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PubMed1993

Segregation analysis of diastolic blood pressure in a large pedigree.

Hypertension, a major risk factor for cardiovascular diseases, is thought to be inherited to some extent. However, the nature of its genetic component remains unresolved. In the present study, data from a single large kindred (the HGAR1 pedigree) were used to search for evidence of single gene and multifactorial effects on diastolic blood pressure. Commingling analyses found that a mixture of three distributions fit the data significantly better than a single normal distribution, suggesting a major effect influencing diastolic blood pressure levels. However, segregation analysis, using regressive models, indicated that the transmission probabilities were not consistent with Mendelian expectations. There was no evidence of either major gene or polygenic effects on diastolic blood pressure levels in this family.

Blood Pressure↗

PubMed1989

Data-reduction problems in biopharmaceutics and pharmacokinetics.

The importance of the use of appropriate biostatistical methods is stressed. In this article some problems and common errors in the data-reduction methods applied in biopharmaceutical and pharmacokinetic research are discussed. A commonly used representation of a set of concentration-time curves is the so-called 'mean curve', a curve through the arithmetic means of concentrations at discrete time points. If individual curves are compared with the 'mean curve' it appears that important characteristics have disappeared while other, incorrect, characteristics have been created. Unreliable conclusions may result from this procedure. Rather every single concentration-time curve should be fitted by appropriate regression methods and the resulting parameters be considered as multiple characteristics of individual pharmacokinetic behaviour. In a second data-analysis step these parameters may be clustered into more or less homogeneous subgroups, which subsequently may be represented by a representative curve. Standard errors of the mean and confidence intervals based on standard errors of the mean instead of the standard deviation are often misused as dispersion measures to characterize the sample or population distribution. Standard errors of the mean and confidence intervals measure the precision of the mean of a sample and are sensitive to the sample size. Vertical bars (in curves) representing standard deviation, standard errors of the mean or confidence intervals suggest symmetrical distributions, but this is sometimes not justified. Deviations from normality appear to occur often. A simple graphical method to indicate the dispersion of non-normal sets is presented. Methods for the determination of confidence intervals for normal and non-normal distributions are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopharmaceutics↗

PubMed1986

A microcomputer program of pulmonary and tissue gas exchange.

A microcomputer program written in BASIC for the IBM-PC and compatibles has been developed to analyze the effects of many parameters on the gas exchange and transport phenomena in the lungs and the tissues. The program is designed for use by medical students and residents concerned with gas exchange (anesthesiology, pulmonary diseases, critical care, etc.) to study the steady state effects on blood and tissue oxygen and carbon dioxide levels. The present program consists of two main subroutines: Pulmonary Gas Exchange and Tissue Gas Exchange. Steady state gas exchange at the lungs can be studied using either a three-compartment model or V/Q relationships. The V/Q subroutine uses single or multiple populations of V/Q distributions to determine gas exchange using a log-normal distribution of V/Q ratios. Other variables can be adjusted which determine the arterial and mixed-venous blood gases. These values are then fed into the second part of the program to analyze factors which determine tissue O2 tension. The Tissue Oxygen Tension subroutine is also subdivided into a modified Krogh-Erlang model, which provides a three-dimensional plot of theoretical capillary and tissue O2 tensions, and a Piiper model which includes the effect of diffusion shunt on O2 tensions and treats the tissue as a well-stirred compartment. Minimal and maximal tissue O2 tensions are calculated using the Piiper model since the intercapillary distance is allowed to vary depending on the O2 delivery by diffusion. Estimates of blood and tissue O2 tensions, diffusion/perfusion coefficients, amount of O2 delivered and the size of the active capillary bed are summarized in a table.

Computers↗

PubMed2004

The impact of the use of multiple risk indicators for fracture on case-finding strategies: a mathematical approach.

