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PubMed2006

Concordance of aqueous humor flow in the morning and at night in normal humans.

PURPOSE: To test the hypothesis that an individual shows concordance of aqueous humor flow in the morning and at night in a prospective inpatient fluorophotometry study in healthy subjects. METHODS: Flow was measured in each eye every hour between 8 AM and noon and every 2 hours between midnight and 6 AM. Morning and nighttime flows were analyzed for differences between eyes and for differences between these two time points. Concordance of individual morning and nighttime flows were studied by categorization into low, medium, or high tertiles, dot plot, and ordinary least-squares regression (OLS) scatter plot. RESULTS: In 28 subjects, the flow was similar between eyes within a subject with healthy eyes. In the one eye examined in each subject, the average flow was 3.12 +/- 1.09 muL/min in the morning, which decreased significantly to 1.59 +/- 0.58 muL/min at night. During each time period, the individual flow data were normally distributed. Concordance of an individual's morning and nighttime flows was 68%. A scatter plot of morning versus nighttime flows also supported concordance with an OLS regression fit of r(2) = 0.45. CONCLUSIONS: The results provide evidence that aqueous humor flow is similar between eyes, that flow variation shows a normal distribution, and that individuals show a concordance of flow in the morning and at night. These observations support the posit that aqueous humor flow, which is a factor that contributes to the important clinical risk factor of IOP variation, is amenable to study as a quantitative trait.

Adolescent↗
PubMed1987

Observations with SPECT on the normal regional distribution of pulmonary blood flow in gravity independent planes.

While the effect of gravity on the pulmonary circulation is well documented, the distribution of pulmonary flow under gravity independent conditions is not as well understood. Single photon emission computed tomography was applied to the study of regional pulmonary blood flow in slices where the effect of gravity was constant. Lung tomography, after the injection of [99mTc]MAA, was carried out in six normal volunteers and in the fully inflated and isolated lungs from six dogs that had been killed. Our tomographic results suggest that pulmonary perfusion in isogravitational planes is inherently nonuniform with preferential flow centrally and reduced circulation more peripherally. Planar imaging of the dissected isogravitational slices from the animals further confirmed the uneven perfusion noted on the tomographic slices.

Adult↗
PubMedDate not supplied

[Multidimensional analysis by Cox's model of the survival of patients with alcoholic cirrhosis].

A group of 249 patients with alcoholic cirrhosis was prospectively studied in order to assess the prognostic value of 23 clinical and biochemical factors. Methods included the Cox model completed with validation by assessing the proportionality and by comparing the estimated and observed results, a study of the influence on the results of the truncated data and the factors with non normal distribution, and an expression of the results using predictive values. Results showed that encephalopathy, age, serum albumin and total bilirubin concentrations and serum gamma glutamyl transpeptidase activity had an independent prognostic value. The Cox model was validated and results showed that taking into account the truncated data and the non normal distribution modified the results. An index using the five independent prognostic factors had a good negative predictive value, permitting to predict, in one third of the patients, survival i. e. which patient had a probability to be alive at two years greater than 90 p. 100.

Factor Analysis, Statistical↗
PubMedDate not supplied

Computer simulations of blood pressure tracking.

Individual blood pressures (BP) tend to remain in the same relative position within a population BP distribution ('tracking'). Individuals in the upper range of the distribution may be predisposed to future hypertension, but this has not been proven epidemiologically. In this study tracking was simulated by computer using 4 simple empirical models to assess commonly reported criteria of BP tracking (correlation coefficient (r) and quintile analysis) and the relationship between the rank position of BP and the subsequent development of 'hypertension' or 'death'. The four models were applied to a population (n = 1500) of normally or log-normally distributed values corresponding to BPs with a mean of 75 and SD of 10 mmHg, also generated by the computer, and to real BP data from a longitudinal population survey. Each iteration of the model represented one year. Changes in BP at each iteration were cumulative. With both normally and log-normally distributed data, r for paired initial and final BPs decreased progressively but remained statistically significant for all models, up to 30 'years'. However, r was low. The patterns resembled that found in the longitudinal survey and data obtained by submitting the initial real BP data from the same survey to the simulations. In agreement with epidemiological studies, there was frequent movement of BP values between distribution quintiles, confirming that tracking is inefficient. In the computer-derived data, the relative risk of 'death' or 'hypertension' was greatest in the topmost quintile. The results suggest that though physiological BP control mechanisms are complex, adequate description of BP trends with time in a population is possible using simple models.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed2004

Growth centiles for Omani premature infants born at 26 weeks of gestation.

