual impairments are a recognized feature of tuberous sclerosis complex (TSC), but the frequency and degree of intellectual impairments has not been systematically studied in large epidemiological samples using standardized measures. As such, the form of the IQ distribution (uni- or bi-modal) has not been established and the relationship between IQ and other features (e.g. epilepsy history) is poorly delineated. To address these shortcomings, we assessed the intellectual abilities of a large epidemiological sample of individuals with TSC, drawn from the 'Wessex' area of SW England and compared them with the abilities of their unaffected siblings. METHOD: Standardized tests were used to estimate the abilities of 108 (56 males, 52 females, median age = 25, range = 4-75) individuals with TSC and 29 unaffected siblings (14 males, 15 females, median age = 18, range = 6-55). Seizure history was obtained from informants and medical records. RESULTS: Estimated IQ was bi-modally distributed: 55.5% had an IQ in the normal range; 14% had mild to severe impairments: and 30.5% had profound disability (IQ < 21). Forty-four per cent of the individuals with TSC had an IQ < 70. In the subset of normally intelligent individuals with TSC, IQ was normally distributed with a mean of 93.6. This mean was significantly lower than the mean IQ of unaffected siblings (IQ = 105.6). All individuals with learning disability had a history of seizures that usually commenced before 12 months of age and that often presented as infantile spasms. Multivariate analyses indicated that a history of seizures as well as a history of infantile spasms was predictive of the degree of intellectual impairment. CONCLUSIONS: Intellectual abilities were bi-modally distributed in a representative sample of individuals with TSC. The likelihood of impairment was associated with a history of seizures, particularly infantile spasms. The genetic and brain basis of these findings requires further investigation.

Adolescent↗

PubMed2006

Localized attraction correlates with bacterial adhesion to glass and metal oxide substrata.

Bacterial adhesion to surfaces does not always proceed according to theoretical expectations. Discrepancies are often attributed to surface heterogeneities that provide localized, favorable sites for bacterial attachment. The presence of these favorable deposition sites for bacteria, however, has never been directly measured. Atomic force microscopy (AFM) was used to quantify the distribution of attractive sites on clean substrata. Surfaces of silica and three different metal oxides mapped by adhesion force with regular or colloidal AFM tips showed a heterogeneous distribution of adhesion forces. Adhesion forces were normally distributed based on a colloid probe, but regular tips revealed a proportionately larger number of relatively more adhesive sites. No correlation was found between the average adhesion force (tip or colloid) and macroscopic adhesion tests using five strains of bacteria. However, when AFM tip results were compared to bacterial adhesion data on the basis of only the stickiest sites (the 5% of sites with the largest adhesion force), there was a good correlation of AFM data with adhesion data. These results demonstrate for the first time how overall bacterial adhesion to a surface effectively correlates with a relatively small fraction of highly adhesive sites rather than averaged adhesion force as detected using AFM.

Adhesiveness↗

PubMed2002

Texture of cooked potatoes (Solanum tuberosum). 1. Relationships between dry matter content, sensory-perceived texture, and near-infrared spectroscopy.

Properties of fresh potatoes, including dry matter (DM) content, starch content, and near-infrared (NIR) spectra, were determined and related to the sensory-perceived texture of the steam-cooked samples. To quantify these relationships, three potato cultivars, respectively representing a firm cooking potato (cv. Nicola), a mealy cooking potato (cv. Irene), and a cultivar (cv. Bintje) with intermediate cooking properties, were classified on the basis of three size categories. For each size category and cultivar a DM distribution was determined on the basis of the underwater weight of the individual potatoes. Each DM distribution was divided into three subcategories based on low, medium, and high DM contents. This categorization was performed for freshly harvested potatoes and for potatoes stored for 3 and 6 months, respectively. In total, this resulted in 27 DM distributions, of which 16 were non-normally distributed, and 81 samples. Linear relationships were established between the DM content, as determined by either underwater weight analysis or oven-drying, and the starch content. On the basis of partial least-squares regression (PLSR), statistical models were developed relating sensory-based texture descriptors with the DM matter content of the samples. It was also shown, by applying PLSR, that the NIR spectra, originating from the potato samples, could be related to the DM content and to the sensory-perceived texture. From the relationships between DM content and sensory-perceived texture, on the one hand, and from the DM content and NIR spectra, on the other, it was concluded that the DM content rather than the cultivar determines the sensory-perceived texture of steam-cooked potatoes. Cultivar-specific elements may also contribute to the perceived texture but are overruled by the DM content. Storage did not affect the mutual relationships between the DM content, the sensory properties, and the NIR spectra.