The value of bone mineral density (BMD) measurements to stratify fracture probability can be enhanced in a case-finding strategy that combines BMD measurement with independent clinical risk indicators. Putative risk indicators include age and gender, BMI or weight, prior fracture, the use of corticosteroids, and possibly others. The aim of the present study was to develop a mathematical framework to quantify the impact of using combinations of risk indicators with BMD in case finding. Fracture probability can be expressed as a risk gradient, i.e. a relative risk (RR) of fracture per standard deviation (SD) change in BMD. With the addition of other continuous or categorical risk indicators a continuous distribution of risk indicators is obtained that approaches a normal distribution. It is then possible to calculate the risk of individuals compared with the average risk in the population, stratified by age and gender. A risk indicator with a gradient of fracture risk of 2 per SD identified 36% of the population as having a higher than average fracture risk. In individuals so selected, the risk was on average 1.7 times that of the general population. Where, through the combination of several risk indicators, the gradient of risk of the test increased to 4 per SD, a smaller proportion (24%) was identified as having a higher than average risk, but the average risk in this group was 3.1 times that of the population, which is a much better performance. At higher thresholds of risk, similar phenomena were found. We conclude that, whereas the change of the proportion of the population detected to be at high risk is small, the performance of a test is improved when the RR per SD is higher, indicated by the higher average risk in those identified to be at risk. Case-finding strategies that combine clinical risk indicators with BMD have increased efficiency, while having a modest impact on the number of individuals requiring treatment. Therefore, the cost-effectiveness is enhanced.

Absorptiometry, Photon↗

PubMed1986

Plasma free amino acid values in normal children and adolescents.

We measured plasma free amino acids in 52 children (mean age 8 years) and 80 adolescents (mean age 16 years); conditions of diet and time of day were similar in the two groups. The protocols allowed us to compare their interindividual variation with values previously reported by us for adults. In children, the values for all but seven amino acids were normally distributed; in adolescents there were only six exceptions. Effects of age were apparent: values for only two amino acids were higher in children than adolescents. Values were significantly lower for ten amino acids in children v adolescents and for 11 amino acids in younger children (1 to 6 years) v older children (7 to 12 years). An effect of sex was apparent for five amino acids in adolescents; such differences were not apparent in children. All differences were quasicontinuous and occurred within the global distributions that define values for plasma amino acids in normal children and adolescents. Two artifacts (choice of anticoagulant and delay in deproteinization) affected values for taurine and cystine, respectively.

Adolescent↗

PubMed2006

Sorption of phenanthrene by soils contaminated with heavy metals.

The fate of polycyclic aromatic hydrocarbons (PAHs) in soils with co-contaminants of heavy metals has yet to be elucidated. This study examined sorption of phenanthrene as a representative of PAHs by three soils contaminated with Pb, Zn or Cu. Phenanthrene sorption was clearly higher after the addition of heavy metals. The distribution coefficient (K(d)) and the organic carbon-normalized distribution coefficient (K(oc)) for phenanthrene sorption by soils spiked with Pb, Zn or Cu (0-1000 mg kg(-1)) were approximately 24% larger than those by unspiked ones, and the higher contents of heavy metals added into soils resulted in the larger K(d) and K(oc) values. The enhanced sorption of phenanthrene in the case of heavy metal-contaminated soils could be ascribed to the decreased dissolved organic matter (DOM) in solution and increased soil organic matter (SOM) as a consequence of DOM sorption onto soil solids. Concentrations of DOM in equilibrium solution for phenanthrene sorption were lower in the case of the heavy metal-spiked than unspiked soils. However, the decreased DOM in solution contributed little to the enhanced sorption of phenanthrene in the presence of metals. On the other hand, the sorbed DOM on soil solids after the addition of heavy metals in soils was found to be much more reactive and have far stronger capacity of phenanthrene uptake than the inherent SOM. The distribution coefficients of phenanthrene between water and the sorbed DOM on soil solids (K(ph/soc)) were about 2-3 magnitude larger than K(d) between water and inherent SOM, which may be the dominant mechanism of the enhanced sorption of phenanthrene by soils with the addition of heavy metals.

Adsorption↗

PubMed2005

Mapping the results of extensive surveys: the case of atmospheric biomonitoring and terrestrial mosses.

