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PubMed2001

Magnetic fluctuations in the classical XY model: the origin of an exponential tail in a complex system.

We study the probability density function for the fluctuations of the magnetic order parameter in the low-temperature phase of the XY model of finite size. In two dimensions, this system is critical over the whole of the low-temperature phase. It is shown analytically and without recourse to the scaling hypothesis that, in this case, the distribution is non-Gaussian and of universal form, independent of both system size and critical exponent eta. An exact expression for the generating function of the distribution is obtained, which is transformed and compared with numerical data from high-resolution molecular dynamics and Monte Carlo simulations. The asymptotes of the distribution are calculated and found to be of exponential and double exponential form. The calculated distribution is fitted to three standard functions: a generalization of Gumbel's first asymptote distribution from the theory of extremal statistics, a generalized log-normal distribution, and a chi(2) distribution. The calculation is extended to general dimension and an exponential tail is found in all dimensions less than 4, despite the fact that critical fluctuations are limited to D=2. These results are discussed in the light of similar behavior observed in models of interface growth and for dissipative systems driven into a nonequilibrium steady state.

Journal Article↗

PubMed1979

Cut-off levels for maternal plasma alpha-fetoprotein in the diagnosis of neural tube defects: validation of the use of multiples of the normal median.

A retrospective study was made of measurement of maternal plasma alpha-feto-protein (AFP) by a standard radioimmunoassay technique, as a method of screening for neural tube defects (NTDs) between 15 and 20 weeks gestation. There was a good fit of a log-normal distribution to the data at each week and multiples of the normal median were equivalent to constant centiles over weeks 15 to 20 and possibly at later weeks also. There were 700 plasma samples from women with normal prenancies and 60 from women with pregnancies complicated by fetal NTDs (30 with anencephaly and 30 with spina bifida). At 15 to 20 weeks of pregnancy, 90 per cent of women with fetuses affected by anencephaly, 70 per cent of those with fetuses affected by open spina bifida and 3 per cent ofthose with normal pregnancies had plasma AFP levels at or above 2.4 times the normal median for each gestational week. It was estimated that 2.1, 2.4 and 3.1 times the normal median maternal plasma AFP levels were equivalent to the 95th, 97th and 99th centiles respectively. The interassay coefficients of variation estimated on control sera throughout the entire study were 4 to 6 per cent.

Female↗

PubMed1998

Measurement of intraocular pressure with a modern noncontact tonometer.

PURPOSE: To evaluate the intraocular pressure (IOP) in a population without known glaucoma as measured by means of a noncontact tonometer (NCT). METHODS: IOP values of 842 persons, measured by means of a Pulsair 2000 NCT (Keeler Instruments, Inc., Broomhall, Pennsylvania) by 5 investigators were evaluated. Three consecutive measurements were taken first on the right eye and then on the left eye in each subject. Topical anesthesia was not used. RESULTS: The distribution of the measured IOP values was significantly different from a normal distribution. The median IOP was 15.0 mmHg (lower quartile/ upper quartile 12.5/17.2). There were no differences in IOP values between male and female subjects or between right and left eyes. There was no correlation between age and IOP values. Ninety percent of the subjects had an IOP within a range of 9-24 mmHg in both eyes. Among the examined subjects, the IOP was above 24 and 21 mmHg in 4,6 and 11%, respectively, in at least one eye. The median range of consecutive IOP measurements in one eye was 3 mmHg (lower quartile/upper quartile 2.0/4.0). The median interocular IOP difference was 1.7 mmHg (0.7/2.7). The median individual coefficient of variation (CV) values were 10.0% for the right eyes, -10.8% for the left eyes. Among the 5 different examiners, the IOP values, range of 3 consecutive IOP readings in one eye, interocular asymmetry and CV values were statistically comparable. CONCLUSION: The Pulsair 2000 NCT is very simple to use and its handling is mostly independent of the operator. The results of the present investigation might be of some value for future screening programs.

Adolescent↗

PubMed2000

Applicability of Hyland's Living with Asthma Questionnaire for Japanese asthmatic patients.

