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PubMed1981

Steiger on refraction: a reappraisal.

Seventy years ago Steiger, a Swiss ophthalmologist, found the distribution of corneal powers to follow a normal (binomial) curve. He noted a wide range of values among emmetropes, and he also knew that their axial lengths varied significantly. He expected that normal distributions would be found for other components of refraction and also for refraction as a whole, and in seeking a controlling mechanism he recalled the multifactorial pattern of inheritance of such characteristics as stature. The present study employs modern mathematical techniques to test the validity of 2 related hypotheses: that the components of refraction are correlated and that a polygenic mode of inheritance is responsible for determining the refractive power of the eye. In the light of this study and of other modern knowledge about refraction Steiger's work is reassessed. Most of his views are vindicated, although his assumption of a normal distribution for refraction as a whole could not be justified. His contribution to the understanding of refraction establishes him among the great names in ophthalmology.

Adult↗

PubMed1981

Radioimmunoassay of SP1 (pregnancy-specific beta1-glycoprotein) in maternal blood and in amniotic fluid normal and pathologic pregnancies.

Sp1, the pregnancy-specific beta 1-glycoprotein, was studied in normal and pathologic pregnancies. We developed a highly specific and sensitive double-antibody-radioimmunoassay by radioiodination of purified placental SP1. This RIA allowed the estimation of SP1 concentrations as low as 2 ng/ml. In a collective of 227 women with normal pregnancies we established the normal distribution curve in maternal plasma from the fifth week of gestation to term. The median value rose steadily from 3 microgram/ml in the 8th week to 140 microgram/ml in the 36th week when a plateau was formed. In more than 400 patients with pregnancies complicated by a variety of pathologic disorders the SP1 levels were controlled by either single assays or serial estimations throughout pregnancy and were compared with the normal distribution range. SP1 was also determined in about 200 samples of amniotic fluid gained by amniocentesis and during parturition of normal pregnant women from the 13th gestational week until term. The normal range was established up to the 20th w.o.p. The concentrations rose from below 0.2 microgram/ml in early pregnancy to 3 microgram/ml and generally amounted to approximately 1% of the respective serum value. Pathologic cases with diverse chromosomal anomalies, Rh-incompatibility, anencephaly, hydramnios and other abnormal conditions were examined. From these only twin-pregnancies with slightly elevated levels and cases with fetal trisomies with reduced SP1 concentrations showed aberrations from the normal distribution. The estimation of serum concentrations in mothers with diabetes or Rh-incompatibility were not significantly different from the normal collective. In diabetes a characteristic course of the follow-up curves was observed. Abortion in early pregnancy was frequently but not always indicated by reduced SP1 values. Threatened abortion with subsequent continuation of pregnancy exhibited SP1 values scattered within the normal range. Since the radioimmunological determination of SP1 is possible in the early stage of gestation (from week 8) it may serve as a useful tool for prediction at times when the determination of placental lactogen is not yet possible. In pregnancies with "small-for-date babies" the correlation between SP1 in maternal plasma and fetal growth retardation was reflected in a pronounced tendency to low SP1 levels. Serial determinations of SP1 in the serum of women with EPH-gestosis were compared with the corresponding HPL determinations and showed the equality of SP1 concerning the assessment of the placental function.

Amniocentesis↗

PubMed1985

Segregation and linkage analysis of alpha-N-acetyl-D-glucosaminidase (NAG) levels in a black family.

Alpha-N-acetyl-D-glucosaminidase (NAG) activities were evaluated on serum samples from 67 persons in a large black family. These data were analyzed in conjunction with those from 126 previously tested unrelated blacks [Vance et al, 1980]. After loge transformation, admixture analysis indicated a significantly better fit (P less than .01) of a mixture of 2 normal distributions for NAG activity versus a single normal distribution. Segregation analysis using the transmission probability model of Elston and Stewart [1971] demonstrated that a genetic model fits the data better than the random "environmental" model. Thus, the existence of a major gene is suggested in the family, although the possibility of polygenic or other familial effects cannot be ruled out. These results confirm the existence of a polymorphism for NAG reported earlier in a series of White half-sib twin families [Vance et al, 1980]. However, the estimates of the means of the three genotypes (AA, AA', A'A') appear to differ in the two racial groups. Thus, the data suggest either a racial polygenic effect and/or different alleles segregating in the two populations. In fact, thermal stability data [Vance et al, 1981a] suggest that at least two alleles are structurally distinct. Linkage analysis of the pedigree with 20 marker loci gave no clear indication of linkage. A lod score of 1.44 was found at 0 recombination with orosomucoid (ORM).

