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PubMed2006

How specific is case specificity?

OBJECTIVES: Case specificity implies that success on any case is specific to that case. In examining the sources of error variance in performance on case-based examinations, how much error variance results from differences between cases compared with differences between items within cases? What is the optimal number of cases and questions within cases to maximise test reliability given some fixed period of examination time? METHODS: G and D generalisability studies were conducted to identify variance components and reliability for each examination analysed, and to optimise the reliability of the given test composition (1, 1.5, 2, 3, 4 and 5 questions per case), using data from 3 key features examinations of the Medical Council of Canada (n = 6342 graduating medical students), each of which consisted of about 35 written cases followed by 1- questions regarding specific key elements of data gathering, diagnosis and/or management. RESULTS: The smallest variance component was due to subjects; the variance due to subject-item interaction was over 5 times the interaction with cases (on average, 0.1106 compared with 0.0195). Relatively little variance was due to differences between cases; about 80% of the error variance was due to variability in performance among items within cases. The D study showed that reliability varied between 0.541 and 0.579, was least with 1 item per case and highest at 2 and 3 items per case. CONCLUSIONS: The main source of error variance was items within cases, not cases, and the optimal strategy in terms of enhancing reliability would use cases with 2-3 items per case.

Analysis of Variance↗
PubMed1994

Dose specification with 3-D dose planning (ICRU 'level 3').

The availability of constantly more sophisticated algorithms and methods for dose planning (denoted 'level 3' procedures by the ICRU) makes it possible to use accordingly more complex treatment techniques. Such procedures have the potential of reducing irradiation of organs at risk and other healthy tissue. However, they suffer from a substantially more difficult set-up of the patient and verification of the treatment. This will introduce additional sources of error, systematic as well as random, which will be of importance for dose reporting. The purpose of this paper is to point out some of these problems and to suggest a method for reporting which is the least sensitive to these 'new' sources of error.

Humans↗
PubMed1975

[Synapse density determination in brain structures based on phosphotungstic acid contrast].

Using the E-PTA procedure of Aghajanian and Bloom we determined the numerical density of synapses in the stratum lacunosun-modeculare of the CA1-region in the hippocampus of male albino rats. On this occasion the sources of error both the natural and the methodical were investigated. As natural causes of remarkable scattering and failing correspondence in the findings the individual variability of the synaptic density and the inhomogeneous distribution of synapses must be taken into consideration. Concerning the methodical sources of error the differences in tissue shrinkage become apparent. But faults resulting from applying morphometric methods are the most serious. The counting of synaptic profiles is based on defined morphological criteria. The portion of the synaptic profiles recorded in this way in relation to all those present in the section depends beside other things on the section thickness. Accordingly the correction factors are in correlation with section thickness. The application of the Floderus correction presupposes the determination of the minimum length of the counted profiles. As a result of these investigated the possibilities for reducing the error have been demonstrated.

Animals↗
PubMed2002

Impact of landmark reliability on the planar Procrustes analysis of tooth shape.

In a recent study, the ideas of Procrustes analysis were introduced to the study of tooth shape for teeth represented as configurations of 'landmarks' from digital images. This study aimed to establish how well the method could be expected to perform (in its standard form) when used on surfaces from a variety of tooth types and, in particular, how much impact inconsistencies in the positioning of landmarks would have on investigations of shape. Using four different operators' images and landmarks from 10 different surfaces from each of 20 patients, the consequences of location inconsistency are evaluated by calculating its effect on the recorded variation in Procrustes fits, obtained for each set of multiple representations. The proportion of variation in shape attributable to actual differences between patients, rather than other sources of error, ranged from only 36 to 65% for the five buccal-surfaces considered and was no more than 30% for any of the five occlusal surfaces. Further examination of these results indicated that consistent orientation differences before imaging might be a particular source of error in obtaining any occlusal-landmark data, as might location ambiguities around the edges of the teeth. Orientation effects were also suggested for the buccal-surfaces of the molar teeth. In contrast, the relatively flatter buccal-surfaces of the incisors and canines produced the most reliable data. Methods of analysis need to accommodate these problems if landmark data are to be used to describe variations in tooth shape. Different surfaces each present their own particular difficulties and so a variety of solutions may be required.

