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PubMed1978

Effect of overall phenotypic selection on genetic change at individual loci.

The selective advantage of an allele Gi (relative to the mean of alleles at this locus) is given by (formula: see text) in which Ai is the average excess of the allele on the character, X; W(X) is the fitness function; F(X) is the frequency function; W is the mean fitness; and the prime denotes differentiation. With truncation selection si = AaF(C)/w in which F(C) is the ordinate at the culling level and w is the proportion saved; this does not depend on any assumption about the distribution of F(X). If the character is normally distributed, si = AiI/sigma2, in which I is the selection differential and sigma2 is the variance of the character distribution. Finally, if the logarithm of the fitness is proportional to the squared deviation from the optimum and the character is distributed normally, si = AiK(Xop--m), in which Xop is the optimum value of the character, m is the mean value, and K is a constant determined by the variances of the fitness function and the frequency function. Truncation is the most efficient form of directional selection in the sense of producing the maximum gene frequency change for a given effect of the gene on the character, but fitness functions can depart considerably from sharp truncation without greatly reducing the efficiency.

Gene Frequency↗

PubMed1994

Parametric analysis of rank transformed data for statistical assessment of genotoxicity data with examples from cultured mammalian cells.

The utility of rank transformation followed by parametric analysis of the ranks has been assessed for determination of the statistical significance of genotoxicity data. Both nonparametric and parametric analytical methods have defects when used to assess the significance of results from routine regulatory tests. Superficially, the rank transformation method followed by parametric analysis of ranks appears to be an ideal solution. However, we considered that such a test might suffer a substantial loss of power when used to analyse normally distributed data with very low sample replication. To test this hypothesis we took 22 data sets from five 'borderline' positive compounds in mouse lymphoma treat-and-plate assays where treatment-related increases were between 1.5- and 3-fold the control and analysed these results by Dunnett's t-test using rank transformed data and weighted, untransformed data. In theory these mouse lymphoma data should show the rank transformation system at its worst in comparison with parametric methodology using weighted data. Surprisingly, the rank transformation methodology showed no loss of power and, overall, performed more consistently than the weighted data methodology. Based on this limited number of data sets, rank transformation followed by parametric analysis of ranks seems to be an approach very suitable for genotoxicity assays in general, particularly where distributions are non-normal or of uncertain form. It combines the general applicability of non-parametric methods with the power of parametric analyses. However, the methodology still requires to be further validated in use and by computer simulation.

Animals↗

PubMedDate not supplied

Determining critical flow conditions for chloride impairment in an effluent-dominated, storm-peaking, Western U.S. stream.

Extensive agricultural land use and intensive urban residential growth of the Calleguas Creek, California, watershed has increased chloride load and impaired beneficial uses. The hydrology of the watershed is typical of the semiarid U.S. West in that nearly all rainfall occurs in a small number of discrete storm events that each produces peak discharges of a duration of several days or less; conversely, during the dry weather season, discharge has historically been near zero. Currently, a year-round flow is sustained by two factors: base line flow sustained by discharges from publicly owned treatment works (POTWs) and increased groundwater discharge from a shallow water table elevated by intensive agricultural irrigation (deep groundwater basins used for water supply have declined into overdraft). Water quality impairment of Calleguas Creek increases during low-flow days, but cannot be defined seasonally because days not influenced by storm discharge occur at substantial proportions during all months. Impairment is greatest not during lowest flows, which are dominated by POTW effluent, but when groundwater and other nonpoint sources are highest, thereby contributing chloride load disproportionately to their flow. The highest nonstorm days are identified through cumulative frequency of mean daily discharge (MDD) as the transition from nonstorm conditions (described by normal distribution) to storm conditions (described by log-normal distribution). Transition occurs at approximately the 80th to 85th percentile MDD at three Calleguas Creek locations. Critical conditions for chloride impairment are defined as volumetric flow at those percentiles of cumulative MDD distribution.

Agriculture↗

PubMed2002

[Research approaches in the behavioral genetics of psychiatric disorders].

