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Pathologists' attitudes to implementing telepathology.

If pathologists will benefit so much from using telepathology, why is it taking so long to be introduced? This question has been discussed between experts, but the potential users are rarely asked for their opinions. A questionnaire was sent to the 256 members of the Austrian Society of Pathology; this addressed general aspects of telemedicine, telepathology in frozen-section services and expert consultation, videoconferencing technologies, teleteaching and teletraining. The response rate was 46%. In general, the pathologists thought that telemedicine could become valuable in their daily routine. However, pathologists were most afraid of sampling errors in remote diagnosis and would not readily accept an alternative to the conventional method of looking at a sample. This is only possible using realtime, remotely controlled microscopes. Telepathology systems providing only still images would not be acceptable to most respondents. There was interest in the use of videoconferencing for clinicopathological conferences. Teleteaching and teletraining were seen as welcome additional techniques, but were nevertheless judged unable to replace classical methods of teaching and training.

Attitude of Health Personnel↗

Is there a way for pathologists to decrease interobserver variability in the diagnosis of dysplasia?

Many obstacles interfere with our efforts to screen patients with Barrett esophagus. Probably the largest is choosing the appropriate patient group for screening. Beyond this problem, sampling error on the part of endoscopists is probably more serious a problem than observer variation among pathologists reviewing patient samples. Pathologists agree well on lesions that merit close follow-up or other intervention (high-grade dysplasia and invasive carcinoma), although interobserver agreement between pathologists interpreting lesser lesions is not good. This lack of agreement is not likely to improve substantially, and many adjunct markers are being sought in an attempt to identify patients with lesions of lower grades that are most likely to progress, allowing doctors to identify patients who would benefit from upgraded surveillance.

Barrett Esophagus↗

Micro CT and Micro MR imaging of 3D architecture of animal skeleton.

Quantitative assessment of three-dimensional (3D) trabecular structural characteristics may improve our ability to understand the pathophysiology of osteoporosis, to test the efficacy of pharmaceutical intervention, and to estimate bone biomechanical properties. Considerable progress has been made in advanced imaging techniques for noninvasive and/or nondestructive assessment of 3D trabecular structure and connectivity. Micro computed tomography (microCT) has been used to measure 3D trabecular bone structure in rats, both in vivo and in vitro. It can directly quantify 3D trabecular bone structure such as trabecular volume, trabecular thickness, number, separation, structure model index, degree of anisotropy, and connectivity, in a model-independent manner. We have used microCT to study ovariectomy (OVX) induced osteopenia in rats and its treatment with agents such as estrogen, and sodium fluoride. We have demonstrated that 3D microCT can quantify mouse trabecular and cortical bone structure with an isotropic resolution of 9 microm(3). It is also useful for studying osteoporosis in mice and in phenotypes of transgenic mice or gene knockout mice. MicroCT can be used to quantify osteogenesis in mouse Ilizarov leg lengthening procedures, to quantify osteoconduction in a rat cranial defect model, and to quantify cortical bone porosity. Recently, microCT using high intensity and tight collimation synchrotron radiation to achieve spatial resolution of 1-2 microm has provided the capability to assess additional features such as resorption cavities. Unlike microCT, micro magnetic resonance imaging (IMRI) is nonionizing. Recently, the ability of microMRI to assess osteoporosis in animal models has been explored. Using a small, high-efficiency coil in a high-field imager, microMRI can give resolutions sufficient to discriminate individual trabeculae. We have shown that, with appropriate settings, it is possible to image trabecular bone in rats in vivo and in vitro. In our study of OVX rats, analysis of microMR images can demonstrate differences in rat trabecular bone that are not detected by DXA measurements. In a rabbit OA model, with the OA induced by meniscectomy or anterior cruciate ligament transection, MRI shows decreased cartilage thickness, subchondral osteosclerosis and osteophytes, while radiographs can only show subchondral osteosclerosis and osteophytes could not be found. Advanced imaging methods are able to measure 3D trabecular structure and connectivity in arbitrary orientations in a highly automated, objective, non-user-specific manner, allowing greater numbers of samples for unbiased comparisons between controls and the disordered or treated. They can be utilized on a large sample leading to fewer sampling errors. They are non-destructive allowing multiple tests such as biomechanical testing and chemical analysis on the same sample; and non-invasive permitting longitudinal studies and reducing the number of animals needed.

