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PubMed2004

PET measurements of CBF, OEF, and CMRO2 without arterial sampling in hyperacute ischemic stroke: method and error analysis.

UNLABELLED: A method for relative measurement of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO2) using positron emission tomography (PET) without arterial sampling in patients with hyperacute ischemic stroke was presented. METHODS: The method requires two PET scans, one for H2(15)O injection and one for 15O2 inhalation, and calculates regional CBF, CMRO2, and OEF relative to those at the reference brain region by means of table-lookup method. In this study, we calculated "relative lookup-tables" which relate relative CBF to relative H2(15)O count, relative CMRO2 to relative 15O2 count, and relative OEF to relative 15O2/H2(15)O count. Two assumptions were applied to the lookup-table calculation: 1) In the reference region. CBF and OEF were assumed to be 50.0 ml/min/100 ml and 0.40, respectively, 2) Cerebral blood volume (CBV) was assumed to be constant at 4.0 ml/100 ml over the whole brain. Simulation studies were done to estimate the error of the present method derived from the assumptions. RESULTS: For relative CBF measurements, 20% variation in reference CBF gave about +/- 10% error for measured relative CBF at maximum. Changes in CBV caused relatively large errors in measured OEF and CMRO2 when relative CBF and OEF decreased. Errors for measured relative OEF caused by 50% variation in CBV were within +/- 8% at 0.8 of relative CBF and +/- 12% at 0.4 of relative CBF when relative OEF was greater than 1.0. CONCLUSION: CBV effects caused larger errors in estimated OEF and CMRO2 in the region of the ischemic core with decreasing relative CBF and/or OEF but only slight errors in the region of "misery perfusion" with relative OEF values greater than 1.0. The present method makes PET measurements simpler than with the conventional method and increases understanding of the cerebral circulation and oxygen metabolism in patients with hyperacute stroke of several hours after onset.

Acute Disease↗
PubMed2004

M error patterns in word reading among primary school children: a cross-orthographic study.

A comparative investigation of word reading efficiency indicates that different strategies may be used by English and Swedish early readers. In a first study, 328 native English speakers from UK Years 3 and 6 completed a pen-and-paper word recognition task (the Wordchains test). Results were analysed for frequency and type of errors committed. A sample of 123 chronological-age-matched Swedish children carried out the same task on a matched Swedish test. For a sub-sample of 68 English/Swedish pairs matched on word recognition score and sex, significant differences were observed in a comparison of average and low scorers from the two language groups. The English children attempted more task items and committed more errors, while the Swedish group corrected their errors more, suggesting a difference in approach to the task. A second study of a larger Swedish sample (241 participants) found the same pattern of errors as Study 1. The implications of these findings are discussed in relation to the effects of orthographic depth and morphemic complexity.

Child↗
PubMed1996

Accuracy of color doppler velocity in the flow field proximal to a regurgitant orifice: implications for color doppler quantitation of valvular incompetence.

Color Doppler is routinely used in estimates of valvular regurgitation. Velocity and subsequently flow measurements are made at about 7-10 cm from the ultrasonic transducer. Error in velocity measurement may occur due to spatial broadening of the color Doppler beam in the axial, azimuthal and lateral directions. Error in velocity may also occur due to wall filters since the filtering process is not uniform throughout the velocity range indicated by the color bar. An attempt to estimate this error was made using an in vitro orifice model, a numerical finite element model (FEM), and information from the manufacturer. We found that the acoustic beam spatial expansion, wall filter sensitivity and Nyquist limit (NYL) have to be considered simultaneously to account for errors. The combined spatial expansion and wall filter effect on velocity was estimated as a weighted average over the sample volume. The error distributions are not universal but depend on orifice size and flow. For a 3-mm orifice and 100 cm s NYL the overall effect was overestimation of low velocities and significant underestimation of high velocities due to the high velocity gradients inside the sample volume. For the 5- and the 10-mm orifice the effect was less accentuated. Based on this overall error distribution, a correction was incorporated on color Doppler obtained data. The incorporated correction yielded better agreement with numerical velocity data. This correction is important in the application of the proximal isovelocity surface area (PISA) technique and the evaluation of regurgitant flowrates.

Blood Flow Velocity↗
PubMed1995

Mechanisms of emmetropization in the aging eye.

