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PubMed1994

Consultation, waiting, prescribing and referral patterns: some methodological considerations.

This paper addresses the question of how large a sample is necessary before valid conclusions can be drawn with regard to average waiting and consultation times and prescribing and referral patterns for individual doctors. The statistical techniques of plotting cumulative means for these measures in relation to sample size, along with a formula using the maximum available sample size, and the mean/standard error of the measure at this sample size was used to determine 'stabilization values' (minimum sample sizes at which statistically valid conclusions can be drawn with a predetermined degree of certainty) regarding these measures. Using these techniques, stabilization values of 120 for consultation time, 200 for mean waiting time, 170 for prescribing pattern and 490 for referral pattern were determined using data collected by 136 experienced general practitioners during 40,363 consultations in the context of UK general practice. Confident conclusions cannot be drawn from studies examining these measures unless at least the sample sizes documented in this paper have been used.

Appointments and Schedules↗
PubMed1996

Adaptive estimation of latency changes in evoked potentials.

Changes in latency of evoked potentials (EP) may indicate clinically and diagnostically important changes in the status of the nervous system. A low signal-to-noise ratio of the EP signal makes it difficult to estimate small, transient, time-varying changes in latency, or delays. Here, we present an adaptive algorithm that estimates small delay (latency change) values even when EP signal amplitudes are time-varying. When the delay is time invariant, the adaptive algorithm produces an unbiased estimate with delay estimation error less than half of the sampling interval. A lower estimation error variance is obtained when, in a pair of signals, the adaptive algorithm delays the signal with the higher SNR. The adaptive algorithm delays the signal with the higher SNR. The adaptive delay estimation algorithm was tested on intra-operative recordings of somatosensory EP, and analysis of those recordings reveals that the anesthetic etomidate produces a step change in the amplitude and latency of the EP signals.

Algorithms↗
PubMed1993

Total error assessment of five methods for cholesterol screening.

We report the accuracy, imprecision, total analytical errors, and patient misclassification errors for cholesterol measured from capillary whole blood, venous whole blood, and venous plasma samples by five devices used in public cholesterol screening environments: Reflotron, Vision, Ektachem DT-60, QuickRead, and Liposcan. None of the methods met the National Cholesterol Education Program (NCEP) performance recommendations of 3% CV with 3% bias. The Vision and Reflotron methods used with venous samples gave individual results with total errors consistent with a combined CV and bias in the 4-5% range; capillary blood samples had total errors > 5% (combined CV and bias criteria). The DT-60 performance was near the 5% total error criterion for capillary samples and was > 5% for venous samples. Misclassification of individuals into desirable or referral groups for venous samples was as great as 5.1% for the DT-60, 5.7% for the Vision, and 7.1% for the Reflotron. Misclassifications for capillary blood samples were as great as 6.7%, 18.3%, and 14.1% for DT-60, Vision, and Reflotron, respectively. The QuickRead and Liposcan results were substantially poorer than those obtained by the other methods.

Adult↗
PubMed2000

Identification and analysis of error types in high-throughput genotyping.

Although it is clear that errors in genotyping data can lead to severe errors in linkage analysis, there is as yet no consensus strategy for identification of genotyping errors. Strategies include comparison of duplicate samples, independent calling of alleles, and Mendelian-inheritance-error checking. This study aimed to develop a better understanding of error types associated with microsatellite genotyping, as a first step toward development of a rational error-detection strategy. Two microsatellite marker sets (a commercial genomewide set and a custom-designed fine-resolution mapping set) were used to generate 118,420 and 22,500 initial genotypes and 10,088 and 8,328 duplicates, respectively. Mendelian-inheritance errors were identified by PedManager software, and concordance was determined for the duplicate samples. Concordance checking identifies only human errors, whereas Mendelian-inheritance-error checking is capable of detection of additional errors, such as mutations and null alleles. Neither strategy is able to detect all errors. Inheritance checking of the commercial marker data identified that the results contained 0.13% human errors and 0.12% other errors (0.25% total error), whereas concordance checking found 0.16% human errors. Similarly, Mendelian-inheritance-error checking of the custom-set data identified 1.37% errors, compared with 2.38% human errors identified by concordance checking. A greater variety of error types were detected by Mendelian-inheritance-error checking than by duplication of samples or by independent reanalysis of gels. These data suggest that Mendelian-inheritance-error checking is a worthwhile strategy for both types of genotyping data, whereas fine-mapping studies benefit more from concordance checking than do studies using commercial marker data. Maximization of error identification increases the likelihood of linkage when complex diseases are analyzed.