Female↗
PubMed2000

A noninvasive method for estimating acoustic admittance at the tympanic membrane.

The acoustic admittance at the tympanic membrane (TM), Y(TM), describes the linear acoustic properties of the ear. Here, a noninvasive measurement procedure is developed for estimating Y(TM) in intact ears. The method consists of (1) measuring the admittance in the ear canal Y(EC) with a commercially available earphone-and-microphone system, and (2) estimating Y(TM) via a uniform-tube approximation of the space between the measurement point and the TM. The dimensions of this space are estimated from Y(EC) via an area-estimation algorithm [Keefe et al., J. Acoust. Soc. Am. 91, 470 (1992)] and measurements made with controlled static pressures in the canal. Measurements in artificial loads are used to test the accuracy of the measurement system and to determine sources of error. For accurate admittance measurements: (1) extension of the microphone tube medially beyond the earphone's port is necessary for frequencies above 2 kHz; (2) the acoustic system must be calibrated in known loads with diameters within 15% of the canal diameter, because the source's output characteristics vary with load diameter. The method is applied to intact ears of anesthetized domestic cats; for frequencies below 5 kHz, the estimated Y(TM) in four ears have features that are similar to those of previous measurements made at the cat TM. Sources of error include nonuniform waves generated at the earphone's narrow port, inaccuracy in estimation of canal dimensions, irregular geometry of the canal, and earphone-microphone cross talk.

Acoustics↗
PubMed2005

A sensitivity analysis of a randomized controlled trial of zinc in treatment of falciparum malaria in children.

BACKGROUND: The randomized trial has long been recognized as a means to assess the efficacy of new interventions, because the investigator can reduce or eliminate many sources of error. As such, clinical trials often do not include quantitative assessments of the extent that systematic error could affect their results. We examined the impact of different sources of bias on a randomized controlled trial of the efficacy of zinc as an adjuvant to malaria therapy in reducing time to total parasite clearance. METHODS: Using data from a previously published study, we identified two sources of bias and used the sensitivity analysis technique developed by Lash and Fink to assess the impact of each source of bias on the outcome. RESULTS: After correcting for each source of bias and reincorporating random error into our results, the point estimate of effect comparing those who received placebo to those who received zinc changed slightly (SMR changed from 0.92 to 0.90) but the 95% interval increased 22% (changing from 0.73-1.16 in the conventional analysis to 0.65-1.26 in the sensitivity analysis). CONCLUSIONS: The findings of this sensitivity analysis serve as a reminder that the frequentist confidence interval underestimates the total error, even in a randomized controlled trial. Authors of randomized controlled trial investigations ought to conduct a complete assessment of the impact of potential sources of bias in their studies. CONSORT guidelines for reporting trial results should be updated to encourage authors to assess the impact of non-random errors on their studies.

Antimalarials↗
PubMedDate not supplied

An assay for monitoring response to therapy in cancer patients.

Immunosuppression is characteristic of patients with advanced malignant neoplasms. However, none of the simple assays for immunocompetence have been found to provide results which correlate with the patients' responses to therapy. The data reported here indicate that this may be because there are artifacts in data from earlier studies which have obscured such a correlation. A simple assay which removes previously unrecognized sources of error is shown to generate data which correlate well with patient responses. In this assay, lymphocytes collected from patients with malignant solid tumors were stimulated with mitogen in their autologous plasma. The amount of radioactive thymidine incorporated during replicative deoxyribonucleic acid (DNA) synthesis was corrected to remove sources of error ignored in the previous studies. A significant improvement in mitogen-stimulated synthesis was observed within two months for patients entering remission. For patients not responding to therapy, there was a progressive deterioration in mitogen-responsiveness.