Acetylglucosaminidase↗

PubMed2007

A cross-sectional study evaluating the relationship between cortisol suppression and asthma control in patients with difficult asthma.

AIM: To examine the relationship between cortisol suppression and asthma symptoms in patients with difficult asthma. METHODS: Patients, referred to a specialist difficult asthma service and who fulfilled the criteria for difficult asthma, were recruited to the study in a sequential, unselected manner. At each clinic visit, all patients completed a validated asthma control questionnaire. For measuring cortisol suppression, early morning urinary cortisol [corrected for creatinine to give urinary cortisol creatinine ratio (UCC ratio)] was used. The urine samples were collected and stored at -70 degrees C until ready for analysis. Urinary cortisol was extracted (solid-phase extraction) and analysed using high-performance liquid chromatography. The Pearson correlation coefficient was used for correlation analysis while t-tests were used for between-group differences for normally distributed data. If the data were not normally distributed, nonparametric statistics were used. A P-value < 0.05 was considered statistically significant. RESULTS: During the study period all the patients who attended the difficult asthma clinic and fulfilled the criteria for difficult asthma (n = 66) agreed to take part in the study. There were moderate to strong and significant associations between several measures of asthma control and UCC ratio. The correlation coefficient with five indicators of asthma control ranged between 0.3 and 0.5 (P < 0.05). CONCLUSIONS: We have demonstrated a relationship between cortisol suppression and asthma control in difficult asthmatics on high-dose steroid therapy. We have proposed a model based on the relationship between symptom control and cortisol suppression, whereby both adherence and therapeutic adjustments could potentially be made. A properly controlled prospective clinical trial should examine the utility of this approach in clinical practice.

Adult↗

PubMed2006

Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA.

CONTEXT: A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy. OBJECTIVE: The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations. DESIGN: An adult control population with heights normally distributed (ACPNH) between -2 and +2 sd score (SDS) and a short non-GH-deficient SGA child population were selected. SETTING: Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. CONTROLS AND PATIENTS: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients. MAIN OUTCOME MEASURES: Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital. RESULTS: In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height or=-2 SDS, n = 60). CONCLUSIONS: Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth.

Adolescent↗

PubMed2002

Exact multivariate tests for brain imaging data.

In positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) data sets, the number of variables is larger than the number of observations. This fact makes application of multivariate linear model analysis difficult, except if a reduction of the data matrix dimension is performed prior to the analysis. The reduced data set, however, will in general not be normally distributed and therefore, the usual multivariate tests will not be necessarily applicable. This problem has not been adequately discussed in the literature concerning multivariate linear analysis of brain imaging data. No theoretical foundation has been given to support that the null distributions of the tests are as claimed. Our study addresses this issue by introducing a method of constructing test statistics that follow the same distributions as when the data matrix is normally distributed. The method is based on the invariance of certain tests over a large class of distributions of the data matrix. This implies that the method is very general and can be applied for different reductions of the data matrix. As an illustration we apply a test statistic constructed by the method now presented to test a multivariate hypothesis on a PET data set. The test rejects the null hypothesis of no significant differences in measured brain activity between two conditions. The effect responsible for the rejection of the hypothesis is characterized using canonical variate analysis (CVA) and compared with the result obtained by using univariate regression analysis for each voxel and statistical inference based on size of activations. The results obtained from CVA and the univariate method are similar.

Algorithms↗

PubMed1995

Quantification of tolerance to lower body negative pressure in a healthy population.