OBJECTIVE: The present growth chart used in the Sultanate of Oman does not contain centile measurements for infants born at 26-weeks of gestation. With the increased survival of these premature infants, there is a growing need to develop such a chart. The present study was conducted with the aim to look at the anthropometric measurements (weight, length and head circumference) of Omani premature infants born at 26-weeks of gestation and to develop centile charts for these measurements. METHODS: The study was conducted at the Special Care Baby Unit (SCBU) of the Royal Hospital, one of the major perinatal institutions in Muscat, Oman. A computerized database is maintained for all the admissions from 1996. We extracted the required anthropometric data for all 26-week gestation premature Omani infants admitted to SCBU from January 1996 to November 2003. A total of 49 babies were admitted during that period. Out of these, 43 had complete information on the growth parameters, including birth weight, length and head circumference. These parameters were noted down and by using the statistical package, an analysis was performed to get the normal distribution curve. By using the Microsoft Excel program, graphs were generated for all the 3 growth parameters. RESULTS: The mean birth weight for the premature infants born at 26-week gestation was noted to be 908 +/- 156 grams, with length and head circumference of 33.5 +/- 2.5 and 24.5 +/- 1.7 centimeters. The normal distribution curve was obtained with minimal skewing. CONCLUSION: We were able to generate centile charts of the anthropometric measurements for Omani infants born at 26-weeks of gestation. The next step is to collect the national data from other institutions in Oman and then incorporate it into the present growth chart to make the charts more valid, reliable and applicable.

Anthropometry↗
PubMed1989

Effects of concurrent infections on growth, development, distribution, and infectivity of adult Philophthalmus megalurus and Philophthalmus gralli.

Chickens were infected concurrently with 10 and 20 metacercariae/eye of Philophthalmus megalurus and Philophthalmus gralli. After 14 and 34 days of growth, the adults were removed and worm lengths, return rates, stage of development, and distribution within the host recorded. In a second experiment, chickens infected on day 1 with 10 metacercariae/eye of P. megalurus were concurrently infected with a similar dose of P. gralli on day 14. At day 34, the worms were removed and evaluated for the same parameters as in the first study. The effect of concurrent infections on worm length of P. gralli but not P. megalurus was significant when compared to single species control groups. In all cases recovery rates of P. megalurus in concurrent infections were significantly lower than controls, whereas P. gralli adults were recovered at lower rates only in 20-metacercariae--14-day infections. Maturation of eggs was delayed in both species in concurrent infections at the higher infection levels. Normal distribution was disrupted more for P. gralli at the higher infection levels and longer growth periods. Philophthalmus megalurus adults rarely left their normal habitat in the conjunctival sac. A delayed infective dose of P. gralli affected both species by disrupting normal distribution patterns, delaying egg development, and, in the case of P. megalurus, reducing the recovery rate. The possible role of crowding and antagonistic effects is discussed.

Animals↗
PubMed2006

Variance stabilization and normalization for one-color microarray data using a data-driven multiscale approach.

MOTIVATION: Many standard statistical techniques are effective on data that are normally distributed with constant variance. Microarray data typically violate these assumptions since they come from non-Gaussian distributions with a non-trivial mean-variance relationship. Several methods have been proposed that transform microarray data to stabilize variance and draw its distribution towards the Gaussian. Some methods, such as log or generalized log, rely on an underlying model for the data. Others, such as the spread-versus-level plot, do not. We propose an alternative data-driven multiscale approach, called the Data-Driven Haar-Fisz for microarrays (DDHFm) with replicates. DDHFm has the advantage of being 'distribution-free' in the sense that no parametric model for the underlying microarray data is required to be specified or estimated; hence, DDHFm can be applied very generally, not just to microarray data. RESULTS: DDHFm achieves very good variance stabilization of microarray data with replicates and produces transformed intensities that are approximately normally distributed. Simulation studies show that it performs better than other existing methods. Application of DDHFm to real one-color cDNA data validates these results. AVAILABILITY: The R package of the Data-Driven Haar-Fisz transform (DDHFm) for microarrays is available in Bioconductor and CRAN.

Algorithms↗
PubMed1993

Clinical birthweight standards for a total population in the 1980s.