Adult↗
PubMed1988

Measurement of local cerebral blood flow with [14C]iodoantipyrine in the mouse.

Local cerebral blood flow was measured in the mouse by means of the [14C]iodoantipyrine method. This method has been previously used in the monkey, dog, cat, and rat, but its application to small mammals such as the mouse requires special attention to potential sources of error. The small size of the mouse brain requires special attention to the rapid removal and freezing of the brain to minimize effects of postmortem diffusion of tracer in the tissue. Because of the relatively low diameter/length ratios of the catheters needed for arterial sampling in small animals, substantial errors can occur in the determination of the time course of the [14C]iodoantipyrine concentration in the arterial blood unless corrections for lag time and dead space washout in the catheter are properly applied. Local cerebral blood flow was measured in seven awake mice with appropriate care to minimize these sources of error. The values were found to vary from 48 ml/100 g/min in the corpus callosum to 198 ml/100 g/min in the inferior colliculus. The results demonstrate that the [14C]iodoantipyrine method can be used to measure local cerebral blood flow in the mouse and that the values in that species are, in general, somewhat higher than those in the rat.

Animals↗
PubMed1986

Computed tomographic volumetric calculation reproducibility.

Previous studies have described computed tomographic (CT) measurement of the total volume of large organs and tumors. This study examines sources of error in the CT volumetric measurement of small anatomic structures, and has potential application to the volumetric measurement of small extravisceral tumors. Volume is determined by multiplying observer measurement of area by the CT slice thickness. We focused on the measurement of small cross-sectional areas as a major source of error in volumetric calculations. One observer made ten area measurements on each of 12 structures of various sizes. For areas larger than 8 to 10 cm2, any single measurement was within 2 to 4% of the mean of ten values. For areas smaller than 8 to 10 cm2, measurements varied more with respect to the mean, and rose approximately exponentially as the measured cross-sectional area approached zero.

Humans↗
PubMed1998

Generalizability theory: a unified approach to assessing the dependability (reliability) of measurements in the health sciences.

The reliability of health promotion program evaluation measures, behavioral and attitudinal measures, and clinical measures is a concern to many health educators. Classical reliability coefficients, such as Cronbach's alpha, apply to narrowly defined, prespecified measurement situations. Classical theory does not provide adequate reliability assessments for criterion-referenced measures, for measurement situations having multiple sources of error, or for aggregate-level variables. Generalizability theory can be used to assess the reliability of measures in these situations that are not adequately modeled by Classical theory. Additionally, Generalizability theory affords a broader view and a deeper understanding of the dependability of measurements and the role of different sources of error in the variability of measures.

Health Promotion↗
PubMed1999

The impact of edema on planning 125I and 103Pd prostate implants.