Refraction and its components were measured on 96 subjects consisting of 48 Young Adults (19 to 31 years old) and 48 Mature Adults (49 to 61 years old) having refractive errors in the range from +2.50 to -2.50 D. Subjects for the two groups were matched on the basis of sex and refractive error. A quota sampling technique was used to obtain subjects for myopic, emmetropic, and hyperopic refractive-error categories. An autorefractor was used to measure refractive error, an autokeratometer was used to measure corneal radius of curvature, and an A-scan ultrasonometer was used to determine the axial dimensions. Crystalline lens radii were determined by submitting Purkinje image data to a ray-tracing program, with the assumption that the index of refraction of the ocular media is constant throughout life. By comparing the results for the two groups of subjects, it was found that there were no significant age-related differences in mean corneal radius of curvature or in mean axial length. However, the following significant age-related differences were found: the Mature Adult eyes had shallower anterior chambers, thicker lenses, shorter vitreous chambers, steeper anterior and posterior lens surfaces (shorter radii of curvature), more highly powered lenses, and higher ocular refracting power than the Young Adult eyes. It was concluded that a decrease in the gradient-index of the lens occurs with increasing age, acting as an emmetropizing mechanism by compensating for the steepening of both the front and back surfaces of the lens.(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗
PubMed1993

A note on the operating characteristics of the modified F test.

Brownie, Boos, and Hughes-Oliver (1990, Biometrics 46, 259-266) suggested a modification to the fixed-effects analysis of variance (ANOVA) F test for use in situations where treatments are likely to affect mean response while simultaneously increasing between-subject variability. These authors suggest that the modified test (1) is robust against departures from population normality, (2) is more powerful than its classical counterpart when the expected alternative form is encountered, and (3) will suffer only minor power losses relative to the usual test when alternatives are in the form of simple shifts in location. This study shows that the modified test is not generally robust when sampling is from nonnormal distributions and is likely to produce unacceptably high Type I error inflations when sampling is from heavy-tailed or skewed distributions. Some power results are also provided for the multisample situation to supplement those of Brownie et al., who generated results only for the two-sample case.

Analysis of Variance↗
PubMed1998

Vitamin B2 interference with TDx drugs-of-abuse assays.

Migraine is a headache condition found in significant frequency in the general population. One recent study has shown that riboflavin, Vitamin B2, is an effective prophylactic treatment for this headache condition. One subject in a recent study conducted by the Division of Forensic Toxicology, Armed Forces Institute of Pathology (AFIP) was taking 200 mg of riboflavin twice daily for the prevention of migraine headaches. When that subject's urine was tested using Abbott TDx drugs-of-abuse assays a number of tests resulted in a MX BKG error and all samples had BLK I values greater than those observed with normal urine specimens. The MX BKG error occurs when the BLK I value is greater than the upper limit determined by the manufacturer for a particular assay. High BLK I values may result if the specimen being analyzed contains a fluorophore that will compete with the fluorescein-labeled antibody used in the assay. This error serves as a notification that an interfering substance may be present and the assay is not performing according to manufacturer-specifications. Upon termination of riboflavin therapy the subject's BLK I values began to decrease within 60 h of the last 200 mg dose. A second subject began chronic riboflavin use to confirm this interferent effect. Elevated BLK I values resulted within 3 h of a single 200 mg dose and MX BKG errors occurred 1 h after a second 400 mg dose. No false negative results were noted with either subject (both subjects used butalbital and the first subject also used hydrocodone and diazepam during the study), suggesting that riboflavin is not an adulterant. Riboflavin use, however, does interfere with the TDx DAU assays and may result in quantitative values being determined which are of questionable validity in the face of an elevated BLK I value or may result in only an MX BKG error and no quantitative value reported. It is unclear if the interfering fluorophore is simply riboflavin itself or a combination of riboflavin and its metabolic products. Results obtained on urine samples collected from individuals using prophylactic riboflavin for migraine prevention and analyzed by TDx may be of questionable validity. Such samples may require analysis utilizing another immunoassay technique that does not employ a fluorescein-labeled antibody.

Fluorescence Polarization Immunoassay↗
PubMed1996

Role of oximeter error in the diagnosis of shunts.