In this paper we discuss some difficulties associated with the process of constructing maps of pollution from data obtained in surveys covering extensive areas. As we show here, these problems may be wide-ranging but are seldom recognized by investigators. The origin of the problems is the existence of multiple sources of pollution in the study area, each of different intensity and affecting areas of different extent. The particular spatial structure of the pollution sources interacts with the spatial layout of the samples, resulting in data sets with distributions that are very different from the usually assumed normal distribution, and characterized by heavy tails and gross outliers. These distributions arise because of incomplete sampling of small-scale pollution processes (i.e. those occurring on a spatial scale smaller than the spatial scale of the sampling grid). After discussion of the potential problems and appropriate techniques for analyzing this kind of data, we applied the proposed techniques to a real data set of heavy metal contents in terrestrial mosses. From the exercise we concluded that a) the first step in analysis of this kind of data must be to check for the presence of spatial structure on scales larger than the sampling grid, to avoid mapping noise, and b) the map generated must not contain information about pollution sources with a spatial scale smaller than the spatial scale of the sampling grid. We present and discuss the performance of robust statistical methods of testing for spatial structure (based on robust variograms and randomization testing) and of filtering the small-scale spatial processes (using median-polishing) prior to mapping.

Atmosphere↗

PubMed1999

Mathematical models of Neospora caninum infection in dairy cattle: transmission and options for control.

The transmission and control of Neospora caninum infection in dairy cattle was examined using deterministic and stochastic models. Parameter estimates were derived from recent studies conducted in the UK and from the published literature. Three routes of transmission were considered: maternal vertical transmission with a high probability (0.95), horizontal transmission from infected cattle within the herd, and horizontal transmission from an independent external source. Putative infection via pooled colostrum was used as an example of within-herd horizontal transmission, and the recent finding that the dog is a definitive host of N. caninum supported the inclusion of an external independent source of infection. The predicted amount of horizontal transmission required to maintain infection at levels commonly observed in field studies in the UK and elsewhere, was consistent with that observed in studies of post-natal seroconversion (0.85-9.0 per 100 cow-years). A stochastic version of the model was used to simulate the spread of infection in herds of 100 cattle, with a mean infection prevalence similar to that observed in UK studies (around 20%). The distributions of infected and uninfected cattle corresponded closely to Normal distributions, with S.D.s of 6.3 and 7.0, respectively. Control measures were considered by altering birth, death and horizontal transmission parameters. A policy of annual culling of infected cattle very rapidly reduced the prevalence of infection, and was shown to be the most effective method of control in the short term. Not breeding replacements from infected cattle was also effective in the short term, particularly in herds with a higher turnover of cattle. However, the long-term effectiveness of these measures depended on the amount and source of horizontal infection. If the level of within-herd transmission was above a critical threshold, then a combination of reducing within-herd, and blocking external sources of transmission was required to permanently eliminate infection.

Animals↗

PubMed1999

Radiotherapy of pelvic malignancies: impact of two types of rigid immobilisation devices on localisation errors.

BACKGROUND AND PURPOSE: To determine the distribution of set-up errors for patients treated with and without two rigid partial immobilisation devices for pelvic malignancies. MATERIALS AND METHODS: 30 patients receiving pelvic irradiation with a four field technique underwent a total of 524 portal films. The patients are divided into 3 cohorts of 10 patients. The first cohort is treated on a standard treatment couch without immobilisation device (NI); the second and third cohorts are treated with a custom-made immobilisation device used in an attempt to improve set-up accuracy: an Alpha-Cradle mattress (AM) or an Orfit cast (OC). Set-up deviations are analysed in the X, Y, Z directions of a fixed coordinate system, corresponding to the lateral, cranio-caudal and antero-posterior direction, respectively. RESULTS: Considering the percentage of discrepancies < or = 5 mm between the simulation films and the portal films as a measure of set-up accuracy, immobilisation devices seem to increase accuracy: 88.5% (X) 79% (Y) and 100% (Z) with AM; 84% (X-Y), 97.5% (Z) with OC and only 76.5% (X), 40% (Y) and 65.5% (Z) for NI. The distribution of the systematic set-up errors for the three patient cohorts, defined as the mean patient displacement for the treatment course, had a mean and a standard deviation of (0.7 +/- 2.7) mm in the X-axis, (-5.5 +/- 2.6) mm in the Y-axis and (-0.9 +/- 2.2) mm in the Z-axis when no immobilisation is added; (0.8 +/- 1.7) mm, (-2 +/- 2.7) mm and (0.3 +/- 0.4) mm for the Alpha-Cradle group; (0.3 +/- 1.4) mm, (0.5 +/- 1.1) mm and (0.5 +/- 0.6) mm for the Orfit cast group. The distribution of random errors about the mean approximated a normal distribution and the standard deviations are 4.4 mm (X), 4.2 mm (Y) and 4.8 mm (Z) for NI; 3.3, 3.5 and 2.5 mm for the AM; 3.4, 3.3 and 2.7 mm for the OC. CONCLUSIONS: The two rigid immobilisation devices improve the reproducibility of a given pelvic field but there is a small benefit comparative to the cost and the cumbersome place of the devices.