OBJECTIVE: To derive clinical standards for singleton birthweight in a population based on area of residence. DESIGN: Analysis of variables recorded in Aberdeen Maternity and Neonatal Databank, calculating for each birth a standardised birthweight score, taking account of determining factors. SUBJECTS: All singleton live births of 32 to 42 weeks gestation to Aberdeen City District residents from 1979 to 1983. RESULTS: Basic standards of birthweight are presented correcting for gestational age, sex of the baby and parity of the mother. Birthweight is not normally distributed and empirical data are presented rather than smoothed curves. Adjustment for maternal height is straightforward but adjustment for maternal weight must take account of the gestation at which the woman was weighed. A method of calculating the appropriate correction for height and weight is described in detail. CONCLUSION: Birthweight is not normally distributed at each week of gestation. Standardisation for parity, gestation and sex of the baby is essential, but adjustment for maternal size is complex.

Birth Weight↗
PubMedDate not supplied

Limited dynamic range of immune response gene expression observed in healthy blood donors using RT-PCR.

The use of quantitative gene expression analysis for the diagnosis, prognosis, and monitoring of disease requires the ability to distinguish pathophysiological changes from natural variations. To characterize these variations in apparently healthy subjects, quantitative real-time PCR was used to measure various immune response genes in whole blood collected from blood bank donors. In a single-time-point study of 131 donors, of 48 target genes, 43 were consistently expressed and 34 followed approximately log-normal distribution. Most transcripts showed a limited dynamic range of expression across subjects. Specifically, 36 genes had standard deviations (SDs) of 0.44 to 0.79 cycle threshold (C(T)) units, corresponding to less than a 3-fold variation in expression. Separately, a longitudinal study of 8 healthy individuals demonstrated a total dynamic range (> 2 standard error units) of 2- to 4-fold in most genes. In contrast, a study of whole blood gene expression in 6 volunteers injected with LPS showed 15 genes changing in expression 10- to 90-fold within 2 to 5 h and returning to within normal range within 21 hours. This work demonstrates that (1) the dynamic range of expression of many immune response genes is limited among healthy subjects; (2) expression levels for most genes analyzed are approximately log-normally distributed; and (3) individuals exposed to an infusion of bacterial endotoxin (lipopolysaccharide), show gene expression profiles that can be readily distinguished from those of a healthy population. These results suggest that normal reference ranges can be established for gene expression assays, providing critical standards for the diagnosis and management of disease.

Adult↗
PubMed1982

On 1/f noise and other distributions with long tails.

It is shown, following Shockley [Shockley, W. (1957) Proc. IRE 45, 279-290], that, when a population is engaged in tasks whose completion requires the successful conclusion of many independent subtasks, the distribution function for successes in the primary task is log normal. It is also shown that, when the dispersion of the log-normal distribution is large, the distribution is mimicked by a 1/x distribution over a wide range of x. This argument provides a generic set of processes that yields the much observed 1/x distribution, and will also lead to a 1/f noise spectrum. It is commonly found that distributions that seem to be log normal over a broad range (say to the 95th percentile of a population) change to an inverse fractional power (Pareto) distribution for the last few percentile. Annual income distributions are examples with this structure. The very wealthy generally achieve their superwealth through amplification processes that are not available to most. We have introduced a simple amplification model to characterize the transition from a log-normal distribution to an inverse-power Pareto tail.

Journal Article↗
PubMed1997

Statistical methods for estimating doubling time in in vitro cell growth.

Doubling time has been widely used to represent the growth pattern of cells. A traditional method for finding the doubling time is to apply gray-scaled cells, where the logarithmic transformed scale is used. As an alternative statistical method, the log-linear model was recently proposed, for which actual cell numbers are used instead of the transformed gray-scaled cells. In this paper, I extend the log-linear model and propose the extended log-linear model. This model is designed for extra-Poisson variation, where the log-linear model produces the less appropriate estimate of the doubling time. Moreover, I compare statistical properties of the gray-scaled method, the log-linear model, and the extended log-linear model. For this purpose, I perform a Monte Carlo simulation study with three data-generating models: the additive error model, the multiplicative error model, and the overdispersed Poisson model. From the simulation study, I found that the gray-scaled method highly depends on the normality assumption of the gray-scaled cells; hence, this method is appropriate when the error model is multiplicative with the log-normally distributed errors. However, it is less efficient for other types of error distributions, especially when the error model is additive or the errors follow the Poisson distribution. The estimated standard error for the doubling time is not accurate in this case. The log-linear model was found to be efficient when the errors follow the Poisson distribution or nearly Poisson distribution. The efficiency of the log-linear model was decreased accordingly as the overdispersion increased, compared to the extended log-linear model. When the error model is additive or multiplicative with Gamma-distributed errors, the log-linear model is more efficient than the gray-scaled method. The extended log-linear model performs well overall for all three data-generating models. The loss of efficiency of the extended log-linear model is observed only when the error model is multiplicative with log-normally distributed errors, where the gray-scaled method is appropriate. However, the extended log-linear model is more efficient than log-linear model in this case.