Alleles↗
PubMed2002

Estimation of pedigree errors in the UK dairy population using microsatellite markers and the impact on selection.

The proportion of cows in the UK dairy herd whose sires were misidentified was estimated using DNA markers. Genetic marker genotypes were determined on 568 cows (from 168 milk samples and 400 hair samples) and 96 putative sires (from semen samples). The estimated pedigree error rate from the hair samples was 8.8%, and from the milk samples, 13.1%, giving an overall estimate of the error rate of 10%. This level of pedigree errors will have a relatively large impact on the efficiency of progeny testing and the accuracy of cow predicted breeding values. We predict a loss of response to selection of approximately 2 to 3% given this error rate.

Animals↗
PubMedDate not supplied

[A survey of the prevalence and causes of eye disorders in primary school children in Antananarivo].

To assess the prevalence and causes of ocular abnormalities in children, we performed a cross-sectional survey with cluster sampling in Madagascar in Antananarivo primary schools in October 1994. Our other aim was to sensitize the sanitary authorities and the students of ophthalmology to the notion of public health ophthalmology in a country where a national blindness prevention program is being established. 1,081 children aged from 8 to 14 years (mean age 10.6 years) were examined. 51, or 4.7%, were diagnosed as having ocular abnormalities. These abnormalities were distributed as follows: 22 cases or 2% of the sample had refractive errors including 0.74% with myopia of less than 6 dioptrics, 0.18% with myopia of more than 6 dioptrics, 0.83% with hypermetropia of less than 6 dioptrics, and 0.28% with hypermetropia of more than 6 dioptrics; 15 cases or 1.4% of the sample had unilateral amblyopia including 0.9% with anisometropia, 0.37% with strabismus, and 0.09% with macular pathology; 8 cases or 0.74% of the sample had strabismus without amblyopia; and 6 cases or 0.57% of the sample had simple medical pathology. The results showed that 29 children were supposed to have an optic correction, including surgical treatment for 12 and medical treatment for 6. The same low frequencies of ocular abnormalities, mainly concerning refractive errors, were found in the literature. However, children suffering from important visual impairment do not attend school, and we cannot generalize the above results for the whole population.

Adolescent↗
PubMed1999

A threshold causal model for clinical trials with departures from intended treatment.

Randomized clinical trials often are planned to study a specific intervention. However, the collection of data on treatment actually received often reveals variable levels of treatment exposure (or 'dose') across subjects, due to non-compliance or other reasons. This paper presents a new method, using such 'dose' data as well as control group responses, to assess a causal dose-response relationship. The specific model utilizes a threshold function and incorporates a random effect term to allow for heterogeneous treatment responses among subjects. Further modelling of the random effects allows for reduction of error variance and control for potential confounders. The threshold dose is estimated using a residual variance criterion based on a transformed model. Estimates of standard errors and confidence intervals are obtained using a bootstrap procedure. The method is applied to data from an AIDS clinical trial. A simulation study demonstrates the adequacy of the threshold estimates for particular sample sizes and error variances. The limitations of this essentially exploratory method, as well as some possible extensions, are discussed. Published in 1999 by John Wiley & Sons, Ltd. This article is a US Government Work and is in the public domain in the United States.

CD4 Lymphocyte Count↗
PubMed2004

Field validation of an active sampling cartridge as a passive sampler for long-term carbonyl monitoring.