Female↗

PubMed1979

Estimating the duration of latency and survival time of snails with schistosomiasis.

By means of techniques of analyses of survival data developed for cancer trials it is possible to study aspects of the natural history of the infection of schistosomiasis on the intermediate host of transmission, the snail. The simultaneous study of three response variables is largely based on a model of Lagakos (1976). When using this approach in the schistosomiasis setting it seems inappropriate to assume that one process, the duration of latency, follows an exponential distribution. Thus this stage is modified to follow a normal distribution and the derivatives required to obtain maximum-likelihood estimates and approximate variances of all parameters are provided. Simple graphical tools for assessing the validity of distributional assumptions in survival data are available from industrial research. The reader's attention is drawn to a paper by Nelson (1972). The relevance and application of these methods to the current problem are described in Section 4. In the event that the times to death of prepatent and patent snails do not follow exponential distributions as assumed in the primary model, a further modification is introduced to enable either or both to follow Weibull densities. Lastly it is possible to adapt both the primary model of Section Three and the modified model of Section Five to allow for the inclusion of auxiliary variables or covariates. Again the required derivatives to obtain maximum likelihood estimates and approximate variances are provided.

Animals↗

PubMed1998

Fluorodeoxyglucose uptake in dysfunctional myocardium subtended by an occluded coronary artery. Relation to dobutamine contractile reserve and Sestamibi uptake.

BACKGROUND: Myocardial segments with impaired function may have the potential for functional recovery. Augmented exogenous glucose uptake in relation to blood flow estimated by [2-18F]2-fluorodeoxyglucose (FDG) and positron emission tomography (PET) frequently indicates functional reversibility. The spectrum of FDG uptake levels in relation to Sestamibi uptake and dobutamine contraction reserve in areas with impaired function subtended by an occluded coronary artery has never been reported. METHODS AND RESULTS: Seventeen patients with stable angina pectoris and dysfunctional myocardium subtended by an occluded coronary artery were studied with FDG-PET, low-dose dobutamine echocardiography and Sestamibi-Single Photon Emission Computerized Tomography. In a 16 segment model dysfunctional myocardial segments showed a normally distributed FDG uptake ranging from 34% to 150% when normalized to peak segmental Sestamibi uptake. Low FDG uptake was associated with both lack of dobutamine induced contractile reserve and low Sestamibi uptake (in 73% of the segments) whereas high FDG uptake displayed both contractile reserve and Sestamibi uptake (57%). Segments with intermediate FDG uptake had either contractile reserve or a preserved Sestamibi uptake (62%). CONCLUSION: Dysfunctional myocardium subtended by an occluded coronary artery represents a continuum of metabolic states with a high degree of heterogeneity with regard to contractile reserve and Sestamibi uptake.

Adult↗

PubMed1997

The AERX aerosol delivery system.

PURPOSE: We describe the AERX aerosol delivery system, a new, bolus inhalation device that is actuated at preprogrammed values of inspiratory flow rate and inhaled volume. We report on its in vitro characterization using a particular set of conditions used in pharmacokinetic and scintigraphic studies. METHODS: Multiple doses of aerosol were delivered from single use collapsible plastic containers containing liquid formulation. The aerosol was generated by forcing the formulation under pressure through an array of 2.5 micron holes. Air was drawn through the device at 70 LPM, and the aerosol was collected onto a filter or Andersen cascade impactor. The emitted dose was quantified from the filter collection data, and the particle size distribution was obtained from the best fit log-normal distribution to the impactor data. RESULTS: 57.0 +/- 5.9% of the dose of drug placed as an aqueous solution in the 45 microL collapsible container was delivered as an aerosol (n = 40). The best fit size distribution had an MMAD = (2.95 +/- 0.06) microns and a geometric standard deviation sigma g = 1.24 +/- 0.01 (n = 6). CONCLUSIONS: The AERX aerosol delivery system generates a nearly monodisperse aerosol with the properties required for efficient and repeatable drug delivery to the lung.