Food Technology↗

PubMed1986

A suitable parameterization of the Michaelis-Menten enzyme reaction.

It is shown here that a suitable form for estimation and inference using the Michaelis-Menten [(1913) Biochem Z. 49, 333-369] model for simple enzymic reactions is one in which the two parameters appear in the denominator of the equation. In this form, convergence to the least-squares estimates using the Gauss-Newton method [see Kennedy & Gentle (1980) Statistical Computing, Marcel Dekker, New York] is virtually ensured, or, as the model in this form is a member of the class of 'generalized linear models', it may be fitted by packages such as those of Rothamsted Experimental Station [(1977) GENSTAT (A General Statistical Program), Rothamsted Experimental Station, Harpenden] and the Numerical Algorithms Group [(1978) GLIM (Generalised Linear Interactive Modeling), Numerical Algorithms Group, Oxford]. Furthermore, the parameters-in-denominator principle is readily extended to more complicated catalytic models. With all parameters in the denominator, the least-squares estimators are close to being unbiased and normally distributed, whereas severe bias and non-normality may result from use of the standard formulations.

Catalysis↗

PubMed2001

Development of a dynamic continuous-discrete-continuous model describing the lag phase of individual bacterial cells.

AIMS: A previous model for adaptation and growth of individual bacterial cells was not dynamic in the lag phase, and could not be used to perform simulations of growth under non-isothermal conditions. The aim of the present study was to advance this model by adding a continuous adaptation step, prior to the discrete step, to form a continuous-discrete-continuous (CDC) model. METHODS AND RESULTS: The revised model uses four parameters: N(0), initial population; N(max), maximum population; p0, mean initial individual cell physiological state; SD(p0), standard deviation of the distribution of individual physiological states. A truncated normal distribution was used to generate tables of distributions to allow fitting of the CDC model to viable count data for Listeria monocytogenes grown at 5 degrees C to 35 degrees C. The p0 values increased with increasing SD(p0) and were, on average, greater than the corresponding population physiological states (h0); p0 and h0 were equivalent for individual cells. CONCLUSION: The CDC model has improved the ability to simulate the behaviour of individual bacterial cells by using a physiological state parameter and a distribution function to handle inter-cell variability. The stages of development of this model indicate the importance of physiological state parameters over the population lag concept, and provide a potential approach for making growth models more mechanistic by incorporating actual physiological events. SIGNIFICANCE AND IMPACT OF THE STUDY: Individual cell behaviour is important in modelling bacterial growth in foods. The CDC model provides a means of improving existing growth models, and increases the value of mathematical modelling to the food industry.

Culture Media↗

PubMed2000

Results of testing for anti-GM1 antibodies.