A carbonyl sampler originally designed for the active sampling method (Sep-Pak XPoSure) was used for long-term passive sampling, and its applicability as a passive sampler was examined through field experiments. The uptake rates of passive sampling were determined experimentally from collocated passive and active samplings for various sampling periods. The obtained uptake rates of formaldehyde, acetaldehyde, and acetone were 1.48, 1.23, and 1.08 mL/min, respectively. These uptake rates were consistent for a wide range of the sampling term (12 hr-2 weeks). Uptake rates of each carbonyl were proportional to the diffusion coefficients of each. Therefore, the ratios of diffusion coefficients were used to calculate the uptake rates of carbonyls for which the rates were not determined experimentally. Lower limits of determination were 2.16-17.5 microg/m3 for 2-week sampling. It was confirmed that 2-week monitoring of carbonyl concentrations up to 118-229 microg/m3 was possible. Relative standard deviations of the passive method generated from the repeatability test were 2-12.3% error for five samplings, and the recovery efficiencies were larger than 90%. Thus, the passive sampler was found to be highly suitable for long-term monitoring of carbonyl compounds.

Adsorption↗
PubMed1985

The development of antioxidant enzymatic defense in the perinatal rat lung: activities of superoxide dismutase, glutathione peroxidase, and catalase.

This report describes the development of superoxide dismutase, glutathione peroxidase, and catalase activities in fetal (days 16-22) and neonatal (day 2 postpartum) lungs of normal rats. Each of the enzymes showed an individual pattern of development in the perinatal period. Glutathione peroxidase activity increased by 135% (p less than 0.001) during the last 3 days before birth, catalase activity by 105% (p less than 0.01) during the first 2 postnatal days, and the activity of superoxide dismutase by 52% (p less than 0.05) from gestational day 19 to 2 days after birth. Contamination by superoxide dismutase from blood in the lung samples accounted for less than 2% of the activity. In contrast, not less than 10-30% of glutathione peroxidase and catalase originated from the blood; and corrections were made for this source of error in each sample.

Animals↗
PubMed2004

All-fiber-optic infrared multispectral radiometer for measurements of temperature and emissivity of graybodies at near-room temperature.

An all-fiber-optic infrared multispectral radiometer for measurements of temperature and emissivity of graybodies at near-room temperature was constructed. Different spectral regions in the radiometer were obtained by use of hollow glass waveguides (HGWs) as filters. Using HGWs instead of bulk filters was advantageous because each HGW can be used as two different spectral filters when a dual-band IR detector is used. In addition, HGWs are much cheaper than the bulk IR filters that are usually used in such applications. For one graybody with a mean emissivity of 0.71, the estimated mean errors obtained for sample temperature, ambient temperature, and sample emissivity for all measured temperatures were 0.50% (approximately 1.65 K), 0.48% (approximately 1.4 K), and 7.3% (approximately 0.052) respectively. For a second graybody with a mean emissivity of 0.8 the estimated mean errors were 0.35% (approximately 1.2 K), 0.48% (approximately 1.4 K), and 5.0% (approximately 0.04), respectively.

Journal Article↗
PubMed1977

Sampling and storage of blood for pH and blood gas analysis.

Techniques used in sampling and storage of a blood sample for pH and gas measurements can have an important effect on the measured values. Observation of these techniques and principles will minimize in vitro alteration of the pH and blood gas values. To consider that a significant change has occurred in a pH or blood gas measurement from previous values, the change must exceed 0.015 for pH, 3 mm Hg for PCO2, 5 mm Hg for PO2, and 2 mEq/L for [HCO-3] or base excess/deficit. In vitro dilution of the blood sample with anticoagulant should be avoided because it will alter the measured PCO2 and base excess/deficit values. Arterial samples should be collected for meaningful pH and blood gas values. Central venous and free-flowing capillary blood can be used for screening procedures in normal patients but are subject to considerable error. A blood sample can be stored for up to 30 minutes at room temperature without significant change in acid-base values but only up to 12 minutes before significant changes occur in PO2. A blood sample can be stored for up to 3.5 hours in an ice-water bath without significant change in pH and for 6 hours without significant change in PCO2 or PO2. Variations of body temperatures from normal will cause a measurable change in pH and blood gas values when the blood is exposed to the normal water bath temperatures of the analyzer.