Journal Article↗

Language differences and the family planning survey.

Language is an important but often neglected source of non-sampling error in family planning surveys. This paper examines the problems of language usage and of translation, in KAP surveys in particular, using examples from African and other research experience. The authors emphasize that language pervades all stages of family planning surveys, pointing out that interpretations of survey results should take into account the possibility of the influence of language differences. Various measures are suggested that can contribute to minimizing this source of response error.

Africa↗

Limitations of child injury data from the CPSC's National Electronic Injury Surveillance System: the case of baby walker related data.

OBJECTIVES: The US Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) is a primary source for children's consumer product injury surveillance data in the US. Differing interpretations of the emergency department based NEISS baby walker data by various parties prompted this detailed examination, reclassification, and analysis of the NEISS data to explain these discrepancies. METHODS: Case selection was performed by searching the NEISS 1982-91 database for the baby walker product code and various text strings for children less than 24 months old. False negative and false positive cases were identified and reclassified. Adjusted population rates were computed and the types and locations of hospitals contributing to the sample were examined. RESULTS: One per cent false positive and 4% false negative misclassification rates were observed. In 1991, two children's hospitals reported 14% of the baby walker related injuries, though these hospitals made up just 2% of the sample frame. Through random allocation, one state currently contains four acute care hospitals and the only two children's hospitals reporting to the NEISS system. These six hospitals contributed 18% of the walker cases whereas the state represents only 3% of the US infant population. CONCLUSIONS: Misclassification in NEISS baby walker reports is minimal, with false negatives outweighing false positives. For trend analysis of product related injuries at the frequency of occurrence observed for baby walkers, NEISS suffers from low sensitivity due to sampling error. For children's injuries, NEISS' estimates have been affected by children's hospitals coming in and out of the sample and currently reflects a random geographic imbalance because one state contributes both of the reporting children's hospitals. To overcome these problems improved multiple product coding, a unique baby walker code, and stratification of children's hospitals in an enlarged NEISS sample is recommended.

Accident Prevention↗

The impact of diagnostic error on testing genetic association in case-control studies.

In case-control studies, subjects in the case group may be recruited from suspected patients who are diagnosed positively with disease. While many statistical methods have been developed for measurement error or misclassification of exposure variables in epidemiological studies, no studies have been reported on the effect of errors in diagnosing disease on testing genetic association in case-control studies. We study the impact of using the original Cochran-Armitage trend test assuming no diagnostic error when, in fact, cases and controls may be clinically diagnosed by an imperfect gold standard or a reference test. The type I error, sample size and asymptotic power of trend tests are examined under a family of genetic models in the presence of diagnostic error. The empirical powers of the trend tests are also compared by simulation studies under various genetic models.

Case-Control Studies↗

Determination of interstitial water chemistry and porosity in consolidated aquifer materials by diffusion equilibrium-exchange.

Diffusion equilibrium exchange (DEE) is presented as a novel, practical alternative to centrifugation for the recovery and chemical analysis of interstitial water in contaminated core samples from consolidated rocks and aquifers. The methodology is suitable for sampling organic and inorganic compounds, including redox sensitive species such as SO4(2-), NO3-, NO2-, Mn(II), Fe(II), and sulfide (HS-). DEE also permits analyte extraction from kilogram quantities of core, which avoids extended centrifugation or sample amalgamation and provides analyte masses appropriate for stable isotope analysis. The procedure involves simple and rapid on-site sectioning of representative core samples, which are preserved in the field by storage in airtight bottles filled with deoxygenated deionized water containing a conservative tracer (Br-). Equilibration times for individual solutes can be estimated in advance to reduce the need for time-series analysis; for an effective diffusion coefficient of 2.5 x 10(-10) m2 s(-1) (Br- in chalk rock) equilibration was >90% completed after 30 h, consistent with the predicted equilibration time. The DEE method presented minimizes sampling errors from temperature changes, oxidation of reduced chemical species, and loss of volatile compounds, which can occur with other interstitial water sampling techniques. It also gives superior resolution of in situ solute distributions and geochemical processes in consolidated sediments than centrifugation and can provide estimates of aquifer porosity in core samples. Laboratory experiments using chalk rock core and simulated extraction procedures confirm the superior performance of the DEE method over centrifugation for a range of solutes. The method has been used to generate detailed interstitial water profiles of electron acceptor and contaminant concentrations along the flow path of a petroleum hydrocarbon plume in the U.K. Upper Chalk aquifer as part of a natural attenuation assessment.