Subtolerance and presyncopal lower body negative pressure (LBNP) has been used extensively to investigate the effect of various forms of exercise training on central hypovolemic tolerance. However, there are no population data concerning LBNP tolerance, and the validity of common LBNP tolerance indices has not been investigated. LBNP tolerance data from 86 males and 33 females were analyzed. All LBNP exposures were terminated with the onset of presyncopal signs and/or symptoms. LBNP tolerance was quantified using duration of exposure (DNP), maximal negative pressure tolerated (MNP, cumulative stress index (CSI), and the LBNP tolerance index (LTI). Average (+/- SD) LBNP tolerance was 22.12 +/- 5.01 min (DNP), -77 +/- 16 mm Hg (MNP), 975 +/- 402 mm Hg.min-1 (CSI), or 222 +/- 50 mm Hg.min-1 (LTI). All cardiovascular parameters exhibited the same responses as have been documented in the literature. While DNP, MNP, and LTI were normally distributed, CSI in this population was not normally distributed. Age, weight, height, gender, and VO2peak were not associated with LBNP tolerance. Compared to this population, it appears that the subjects that have participated in previous LBNP tolerance studies have had abnormally high LBNP tolerances and that the LTI is the most valid index of LBNP tolerance. Furthermore, in this population LBNP tolerance could not be predicted from physical characteristics.

Adult↗

PubMed1995

Analysis of statistical tests to compare visual analog scale measurements among groups.

BACKGROUND: A common type of study performed by anesthesiologists determines the effect of an intervention on pain reported by groups of patients. The goal of this study was to evaluate the effectiveness of t, analysis of variance (ANOVA), Mann-Whitney, and Kruskal-Wallis tests to compare visual analog scale (VAS) measurements between two or among three groups of patients. These results may be particularly helpful during the design of studies that measure pain with a VAS. METHODS: One VAS measurement was obtained from each of 480 nulliparous women in labor who were receiving oxytocin (149), nalbuphine (159), or epidural bupivacaine (172). Multiple simulated samples were then drawn from these data. These simulated samples were used in computer simulations of clinical trials comparing VAS measurements among groups. t and ANOVA tests were performed before and after an arcsin transformation was used, to make the data closer to a normal distribution. VAS measurements were also compared after they were divided into five ranked categories. RESULTS: The statistical distributions of VAS measurements were not normal (P < 10(-7)). Arcsin transformation made the distributions closer to normal distributions. Nevertheless, no statistical test incorrectly suggested that a difference existed among groups, when there was no difference, more often than the expected rate. t or ANOVA tests had a slightly greater statistical power than the other tests to detect differences among groups. Because arcsin transformation both decreased differences among means and reduced the variance to a lesser extent, it decreased power to detect differences among groups. Statistical power to detect differences among groups was not less for a five-category VAS than for a continuous VAS. CONCLUSIONS: We conclude that t and ANOVA, without an accompanying arcsin transformation, are good tests to find differences in VAS measurements among groups.

Analgesia, Epidural↗

PubMed2001

A longitudinal study of time trends in the eruption of permanent teeth in Danish children.

The purpose was: (1) to estimate mean eruption times of permanent teeth in Danish schoolchildren for the birth cohorts from 1969 to 1982; and (2) to determine any time trends in eruption. For teeth with a low proportion of aplasia, the distribution of the eruption time was close to normal. For teeth with a higher proportion of aplasia there was a slight deviation from the normal distribution in the right-hand part of the distribution. For erupted teeth, the time to eruption was, however, again very close to the normal distribution. A small, but statistically significant, increase in mean eruption times was found for both sexes and almost all teeth. Averaged over all teeth the increase was 1.5 days per year (95% CI: 0.9--2.2) for boys and 2.6 days per year (95% CI: 2.2--2.9) for girls.

Adolescent↗

PubMed1975

[Diagnostic aspects of complex blood-protein analyses in screening].

During a screening at a testing of 5 different protein parameters (IgG, IgA, IgM, Hp, Tf) different types of distribution were found. While IgG, Hp and Tf have a normal distribution, IgG and IgM are not normally distributed in the uncleansed group. Measures of elimination of suggested sizes of influence ("liver parameters") remained without effect.

