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PubMed1993

Carbonyl (phenone) reductase in human liver: inter-individual variability.

The enzyme family carbonyl reductase, which catalyses the reduction of xenobiotic as well as endogenous ketones and aldehydes, has not been very well studied in terms of its biological functions and structural aspects. The aim of the present study was to check for the occurrence of inter-individual variability of carbonyl reductase activity in human liver. In vitro metabolism of p-nitroacetophenone (PNAP, a prototype substrate) indicated the presence of a high- and low-affinity enzyme site. The reductase activity of 17 kidney donor livers was screened at two concentrations (0.05 and 0.5 mM PNAP, below and above Km). The rates of reductase activity at 0.05 mM suggested a normal distribution. In contrast, at 0.5 mM the rates indicated a non-normal distribution, i.e. bi- or tri-modality. As an index of variability of enzyme affinity, ratios of velocities at 0.5 to 0.05 mM PNAP were calculated in order to check their frequency distributions. Three out of 17 kidney donor livers showed an atypical ratio. In these three cases, the high ratio was due to the low activity of the high affinity form of carbonyl reductase. Autopsy livers are a more readily available tissue source and about half the activity of the kidney donor livers was found in 43 autopsy livers indicating that they are a useful source of human tissue for studies of carbonyl reductase.

Acetophenones↗

PubMed2006

Single-point velocity statistics of forced and decaying two-dimensional turbulence.

The single-point (SP) velocity statistics are investigated in forced and decaying two-dimensional turbulence in a flowing soap film. It is shown that the probability distribution functions (PDF) in both cases deviate from a Gaussian distribution, which is normally anticipated in turbulent fluid flows. In the forced turbulence case, the tail of the SP velocity PDF decays faster than Gaussian (termed the sub-Gaussian) and can be correlated with the forcing statistics on small scales. In the decaying-turbulence case, the SP velocity PDF evolves from a sub-Gaussian to a super-Gaussian behavior as a function of time. However, in all times, the locally averaged vorticity remains normally distributed. While our forced turbulence data may be explained by a recent theory proposed by Falkovich et al., the decaying-turbulence data remain unexplained.

Journal Article↗

PubMed2001

Likelihood contour method for the calculation of asymptotic upper confidence limits on the risk function for quantitative responses.

This article develops a computationally and analytically convenient form of the profile likelihood method for obtaining one-sided confidence limits on scalar-valued functions phi = phi(psi) of the parameters psi in a multiparameter statistical model. We refer to this formulation as the likelihood contour method (LCM). In general, the LCM procedure requires iterative solution of a system of nonlinear equations, and good starting values are critical because the equations have at least two solutions corresponding to the upper and lower confidence limits. We replace the LCM equations by the lowest order terms in their asymptotic expansions. The resulting equations can be solved explicitly and have exactly two solutions that are used as starting values for obtaining the respective confidence limits from the LCM equations. This article also addresses the problem of obtaining upper confidence limits for the risk function in a dose-response model in which responses are normally distributed. Because of normality, considerable analytic simplification is possible and solution of the LCM equations reduces to an easy one-dimensional root-finding problem. Simulation is used to study the small-sample coverage of the resulting confidence limits.

Dose-Response Relationship, Drug↗

PubMed1986

Quantification of scalp hair--a computer-aided methodology.

A method for obtaining a quantitative assessment of hair density is described. First, a photographic image of the scalp is digitized onto a high-resolution computer graphics screen. Second, the frequency of each of 256 gray levels (one for each of 500 vertical X 500 horizontal = 250,000 locations on the screen) is obtained and the frequency histogram of gray levels is displayed. Third, a statistical procedure, gaussian mixture analysis, is used to resolve the frequency distribution into two normally distributed component distributions. The first component distribution describes the range of gray levels that are typically associated with hair. The second component distribution describes shades of gray that are typically associated with scalp. The statistical model provides a precise measure of the proportion of the head that exhibits gray levels in each of the two component distributions (hair or scalp). The proportion of the first component distribution is a scale-independent measure of hair density. The difference in this quantity before and after treatment provides an accurate quantitative determination of the change in hair density and hence of the efficacy of treatment.