Multi-factorial inheritance combines genetic and environmental effects. Each factor contributes a relatively small part to the overall phenotype. Multi-factorial multi-genetic illnesses are usually divided into two categories: 1. Continuous variation of the normal distribution--phenotypes that can be measured within the normal scale (i.e. blood pressure). A normal distribution is obtained and the mean is in the middle. 2. Multi-factorial threshold trait--a threshold separates between the existence or absence of the phenotype. The curve of distribution obtained only predicts sensitivity for the illness rather than it's existence, since the illness appears only beyond a specific threshold, which represents a specific combination of defected genes. Mental illnesses (psychoses, affective disorders and neuroses) are multi-factorial illnesses, affected at a level of approximately 50% by inheritance. These diseases are not inherited in a simple Mendelian way, and, most probably, many genes are involved. Today, there is still no biochemical or molecular marker for any of the mental illnesses, and diagnosis of patients is obtained according to behavioral accepted scales. The aim of behavioral genetics is to understand the interaction between genes and behavioral variability among individuals. Most behaviors are complex, and when a genetic influence is observed, we can not point at a single responsible gene. Behavioral genetics targets to identify multiple genes and to understand the contribution of each of them to a specific behavioral trait. Methods to study multi-gene diseases include linkage analysis, family studies, twin and adoption studies, search for candidate genes affected by drug therapy of the patients, analysis of candidate genes using knockout mice and SNP's, methods that identify the effect of specific genes on behavior by QTL, and gene expression using DNA differential display and DNA microarray chips. The present review summarizes and exemplifies these issues.

Genetics, Behavioral↗

PubMed1992

Interindividual variability in the concentrations of albumin and alpha-1-acid glycoprotein in patients with renal or liver disease, newborns and healthy subjects: implications for binding of drugs.

The concentrations of human plasma albumin (HPA) and alpha-1-acid glycoprotein (AAG) were measured in the serum obtained from 84 healthy subjects, 56 umbilical cords, 41 patients with renal failure, 65 patients maintained on chronic hemodialysis and 46 patients with liver cirrhosis. Severity of liver dysfunction was assessed with the use of Pugh et al. [1973] classification. Of the cirrhotic patients, 12, 22 and 12 patients were classified as mild, moderate and severe liver dysfunction, respectively. The coefficient of variation of AAG was greater than HPA in all groups of subjects, and the variability of HPA and AAG is increased in patients compared to healthy subjects. As the liver dysfunction progresses, HPA concentration decreases whereas, the average AAG concentration is not changed in mild, moderate and severe liver dysfunction. The coefficients of variation for HPA and AAG in moderate and severe liver disease is over twice those for healthy subjects. The concentration of HPA is normally distributed in all groups of subjects, with the exception of the cord serum. The frequency distribution of AAG was normal in healthy subjects whereas, it was asymmetric, being positively skewed, in newborn, in renal and liver patients. The wide interindividual variability and the not-normal frequency distribution of AAG in liver or renal patients make its mean of little value in defining a group. Neither HPA nor AAG correlated with the clearance of creatinine in renal patients. In liver disease, HPA and AAG did not correlate with GPT and GOT activities, prothrombinic activity and bilirubin concentration. HPA did not correlate with AAG in any group.

Adolescent↗

PubMed1979

The correlation between relatives under assortative malting for an X-linked and autosomal trait.

Correlations between various relatives are derived for phenotypic assortative mating at equilibrium for a trait determined by additive autosomal and X-linked loci without dominance, with proportional gene effects in the two sexes, and with an uncorrelated environment. It is assumed that genotype and environment are normally distributed, that phenotypes of mates are bivariate-normally distributed, and that regression of an individual's phenotype or genotype on the phenotype or genotype of any of his relatives is linear.

Alleles↗

PubMed1999

Distribution of normal saline and 5% albumin infusions in septic patients.