Blood Proteins↗

PubMed1994

Classification of diagnostic tests.

A method is described for classifying diagnostic tests. It is valid for the large subgroup of tests for which the measured diagnostic variable has a normal distribution for the affected and non-affected individuals. It is based on placing each diagnostic test as a point on a two-dimensional graph, called a separation-asymmetry (SA) diagram, whose x-axis is the separation between the two normal distributions and whose y-axis is the logarithm of the ratio of their standard deviations. The SA diagram is partitioned into functional regions by curves of constant performance, as measured by the percent overlap between the two normal distributions. The concept of 'eccentricity' in a diagnostic test is defined, and the relationship between eccentricity and test validity is discussed. This quantity is also incorporated into SA diagrams, thus allowing a clinician to determine, by inspection, if a given diagnostic test positioned on an SA diagram is valid for clinical use. The logic engine used for calculating iso-performance curves is given, as well as the computer programs which utilize it. Possible ways of using this classification scheme are suggested.

Algorithms↗

PubMedDate not supplied

Bayesian QTL mapping using skewed Student-t distributions.

In most QTL mapping studies, phenotypes are assumed to follow normal distributions. Deviations from this assumption may lead to detection of false positive QTL. To improve the robustness of Bayesian QTL mapping methods, the normal distribution for residuals is replaced with a skewed Student-t distribution. The latter distribution is able to account for both heavy tails and skewness, and both components are each controlled by a single parameter. The Bayesian QTL mapping method using a skewed Student-t distribution is evaluated with simulated data sets under five different scenarios of residual error distributions and QTL effects.

Algorithms↗

PubMed2002

Birthweight centiles in preterm infants. A new approach.

BACKGROUND: To analyze the birth weight of preterm infants developing a new methodology in order to efficiently collect data. METHODS: We have analyzed the birthweight of 2,482 preterm babies with a gestational age between 24 and 36 weeks admitted to a Neonatal Intensive Care Unit from 1991 to 1998. The gestational age was determined from obstetric data. No selections were performed at the earlier stages of the study by excluding newborns with congenital defects, sepsis, intrauterine growth retardation or obstetric pathologies. More selective criteria were applied at the final stage by using statistical tests. The anomalous and extreme weights for every gestational age were identified with Box and Whisker graphs. The clinical records of these cases were analyzed and their characteristics described but these weights were excluded from the calculation of the percentiles. For each gestational age we evaluated if the weight distribution was assimilable to normal distribution by calculating the kurtosis, asymmetry by applying the Kolmogorov-Smirnov and Shapiro test. RESULTS: In the majority of cases we found a normal weight distribution. CONCLUSIONS: The proposed methodology seems useful in making data collection for preterm centiles calculation simpler. A study of the clinical characteristics of the SGA and LGA identified with the normal procedure or with the proposed method might be useful in validating our approach to the definition of the percentiles.

Birth Weight↗

PubMed1987

Non-Gaussian distribution of differences between duplicate probing depth measurements.

The present study aims to determine the accuracy and the distribution of the error of probing depth measurements. Duplicate measurements were performed at 1069 sites in 13 subjects. Measurements in shallow pockets (less than or equal to 3 mm) were significantly (p less than 0.001) more reproducible than measurements in deep pockets (greater than 3 mm). The overall standard deviation of the measurements was 0.74 mm. Differences between duplicate measurements were not normally distributed. Differences of 2 mm or more were recorded more frequently than one would expect on basis of the standard deviation and a hypothetical normal distribution. The observed frequency of large differences (greater than or equal to 3 mm) is much higher than the theoretical change as suggested in the literature that such differences may occur as a result of the inaccurate probing measurements. This finding implies consequences for the chance of making false claims that true changes in probing depth and attachment level have occurred over time, if the claims are based on the standard deviation and the wrong assumption that the error of the measurement is normally distributed.

Adult↗

PubMed1981

Blood components in a 70-year-old population.