Alopecia Areata↗

PubMed1977

Biochemical measurements in Paget's disease of bone.

In a group of eighty-three patients with untreated Paget's disease of bone, plasma alkaline phosphatase activity (AP), plasma non-protein-bound hydroxyproline concentration (PHP) and urinary excretion rate of total hydroxyproline (THP) were closely correlated with each other but not with fasting plasma concentrations of calcium or inorganic phosphate. Probit plots of AP and THP showed log-normal distributions overlapping the normal ranges.

Adult↗

PubMed1996

Prerace venous blood acid-base values in standardbred horses.

The administration of sodium bicarbonate (NaHCO3) or 'milk shakes' to Standardbred horses before racing is widespread. This study analysed nonrace day (CTL) and prerace venous acid-base values from Standardbred horses racing in Pennsylvania (PA) and New Jersey (NJ). Mean +/- s.d. CTL bicarbonate (HCO3) and base excess (BE) values, for a group of horses stabled during the 1993 racing season at Pocono Downs, Pennsylvania, were 28.6 +/- 1.9 and 2.6 +/- 1.7 mmol/l, respectively. In the same population of horses, mean +/- s.d. values for prerace HCO3- and BE values were 33.1 +/- 2.8 and 7.0 +/- 2.3 mmol/l, respectively, for horses administered frusemide (F) 4 h before race time and 31.5 +/- 2.4 and 5.5 +/- 2.0 mmol/l for the horses not administered frusemide (NF). There were differences (P < 0.05) in pHv, PvCO2, HCO3- and BE values between the CTL and prerace samples. The venous acid-base values of the CTL horses were normally distributed. The prerace acid-base values measured during 1993 were not normally distributed, indicating changes due either to the administration of alkalising substances or other manipulations of the horses on race day. Changes in all acid-base values were observed during the subsequent 1994 racing season with further changes observed when horses were placed in a secured stable 8 h before the race. The criteria used in some racing jurisdictions for disqualifying a horse were the elevations in HCO3-, Na+ and pH. The correlation coefficients (r2) for the least squares regression for HCO3- vs. pH and HCO3- vs. Na+ in prerace venous blood samples were 0.31 and 0.21, respectively, indicating a poor relationship between the 3 acid-base values. To discourage the administration of NaHCO3 to horses before a race, the use of a BE value of > or = 10 mmol/l for NF and > or = 12 mmol/l for F was adopted as a single index for the disqualification of horses from a race. The results of this study indicate that the use of a single index and, in this case BE, has curtailed the prerace administration of NaHCO3 to horses.

Acid-Base Equilibrium↗

PubMedDate not supplied

Analysis of sampling volume and tissue heterogeneity on the in vivo detection of fluorescence.

The effect of sampling region size and tissue heterogeneity is examined using fluorescence histogram assessment in a rat prostate tumor model with benzoporphyrin derivative fluorophore. Spatial heterogeneity in the fluorescence signal occurs on both macroscopic and microscopic scales. The periphery of the tumor is more fluorescent than the center. Fluorescence is also highest nearest the blood vessels immediately after injection, but over time this fluorescence becomes uniform through the tumor tissue. Using microscopy analysis, the fluorescence intensity histogram distributions follow a normal distribution, yet as the sampling area is increased from the micron scale to the millimeter scale, the variance of the distribution decreases. The mean fluorescence intensity is accurately measured with a millimeter size scale, but this cannot provide accurate measurements of the microscopic variance of drug in tissue. Fiber probe measurements taken in vivo are used to confirm that the variance observed is smaller than would be expected with microscopic sampling, but that the average fluorescence can be measured with fibers. Sampling tissue with fibers smaller than the intercapillary spacing could provide a way to estimate the spatial variance more accurately. In summary, sampling fiber size affects the fluorescence intensities detected and use of multiple region microscopic sampling could provide better information about the distribution of values that occur.

Algorithms↗

PubMedDate not supplied

Correlation between the perceptual rating of speech in Dutch patients with velopharyngeal insufficiency and composite measures derived from mean nasalance scores.