We have analyzed the role that instrument error plays in the oximetric diagnosis of shunts. First, we review the accuracy specifications of instruments currently available for measuring oxyhemoglobin saturation during cardiac catheterization. Then we derive a mathematical model of a left-to-right shunt and illustrate the relationships between the magnitude of shunts and the saturation step-ups they generate. Using the shunt model and statistical methods, we show how oximeter error affects the likelihood of success in detecting shunts of a given magnitude. By computing the probabilities of false negative and false positive diagnoses, the model can be used to determine how the likelihood of successful shunt detection is influenced by factors such as shunt flow, the minimum saturation step-up considered indicative of a shunt, oximeter error, hemoglobin concentration, and the number of blood samples. A spreadsheet is included for those who wish to analyze the diagnostic capabilities of their own instrumentation and clinical methods. Conclusions. (1) Modern instruments for use during cardiac catheterization analyze blood samples with a measurement error ranging from 2.5 to 1% saturation or better. (2) Until more information is available regarding the accuracy of such devices in measuring oxygen content, the detection of shunts should be made on the basis of step-ups in saturation rather than oxygen content (even though step-ups in oxygen content have the potential advantage of being independent of the oxygen-carrying capacity of blood). (3) Averaging the analyses of two or more blood samples from each site and using an oximeter with 1% error greatly improve the probability of reaching the correct diagnosis. (4) Oximeter error of 2.5% or greater is unacceptable by today's standards. (5) With the instrumentation currently available, oximetry can potentially detect saturation step-ups as small as 3.6% and still keep both false negative and false positive diagnoses below 10% if venous blood is adequately mixed.

Blood Flow Velocity↗
PubMed1987

Determination of 18O by prompt nuclear reaction analysis: application for measurement of microsamples.

A method is described for the routine determination of 18O concentrations in microsamples of biological fluids. The method utilizes the prompt nuclear reaction 18O(p, alpha o)15N, and 846-keV protons from a 3-MeV Van de Graaff Accelerator are focused on approximately 2,000-A-thick Ta2O5 targets prepared by anodic oxidation from 50-microliter samples of water distilled from blood or other biological fluids. The broad cross section of the resonance peak for this nuclear reaction (47 keV) ensures high yields, especially at small reaction angles, and the high-energy alpha particles produced by the reaction (4 MeV) are readily separated from scattered protons by the use of an aluminized Mylar foil of suitable thickness. Background levels of 18O (0.204 atom%) can be detected with run times of approximately 5-8 min, and the sensitivity of the method is of the order of 0.05 atom %. Experimental error due to sample preparation was found to be 1.7%, and counting errors were close to theoretical limits so that total error was of the order of 2.5%. Duplicate samples were analyzed by use of the 18O(p, alpha o)15N reaction at Lucas Heights, Australia, and the 18O(p,n)18F reaction by the method of Wood et al. (Anal. Chem. 47: 646-650, 1975) at the University of California, Los Angeles, and the agreement was excellent (y = 1.0123x - 0.0123, r = 0.991, P less than 0.001). The theoretical limitations and the general applicability of the method in biological studies designed to estimate the rate of metabolism of free-ranging animals are discussed.

Animals↗
PubMed1999

Protein fold class prediction: new methods of statistical classification.

Feed forward neural networks are compared with standard and new statistical classification procedures for the classification of proteins. We applied logistic regression, an additive model and projection pursuit regression from the methods based on a posterior probabilities; linear, quadratic and a flexible discriminant analysis from the methods based on class conditional probabilities, and the K-nearest-neighbors classification rule. Both, the apparent error rate obtained with the training sample (n = 143) and the test error rate obtained with the test sample (n = 125) and the 10-fold cross validation error were calculated. We conclude that some of the standard statistical methods are potent competitors to the more flexible tools of machine learning.

Algorithms↗
PubMed1999

Development and validation of an automated, microscopy-based method for enumeration of groups of intestinal bacteria.