Cell Division↗
PubMed1987

Emphysema alters the deposition pattern of inhaled particles in hamsters.

How does pulmonary emphysema affect aerosol deposition? Groups of awake hamsters with emphysema (intratracheal elastase, 0.2 mg/100 g body wt) and age-matched controls (intratracheal saline) were exposed for 30 minutes to an insoluble radioactive aerosol (0.45 mu aerodynamic diameter) at 30, 60, or 90 days after instillation. Immediately after exposure, the animals were sacrificed. The lungs were excised, dried at total lung capacity, and sliced into 1-mm thick sections. Each slice was cut into pieces, which were counted for radioactivity and weighed. Then a measure of the uniformity of deposition, the evenness index (EI), was calculated. With perfect uniformity, all EIs would be one. We found fewer particles in the emphysematous, as compared with the control, lungs at 60 or 90 days after elastase instillation. The deposited particles were distributed less uniformly throughout the emphysematous lungs than in the control lungs. In controls, the standard deviation (SD) of the EI distribution (mean 1.0) averaged 0.33 for the three times studied. In elastase animals, the SD increased to 0.48 at 30 days, and at 60 days and 90 days the distributions were no longer normally distributed. This increased heterogeneity of deposition was also manifested as a loss of the normal apex-base gradient observed in control animals, an increase in the amount of nonventilated parenchyma, enhanced airway deposition, and an altered lobar deposition pattern. Morphometric analysis showed an increase in the mean linear intercept (MLI) of emphysematous lungs as compared with control lungs. However, the author found no correlation between MLI, a measure of emphysema, and EI, a measure of deposition, quantified in the same lung pieces. It is concluded that the emphysematous lesions produced by elastase markedly alter the deposition of an inhaled submicrometric aerosol. Factors that may contribute to these changes include airway obstruction and differences in breathing pattern in emphysematous as compared with control animals.

Aerosols↗
PubMed1995

Wrist kinematics. Row, column or both?

Analysis of radiographs of 52 wrists showed that, from ulnar to radial deviation, the amount of scaphoid shortening and ulnar translation of the scaphoid varies in a normal distribution. There is a significant correlation between the two measurements, such that the more the scaphoid shortens the less it translates and vice versa. Females subjects were more likely to have greater scaphoid shortening and less translation. It is felt that carpal kinematics thus cover a spectrum from the "row" theory to the "column" theory which is normally distributed and that women are more likely to have a column type wrist. This variation may affect the result of treatment of scapholunate dissociation by techniques such as scapho-lunate fusion. A "CR index" is proposed so that the tendency of a wrist towards row or column theory can be quantified. This may be used to predict the success of some surgical procedures in the treatment of scapho-lunate dissociation.

Adult↗
PubMed2003

Individual inflammatory response of human blood monocytes to mesh biomaterials.

BACKGROUND: Alloplastic implants such as those employed in hernia repair induce distinct local inflammation and seroma production. As monocytes take a key position in the inflammatory foreign body reaction, their specific release of cytokines was investigated in vitro after incubation with alloplastic materials. METHODS: Human blood monocytes were isolated from buffy coats of 42 healthy blood donors. Cells were cultivated in polystyrene culture wells (4 x 10(6) cells/well) on polypropylene-polyglactin mesh, on polytetrafluoroethylene, in control wells with the addition of 1 micro g lipopolysaccharide (LPS) and on pure polystyrene. Supernatant was taken after 1 h and 5 days, and concentrations of tumour necrosis factor (TNF) alpha, interleukin (IL) 6 and IL-10 were determined. Donors were defined as 'high' or 'low' responders when concentrations of TNF-alpha were above the 75th or below the 25th percentiles, respectively. RESULTS: In contact with biomaterials, the monocytes liberated TNF-alpha, IL-6 and IL-10, similar to levels observed after stimulation with LPS. Median cytokine concentrations were not normally distributed and were influenced by donor, timepoint and applied stimulus. One donor matched the criteria for low responder and three for high responder. CONCLUSION: The individual was identified as an independent factor for the inflammatory response of monocytes to biomaterials. Moreover, high and low responders could be identified. The variability of cytokine release and the lack of a normal distribution suggest that a larger sample size should be used in future studies of cellular response.