OBJECTIVE: To determine the relative distribution of fluid within the extracellular fluid volume (ECFV) after infusing either normal saline or 5% albumin in septic, critically ill patients. DESIGN: Prospective, randomized, unblinded, interventional study. SETTING: Intensive care unit in a 450-bed, tertiary care, teaching hospital. PATIENTS: Septic, critically ill patients (n = 18). INTERVENTIONS: Infusion of either normal saline or 5% albumin to a hemodynamic end point determined by the patient's clinician. MEASUREMENTS AND MAIN RESULTS: Plasma volume (PV), ECFV, cardiac index, and arterial oxygen content were measured immediately before (baseline) and after each fluid infusion. PV and ECFV were measured by dilution of 131I-albumin and 35S sodium sulfate, respectively. Interstitial fluid volume (ISFV) was calculated as ECFV - PV. Baseline values for PV, ISFV, ECFV, and oxygen delivery index did not differ between treatment groups. Infusion of normal saline increased the ECFV by approximately the volume infused, and the expansion of the PV to ISFV was in a ratio of 1:3. Infusion of 5% albumin increased the ECFV by double the volume infused, with both the PV and ISFV expanding by approximately equal amounts. Oxygen delivery index did not increase after either infusion due to the effect of hemodilution. CONCLUSION: Expansion of the ECFV in excess of the volume of 5% albumin infused suggests that fluid may move from the intracellular fluid volume to the ECFV in septic patients who receive this fluid.

APACHE↗

PubMed1987

Extrapolation of thermodilution curves obtained during a pause in artificial ventilation.

The feasibility of three mathematical models to extrapolate the tail of thermodilution curves, when flectures are present in the descending limb, was tested in anesthetized pigs. The models were a local random walk model (LDRW), a log-normal distribution, and a two-compartment model. First, the accuracy of the extrapolation of the tail by each model was tested on two undisturbed curves by taking the truncation at five different points on the descending limb. The extrapolated curve area obtained from each model was compared with total area of the undisturbed curve. Next, dilution curves obtained during inspiratory hold maneuvers and characterized by deflection points were analyzed, taking the truncation just before deflection. The estimates of cardiac output by the models were compared with electromagnetically measured flow in the pulmonary artery. The area of the dilution curve was estimated more accurately when more information on the descending limb was available. The LDRW model and the log-normal distribution were superior to the two-compartment model regarding accuracy of cardiac output estimation and root-mean-square errors of the fit. Both models estimated curve area with an error less than 5% when truncation of the descending limb occurred below 60% of the peak value. In circumstances of mechanical ventilation, where only short periods of constant flow will be present, analyses of dilution curves based on the LDRW model or the log-normal distribution are recommended.

Animals↗

PubMed2000

Small valve area index: its influence on early mortality after mitral valve replacement.

OBJECTIVE: To test the hypothesis that mitral valve prosthesis-patient mismatch increases postoperative mortality. METHODS AND RESULTS: The effect of mitral valve prosthesis-patient mismatch on survival in a cohort of consecutive patients after mitral valve replacement with a mechanical prosthesis was measured, focusing on the lower tail of the normal distribution curve of the prosthetic valve area index. For the calculation of the geometric valve area index (cm(2)/m(2) body surface area), we used specifications for the geometric valve area supplied by the manufacturer. The cut-off value of the 10th percentile of the valve area index was 1.919 cm(2)/m(2). The study population consisted of 428 adult patients who underwent mitral valve replacement by a Medtronic Hall (n=270, 63%) or a St. Jude Medical prosthesis (n=158, 37%). The size of the valves implanted ranged from 25 mm to 31 mm. The valve area index showed a normal distribution curve ranging from 1.43 to 2.98 cm(2)/m(2) with a mean of 2.2 cm(2)/m(2). Group 1 (n=33) had a valve area index <1.9 cm(2)/m(2) and group 2 (n=395), > or =1.9 cm(2)/m(2). The 30-day mortality was higher in group 1 than in group 2 (18.2 vs. 4.1%, P=0.005). Multivariate logistic regression analysis of the determinants of the 30-day mortality rendered a small valve area index (<1.9 cm(2)/m(2)) as an independent risk indicator: relative risk 4.3 (95% CI 1.6-9.5; P=0. 0043). The difference in overall survival between the two groups was entirely due to the high 30-day mortality in the patients with small valve area indices, congestive heart failure being the main cause of death. CONCLUSIONS: By concentrating on the extreme lower tail of the normal distribution of the valve area index, a strong and independent relation was found between relatively small valves (valve area index <1.9 cm(2)/m(2)) and 30-day mortality. We found no influence of valve size on late mortality beyond the first 30 days.

Adult↗

PubMed2005

Analysis of Z-score distribution for the quality control of fetal ultrasound measurements at 20-24 weeks.