An automated microscopy-based method using fluorescently labelled 16S rRNA-targeted oligonucleotide probes directed against the predominant groups of intestinal bacteria was developed and validated. The method makes use of the Leica 600HR image analysis system, a Kodak MegaPlus camera model 1.4 and a servo-controlled Leica DM/RXA ultra-violet microscope. Software for automated image acquisition and analysis was developed and tested. The performance of the method was validated using a set of four fluorescent oligonucleotide probes: a universal probe for the detection of all bacterial species, one probe specific for Bifidobacterium spp., a digenus-probe specific for Bacteroides spp. and Prevotella spp. and a trigenus-probe specific for Ruminococcus spp., Clostridium spp. and Eubacterium spp. A nucleic acid stain, 4',6-diamidino-2-phenylindole (DAPI), was also included in the validation. In order to quantify the assay-error, one faecal sample was measured 20 times using each separate probe. Thereafter faecal samples of 20 different volunteers were measured following the same procedure in order to quantify the error due to individual-related differences in gut flora composition. It was concluded that the combination of automated microscopy and fluorescent whole-cell hybridisation enables distinction in gut flora-composition between volunteers at a significant level. With this method it is possible to process 48 faecal samples overnight, with coefficients of variation ranging from 0.07 to 0.30.

Adult↗
PubMed2002

Powder sampling.

The factors involved when sampling powder mixes have been reviewed. The various methods are evaluated (manual, automatic, and sub-sampling) and the errors incurred are discussed. Certain rules have been applied to various samplers and their suitability for powder mixtures are described. The spinning riffler is apparently the most suitable, while the use of sample thieves should be avoided due to error and bias.

Automation↗
PubMed1997

A new method for measurement of anaesthetic partial pressure in blood.

We have developed a simple, reliable method for rapid analysis of the partial pressure of volatile anaesthetic agents, based on a two-stage, head-space analysis. It is designed to solve the problems associated with reduced solubility of modern anaesthetics. After equilibration and analysis of a 2-ml sample of blood at 37 degrees C, 1 ml is transferred to another vial for a second equilibration. This ensures that there is no vapour in the headspace before the second equilibration. Measurements were performed on human blood samples equilibrated with 1% sevoflurane, 2.5% isoflurane or 3% desflurane in a tonometer. The mean error in the sample measurements was -2.3% of the tonometer reading and the 95% confidence interval for an individual measurement was +/- 8.5%. Blood samples may be stored overnight without any significant change in the results.

Anesthetics, Inhalation↗
PubMed1990

A comparison of venous versus capillary measurements of drug concentration.

Accessing patient's veins for drug level sampling is not always feasible. The use of capillary sampling techniques is often utilized when venous access is hampered. In the therapeutic monitoring of patients, unexpected drug level results often occur that can be caused by a number of different factors. The possibility that differences in assay results might occur if samples were collected by capillary stick vs. venous phlebotomy was examined by simultaneous sampling in 18 patients. Although correlation was very high (0.999) and percentage differences fairly low (range of 0 to 15.4%), a statistical difference was noted in the sampling methods. The precision was 6.5 +/- 6.58% and there was a slight negative bias (-3.76%), with capillary samples less than venous samples. Although there were statistical differences for the drugs studied in the concentration ranges evaluated, capillary samples should provide fairly small errors when compared to venous samples.

Adult↗
PubMed2003

Repeated measures one-way ANOVA based on a modified one-step M-estimator.

Wilcox, Keselman, Muska and Cribbie (2000) found a method for comparing the trimmed means of dependent groups that performed well in simulations, in terms of Type I errors, with a sample size as small as 21. Theory and simulations indicate that little power is lost under normality when using trimmed means rather than untrimmed means, and trimmed means can result in substantially higher power when sampling from a heavy-tailed distribution. However, trimmed means suffer from two practical concerns described in this paper. Replacing trimmed means with a robust M-estimator addresses these concerns, but control over the probability of a Type I error can be unsatisfactory when the sample size is small. Methods based on a simple modification of a one-step M-estimator that address the problems with trimmed means are examined. Several omnibus tests are compared, one of which performed well in simulations, even with a sample size of 11.

Analysis of Variance↗
PubMed2000

Saline for peripheral intravenous locks in neonates: evaluating a change in practice.