Permanent transperineal interstitial 125I and 103Pd prostate implants are generally planned to deliver a specific dose to a clinically defined target volume; however, the post-implant evaluation usually reveals that the implant delivered a lower or higher dose than planned. This difference is generally attributed to such factors as source placement errors, overestimation of the prostate volume on CT, and post-implant edema. In the present work we investigate the impact of edema alone. In routine prostate implant planning, it is customary to assume that both the prostate and seeds are static throughout the entire treatment time, and post-implant edema is not taken into consideration in the dosimetry calculation. However, prostate becomes edematous after seed implantation, typically by 50% in volume [Int. J. Radiat. Oncol., Biol., Phys. 41, 1069-1077 (1998)]. The edema resolves itself exponentially with a typical half-life of 10 days. In this work, the impact of the edema-induced dynamic change in prostate volume and seed location on the dose coverage of the prostate is investigated. The total dose delivered to the prostate was calculated by use of a dynamic model, which takes edema into account. In the model, the edema resolves exponentially with time, as reported in a separate study based on serial CT scans [Int. J. Radiat. Oncol., Biol., Phys. 41, 1069-1077 (1998)]. The model assumes that the seeds were implanted exactly as planned, thus eliminating the effect of source placement errors. Implants based on the same transrectal ultrasound (TRUS) images were planned using both 125I and 103Pd sources separately. The preimplant volume and planned seed locations were expanded to different degrees of edema to simulate the postimplant edematous prostate on day 0. The model calculated the dose in increments of 24 h, appropriately adjusting the prostate volume, seed locations, and source strength prior to each time interval and compiled dose-volume histograms (DVH) of the total dose delivered. A total of 30 such DVHs were generated for each implant using different combinations of edema half-life and magnitude. In addition, a DVH of the plan was compiled in the conventional manner, assuming that the prostate volume and seeds were static during treatment. A comparison of the DVH of the static model to the 30 edema corrected DVHs revealed that the plan overestimated the total dose by an amount that increased with the magnitude of the edema and the edema half-life. The maximum overestimation was 15% for 125I and 32% for 103Pd. For more typical edema parameters (a 50% increase in volume and a 10 day half-life) the static plan for 125I overestimated the total dose by about 5%, whereas that for 103Pd overestimated it by about 12%.

Brachytherapy↗
PubMed2005

Infovigilance: reporting errors in official drug information sources.

INTRODUCTION: The French drug database Thériaque (http://www.theriaque.org) developed by the (Centre National Hospitalier d'Information sur le Médicament) (CNHIM), is responsible for the dissemination of independent information about all drugs available in France. Each month the CNHIM pharmacists report problems due to inaccuracies in these sources to the French drug agency. In daily practice we devised the term "infovigilance": "Activity of error or inaccuracy notification in information sources which could be responsible for medication errors". The aim of this study was to evaluate the impact of CNHIM infovigilance on the contents of the Summary of Product Characteristics (SPCs). METHOD: The study was a prospective study from 09/11/2001 to 31/12/2002. The problems related to the quality of information were classified into four types (inaccuracy/confusion, error/lack of information, discordance between SPC sections and discordance between generic SPCs). MAIN OUTCOME MEASURES: (1) Number of notifications and number of SPCs integrated into the database during the study period. (2) Percentage of notifications for each type: with or without potential patient impact, with or without later correction of the SPC, per section. RESULTS: 2.7% (85/3151) of SPCs integrated into the database were concerned by a notification of a problem. Notifications according to type of problem were inaccuracy/confusion (32%), error/lack of information (13%), discordance between SPC sections (27%) and discordance between generic SPCs (28%). 55% of problems were evaluated as 'likely to have an impact on the patient' and 45% as 'unlikely to have an impact on the patient'. 22 of problems which have been reported to the French drug agency were corrected and new updated SPCs were published with the corrections. CONCLUSIONS: Our efforts to improve the quality of drug information sources through a continuous "infovigilance" process need to be continued and extended to other information sources.

Contraindications↗
PubMed2004

The EDNAP mitochondrial DNA population database (EMPOP) collaborative exercises: organisation, results and perspectives.

This paper presents an overview of the organisation and the results of the collaborative exercises (CE) of the European DNA Profiling (EDNAP) Group's mitochondrial DNA population database project (EMPOP). The aim of the collaborative exercises was to determine whether uniformity of mtDNA sequencing results could be achieved among different laboratories. These were asked to sequence either the complete mtDNA control region or the two hypervariable regions HVI (16024-16365) and HVII (73-340) from DNA extracts, buccal swabs or bloodstains, proceeding in accordance with the protocol and strategies used in each individual laboratory. The results of the collaborative exercises were employed to identify possible sources of errors that could arise during the analysis and interpretation of mtDNA profiles. These findings were taken as a basis to tentatively make suitable arrangements for the construction of a high quality mtDNA database. One hundred fifty mtDNA profiles were submitted to the evaluating laboratory, and disaccording profiles were classified into four groups corresponding to the source of error: clerical errors, sample mix-ups, contaminations and discrepancies with respect to the mtDNA nomenclature. Overall, 14 disaccording haplotypes (16 individual errors) were observed. The errors included 10 clerical errors, 3 interpretation problems, 2 cases of sample mix-up and 1 case of point heteroplasmic mixture, where the 2 sequencing reactions brought inconsistent base calls. This corresponds to an error rate of 10.7% in a virtual mtDNA database consisting of the collaborative exercise results. However, this estimate is still conservative compared to conclusions drawn by authors of meanwhile numerous publications critically reviewing published mtDNA population databases. Our results and earlier published concerns strongly emphasize the need for appropriate safety regulations when mtDNA profiles are compiled for database purposes in order to accomplish the high standard required for mtDNA databases that are used in the forensic context.