The concentrations of many blood components change with age, and the aim of the present study was to determine, at the age of 70, the concentrations of blood components commonly used in clinical routine, and to examine how the exclusion of probands with disease influenced their distribution. In connection with a longitudinal population study "70-year-old people in Göteborg" 30 blood components have been analyzed in a representative sample of 973 70-year-old men and women. 29% of the probands were found to be without definable disease or treatment for presumed disease. Concentrations of 13 components were found to have a gaussian distribution which was not altered after the exclusion of probands with definable disease. Three components were asymmetrically distributed in the total material and showed a normal distribution with decreased concentrations at the 97.8% level after the exclusion of probands with definable disease. The remaining 14 components had asymmetrically distributed concentrations both in the total material and in the subjects without definable diseases. For blood components with normally distributed concentrations in the probands without definable disease, acceptable reference values could be obtained without exclusion of sick probands. For asymmetrically distributed blood components the concentration at the 97.8% level usually decreased more, after exclusion of probands with definable disease, the more asymmetric the distribution was. Examples of reference intervals are (men and women) B-Hb: 130--171 and 119--159 g/l, S-iron: 6--29 and 5--28 mumol/l, S-creatinine: 52--110 and 44--100 mumol/l, P-cholesterol: 3.6--9.2 and 4.6--9.7 mmol/l, P-B12: 50--350 and 65--390 pmol/l, B-ESR: 1--30 and 2--34 mm/h and B-glucose: 4.0--7.2 and 4.0--6.8 mmol/l.

Age Factors↗

PubMed1994

Application of a statistical bootstrapping technique to calculate growth rate variance for modelling psychrotrophic pathogen growth.

The inherent variability or 'variance' of growth rate measurements is critical to the development of accurate predictive models in food microbiology. A large number of measurements are typically needed to estimate variance. To make these measurements requires a significant investment of time and effort. If a single growth rate determination is based on a series of independent measurements, then a statistical bootstrapping technique can be used to simulate multiple growth rate measurements from a single set of experiments. Growth rate variances were calculated for three large datasets (Listeria monocytogenes, Listeria innocua, and Yersinia enterocolitica) from our laboratory using this technique. This analysis revealed that the population of growth rate measurements at any given condition are not normally distributed, but instead follow a distribution that is between normal and Poisson. The relationship between growth rate and temperature was modeled by response surface models using generalized linear regression. It was found that the assumed distribution (i.e. normal, Poisson, gamma or inverse normal) of the growth rates influenced the prediction of each of the models used. This research demonstrates the importance of variance and assumptions about the statistical distribution of growth rates on the results of predictive microbiological models.

Bacteria↗

PubMed2003

Relationship between detection limit and bias of accuracy of quantification of RNA by RT-PCR.

Evidence is presented demonstrating that the distribution of data obtained applying a given RT-PCR method deviates from a normal distribution depending on the limit of detection. The effect of this is a bias towards higher values and concomitantly a systematic error in respect to the accuracy of the evaluation due to this deviation from normality. In addition, evidence is presented that an evaluation assuming a log-normal distribution is more appropriate.

Data Interpretation, Statistical↗

PubMed1982

Nutritional status of dairy cows indicated by analysis of blood.

A study of 395 cows in 21 herds tested the suitability of applying the normal distribution to 23 blood variables in setting reference ranges and the potential of multiple regression equations for predicting energy and nutrient intakes, milk and fat production, and reproductive variables from blood measurements. After adjustment for herd and lactational group within herd, deviations from the normal distribution were significant for nine blood variables: glucose, cholesterol, glycerol, triglyceride, acetoacetate, urea, uric acid, creatinine, and chloride. Multiple regressions were calculated for group-averages of ration variables on group-medians of blood variables, and for production and reproductive variables on blood variables in individual cows. Coefficients of determination were .06 to .14 for milk production and reproductive variables and .55 to .79 for ration variables. Best serum predictors of ration variables were glutamic-oxaloacetic and glutamicpyruvic transaminases and cholesterol, phosphorus, triglyceride, and globulin. These results suggest that the normal distribution should not be assumed for blood variables: instead it should be tested. Multiple regressions on blood variables may be useful in predicting energy and nutrient intakes, and regression analysis may help in selection of blood measurements for inclusion in profiles.

Animal Nutritional Physiological Phenomena↗