Environmental Monitoring↗

Precision and accuracy of foundry dust exposure estimates from air sampling data.

Errors in the sampling methods and in the determination of respirable size quartz in foundry dust have been evaluated and discussed. In general, the total precision of dust sampling and analysis was better than 20%. The term "exposure dose" is introduced and defined. The temporal variation associated with measuring exposure dose is assessed with reference to the use of a log-normal distribution of air sampling results. The logarithmic standard deviations of dust concentrations at fixed sites and jobs are calculated.

Air Pollutants↗

Statistical characterization of the random errors in the radioimmunoassay dose--response variable.

We have developed practical methods for evaluating the magnitude of the random errors in radioimmunoassay dose--response variables, and the relationship between this error and position on the dose--response curve. This is important: to obtain appropriate weights for each point on the dose--response curve when utilizing least-squares curve-fitting methods; to evaluate whether the standards and the unknowns are subject to error of the same magnitude; for quality-control purposes; and to study the sources of errors in radioimmunoassay. Both standards and unknowns in radioimmunoassays for cAMP and cGMP were analyzed in triplicate. The same mean (Y), sample standard deviation, sy, and variance (2-y) of the response variable were calculated for each dose level. The relationship between s 2-y and y was calculated utilizing several models. Results for standards and unknowns from several assays were pooled, and a curve smoothing procedure was used to minimize random sampling errors. This pooling increased the reliability of the analysis, and confirmed the presence of the theoretically predicted nonuniformity of variance. Thus, the calculation of results from these radioimmunoassays should utilize a weighted least-squares curve-fitting program. These analyses have been computerized, and can be used as a "pre-processor" for programs for routine analysis of results of radioimmunoassay.

Analysis of Variance↗

Histomorphometric analysis: comparative study of manual and digital image analysis using reproductive organ as a model.

A preliminary analysis of the histological features of testes was carried out on vertical serial sections stained with hematoxylin and eosin techniques. The total spermatogonia per view and areas of seminiferous tubules by means of digitizing the tissue followed by morphometric analysis using software run on a personal computer. The data generated was then compared with traditional manual determinations made by using the ocular scale as well as the x and y coordinated on the light microscope. The data obtained showed that the modified Image Pro system for digitizing and data analysis allowed for high-resolution acquisition of the images as well as relatively high sensitivity of image integration. The results also show more accuracy and repeatability of sampling and a decrease in sampling error between repeated measures compared with the conventional manual measurements. Overall, the use of modified Image Pro digital technology will offer a more accurate and quantitative method to perform routine histomorphometric analysis, as well as allow for repeated measurements of the same sample from several reviewers in a blinded fashion with substantially less error.

Animals↗

Grading prostate cancer.

Histologic tumor grade is a strong predictor of outcome for men with prostate cancer. All existing grading systems successfully identify well-differentiated cancer, which progresses slowly, and poorly differentiated cancer, which progresses rapidly, but they are less successful in subdividing most moderately differentiated cancers, which have an intermediate malignant potential. The Gleason system, the de facto standard for grading, identifies histologic patterns by the degree of glandular differentiation without relying on morphogenetic or histogenetic models; it reflects tumor heterogeneity by combining primary and secondary patterns into a cancer score. Modifications that have been proposed for Gleason grading include morphometric nuclear grading, grouping of grades, estimating the amount of high-grade cancer (Gleason patterns 4 and 5), and including the cribriform pattern as Gleason pattern 4 rather than 3. Most variants of prostate cancer are high grade (Gleason patterns 4 and 5), including small cell undifferentiated carcinoma, signet ring cell carcinoma, sarcomatoid carcinoma, and carcinosarcoma. The Gleason system can be reproduced by most investigators, although there is a small but significant level of interobserver and intraobserver variability that is unavoidable. When compared with matched prostatectomy specimens, contemporary 18-gauge needle core biopsy underestimates tumor grade in 33% to 45% of cases and overestimates grade in 4% to 32% of cases, similar to results with traditional 14-gauge biopsies. Grading errors are common in biopsy specimens with small amounts of tumor and low-grade tumor, and are probably due to tissue sampling error and tumor heterogeneity. Upgrading of prostate cancer may occur after radiation therapy but is common after androgen-deprivation therapy. Univariate and multivariate analyses of prognosis in prostate cancer almost always identify cancer grade as one of the most significant predictors of patient outcome. The combination of cancer grade with other prognostic variables to create a multiple prognostic index should allow greater precision in predicting outcome for individual patients.