Animals↗
PubMed1993

The analysis of case-control studies under validation subsampling.

In case-control studies, one often finds that covariates are missing or measured with error in the entire sample, whereas complete or exact covariate information is available only in a subsample. This paper discusses the analysis of case-control studies under a double-sampling scheme, where at the first stage covariates are measured with error or missing, and at the second stage are validated in a subsample. The method proposed combines the risk information from both samples by assuming that (1) the disease incidence model is logistic, (2) the partial or proxy information takes on finitely many values, and (3) the error is non-differential. The estimator is obtained by jointly fitting logistic models to the first and second stage data, a variance formula is presented. Parameters can be estimated by use of standard packages for dose-response data. Data from an ongoing case-control study on lung cancer serve as an example.

Aged↗
PubMed1989

Volumetric sampling strategies for heterogeneous brainstem nuclei.

Many brainstem nuclei are heterogeneous structures in which neuronal and glial populations are unevenly distributed, and focal normal or pathologic deviations in cell density, so-called "features," are found. Examples of features include subnuclei, focal neuronal loss, and focal gliosis. We present a statistical test that justifies an investigator's claim that a feature is present in a nucleus at a selected level of confidence after completion of a cell counting experiment. The computer program developed for the test also indicates the most probable location of the feature within the nucleus, and its most probable density and length, and potentially allows one to make comparisons of feature characteristics among cases. We also present quantitative guidelines for the selection of a sampling periodicity in a heterogeneous nucleus before a cell counting experiment. Sampling periodicity is based upon analysis of computer-generated simulations of the nucleus with features of different sizes; for each feature the probability of Type I (false positives) and Type II (false negatives) errors are examined against one another. Type II error rate is dependent upon feature length and density, acceptable Type I error rate, and sampling periodicity. Feature detection is important for devising sampling strategies in brainstem nuclei.

Astrocytes↗
PubMed2004

Calculation of free energy through successive umbrella sampling.

We consider an implementation of umbrella sampling in which the pertinent range of states is subdivided into small windows that are sampled consecutively and linked together. This allows us to simulate without a weight function or to extrapolate the results to the neighboring window in order to estimate a weight function. Additionally, we present a detailed error analysis in which we demonstrate that the error in umbrella sampling is controlled and, in the absence of sampling difficulties, independent of the window sizes. In this case, the efficiency of our implementation is comparable to a multicanonical simulation with a very good weight function, which in our scheme does not need to be known ahead of time. The analysis also allows us to detect sampling difficulties such as correlations between adjacent windows and provides a test of equilibration. We exemplify the scheme by simulating the liquid-vapor coexistence in a Lennard-Jones system.

Journal Article↗
PubMed1989

Optimization of blood sampling time after intravenous bolus doses of gentamicin.

Comparisons were made, based on a one-compartment model, between predicted serum concentrations obtained at various sampling times after i.v. bolus and i.m. injections of gentamicin. Post-dose concentrations 1 h after i.m. injection were within 3% of the maximum concentration at steady-state, indicating that this was the optimal sampling time. Serum concentrations 1 h post-i.v. bolus were less than 7% different from those 1 h post-i.m. injection. In a clinical trial, blood samples taken earlier during the distribution phase of the drug, after an i.v. bolus, resulted in serum concentrations which were up to 74% higher than concentrations at 1 h. A survey of a sample of U.K. hospitals showed that only 41% were taking samples at 1 h post i.v. bolus of gentamicin. The majority of hospitals recommended a range of post-dose serum concentrations between 4 and 12 mg/l for patients with septicaemia, but when adjusted for errors related to sampling time, 36% of hospitals recommended a minimum which was equivalent to less than 4 mg/l at 1 h post dose. Post-dose concentrations of gentamicin should be measured in samples taken 1 h after either i.v. bolus and i.m. injections.

Gentamicins↗
PubMed2006

Regional and species specific bioaccumulation of major and trace elements in Arctic seabirds.