We used an ELISA technique to measure IgG and IgM antibodies to the ganglioside GM1, with the results expressed in arbitrary units. We tested 1007 sera from patients with peripheral neuropathy or muscle weakness. For IgG and IgM antibodies, the distribution of results differed significantly from a normal distribution. In the patient group, 81 of 1007 sera had elevated levels of IgG antibodies (> 10 units). Of these, 11 patients had very high levels (> 50 units). These 11 patients had diagnoses of GBS (4), motor neurone disease (3) or non-specific idiopathic neuropathy (4). For IgM antibodies, 115 of 1007 sera were positive (> 20 units). Of these, 18 patients had very high levels (> 50 units). These 18 patients had diagnoses of Guillain-Barré syndrome or Miller Fisher syndrome (4), multifocal motor neuropathy (4), motor neurone disease (2), non-specific neuropathy (2). We conclude that anti-GM1 antibodies in high titre are uncommon. Patients with multifocal motor neuropathy have high levels of antibody. However, patients with other disorders may also have high levels, so that anti-GM1 antibody levels alone are not a specific test for multifocal motor neuropathy. We found that antibodies to GM1 were present in the sera of patients with chronic idiopathic neuropathy, leading us to suggest that these antibodies may sometimes arise as a secondary response to disease.

Adult↗

PubMed1995

Characteristics of pulsatile and circadian prolactin release and its variability in men.

In order to investigate the intra- and interindividual variability of spontaneous prolactin (PRL) secretion, 24 h blood sampling at 10 min intervals was performed in ten healthy young men (age 19 to 25 yrs) on three occasions (intervals 2 weeks and 3 months). Plasma PRL concentrations were determined in duplicate by immunoradiometric assay. Peak detection was carried out with the PULSAR program. The circadian rhythm was analyzed by a complex cosinor method combining fundamental (24 h), 1st harmonic (12 h), and 2nd harmonic (6 h) frequencies. The original data was well represented by this calculation as shown by mean (+/- SD) correlation coefficients of 0.84 +/- 0.08. Mean and integrated PRL concentrations showed the lowest intraindividual variability (range 2.8 to 19.6%) of all parameters tested. For the number of peaks per 24 h, a median intraindividual variability of 24.2% (range 6.9 to 50%) was seen. In general, intraindividual variability of parameters of pulsatile PRL release was lower than the variability between subjects. The complex cosinor analysis revealed a bimodal pattern of PRL secretion in most profiles. Acrophases (times of highest PRL levels) were found between 0040 and 1000 h, nadirs between 0030 and 2300 h. The amplitude of the circadian rhythm (Max-Min) ranged from 3.8 to 16.9 ng/ml. The time lag between onset of sleep and acrophase was variable (1.75 to 7.38 hrs). Variability of nadir, minimal and maximal PRL, amplitude, and minimal PRL as percent of the mesor was significantly lower within individuals than between subjects (p < 0.02). During sleep, peak heights and peak amplitudes were significantly higher than during waking periods (p < 0.004). No statistically significant differences were found in the distribution of relative frequencies of peak number, peak amplitudes and peak heights between the three series of profiles. The distribution of peak heights was compatible with a normal distribution. In conclusion, it was shown that the circadian rhythm of PRL secretion in normal men can be analysed accurately and reliably with the complex cosinor method, which is relatively easy to perform and yields results comparable to those obtained by much more complicated programs.(ABSTRACT TRUNCATED AT 400 WORDS)

Activity Cycles↗

PubMed1997

Keratan sulphate in the trabecular meshwork and cornea.

PURPOSE: A study was made of the distribution of keratan sulphate in the human anterior chamber. METHODS: The monoclonal antibody, 5-D-4, was used in immuno-electron microscopy to visualise keratan sulphate distribution in the anterior chamber of 16 normal eyes, 7 Fuchs' dystrophy corneas, and a macular dystrophy cornea. RESULTS: Keratan sulphate was detected in normal human aqueous humour and also on the surface of trabecular cells in the uveal meshwork. Normal corneal stroma showed an increase in keratan sulphate labelling from anterior to posterior, with marked labelling in the posterior region of Descemet's membrane. The apical surface of the corneal endothelium labelled positively, but showed considerable variation in the level of labelling from cell to cell. The macular dystrophy cornea had the classic histopathological features of a type I case, including a highly abnormal Descemet's membrane. No keratan sulphate was detected in the macular dystrophy patient's corneal stroma or serum. The Fuchs' endothelial dystrophy corneas showed a normal distribution of keratan sulphate labelling in the stroma. The Fuchs' endothelial cells labelled for keratan sulphate but were highly abnormal in appearance, often exhibiting long filopodia and appearing to be actively migrating. CONCLUSIONS: This work has shown that keratan sulphate has a much wider distribution than was previously believed. The detection of keratan sulphate on the trabecular and endothelial cell surfaces also suggests a possible role for this molecule in cell adhesion and/or migration.