Clinical Laboratory Techniques↗
PubMed1996

Measurement of spin-lattice relaxation times and kinetic rate constants in rat muscle using progressive partial saturation and steady-state saturation transfer.

31P spin-lattice relaxation times (T1) of metabolites in rat calf muscle at 1.9 Tesla and the forward rate through the creatine kinase (CK) reaction have been measured using a new method based on modeling progressive saturation explicitly incorporating the effect of chemical exchange. In a separate series of experiments, we compared our method with inversion recovery both in vitro and in vivo, finding agreement between the techniques. We found that the T1 values of phosphocreatine (PCr) (6.6 +/- 0.3 s), gamma-ATP (2.6 +/- 0.6 s), alpha-ATP (2.4 +/- 0.4 s) and beta-ATP (2.2 +/- 0.2 s) are unchanged by stimulation of sufficient intensity to induce a 32% drop in PCr level. The errors in T1 values which arise when chemical exchange is neglected are calculated. These are found to be on the order of 20% for PCr and 30-50% for gamma-ATP under typical conditions. Use of longer repetition times results in larger errors in measured values of T1. This source of error can be effectively eliminated by use of sufficiently short repetition times. We found that the rate constant of the forward CK reaction was increased 60% by stimulation, from 0.20 +/- 0.03 s-1 to 0.32 +/- 0.03 s-1, but that the phosphorus flux did not change.

Animals↗
PubMed2001

Extraction of CO2 from air samples for isotopic analysis and limits to ultra high precision delta18O determination in CO2 gas.

The determination of delta18O values in CO2 at a precision level of +/-0.02 per thousand (delta-notation) has always been a challenging, if not impossible, analytical task. Here, we demonstrate that beyond the usually assumed major cause of uncertainty - water contamination - there are other, hitherto underestimated sources of contamination and processes which can alter the oxygen isotope composition of CO2. Active surfaces in the preparation line with which CO2 comes into contact, as well as traces of air in the sample, can alter the apparent delta18O value both temporarily and permanently. We investigated the effects of different surface materials including electropolished stainless steel, Duran glass, gold and quartz, the latter both untreated and silanized. CO2 frozen with liquid nitrogen showed a transient alteration of the 18O/16O ratio on all surfaces tested. The time to recover from the alteration as well as the size of the alteration varied with surface type. Quartz that had been ultrasonically cleaned for several hours with high purity water (0.05 microS) exhibited the smallest effect on the measured oxygen isotopic composition of CO2 before and after freezing. However, quartz proved to be mechanically unstable with time when subjected to repeated large temperature changes during operation. After several days of operation the gas released from the freezing step contained progressively increasing trace amounts of O2 probably originating from inclusions within the quartz, which precludes the use of quartz for cryogenically trapping CO2. Stainless steel or gold proved to be suitable materials after proper pre-treatment. To ensure a high trapping efficiency of CO2 from a flow of gas, a cold trap design was chosen comprising a thin wall 1/4" outer tube and a 1/8" inner tube, made respectively from electropolished stainless steel and gold. Due to a considerable 18O specific isotope effect during the release of CO2 from the cold surface, the thawing time had to be as long as 20 min for high precision delta18O measurements. The presence of traces of air in almost all CO2 gases that we analyzed was another major source of error. Nitrogen and oxygen in the ion source of our mass spectrometer (MAT 252, Finnigan MAT, Bremen, Germany) give rise to the production of NO2 at the hot tungsten filament. NO2+ is isobaric with C16O18O+ (m/z 46) and interferes with the delta18O measurement. Trace amounts of air are present in CO2 extracted cryogenically from air at -196 degrees C. This air, trapped at the cold surface, cannot be pumped away quantitatively. The amount of air present depends on the surface structure and, hence, the alteration of the measured delta18O value varies with the surface conditions. For automated high precision measurement of the isotopic composition of CO2 of air samples stored in glass flasks an extraction interface ('BGC-AirTrap') was developed which allows 18 analyses (including standards) per day to be made. For our reference CO2-in-air, stored in high pressure cylinders, the long term (>9 months) single sample precision was 0.012 per thousand for delta13C and 0.019 per thousand for delta18O.