OBJECTIVE: To assess the applicability of Hyland's Living with Asthma Questionnaire (LWAQ, 1991), one of the international health-related quality of life scales, for Japanese asthmatic patients with reference to its reproducibility and validity. SUBJECTS AND METHODS: The LWAQ was given to randomly selected asthmatic patients on two occasions separated by a 12-week interval. RESULTS: The mean scale score in the first study (n=304) was 1.83 (range, 1.14-2.77) and logarithmic values of the scores approached normal distribution. The scale scores in the first and second (n=158) studies were well correlated (r=0.81), however, the mean score decreased (0.08) significantly. The questions were further separated into 11 domains. The sex-domain was notable for a low response rate (68%), and scale scores in the sleep-, colds- and sex-domains in the first study varied considerably from those of the other domains. Frequency distributions of scores in the five constructs (Hyland 1996) were not normal and, with the exception of the colds construct, the relations among the remaining four constructs were similar to those previously reported (Hyland 1996). CONCLUSION: Analysis using the mean scale score, domain and construct in the LWAQ is applicable to Japanese asthmatic patients.

Asthma↗

PubMed2002

Defining and detecting malaria epidemics in the highlands of western Kenya.

Epidemic detection algorithms are being increasingly recommended for malaria surveillance in sub-Saharan Africa. We present the results of applying three simple epidemic detection techniques to routinely collected longitudinal pediatric malaria admissions data from three health facilities in the highlands of western Kenya in the late 1980s and 1990s. The algorithms tested were chosen because they could be feasibly implemented at the health facility level in sub-Saharan Africa. Assumptions of these techniques about the normal distribution of admissions data and the confidence intervals used to define normal years were also investigated. All techniques identified two "epidemic" years in one of the sites. The untransformed Cullen method with standard confidence intervals detected the two "epidemic" years in the remaining two sites but also triggered many false alarms. The performance of these methods is discussed and comments made about their appropriateness for the highlands of western Kenya.

Adolescent↗

PubMed2003

A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses.

The nature of CD8(+) T cell memory is still incompletely understood. We have previously reported that the response to an HLA-A2-restricted influenza-derived peptide results in a complex T cell repertoire. In this study we extend this analysis and describe the repertoire with more rigor. In one individual we defined 141 distinct T cell clonotypes on the basis of the unique DNA sequence of the third complementarity-determining region of the TCR beta-chain. The frequency distribution of the clonotypes is not what is expected of a normal distribution but is characterized by a large low-frequency tail. The existence of a complex population indicates a mechanism for maintaining a large number of Ag-specific clonotypes at a low frequency in the memory pool. Ranking the clonotypes allowed us to describe the population in terms of a power law-like distribution with a parameter of decay of approximately 1.6. If the repertoire is divided into subsets, such as clonotypes that use BJ2.7 or those whose third complementarity-determining region encodes the amino acid sequence IRSS, the clonotype frequencies could also be described by a power law-like distribution. This indicates a self similarity to the repertoire in which smaller pieces are slightly altered copies of the larger piece. The power law-like description is stable with time and was observed in a second individual. The distribution of clonotypes in the repertoire could be mapped onto a polygonal spiral using a recursive algorithm. Self similarity, power laws, and recursive mapping algorithms are associated with fractal systems. Thus, Ag-specific memory CD8 T cell repertoires can be considered as fractal, which could indicate optimized flexibility and robustness.

CD8-Positive T-Lymphocytes↗

PubMed1976

[A contribution to the subject of the parameters PQ, QRS and QT being functions of heart rate in the ECG of the beagle dog (author's transl)].

We examined the degree of dependency of the ECG parameters PO, QRS and QT on the heart rate. In 252 beagles of standardised breeding and accommodation (strain: Chbi : BEAGLE), a total of 1456 ECG recordings was made from the three Einthoven extremity leads, and the heart rate and PQ-, QRS-, and QT-times were measured. The animals used were dogs from eleven subacute toxicity studies. 683 of the registrations were obtained from control animals and 773 from drug-treated animals whose ECG curves had remained unchanged and in which no histopathological changes were found in the heart at the end of the toxicity studies. The data obtained were biometrically evaluated by regression and correlation analyses. The range of the heart rate was 34-238 actions/min, median value 108. The range of the PQ interval was 0.07-0.18 sec, the QRS interval 0.03-0.09 sec and the QT interval 0.14-0.26 sec. The median values were 0.11, 0.05 and 0.19 sec, respectively. Positive skew distributions were found. The data were transformed to obtain values with normal distribution. The various correlation coefficients were then heart rate/PQ time: -0.408 (p less than 0.001), heart rate/QRS time: -0.057 (p less than 0.05), heart rate/QT time: - 0.611 (p less than 0.001). This means that the PQ and QT intervals clearly decrease as the heart rate increases, whereas the QRS interval is only minimally affected. Correlation ellipses were also calculated and presented graphically. These show areas within which 50, 75, 90 and 95% of our values are to be expected.