Antibodies, Monoclonal↗

PubMed2000

The adjuvants aerosil 200 and Gelita-Sol-P influence on the technological characteristics of spray-dried powders from Passiflora edulis var. flavicarpa.

Passiflora edulis (passionflower) is a plant widely used in the Brazilian popular medicine and phytopharmaceutical industry for its sedative activity. This work refers to the development of spray-dried powders (SDPs) from the 40% ethanolic extractive solution of P. edulis aerial parts. The SDPs were prepared with a Büchi 190 Mini-spray dryer using as drying adjuvants Aerosil 200 alone (SDP1), an Aerosil 200: Gelita-Sol-P (1:1) mixture (SDP2) and an Aerosil 200:Gelita-Sol-P (1:3) mixture (SDP3). All the powders were obtained using 40 parts adjuvant and 60 parts extract dried residue. The comparison criteria applied were particle size distribution, hygroscopicity at 95%, 60%, and 35% relative humidity (RH), as well as the flavonoid process recovery. The particle size distributions were analyzed by way of (a) normal distribution parameters, (b) the RRSB grid and (c) considering diameter values in terms of an equivalent sphere. All the powders presented nonnormal distribution, and the RRSB analysis appeared to be, therefore, the analysis method of choice. The total flavonoid recovery was around 80%, and it was practically not affected by the SDP1, SDP2, and SDP3 compositions. At the 60% and 90% RH atmospheres, the SDP3 and SDP2 moisture uptakes were higher than that of the SDP1. All the formulations were, on the contrary, stable at 35% RH, showing a slight moisture loss tendency. The results showed in sum that the SDP prepared using Aerosil 200 as the drying adjuvant alone presented the best technological characteristics of all.

Adjuvants, Pharmaceutic↗

PubMed2005

FPA-based infrared thermography as applied to the study of cutaneous perspiration and stimulated vascular response in humans.

This review gives an overview of focal plane array (FPA)-based infrared (IR) thermography as a powerful research method in the field of physiology and medicine. Comparison of the gained results with the data previously obtained by other authors with other research tools is given. Outer thermoregulatory manifestations displayed by the human organism subjected to whole-body heating (sauna bath) and physical loads (exercise bicycling) are quantitatively analysed. Some details of human body emotional sweating (psycho-physiological effect) are reported. Particular attention is paid to studying active sweat glands as individual objects. All experimental data were obtained with the help of a high-sensitivity (0.03 degrees C) fast 128 x 128 InAs IR detector-based thermal imaging system operating in the short-wave spectral region (2.5 to 3 microm) and perfectly suiting medical purposes. It is shown that IR thermography makes it possible to overcome limitations inherent to contact measuring means that were traditionally used before in thermal studies. It is also shown that heterogeneous thermograms displayed by organisms with disturbed inner equilibrium can be quantitatively analysed in terms of statistical parameters of related surface-temperature histograms, such as the mean temperature and the standard deviation of temperature (SDT). The increase and the decrease in SDT turned out to be typical of prolonged physical load and subsequent relaxation, and of external whole-body heating, respectively. Explanation of this result based on a hypothesis advanced within the context of the doctrine of human-organism evolution is given. Skin-temperature distribution function accompanying the relaxed organism in normality was found to closely resemble normal-distribution function. Symmetry break down and variation of the shape of this characteristic may serve as an indicator of homeostasis shift and can be used as a quantitative criterion for the latter. A new phenomenon, stable punctate hidrosis, is discovered and described. The term sweatology is introduced to refer to the discussed specific research area in biomedical science.

Body Temperature↗