Biopsy, Needle↗

Accuracy of stereotactic brain tumor biopsy: comparison of the histologic findings in biopsy cylinders and resected tumor tissue.

Appropriate treatment for intracranial mass lesions depends upon accurate morphological diagnosis. In 47 of 360 patients the findings in stereotactically obtained tissue cylinders were compared with tumor resection (n = 38) or autopsy (n = 9) tissue material to define the accuracy of our stereotactic biopsy method. These biopsies were performed using the LEKSELL CT stereotactic frame and a spiral needle which procured about 10-mm-long tissue cylinders. Usually, three to four successive biopsy specimens were taken along the target trajectory placed through the whole lesion and its margins according to the CT imagings. Final morphological diagnosis was exclusively based on the histological findings of permanent paraffin sections. In 42 cases (89%), the histological results in biopsy and resection/autopsy tissue were identical, including mainly cases of low and high grade gliomas as well as some brain lymphomas, metastases, and cases of inflammatory brain lesions (aspergillosis, toxoplasmosis). In 3 patients with a diagnosis of brain lymphoma and low grade glioma on the basis of the surgical specimens, stereotactic biopsy revealed only unspecific reactive tissue changes. In two cases of the early part of the study, sampling errors occurred. This study provides evidence for the high diagnostic accuracy of the established stereotactic biopsy method which is characterized by representative tissue sampling and histological processing of the specimens.

Astrocytoma↗

Analytical aspects of the CEEM soil project.

In the past, exercises aiming at an assessment of data uncertainty in environmental analysis were usually restricted to the analysis step, while sampling and pre-analytical sample treatment was largely ignored. Collaborative studies on the quantification of sampling errors require, besides a suitable and well characterized test site, the availability of a reference laboratory for the analysis of all of the samples taken in the context of the study by all participants and also test methods which do not contribute large and variable uncertainties due to long and complex analytical methodologies. Here we summarize the major analytical aspects of a European project on the identification and quantification of sampling influences on the determination of lead, cadmium, copper and zinc in soil. The participant group included the leading soil analysis laboratories in Europe; the test site at Dornach (CH) was well suited for the purpose and showed high metal gradients and differentiated land use. The analytical methods (wavelength-dispersive X-ray fluorescence spectrometry and solid-state Zeeman AAS) used in the study showed stable performance characteristics within the confidence interval of the certified reference materials used for the measurement quality control over the entire project period. Additionally, double-blind tests on split samples showed agreement of data in very narrow limits thus demonstrating the reliability of the reference database.

Databases, Factual↗

Free energy perturbation study of water dimer dissociation kinetics.

An efficient approach is described for using accurate ab initio calculations to determine the rates of elementary condensation and evaporation processes that lead to nucleation of aqueous aerosols. The feasibility of the method is demonstrated in an application to evaporation rates of water dimer at 230 K. The method, known as ABC-FEP (ab initio/classical free energy perturbation), begins with a calculation of the potential of mean force for the dissociation (evaporation) of small water clusters using a molecular dynamics (MD) simulation with a model potential. The free energy perturbation is used to calculate how changing from the model potential to a potential calculated from ab initio methods would alter the potential of mean force. The difference in free energy is the Boltzmann-weighted average of the difference between the ab initio and classical potential energies, with the average taken over a sample of configurations from the MD simulation. In principle, the method does not require a highly accurate model potential, though more accurate potentials require fewer configurations to achieve a small sampling error in the free energy perturbation step. To test the feasibility of obtaining accurate potentials of mean force from ab initio calculations at a modest number of configurations, the free energy perturbation method has been used to correct the errors when some standard models for bulk water (SPC, TIP4P, and TIP4PFQ) are applied to water dimer. To allow a thorough exploration of sampling issues, a highly accurate fit to results of accurate ab initio calculations, known as SAPT-5s, as been used a proxy for the ab initio calculations. It is shown that accurate values for a point on the potential of mean force can be obtained from any of the water models using ab initio calculations at only 50 configurations. Thus, this method allows accurate simulations of small clusters without the need to develop water models specifically for clusters.