Administration, Inhalation↗

PubMed2000

Blood pressure and Turner syndrome.

INTRODUCTION: Elevated blood pressure (BP) is an important predictor of morbidity and mortality from cardiovascular disease. Patients with Turner syndrome (TS) have a higher morbidity and mortality in middle age than the normal population. As BP in childhood or early adulthood is predictive of BP later in adult life, we assessed manual and 24 h ambulatory BP in patients with TS to determine whether the BP pattern is altered at an early stage in these patients who are known to be at risk of cardiovascular disease. PATIENTS AND METHODS: We studied manual and 24 h ambulatory BP profiles in 75 girls with Turner syndrome, age range 5.4-22.4 years. A monitor with an oscillometric device (SpaceLabs model 90207) and an appropriate sized cuff was used. BP was measured during the day-time (0800-2000 h) and the night-time periods (2200-0800 h). The BP measured were compared with population standards. The effect of different growth promoting agents on BP was also evaluated. RESULTS: Mean manual and 24 h ambulatory BP measurements were 118/77 mmHg (range 95/60-140/102) and 115/70 mmHg (range 93/57-154/99), respectively. There was minimal difference between the two methods with a positive bias of 2.4 mmHg for diastolic BP and a negative bias of 2.1 mmHg for systolic BP. The mean standard deviation scores (SDS) corresponding to the mean BP recordings were 24 h systolic + 0. 81 (range - 1.26 to + 4.45), 24 h diastolic + 0.43 (range - 0.85 to + 3.42), day-time systolic + 1.08 (range - 0.95 to + 4.72), day-time diastolic + 0.70 (range - 0.94 to + 3.71), night-time systolic + 0. 22 (range -2.2 to + 3.64) and night-time diastolic - 0.18 (range -2. 0 to + 2.43). The SDS for both the mean 24 h and day-time systolic and diastolic BP were shifted to the right of the normal distribution. 57% of the girls had less than the normal 10% reduction in nocturnal systolic blood pressure. 17% had diastolic and 21% had systolic blood pressure above the 95th percentile for age and sex. There was no significant difference in the BP SDS between girls on no treatment and those receiving treatment. CONCLUSION: Over 50% of girls with Turner syndrome have an abnormal BP circadian rhythm, which is similar to adult patients with secondary hypertension. Patients with Turner syndrome have higher blood pressure measurements compared to published population standards, as evidenced by the shift to the right of both the systolic and diastolic BP SDS. These findings suggest that girls with Turner syndrome should be carefully monitored in childhood and adulthood for blood pressure and other cardiovascular risk factors.

Adolescent↗

PubMed1989

[Descriptive epidemiology and prognosis of malignant gynecologic tumors].

Based on data from the Saarland (W. Germany) Cancer Registry, epidemiology and prognosis of gynaecological malignancies is presented for the period 1971-1985. Breast cancer is the most frequent gynaecological tumour followed by tumours of the uterus (cervix + corpus). This is in accordance with worldwide observations. The age distribution of all analysed tumour localisations follows approximately a normal distribution with a maximum between 60 and 65 years of age. Tumours of the breast, cervix and corpus have almost the same prognosis (5-year-survival-rate greater than 60%); the prognosis of ovarian cancer is distinctly poorer. A clear decrease in the incidence is observed only for cervical cancer. The indications are that the proportion of aged patients is continually rising. The mortality, on the other hand, does not increase to the same extent, which indicates a progressive success of therapy of gynaecological malignancies. Since the Saarland Cancer Registry is the only population-based unit functioning for a sufficiently long period, the results represent a model of the situation in the Federal Republic of Germany.

Adolescent↗

PubMed1993

Determination of cell dose-survival relationships from endpoint dilution assays.