Air Pollution↗
PubMed1988

Error analysis in equilibrium dialysis: evaluation of adsorption phenomena.

Various sources of error in equilibrium dialysis may lead to inaccurate results of binding experiments: (i) the finite time of dialysis; (ii) the Donnan effects; (iii) the adsorption of ligand to the membrane; and (iv) release of contaminating material from dialysis casings. These errors were analyzed for a polynucleotide-oligopeptide model system with particular regard to adsorption phenomena and the underlying mechanisms. Adsorption data were treated according to Freundlich and Langmuir isotherms. The latter turned out to be more appropriate for the consideration of adsorption phenomena with respect to a minimum error propagation. Furthermore, it was shown that the degree of adsorption varies with ionic strength and temperature and could be interpreted in terms of polyelectrolyte theory. The kinetics of both adsorption and of the ligand distribution between the polymer and buffer compartments follow first order at the beginning of dialysis which is in line with a simple diffusion process. After 13-15 h data deviate from first order kinetics indicating an alteration in the transport mechanism. The effects of errors on binding parameters were determined and a detailed protocol for correction is presented allowing one to obtain binding data from equilibrium dialysis experiments with the required degree of accuracy. The fundamental principles and results for the system under investigation generally apply to all protein-ligand systems.

Adsorption↗
PubMed2004

Two dimensions of measurement error: classical and Berkson error in residential radon exposure assessment.

Measurement error in exposure assessment is unavoidable. Statistical methods to correct for such errors rely upon a valid error model, particularly regarding the classification of classical and Berkson error, the structure and the size of the error. We provide a detailed list of sources of error in residential radon exposure assessment, stressing the importance of (a) the differentiation between classical and Berkson error and (b) the clear definitions of predictors and operationally defined predictors using the example of two German case-control studies on lung cancer and residential radon exposure. We give intuitive measures of error size and present evidence on both the error size and the multiplicative structure of the error from three data sets with repeated measurements of radon concentration. We conclude that modern exposure assessment should not only aim to be as accurate and precise as possible, but should also provide a model of the remaining measurement errors with clear differentiation of classical and Berkson components.

Bias↗
PubMed1993

Rounding error, an unexpected fault in the output from a recording spectrophotometer: implications for model discrimination.

Although commonly ignored in discussions of experimental error, rounding may sometimes be the major source of error, especially with modern precision instruments: some recording spectrophotometers are optically and photometrically capable of making absorbance measurements with errors less than 0.0003, but provide no numerical information more precise than +/- 0.001. The problem may be diagnosed by a characteristic arrangement of points in a residual plot, which resembles the result of cutting a stroboscopic picture of a bouncing ball into several strips and modifying it by sliding the strips relative to one another to bring the points closer to the axis. Harmful effects of rounding error can be critical in experiments designed for model discrimination.

Enzymes↗