OBJECTIVE: To evaluate the potential clinical use of composite measures derived from mean nasalance scores. PROCEDURE: Speech samples with a normal distribution of phonemes (normal text, NT) and speech samples free of nasal consonants (denasal text, DT) of 43 patients with perceived hypernasality were used. The overall grade of severity, hyperrhinophonia, audible nasal emission, misarticulations associated with velopharyngeal insufficiency and intelligibility were perceptually rated on separate visual analog scales. Mean nasalance scores were computed by the Nasometer for the same speech samples on which the perceptual ratings were performed. From the mean nasalance scores computed for the NT and DT passages the difference and the quotient were calculated. The advantage could be that the derived measures provide some normalization with regard to the performance of the individual speaker. Spearman correlation coefficients were computed between these composite measures and the perceptually rated parameters. The results were compared with the correlation coefficients between the mean nasalance scores and the ratings. SETTING: The Institute of Phoniatrics, Utrecht University Hospital, The Netherlands. RESULTS: The correlations between the composite measures and the perceptual ratings were generally lower than the correlations between mean nasalance scores and the ratings. CONCLUSION: Normalization of the nasalance scores did not enhance the correlation with the perceptual ratings in this study.

Adolescent↗

PubMedDate not supplied

A generalized estimating equations approach to quantitative trait locus detection of non-normal traits.

To date, most statistical developments in QTL detection methodology have been directed at continuous traits with an underlying normal distribution. This paper presents a method for QTL analysis of non-normal traits using a generalized linear mixed model approach. Development of this method has been motivated by a backcross experiment involving two inbred lines of mice that was conducted in order to locate a QTL for litter size. A Poisson regression form is used to model litter size, with allowances made for under- as well as over-dispersion, as suggested by the experimental data. In addition to fixed parity effects, random animal effects have also been included in the model. However, the method is not fully parametric as the model is specified only in terms of means, variances and covariances, and not as a full probability model. Consequently, a generalized estimating equations (GEE) approach is used to fit the model. For statistical inferences, permutation tests and bootstrap procedures are used. This method is illustrated with simulated as well as experimental mouse data. Overall, the method is found to be quite reliable, and with modification, can be used for QTL detection for a range of other non-normally distributed traits.

Animals↗

PubMed2004

Statistical methods in G-protein-coupled receptor research.

In this chapter we provide an introduction to statistical methods appropriate in G-protein-coupled receptor research, including examples. Topics covered include the choice of appropriate averages and measures of dispersion to summarize data sets, and the choice of tests of significance, including t-tests and one- and two-way analysis of variance (ANOVA) plus posttests for normally distributed (Gaussian) data and their nonparametric equivalents. Techniques for transforming non-normally distributed data to more Gaussian distributions are discussed. Concepts of statistical power, errors, and the use of these in determining the optimal size of experiments are considered. Statistical aspects of linear and nonlinear regression are discussed, including tests for goodness-of-fit to the chosen model and methods for comparing fitted lines and curves.

Analysis of Variance↗

PubMed2006

Quantitative trait linkage analysis using Gaussian copulas.

Mapping and identifying variants that influence quantitative traits is an important problem for genetic studies. Traditional QTL mapping relies on a variance-components (VC) approach with the key assumption that the trait values in a family follow a multivariate normal distribution. Violation of this assumption can lead to inflated type I error, reduced power, and biased parameter estimates. To accommodate nonnormally distributed data, we developed and implemented a modified VC method, which we call the "copula VC method," that directly models the nonnormal distribution using Gaussian copulas. The copula VC method allows the analysis of continuous, discrete, and censored trait data, and the standard VC method is a special case when the data are distributed as multivariate normal. Through the use of link functions, the copula VC method can easily incorporate covariates. We use computer simulations to show that the proposed method yields unbiased parameter estimates, correct type I error rates, and improved power for testing linkage with a variety of nonnormal traits as compared with the standard VC and the regression-based methods.

Analysis of Variance↗

PubMed2001

Incidence and prevalence of diabetes mellitus in the Americas.