Biocompatible Materials↗
PubMed1983

Freeze-fracture analysis of plasma membranes of isolated astrocytes from rat brain.

Plasma membranes of mature rat astrocytes separated by differential centrifugation have been reported to be intact, based on electron microscopic examination of thin plastic sections. However, the effects of the separation procedure on the internal structure of the plasma membranes are unknown. The degree of membrane integrity is of concern to us since our goal is the separation of astrocytic plasma membranes and characterization of the specific intramembranous particle groups called assemblies. We have taken advantage of the astrocyte membrane-marker, the assembly, in order to monitor, by freeze-fracture, the identity of the separated astrocytes and the integrity of their cell membrane. Since some processes of an astrocyte contain assemblies whereas other processes of the same cell do not, it was also necessary to determine if processes with assemblies were separated by this technique. Astrocytic cell membranes were also examined to determine if trypsinization or the mechanical disruption steps of the separation affected the intramembranous particles. Freeze-fracture of the plasma membranes revealed that the particles were rearranged resulting in patches of clumped intramembranous particles and areas of bare membrane. The assemblies were rearranged rather than lost from the membrane since they could be identified among the clumped particles. More astrocytic plasma membranes contained non-clumped, normally distributed particles in the trypsin treated fractions. The non-trypsinized fractions had more damaged astrocytes with aggregated intramembranous particles and much more cellular debris. We interpret the findings for the non-trypsinized astrocytes as due to greater mechanical stress placed on the cells during tissue disruption. Trypsin treatment lessens this stress, thereby, tending to preserve the normal distribution of intramembranous particles.

Animals↗
PubMed2006

Validation of growth charts for girls with Turner syndrome.

Growth charts, which describe the natural course of growth in Turner syndrome (TS) patients, are commonly used in studies in lieu of control groups. While analysing data, various charts produce different final height estimations and height-gain predictions. The choice of an appropriate chart should be the first task when assessing effects of growth hormone treatment. The purpose of this study was to establish the most appropriate growth chart for the subsequent analysis of growth rate in the patients with TS observed initially for a short time without treatment in our clinic. We propose the criteria that a standardised chart should meet. The obtained height-standardised values (height standard deviation score -- Ht SDS) should represent normal distribution with a mean of 0 and standard deviation of 1; their initial mean value and mean change in these values during observation without treatment should not be different from 0. We studied 62 untreated girls with TS using three different growth charts. The values of Ht SDS based on the Lyon chart showed a significant difference from normal distribution (p < 0.05). Only the mean value of an initiaent from 0 (p = 0.088). The mean change of the Ht SDS value based on Lyon and Ranke charts during the follow-up period was not statistically different from 0 (p > 0.05), whereas the difference was statistically significant when the Wisniewski chart was used. Only the Ranke chart correctly characterised TS girls in our clinic. This analysis indicates the importance of careful selection of an appropriate growth chart for an observed population, before applying it to evaluate the effects of hormonal therapy.

Adolescent↗
PubMed1978

[Occurrence of various enzymes in synovial fluid of cattle and swine].

The activities of lactate dehydrogenase (LDH), fructose-1.6-diphosphate aldolase (ALD), aspartate aminotransferase (AspAT), alkaline phosphatase (AP), and N-acetyl-beta-glucosaminidase (NAG) were determined on the basis of 75 synovia samples taken from the tarsal joints (Art. talocruralis) of 41 cattle for slaughter of different sexes and aged between one and 13 years as well as on the basis of 56 synovia samples taken from the knee joints (Art. femoropatellaris), tarsal joints (Art. talocruralis), and carpal joints (Art. intercarpicus) of 20 fattening pigs. Both the general condition and cell content of synovial fluid in clinically intact joints are described. The activities of ALD and AspAT (less than 15 IU/l), LDH (less than 200 IU/l), and NAG (less than 6,000 IU/l) in synovial fluid of cattle were much lower than those in blood serum of the same species. They were normally distributed. AP activity (less than 150 IU/l) in synovial fluid, however, was higher by several factors as compared to activity in blblished. In swine synovial AspAT and AP activities were just as high as in blood serum, while LDH activities were higher by 1.5 times. Major NAG activity was observed, as well. All enzyme activities were characterised by normal distribution. All five LDH isoenzymes but only one AP isoenzyme were established. The above data were compared with findings reported by other authors, and the comparison showed these results as being characteristic of synovial enzyme activities in clinically intact joints of the two species under review.

Acetylglucosaminidase↗