OBJECTIVES: To develop and evaluate the feasibility of Z-score distribution-based quality assessment for fetal biometry at 20-24 gestational weeks. METHODS: Four sonographers measured fetal biparietal diameter, head circumference, abdominal circumference and femur length in unselected pregnancies undergoing routine sonography at 20-24 weeks in our center between June 2001 and January 2004. All measurements were transformed into Z-scores. Distributions of Z-scores were compared with the expected standard normal distribution based on mean, SD and the Kolmogorov-Smirnov test. Modelling was performed to assess the sensitivity, specificity and Youden's index (sensitivity + specificity - 1) of each sonographer, reflecting their ability to detect fetuses with abnormal biometry in our population. RESULTS: A total of 5241 ultrasound examinations were included. None of the Z-score distributions could be considered similar to the standard normal distribution: means of Z-scores ranged from -0.604 to 0.73 and the SD ranged from 0.726 to 0.896. Sensitivity and specificity ranged from 25.31% to 68.67% and 93.44% to 100%, respectively; Youden's index ranged from 0.25 to 0.69. CONCLUSION: Analysis of Z-score distribution can be used to assess the quality of fetal measurements. Several indices can be extracted from this analysis in order to improve quality assessment of fetal biometry measured by ultrasound.

Abdomen↗

PubMed2002

Potential scans and potential energy distributions of normal vibrational modes of trichloroacetyl isocyanate.

The conformational stability and vibrational infrared and Raman spectra of trichloroacetyl isocyanate (CCl3CONCO) were investigated by ab initio MP2 and density functional B3LYP calculations using the 6-311++G** basis set. From the potential energy scans of the internal rotations in both the halomethyl and the isocyanate rotors, the molecule was predicted to exist predominantly in the cis-cis conformation. The steric hindrance between the halomethyl group and the nitrogen lone-pair was found to favor the staggered configuration for the chlorine atom, while conjugation effects favor the planar configuration for the C=O and the NCO groups. Vibrational wavenumbers were computed for the molecule at the DFT-B3LYP/6-311++G** level. Normal coordinate calculations were carried out to obtain the potential energy distributions (PED) among the symmetry coordinates of the normal modes for the molecule. The theoretical vibrational assignments were compared with experimental ones and ratios of observed to calculated wavenumbers of about 0.97-1.04 were obtained.

Isocyanates↗

PubMed1992

Fractal properties in fetal breathing dynamics.

The dynamic pattern of fetal breathing was studied in 17 fetal lambs with chronically implanted electromyographic electrodes in the diaphragm. The instantaneous breathing rate time series appeared similar on different time scales, with clusters of faster breathing rates interspersed with periods of relative quiescience, suggesting self-similarity. Distribution histograms of the interbreath intervals (IBIs) showed log-normal distribution for IBIs less than 1 s and inverse power-law distribution for IBIs greater than 1 s. The ratio of log-normal distribution to power-law distribution varied from approximately 2 at 102 days to approximately 30 by 130 days of gestation. Fast Fourier transform of the breathing rate time series revealed 1/f beta power spectra for all animals, with beta increasing linearly from 0.43 to 0.88 between 102 and 139 days. Studies in the newborn lamb showed further maturation in both the distribution characteristics of the IBIs, as well as in the 1/f power spectra, with beta approaching 1.0 at 2 days after birth. The inverse power-law relationship in the distribution of the IBIs, together with the 1/f beta power spectra, indicate scale invariance and suggest that fractal mechanisms are involved in the regulation of fetal breathing.

Animals↗

PubMed2005

Spatial fiber type distribution in normal human muscle Histochemical and tensiomyographical evaluation.

The variability of fiber type distribution in nine limb muscles was examined with histochemical and tensiomyographical (TMG) methods in two groups of 15 men aged between 17 and 40 years. The aim of this study was to determine the extent to which the relative occurrence of different fiber types and subtypes varies within human limb muscles in function to depth and to predict fiber type proportions with a non-invasive TMG method. The distribution of different fiber types varied within the muscles, as a function of depth, with a predominance of type 2b fibers at the surface and type 1 fibers in deeper regions of the muscle. For all the analyzed muscles the contraction times measured at stimulus intensity 10% of supramaximal stimulus (10% MS) were significantly (p<0.05) shorter than the contraction times measured at 50% of supramaximal stimulus intensity (50% MS). The Pearson's correlation coefficient between percentage of type 1 muscle fibers measured at the surface of the muscle and contraction time at 10% MS, obtained by TMG was statistically significant (r=0.76,P<0.01). Also the Pearson's correlation coefficient between percentage of type 1 muscle fibers measured in the deep region of the muscle and contraction time at 50% MS obtained by TMG was also statistically significant (r=0.90,P<0.001). These findings suggest that the contraction time obtained by TMG may be useful for non-invasive examining of muscle fiber types spatial distribution in humans.