Animals↗

PubMedDate not supplied

[The investigation of the influence of cryopreservation and inbreeding on the variability of morphological characteristics of the evening-primrose biennial (Oenothera biennis L.)].

The effect of deep freezing of seeds at -196 degrees C (-320.8 degrees Fahrenheit) and inbreeding on the morphological characteristics of the evening-primrose biennal (Oenothera biennis L.), such as the size of plant parts and the amount of fruits, cauline nodes, and generative and vegetative shoots was investigated. The variation coefficients for these characteristics after treatment with low temperatures and inbreeding were calculated. It was shown that the characteristics of plant size show a low and a middle level of variability in the control group. The variation curves for these characteristics are similar to normal distribution curves. After stresses they slightly change or remain invariant. Large adventive shoots show a high level of variability. The distribution of the results in this case significantly differs from the normal. The branching of plants changes after both stress factors: the amount of all kinds of shoots decreases by half or even more.

Cryopreservation↗

PubMed1990

Statistical analysis of pharmacokinetic data with special applications to bioequivalence studies.

The objectives of this investigation are: 1) to describe techniques for determining the validity of the assumptions; 2) to suggest data transformations which may validate the use of parametric procedures; and 3) to describe a non-parametric alternative to the analysis of variance for crossover designs. Two assumptions common to all parametric procedures include the underlying normal distribution of the observations and equality of variances across treatment groups. Normal probability plots and/or stem and leaf plots are good diagnostic techniques to address the assumption of normality, while Bartlett's test is the most common method of determining equality of variances. To evaluate bioequivalence data, the Food and Drug Administration suggests the use of analysis of variance for crossover designs. If the underlying assumptions are valid, the appropriate statistical models are well known. On the other hand, if the assumptions are not valid, the investigator has one of two choices: 1) transform the data in such a way as to satisfy the assumptions, or 2) use a non-parametric procedure. Square root or logarithmic transformations are commonly used in this situation. However, if a suitable transformation cannot be found, then a non-parametric procedure should be used. Koch (Biometrics (1972) 28, 577-584) developed a non-parametric crossover test, which is relatively easy to apply, but the corresponding power calculations required by the FDA are less obvious.

Animals↗

PubMed1990

Monitoring of genotoxic exposure of humans by the sister chromatid exchange test. Methodology and confounding factors.

During the last decades several in vitro assays for measurement of genotoxic exposure have been developed. Exposure of humans to genotoxic products in their workplaces and the environment may be evaluated by means of the sister chromatid exchange test (SCE), which visualize exchange of DNA material between sister chromatids of a chromosome. This thesis deals with the development of SCE methodology and screening of confounding factors to make the method useful in population monitoring of genotoxic exposure of chemicals in vivo. Human lymphocytes are cultured under standardized conditions. The cells are prepared for chromosome analysis by means of new-developed apparatuses treating 12 samples simultaneously. By this method the preparation is speeded up and breathing of glacial acetic acid is minimized. Slides are prepared and stained. The staining procedure includes irradiation of the slides with long wave UV light. The light source has been optimized with regard to simplicity and spectral distribution to fit the absorption spectrum of the dye bisbenzimid. The irradiation time and dose to produce distinct harlequin stained chromosomes has been found. Population screening demands analysis in microscope of a great number of chromosomes. The working time at microscope is long and improvement of ergonomics and automation to speed up the procedure was obtained by development of a special microscope which projects the picture of SCEs at table level. The scanning table was motorized. These changes gave excellent ergonomic proporties as fixed positions of the eyes and hands were avoided. The system is fast and flexible and may semiautomatically produce karyotypes. By pointing out SCEs the system automatically registers SCE number, cell coordinates, mitosis quality and perform statistics. The statistical model which best describe the distributions of SCE data has been analysed. This was a negative binomial distribution, which is close to the Poisson distribution. The transformation y = (S).5 + (S + 1).5 follows a normal distribution. Variances of the transformation of the sum of SCEs in 30 cells within subjects and between subjects have been calculated, and on that basis the demands to sample size have been calculated. To avoid to make false statements about a connection between an exposure and SCE a detailed knowledge of confounding factors is essential. Of endogenous factors gender, age, race, and heredity have been considered. Of these gender and age contribute to the variation in SCE. Very high SCE level has been found in healthy members of a family and such cases have to be excluded from exposure studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1978

The tissue cage model in the distribution of antibacterial agents.