Aerosols↗

Cotton dust sampling, III-estimation of statistical errors with vertical elutriators.

Cotton dust levels measured by vertical elutriators have been studied in terms of the variance components associated with statistical errors due to sampling equipment, location, time and repeated sampling. A thumb-rule is proposed for estimating sampling errors of three-hour vertical elutriator samples as a function of average dust level. Relative efficiency of three-hour samples is shown to be superior to that of six-hour samples at moderate dust levels (0.4-0.6 mg/m3) but inferior at low dust levels (0.1-0.2 mg/m3. Errors due to location and equipment are found insignificant from this particular study.

Air Pollutants↗

Gender-specific effects of drugs on hearing levels of older persons.

As part of a study of human presbyacusis, a questionnaire on medicinal drug usage was given to 357 subjects (184 females, 173 males). Previous results from 211 subjects showed gender effects, that is, for males, none of the drugs had any measurable effects on hearing, whereas women taking calcium channel blockers (CCBs) had hearing levels 12 dB better than women not taking them; women taking beta adrenergic medication had hearing levels 20 dB poorer, and women taking antihistamine/cold preparations had hearing levels 9 dB poorer. Results from the original 211 subjects were confirmed when the sample size was increased from 211 to 357 subjects only for the beta adrenergic medications. Results for antihistamine/cold preparation medications showed small effects only for female subjects. Data from 13 additional female subjects who used CCBs showed hearing levels 10-14 dB poorer than predicted from the original data. Male data were consistent in both samples. The inconsistency for females could reflect sampling error. A more likely possibility is that since the original 10 subjects using CCBs had a mean age of 72 yr and the second sample of 13 had a mean age of 79.5 yr, poorer hearing levels might be anticipated because of the difference in chronological age and possibly duration of drug usage.

Adrenergic beta-Agonists↗

Possible alterations in correspondence associated with asymmetric convergence.

Available nonius horopter data in asymmetric convergence has been reanalyzed by computing the binocular disparity of each horopter datum point relative to the Vieth - Müller circle. The results of this analysis on the best available data indicate that some corresponding points do shift upon asymmetric gaze. Because such convergence postures involve different eye movement innervational patterns, it is suggested that this is the cause of these apparent alterations. Some of the remaining data showed nonsystematic changes in experimental errors, suggesting that unintentional shifts in fixation may have occurred; unintentional tactile cues (used in making the actual settings) may have been present; and sampling errors may have influenced these particular findings.

Eye Movements↗

Effects of systematic exposure assessment errors in partially ecologic case-control studies.

BACKGROUND: In ecologic studies, group-level rather than individual-level exposure data are used. When using group-level exposure data, established by sufficiently large samples of individual exposure assessments, the bias of the effect estimate due to sampling errors or random assessment errors at the individual-level is generally negligible. In contrast, systematic assessment errors may produce more pronounced errors in the group-level exposure measures, leading to bias in ecologic analyses. METHODS: We focus on effects of systematic exposure assessment errors in partially ecologic case-control studies. Individual-level information on disease status, group membership, and covariates is obtained from registries, whereas the exposure is a group-level measure obtained from an established exposure database. Effects on bias and coverage of 95% CI in various error situations are investigated under the linear risk model, using both simulated and empirical ecologic data on exposures that are binary at the individual level. RESULTS: Our simulations suggest that the bias produced by systematic exposure assessment errors under the linear risk model is generally approximately equal to the ratio of the slope bias and the intercept bias in ordinary linear regression with measurement errors in the independent variable. Consequently, bias in either direction can occur. Exposure assessment errors that systematically distort the group-level exposure measures have more pronounced effects on bias and coverage than errors producing random fluctuations of the group-level measures, which imply bias towards the null. CONCLUSIONS: The results indicate the need for careful consideration of potential effects of systematic distortions of the group-level exposure measures when constructing and applying group-level exposure databases, such as probabilistic job exposure matrices.

Bias↗