Adolescent↗

PubMedDate not supplied

Nerve conduction velocity distribution in normal subjects and in diabetic patients without clinical neuropathy. I. Motor nerve.

A computer-assisted collision method to evaluate motor conduction velocity distribution of the ulnar and external peroneal nerves in normal subjects and in insulin-dependent and non-insulin-dependent diabetics without clinical signs of neuropathy is described. Distribution curves were sigmoidally (bimodally) shaped in normal and in insulin- and non-insulin-dependent subjects. In insulin-dependent patients, motor conduction velocity of the peroneal nerves was globally impaired, whereas of the ulnar nerves it was normal. In non-insulin-dependent patients, slower conduction velocity was involved in both nerves.

Action Potentials↗

PubMed1998

Electrophysiological and morphological heterogeneity of neurons in slices of rat suprachiasmatic nucleus.

1. Whole cell patch clamp recordings of neurons in slices of the suprachiasmatic nucleus (SCN) were made in order to assess their electrophysiological and morphological heterogeneity. This assessment was accomplished by (i) quantification of intrinsic membrane properties recorded in current clamp mode, (ii) studying frequency distributions of these properties, (iii) grouping of cells based on visual inspection of data records, and (iv) use of cluster analysis methods. 2. Marked heterogeneity was found in the resting membrane potential, input resistance, time constant, rate of frequency adaptation, size of rebound depolarization (low-threshold Ca2+ potential) and regularity of firing. The frequency distribution of these membrane properties deviated significantly from a normal distribution. Other parameters, including spike amplitude and width, amplitude and rising slope of the spike after-hyperpolarization (AHP) and amplitude of the spike train AHP, showed considerable variability as well but generally obeyed a normal distribution. 3. Visual inspection of the data led to partitioning of cells into three clusters, viz. cluster I characterized by monophasic spike AHPs and irregular firing in the frequency range from 1.5 to 5.0 Hz; cluster II with biphasic spike AHPs and regular firing in the same range; and cluster III with large rebound depolarizations and biphasic spike AHPs. In a post hoc analysis, these clusters also appeared to differ in other membrane properties. This grouping was confirmed by hierarchical tree clustering and multidimensional scaling. 4. The light microscopic properties of recorded neurons were studied by biocytin labelling. Neurons had monopolar, bipolar or multipolar branching patterns and were often varicose. Axons sometimes originated from distal dendritic segments and usually branched into multiple collaterals. Many cells with extra-SCN projections also possessed intranuclear axon collaterals. We found no morphological differences between clusters except that cluster III neurons possessed more axon collaterals than cluster I or II cells. 5. These results suggest that SCN neurons are heterogeneous in some basic as well as active membrane properties and can be partitioned into at least three clusters. Cluster I and II cells fire spontaneously in a regular and irregular mode, respectively, and sustain prolonged spike trains. In contrast, cluster III cells have low firing rates but may adopt a burst-like firing mode when receiving appropriate input. While all clusters transmit output to target cells within and outside SCN, cluster III cells in particular are suggested to affect excitability of large numbers of SCN neurons by their extensive local network of axon collaterals.

Animals↗

PubMed2006

Distribution characteristics, reproducibility, and precision of region of interest-based hippocampal diffusion tensor imaging measures.