PURPOSE: To evaluate the efficacy of saline versus 10 units/ml heparin for peripheral i.v. flushes in neonates. DESIGN: A nonexperimental group design was used to compare the longevity of heparin and saline i.v. locks. A research utilization method was chosen to increase the study power while simultaneously implementing a practice change and evaluating the outcomes. Power analysis showed that a sample size of approximately 120 per group was needed to decrease the risk of beta error to 0.1. SAMPLE: Subjects included neonates in the Special Care Nurseries at a Level III large midwestern university teaching hospital. Data were collected from a convenience sample of 123 neonates receiving 10 units/ml heparin flush into a peripheral i.v. Practice was then changed to preservative-free normal saline, and data collection continued for 117 neonates. MAIN OUTCOME VARIABLE: I.v. catheter longevity. RESULTS: There was no significant statistical difference in i.v. catheter longevity between i.v. locks flushed with 10 units/ml heparin and those flushed with normal saline. Patient weight accounted for a significant proportion of the variance in i.v. catheter life.

Catheterization, Peripheral↗
PubMed1993

[Preclinical and clinical studies on a tumor marker, galactosyltransferase associated with tumor (GAT), in ovarian cancer (first report)--preclinical study of GAT assay kit and clinical study of normal level].

We conducted preclinical and clinical studies on GAT: Galactosyltransferase Associated with Tumor, a newly developed tumor marker of ovarian carcinoma. This paper presents the results of evaluation of a GAT assay kit, the normal range of its values, and analysis of its value relative to age, menstrual cycle, and stage of pregnancy. Calibration curve, reproducibility, analytical recovery test, and dilution test all yielded favorable results, and the assay system was proved to be reliable in both precision and reproducibility. However, special attention must be paid to highly hemolytic samples because of a positive error in GAT value for samples with a high concentration of hemoglobin. The cut-off value was set at 16U/ml based on the mean+2SD of healthy females. A uniform cut-off value could be employed since neither age nor stage of menstrual cycle had any observable influence on the level. The positive rate for healthy subjects was 3.1%, when the cut-off value of 16 U/ml was used. On the other hand, elevation of the GAT value was observed during the progression of pregnancy.

Adult↗
PubMedDate not supplied

[Sampling limitations in studies of primary care: comparison of 4 sampling designs].

Different sampling methodologies have been used to avoid the great amount of information which arises in Primary Health Care. The objective of this study is to compare the estimates of four sampling schemes, analyzing variables of utilization, referral activity and diagnostic morbidity, based on data obtained from consultations in a health centre over a one-year period. The percentage of error between each sample estimation and the real value for the whole data set was obtained. Sampling schemes using week periods showed the worst results (40% of error in the estimation of chronic consultations, 18% of error in the percentage of radiology requests and more than 13% in the estimation of morbidity). The findings of this study suggest that some of the sampling schemes usually applied in primary care studies have important limitations, showing the need for more research in this field.

Community Health Services↗
PubMed2004

Multiplicity-adjusted sample size requirements: a strategy to maintain statistical power with Bonferroni adjustments.

BACKGROUND: A researcher must carefully balance the risk of 2 undesirable outcomes when designing a clinical trial: false-positive results (type I error) and false-negative results (type II error). In planning the study, careful attention is routinely paid to statistical power (i.e., the complement of type II error) and corresponding sample size requirements. However, Bonferroni-type alpha adjustments to protect against type I error for multiple tests are often resisted. Here, a simple strategy is described that adjusts alpha for multiple primary efficacy measures, yet maintains statistical power for each test. METHOD: To illustrate the approach, multiplicity-adjusted sample size requirements were estimated for effects of various magnitude with statistical power analyses for 2-tailed comparisons of 2 groups using chi2 tests and t tests. These analyses estimated the required sample size for hypothetical clinical trial protocols in which the prespecified number of primary efficacy measures ranged from 1 to 5. Corresponding Bonferroni-adjusted alpha levels were used for these calculations. RESULTS: Relative to that required for 1 test, the sample size increased by about 20% for 2 dependent variables and 30% for 3 dependent variables. CONCLUSION: The strategy described adjusts alpha for multiple primary efficacy measures and, in turn, modifies the sample size to maintain statistical power. Although the strategy is not novel, it is typically overlooked in psychopharmacology trials. The number of primary efficacy measures must be prespecified and carefully limited when a clinical trial protocol is prepared. If multiple tests are designated in the protocol, the alpha-level adjustment should be anticipated and incorporated in sample size calculations.

Clinical Protocols↗