OBJECTIVE: To present the incidence and prevalence of diabetes mellitus in the Americas as found through a thorough review of published information on the subject. METHODS: Data were obtained through a comprehensive review using the MEDLINE and BIREME bibliographical databases. In addition, government publications, conference reports, and meeting documents were identified by contacting government and nongovernmental organizations and other institutions. Incidence and prevalence rates were adjusted by age and sex, when possible, by the direct method using the world Segi population as the standard. The 95% confidence intervals were calculated using the Poisson distribution or the normal distribution. RESULTS: Diabetes mellitus represents a major public health problem in the Americas, and there is evidence that its prevalence is increasing in some countries. CONCLUSIONS: Given that most Latin American and Caribbean nations are experiencing a demographic transition, it is expected that the prevalence of diabetes will continue to increase rapidly in the near future. Despite the economic constraints faced by the countries of the Americas, there is a clear need for more efforts in the area of diabetes prevention and control.

Adolescent↗

PubMed2002

The correlation between nasalance and a differentiated perceptual rating of speech in Dutch patients with velopharyngeal insufficiency.

OBJECTIVE: The correlation between the nasalance score and the perceptual rating of several aspects of speech of speakers with velopharyngeal insufficiency (VPI) by six speech-language pathologists was evaluated. PROCEDURE: The overall grade of severity, hypernasality, audible nasal emission, misarticulations, and intelligibility were rated on visual analog scales. Speech samples with a normal distribution of phonemes (normal text [NT]) and those free of nasal consonants (denasal text [DT]) of 43 patients with VPI were used. Mean nasalance scores were computed for the speech samples, and Spearman correlation coefficients were computed between the mean nasalance score and the five parameters of the differentiated rating. SETTING: The Institute of Phoniatrics, Utrecht University Hospital, The Netherlands. RESULTS: The correlation coefficient between the mean nasalance and the perceptual rating of hypernasality ranged among judges from .31 to .56 for NT speech samples and .36 to .60 for DT speech samples. Only small differences were found between speech pathologists with and without expertise in cleft palate speech. The rating of the overall grade of severity appeared to correlate quite well with the rating of the intelligibility (r(NT) = .77, r(DT) = .79). Lower correlation coefficients, ranging from .34 to .71, were found between overall grade of severity and hypernasality, audible nasal emission, and misarticulations. CONCLUSIONS: A low correlation between the nasalance and the perceptual rating of hypernasality was found. The parameter overall grade of severity appeared to be determined mainly by the parameter intelligibility. Expertise in rating of cleft palate speech does not guarantee a high correlation between instrumental measurement and perceptual rating.

Adolescent↗

PubMed1980

The normal middle ear reflex thresholds towards white noise and acoustic clicks in young adults.

The acoustic middle ear muscle reflex thresholds towards white noise and fast sequences of clicks were determined in 46 normal-hearing young adults using electronic averaging. For white noise the thresholds were normally distributed around an average value of 72.7 dB SPL. With sequences of clicks the threshold depended above all on the click repetition rate within each stimulus sequence. When the repetition was 128/sec the threshold distribution was almost normal around an average value of 73.9 dB SPL. For the individual test subject there was good correlation between the white noise and the click reflex thresholds. It was our impression that the click generated reflexes had a more well defined threshold than with white noise stimuli, but this impression needs further validation.

Acoustic Impedance Tests↗

PubMed1993

[Bivariate normal values of optokinetic nystagmus test].

Comparisons of right and left optic stimulations with the two optokinetic pattern tests (OKP) are available for diagnosing equilibrium disorders. Also available are numerical data of OKP, which are calculated by an OKP--analyzing computer to assist the thinking of clinicians. But there is no criterion for deciding normal or abnormal two-dimensional numerical results of OKP by right and left directional optic stimulation. We established bivariate normal values and normal ranges based on the numerical data of OKP. Variables of OKP for establishing bivariate normal values and ranges were the total number of nystagmus, the cumulative slow phase amplitudes and velocities of nystagmus, and the average fast phase velocities. The reference samples were selected from 1482 numeric data of OKP regarded as normal. Normal ranges are shown as ellipses, which were drawn intuitively through the 5% critical ratio points of bivariate normal distributions, to distinguish normal from abnormal. Normal values were expressed by Mahalanobis generalized distance (MGD), which is the distance from mean values to sample values of bivariates. The normal values of each variable had a 95% confidence coefficient for calculating the MGD from the center to the margin of the ellipses. It seems that simple discrimination between normal and abnormal bivariable OKPs was obtained using our normal values and ranges calculated by Mahalanobis generalized distance.