BACKGROUND AND PURPOSE: For adequate interpretation of diffusion tensor imaging (DTI) parameters empirical distribution characteristics, precision, and reproducibility should be known. The present study investigated distribution and reliability parameters of hippocampal fractional anisotropy (FA) and mean diffusivity (MD). METHODS: FA and MD values were averaged in hippocampal regions of interest in 20 subjects (10 women and 10 men; age range, 25-69 years). Regions of interest were manually placed bilaterally by one investigator at 2 occasions, and by a second independent investigator. Sample distributions of FA and MD values were compared with normal distributions. Intraclass coefficients (ICCs), standard errors of measurement (SEMs), and coefficients of variation (CVs) with confidence intervals (CI95s) were computed. RESULTS: The results did not show any deviation of averaged FA (0.237 +/- 0.017) and MD (775 +/- 28 microm2/s) values from normal distribution. Intraobserver reliability (ICC > or = 0.90) and precision (CV < or = 3.5%) were high for all measures. Interobserver reliability reached values of ICC > or = 0.84 and CV < or = 4.1%. FA yielded lower precision (CV 2.2-4.1%) than MD (CV 1.3-2.5%), CI95s were around +/-0.015-0.020 and +/-25-30 microm2/s for FA and MD, respectively. FA differences of 0.020-0.030 and MD differences of 40-50 microm2/s can be assumed to reflect reliably distinct values in hippocampal regions. CONCLUSION: The results are in line with previous reports on reliability of DTI measures by using different designs and methodology. Notwithstanding the difficulties associated with region of interest-derived DTI measurements in hippocampal regions, the present approach provides estimates of distribution characteristics and precision applicable to routine assessments of DTI parameters in clinical and research context.

Adult↗

PubMed1982

Higher incidence of small Y chromosome in humans with trisomy 21 (Down syndrome).

The length of the Y chromosome was measured in 42 black patients with trisomy 21 (47,XY,+21) and a similar number of normal individuals of American black ancestry. The length of the Y was expressed as a function of Y/F ratio and arbitrarily classified into five groups using subjectively defined criteria as follows: very small, small, average, large, and very large. Thirty-eight % of the trisomy 21 patients had small or very small Ys compared to 2.38% of the controls (P less than 0.01). In both populations the size of the Y was not normally distributed. In the normals it was skewed to the left, whereas in the Downs the distribution was flat (platykurtic). A significantly higher incidence of Y length heteromorphisms was noted in the Down as compared to the normal black population. In the light of our current understanding that about one-third of all trisomy 21 patients are due to paternal nondisjunction, it may be tempting to speculate that males with small Y are at an increased risk for nondisjunction of the 21 chromosome.

Adolescent↗

PubMed1995

Dual X-ray absorptiometry of the proximal femur: normal European values standardized with the European Spine Phantom.

Measurements of the proximal femur by dual X-ray absorptiometry (DXA) are assuming increasing importance in clinical and epidemiological studies. However, different DXA manufacturers have adopted varying approaches to measuring the femoral neck and trochanter regions with the result that there is as yet no agreement on normal ranges and how to cross-calibrate between different machines. In this Concerted Action (of the EU's 2nd Framework Programme), 12 clinical centers in eight countries recruited a total of 855 female and 517 male Caucasian subjects who were judged to be free of conditions known to cause secondary osteoporosis and who had not been treated with drugs known to affect bone mass. The DXA machines used were made by Hologic, Lunar, and Norland. Each machine was cross-calibrated with the European Spine Phantom prototype designed by Kalender. All femoral neck and trochanter results were expressed as standardized values and were first examined for possible bias due to between-brand differences in choice of areas for measurement. On average, trochanter areas were similar between brands but Norland chose a narrower neck region for analysis. Bone mineral density (BMA or BMD g/cm2) was log-normally distributed for all groups at the femoral neck but normally distributed at the trochanter in men and postmenopausal women. There were substantial between-center differences after cross-calibration in age-adjusted mean values at both sites and also in the rates of apparent bone loss with age and the amounts of scatter within populations about mean age-adjusted values. With the proviso that locally derived normal ranges would allow more accurate comparisons for clinical purposes, European normal ranges were derived for both neck and trochanter. Data obtained with the three individual brands of machine fitted these overall ranges well. Bone loss was apparent in premenopausal women at the femoral neck but not the trochanter. Postmenopausal women's data was somewhat better fitted by reference to years since menopause than to chronological age. This work provides a basis for conducting future epidemiological and clinical studies with more than one brand of machine as long as each individual subject, if measured consecutively, is measured on the same machine throughout.

Absorptiometry, Photon↗