Developments in the measurement of interstitial tissue fluid using the tissue cage model are described. The design and physical characteristics of tissue cages are examined and evidence is presented to show that the fluid contained within these cages is representative of interstitial tissue fluid. The distribution of a variety of antibacterial agents into tissue cage fluid is examined and shows that this technique is a reliable experimental model for the study of drug distribution. The results also show that some antibacterial agents may never, normally, distribute into the tissue fluid and that the use of tissue homogenates, especially the kidney, is unreliable as a guide to the tissue concentration of a drug.

Animals↗

PubMed1984

Sensitive radioimmunoassay for measurement of circulating peptide YY.

A radioimmunoassay with sufficient sensitivity to detect the recently discovered, circulating peptide YY in the majority of healthy adults has been developed. The antiserum to synthetic peptide YY raised in rabbits essentially showed no cross-reactivity with bovine or porcine synthetic pancreatic polypeptide, neurotensin, or neuropeptide Y, but cross-reacted to the extent of 0.03% with synthetic peptide HI. The minimum detectable limit of the assay for plasma peptide YY was 20 pg/ml with coefficients of variation less than 16%. The immunoreactivity of peptide YY isolated from healthy adult plasma had a gel-filtration chromatographic profile similar to that of synthetic peptide YY. Fasting levels of peptide YY in plasma from 127 of 137 (92.7%) ostensibly healthy adults were measurable and showed a log-normal distribution. Using the maximum-likelihood estimation method, we calculated the normal range to be 13-178 pg/ml with a geometric mean value of 49 pg/ml. The fasting plasma peptide YY levels showed no significant age or sex dependency.

Adult↗

PubMedDate not supplied

[Giardiasis in children. Ultrastructural study of the parasite].

Giardia lamblia is the first protozoan to be identified and recognized as an important pathogen in human disease. We studied 8 pediatric patients with giardiasis in order to examine the clinical spectrum, the structural changes of the small intestinal mucosa and mainly the protozoan's ultrastructural features. The most common clinical manifestations were diarrhea, abdominal pain, anorexia, vomiting, failure to thrive. Infection was confirmed by excreted cysts in the stools in one patient, by the presence of trophozoites in duodenal aspirate and on jejunal mucosa. Giardiasis was not associated with hypogammaglobulinemia in our patients and no or only slight mucosal abnormalities were present in jejunal biopsies, except one which showed a flat mucosa. Specimens for transmissions and scanning electron microscopy were taken. We could establish the protozoan's features, its normal distribution, its relationship to intestinal mucosa and structural indications of the normal reaction of intestine with the use of ultrastructural techniques. The trophozoites colonized the proximal intestine, adhered to microvilli of columnar cells near the bases of villi, wedged or lodged in mucus. The sticky mucus producing an effective diffusion barrier to nutrients could explain malabsorption phenomena. Numerous intraluminal lymphocytes were seen, suggesting an immune response. These observations indicate that in giardiasis the clinical spectrum and structural changes of the small intestinal mucosa vary widely, suggesting a different reaction of immune system and/or a different degree of infection.

Child, Preschool↗

PubMed1995

Clinical expression correlates with location of rhodopsin mutation in dominant retinitis pigmentosa.

PURPOSE: To determine whether severity of retinitis pigmentosa caused by dominant rhodopsin mutations depends on the location altered by the mutation. METHODS: Data from 128 patients (age range, 7 to 73 years), each with 1 to 27 rhodopsin mutations, were analyzed. To approximate normal distributions, visual acuities were converted to ranks and then to the normal form, kinetic visual fields to a V4e test light were converted to equivalent diameters, and dark-adapted sensitivities to an 11 degrees diameter stimulus and electroretinogram (ERG) amplitudes to full-field 0.5-Hz and 30-Hz flashes were converted to common logarithms. Each of these measures was then regressed on age, refractive error (for the ERG), and domain (intradiscal, transmembrane, or cytoplasmic) or codon number of the opsin molecule altered by the mutation. RESULTS: All five measures of function varied significantly with the domain (P < or = 0.0007) or codon number (P < 0.0001) altered by a mutation; visual acuity, visual field diameter, dark-adapted sensitivity, and ERG amplitudes were highest for mutations altering the intradiscal domain or low-numbered codons and lowest for mutations altering the cytoplasmic domain or high-numbered codons. CONCLUSIONS: These data indicate that severity of disease correlates with the location of the amino acid residue altered by a rhodopsin mutation in dominant retinitis pigmentosa.

Adolescent↗

PubMed1994

[Evidences for genetic transmission of pulse arterial pressure].