Humans↗

PubMed1998

[Study on certified reference material of germanium in Ganoderma lucidum].

Analytical reference material of Ge in Ganoderma lucidum is designed and prepared for accurete analysis, monitoration and evaluation in trades of farming, forestry, medicine and food hygiene for Ge. It is used in technical training, technical assessing, monitoring, data arbitrating and analytic method verifing for professional supervisors. This reference material has been certified by graphitic oven atomic absorption spectrometry, hydride spectrophotometry, polarography, chemical separation spectrophotometry, atomic fluorescence method and x-ray fluorescence method. According to Grubb's law to judge the data of each group, it is confirmed that all of seven groups certified crude data are normal distribution by checking normality D. The arithmatic mean value of all data is 0.38 microgram/g. Standard deviation is 0.08 microgram/g.

Drugs, Chinese Herbal↗

PubMed2000

Conventional gas ventilation, liquid-assisted high-frequency oscillatory ventilation, and tidal liquid ventilation in surfactant-treated preterm lambs.

This study was designed to compare the efficacy and potential protective or injurious effects of tidal liquid ventilation (TLV), liquid-assisted high-frequency oscillatory ventilation (LA-HFOV), and high PEEP conventional mechanical ventilation (CMV) in neonatal respiratory distress syndrome. Preterm lambs (124-126 days gestation), prophylactically treated with natural surfactant, were allocated to one of the treatment modalities or to an untreated fetal control group (F), euthanised after tracheal ligation. LA-HFOV animals received an intratracheal loading dose of 5 mL x kg(-1) followed by a continuous intrapulmonary instillation of 12 mL x kg(-1);h(-1) FC-75 perfluorocarbon liquid. The ventilation strategies aimed at keeping clinically appropriate arterial blood gases for a study period of 5 hours. A histological lung injury score was calculated and semiquantitative morphometry was performed on lung tissue fixed by vascular perfusion. The alveolar-arterial pressure difference for O2 was significantly lower throughout the study in TLV compared to CMV lambs; at 1, 2, and 5 hours, oxygenation was better in TLV when compared to LA-HFOV. Total lung injury scores in TLV lambs were significantly lower than in either CMV or LA-HFOV animals, but higher when compared to F. CMV and LA-HFOV induced an excess of collapsed and overdistended alveoli, whereas in TLV alveolar expansion was normally distributed around predominantly normal alveoli. CMV and LA-HFOV, but not TLV, were associated with an excess of dilated airways. Thus, in the ovine neonatal RDS model, TLV compared favourably to either gas ventilation strategy by its more uniform ventilation, reduced lung injury, and improved gas exchange.

Analysis of Variance↗

PubMed2002

Angular regression and the detection of the seasonal onset of disease.

BACKGROUND: In examining the seasonality of onset of a disease over the year, investigators attempt to identify the peak of onset, and its magnitude. A second objective is to see if the day in which the disease manifests itself is related to subject-specific characteristics or environmental factors. METHOD: This paper describes appropriate statistical methodology for the situation where seasonality can be summarised by either a single peak or several peaks, possibly determined by patient characteristics or external influences. The circular, rather than linear, nature of the day of onset of a disease (irrespective of year) requires angular regression techniques to assess these relations, and the von Mises distribution replaces the normal distribution in this context. RESULTS: The methods outlined are illustrated by a national study of those experiencing an attack of acute primary angle-closure glaucoma in Singapore. CONCLUSIONS: We recommend re-analyses of already published work on seasonality of disease using this angular methodology. We anticipate that this may provide both useful further insight into aspects of aetiology and case studies for the methods themselves.

Acute Disease↗