Twenty-five essential and nonessential elements were analyzed in Arctic seabirds to study the influence of phylogeny, tissue, Arctic region, and diet on avian element accumulation and to identify co-occurrence among metals. Muscle and liver concentrations were positively correlated, generally being higher in liver than in muscle, and generally did not differ by sex. Zinc showed the highest absolute concentrations in all samples (mean, 11.2-26.7 microg/g in muscle, depending on species and area), followed by copper (5.2-7.5 microg/g), arsenic (0.5-5.4 microg/g), selenium (1.0-5.8 microg/g), rubidium (1.4-2.2 microg/g), and cadmium (0.04-1.2 microg/g). Mercury levels ranged from 0.05 to 0.8 microg/g in muscle. The concentrations varied among species (dovekie [Alle alle], black guillemot [Cepphus grylle], thick-billed murre [Uria lomvia], black-legged kittiwake [Rissa tridactyla], northern fulmar [Fulmaris glacialis], ivory gull [Pagophila eburnean], Thayer's gull [Larus thayeri], and glaucous gull [Larus hyperboreus]), and between the northern Baffin Bay (Canada) and the Barents Sea, depending on the element. Whereas some elements (e.g., mercury and zinc) increased in absolute and standardized concentrations with trophic level in the northern Baffin Bay, most elements showed no relationship with trophic level or other dietary descriptors. In absolute concentrations, nonessential elements differed between regions, whereas essential elements differed among species but not within a species across the two regions. Standardized concentrations (element pattern) of both essential elements and nonessential elements generally did not differ between regions but was highly species specific and, thus, determined by the phylogenetic element regulation capacity. The usefulness of multivariate ordination in element wildlife studies is illustrated, which provides additional insight regarding element co-occurrence in wildlife, allows inclusion of species with low sample number, and reduces the possibility of type II errors created by low sample size.

Animals↗
PubMed2001

Signal estimation and denoising using VC-theory.

Signal denoising is closely related to function estimation from noisy samples. The same problem is also addressed in statistics (non-linear regression) and neural network learning. Vapnik-Chervonenkis (VC) theory has recently emerged as a general theory for estimation of dependencies from finite samples. This theory emphasizes model complexity control according to Structural Risk Minimization (SRM) inductive principle, which considers a nested set of models of increasing complexity (called a structure), and then selects an optimal model complexity providing minimum error for future samples. This paper applies the framework of VC-theory to signal estimation/denoising. There are three factors important for accurate signal estimation from finite samples: (1) the type of (orthogonal) basis functions used (i.e. Fourier basis, wavelets etc.). (2) The choice of a structure, i.e. ordering of the basis functions according to their 'importance' for accurate signal estimation. This corresponds to the choice of a 'structure' under SRM formulation. (3) Selecting an optimal number of terms (basis functions) from the ordered sequence of basis functions (2), aka model selection or complexity control (in statistics). We propose a methodology for specifying appropriate orderings (2) and an analytic expression for model selection (3) for signal processing applications. We also present empirical comparisons between the proposed methodology and current state-of-the-art wavelet thresholding methods for univariate signals. These comparisons suggest that the prudent choice of a structure (2) and the use of VC-based model selection (3) are critical for accurate signal estimation with finite samples.

Neural Networks, Computer↗
PubMedDate not supplied

Effects of measurement error on estimating biological half-life.

Direct computation of the observed biological half-life of a toxic compound in a person can lead to an undefined estimate when subsequent concentration measurements are greater than or equal to previous measurements. The likelihood of such an occurrence depends upon the length of time between measurements and the variance (intra-subject biological and inter-sample analytical) associated with the measurements. If the compound is lipophilic the subject's percentage of body fat at the times of measurement can also affect this likelihood. We present formulas for computing a model-predicted half-life estimate and its variance; and we derive expressions for the effect of sample size, measurement error, time between measurements, and any relevant covariates on the variability in model-predicted half-life estimates. We also use statistical modeling to estimate the probability of obtaining an undefined half-life estimate and to compute the expected number of undefined half-life estimates for a sample from a study population. Finally, we illustrate our methods using data from a study of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure among 36 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam.

Environmental Exposure↗