Systolic (PS), diastolic (PD), and pulse (PULS) arterial blood pressure were examined in 151 French-West-Indies families. After adjustment for sex, age, Na/K urinary ratio, alcohol consumption, use of anti-hypertensive drug, the distributions of PS and PD were correctly fitted by two commingled normal distributions, one of them including 5% of the highest values of blood pressure which have to be compared to the high prevalence of hypertension in this population (10 to 20%). By performing segregation analyses under Lalouel et al.'s unified model we do not support any genetic transmission for PS and PD. On the contrary, large evidence for genetic transmission of PULS was found, involving one locus, two equally frequent alleles. However dominance cannot be correctly inferred. Accordingly, PULS appears to be of larger interest than PS and PD to study the genetic regulation of the arterial blood pressure.

Blood Pressure↗

PubMed1976

[Individual variations in the frequency of chromosome aberrations following exposure to chemical mutagens. II. Interindividual variation in the frequency of chromosome aberrations in the presence of different mutagen concentrations].

The object of this investigation was the distribution of human periferal blood cultured obtained from different donors with respect to their sensitivity to different concentrations of thiophosphamide (10, 20 and 30 mcg/ml for 1 hour). Two test characteristics were studied, "the proportion of aberrant metaphases" and "the number of chromosome breaks per 100 cells". It is shown that the distribution of individuals does not depend on the mutagen concentration, being normal in all the series of experiments. The same results were obtained when two different statistical methods were used, viz. the method of four moments and the chi-square test. Since the former method is less labour-consuming, the authors recommend it for fitting the normal distribution in cytogenetic investigations. The variances of the test-characteristics studies ("percent aberrant metaphases" and "total number of breaks per 100 cells") increased with the increase of the mean values. Therefore, before the analysis of variance and the regression analysis the cytogenetic data should be preliminary transformed for the purpose of stabilization of variances.

Chromosome Aberrations↗

PubMed1993

Median facial dysplasia in unilateral and bilateral cleft lip and palate: a subgroup of median cerebrofacial malformations.

The median facial dysplasia group of patients is a unique, distinct, definable group characterized by mid-line facial deficiencies in the presence of a unilateral or bilateral cleft lip with or without cleft palate and without clinically detectable anomalies of the brain. This group of patients comprised 2 percent of new cleft lip and palate patients. The midline facial deficiencies in median facial dysplasia are characterized by a poorly defined Cupid's bow, absence of the labial frenulum and anterior nasal spine, deficient columella, and poorly developed septal cartilage and premaxilla. One of the central incisors may be absent or rudimentary. There are no definable gross abnormalities of the brain. The results of intelligence tests of median facial dysplasia patients have a normal distribution and are not significantly different from those of a noncleft normal population. Unoperated and operated median facial dysplasia patients all have typical midfacial growth disturbances below the norm for their ages. The classification of median facial dysplasia patients as well as other median cerebrofacial anomalies, the embryologic basis of these deformities, and the clinical results of their treatment are helpful in understanding some of the problems related to the treatment of the cleft lip and palate patient. Median facial dysplasia patients demonstrate an inherent potential for poor midfacial growth. Deficiencies of soft tissue such as a lack of the Cupid's bow make it difficult to reconstruct the lip and nose satisfactorily.

Abnormalities, Multiple↗

PubMed1998

Three approaches to regression analysis of receiver operating characteristic curves for continuous test results.

The accuracy of a medical diagnostic test is typically summarized by the sensitivity and specificity when the test result is dichotomous. Receiver operating characteristic (ROC) curves are measures of test accuracy that are used when test results are continuous and are considered the analogs of sensitivity and specificity for continuous tests. ROC regression analysis allows one to evaluate effects of factors that may influence test accuracy. Such factors might include characteristics of study subjects or operating conditions for the test. Unfortunately, regression analysis methods for ROC curves are not well developed and methods that do exist have received little use to date. In this paper, we propose and compare three very different regression analysis methods. Two are modifications of methods previously proposed for radiology settings. The third is a special case of a general method recently proposed by us. The three approaches are compared with regard to settings in which they can be applied and distributional assumptions they require. In the setting where test results are normally distributed, we elucidate the correspondence between regression parameters in the different models. The methods are applied to simulated data and to data from a study of a new diagnostic test for hearing impairment. It is hoped that the presentation in this paper will both encourage the use of regression analysis for evaluating diagnostic tests and help guide the choice of the most appropriate regression analysis approach in applications.

Biometry↗