Methods for fitting radiation survival curves to data obtained from endpoint-dilution assays are described. It is shown that for functional forms such as the linear-quadratic model the problem can be recast as a generalized linear model (GLM) and the data fitted using standard software. For functional forms which are not capable of being linearized, such as the multitarget model, the direct maximum likelihood (DML) techniques of Thames et al. (1986) can be used. Both these techniques produce exact maximum likelihood parameter estimates. Compared with the weighted least-squares (WLS) approach traditionally employed, these approaches avoid the need to approximate the binomial distribution of the number of negative wells by a normal distribution, and avoid the biases introduced by the need for arbitrary treatment of data points with 0 or 100% negative wells. The results of fittings using the novel GLM and DML approaches are compared with those obtained using the WLS method on a large series of datasets. For most datasets the WLS method performs well, compared with the exact method, but in a small number of cases the WLS predicted parameter estimates can be in error by as much as their estimated standard errors. A method for the use of a concurrent control to correct for interexperimental variation is outlined. The methods have been implemented in a Fortran computer program using the NAG subroutine library.

Cell Survival↗

PubMed2004

A quantitative description of vehicle exhaust particle size distributions in a highway tunnel.

During the period May 18-May 22, 1999, a comprehensive study was conducted in the Tuscarora Mountain Tunnel on the Pennsylvania Turnpike to measure real-world motor-vehicle emissions. As part of this study, size distributions of particle emissions were determined using a scanning mobility particle sizer. Each measured size distribution consisted of two modes: a nucleation mode with midpoint diameter less than 20 nm and an accumulation mode with midpoint diameter less than 100 nm. The nucleation and accumulation components in some distributions also exhibited second maxima, which implies that such particle size distributions are superpositions of two particle size distributions. This hypothesis was utilized in fitting the particle size distributions that exhibited second maxima with four lognormal distributions, two for the nucleation mode and two for the accumulation mode. The fitting assumed that the observed particle size distribution was a combination of two bimodal log-normal distributions, one attributed to the heavy-duty diesel (HDD) vehicles and another attributed either to a different class of HDD vehicles or to the light-duty spark ignition vehicles. Based on this method, estimated particle production rates were 1.8 x 10(13) and 2.8 x 10(14) particles/vehicle-km for light-duty spark ignition and HDD vehicles, respectively, which agreed with independently obtained estimates.

Models, Theoretical↗

PubMed2005

Modeling menstrual cycle length using a mixture distribution.

In reproductive health studies, epidemiologists are often interested in examining the effects of covariates on menstrual cycle length which is a convenient, noninvasive measure of women's ovarian and reproductive function. Previous literature (Harlow and Zeger, 1991) suggests that the distribution of cycle length is a mixture of a major symmetric distribution and a component featuring a long right tail. Motivated by the shape of this marginal distribution, we propose a mixture distribution for cycle length, representing standard cycles from a Normal distribution and nonstandard cycles from a shifted Weibull distribution. The parameters are estimated using an estimating equation derived from the score function of an independence working model. The fitted mixture distribution agrees well with the distribution estimated using nonparametric approaches. We propose two measures to help determine whether a cycle is standard or nonstandard, developing tools necessary to identify characteristics of the menstrual cycles that are biologically indicative of ovarian dysfunction. We model the effect of a woman's age on the mean and variation of both standard and nonstandard cycle lengths using multiple measurements of women.

Adult↗

PubMed1975

A mathematical model of aging processes. III. Comments on the relative importance of serum cholesterol and blood pressure levels on mortality.

The distributions of serum cholesterol, blood pressure, and their values added together, were examined on a cross-sectional basis for a Montreal population. The results showed that all three distributions seem to be represented better by a log normal than by a normal distribution; but in each case, there was no pronounced increase in the skew with age. The distribution of the systolic blood pressure values exhibited an increasing variance with age, whereas the distribution of the serum cholesterol values remained approximately similar with age. The distribution of the two parameters added together also did not alter significantly with age. These results are consistent with the assumption that, if the serum cholesterol value of an individual changes, the individual will be placed at a substantially greater risk than if changes occur for blood pressure levels. Subpopulations of particular concern, with respect to changes in serum cholesterol levels, are those which undergo weight changes and those which smoke cigarettes.

Adult↗