SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Sample convection can severely attenuate the signals observed in pulsed field gradient spin--echo experiments such as those used for gradient shimming. A new class of pulse sequences is proposed, in which a double spin--echo refocuses the phase errors caused by sample convection, enabling gradient shimming to be performed reliably over a wide range of temperatures.
Explore the source record for details and available documents.
The short-term retention of nonhuman primates for a single sample or for two successively presented samples was assessed in four delayed matching-to-sample experiments with delays of .03, 4, 8, 16, and 32 sec. The single sample tasks included one (Experiment 1) or two (Experiment 4) distractor stimuli in the choice set (matching test). In the two successive samples tasks, the animals matched (reconstructed) the order of presentation of two samples with (Experiment 3) and without (Experiment 2) a distractor stimulus. Also, the possible combinations of eight stimuli (four colors and four shapes) were arranged to test the effects of sample set and choice set similarity. Taken together, analyses of the errors indicated that both sample and choice set similarity were significant sources of confusions in delayed matching. Order errors occurred independently of similarity but were a source of forgetting primarily at the longest delays (16 and 32 sec). Two exceptions to the similarity effect (second response errors in Experiment 3 and errors of an inexperienced group in Experiment 4) were observed. Possible reasons for the exceptions and several implications of these findings for theories of short-term memory are discussed.
Conceptual river water quality models are widely known to lack identifiability. The causes for that can be due to model structure errors, observational errors and less frequent samplings. Although significant efforts have been directed towards better identification of river water quality models, it is not clear whether a given model is structurally identifiable. Information is also limited regarding the contribution of different unidentifiability sources. Taking the widely applied CSTR river water quality model as an example, this paper presents a theoretical proof that the CSTR model is indeed structurally identifiable. Its uncertainty is thus dominantly from observational errors and less frequent samplings. Given the current monitoring accuracy and sampling frequency, the unidentifiability from sampling frequency is found to be more significant than that from observational errors. It is also noted that there is a crucial sampling frequency between 0.1 and 1 day, over which the simulated river system could be represented by different illusions and the model application could be far less reliable.
The most commonly used estimator for a log-normal mean is the sample mean. In this paper, we show that this estimator can have a large mean square error, even for large samples. Then, we study three main alternative estimators: (i) a uniformly minimum variance unbiased (UMVU) estimator; (ii) a maximum likelihood (ML) estimator; (iii) a conditionally minimal mean square error (MSE) estimator. We find that the conditionally minimal MSE estimator has the smallest mean square error among the four estimators considered here, regardless of the sample size and the skewness of the log-normal population. However, for large samples (n > or = 200), the UMVU estimator, the ML estimator, and the conditionally minimal MSE estimators have very similar mean square errors. Since the ML estimator is the easiest to compute among these three estimators, for large samples we recommend the use of the ML estimator. For small to moderate samples, we recommend the use of the conditionally minimal MSE estimator.
OBJECTIVE: To assess use of quality control (QC) material, supplemental to internal kit controls (calibrators), as protection against errors in enzyme immunoassay testing for human immunodeficiency virus type 1 antibodies. DESIGN: From August 1994 to January 1996, enzyme immunoassay testing accuracy was assessed for laboratories participating in the Centers for Disease Control and Prevention Model Performance Evaluation Program that provided information regarding their use of QC material. Error rates were examined for human immunodeficiency virus type 1 antibody-negative, strongly positive, and weakly positive samples. RESULTS: The overall error rate with QC (2.20%) was significantly (P = .0023) lower than the error rate without QC (2.90%). With QC use there was a significant reduction in the relative risk of error for negative (P = .014) and weakly positive (P = .0067) samples. After multivariate analysis, use of QC lowered overall error rate by 29% (P = .0009). Laboratories not using QC were at increased risk of systematic error. Following the Clinical Laboratory Improvement Amendments of 1988 guidelines for QC material was relatively more protective against error than lower frequencies/number of levels. CONCLUSIONS: Using QC protected against errors in enzyme immunoassay testing for human immunodeficiency virus type 1 antibodies. Two levels of QC should be used with each run as mandated by the Clinical Laboratory Improvement Amendments of 1988.
AIMS: Determination of the peak cyclosporine blood level instead of the trough level promises to represent an improvement in cyclosporine therapy monitoring due to better correlation with the AUC. In kidney transplant recipients we investigated whether this conclusion applies also to a new dispersion formulation of cyclosporine (Cicloral). PATIENTS: 42 stable kidney transplant recipients were converted from Sandimmun Neoral (NEO) to Cicloral (CIC) in a 1:1 dose relation. METHODS: On the last day of NEO administration and 14 days after conversion to CIC a full 12 h cyclosporine AUC was performed using blood samples obtained prior to and at serial times after dosing. The correlations between cyclosporine levels at these time points and the AUC were determined for NEO and CIC. For each measurement, a predicted AUC was calculated by regression analysis. The prediction error for each sampling time was calculated separately for NEO and CIC. RESULTS: The cyclosporine trough levels showed the poorest correlation with AUC for both preparations (NEO: r = 0.187 vs CIC: r = 0.554). The best correlation was observed for samples obtained at three hours after intake of either CIC (r = 0.807) or NEO (r = 0.611). The number of 2 hours measurements that lead to an unacceptable estimate from the real AUC was somewhat lower for CIC (8/40 vs 11/41 with NEO). CONCLUSIONS: Two- or three-hour cyclosporine level monitoring with the newer cyclosporine preparation Cicloral has at least the same precision as that of the original Neoral(R). In this study, the newer preparation even showed a tendency towards superior monitoring properties.
We compared retrospectively the distribution of refractive errors in a sample of adolescent and adult albinos (n = 19) with that in persons with idiopathic congenital nystagmus (CN) (n = 46), whose eye movements are similar to those of albinos but whose visual acuity is better. The distribution of spherical-equivalent refractive errors is more broadly distributed and slightly less myopic in albinos than in persons with idiopathic CN. On average, albinos also have more astigmatism (primarily with-the-rule), than persons with idiopathic CN. Unlike the leptokurtic distribution of refractive error that characterizes the normal adolescent and adult population, the distributions of refractive error for albinos and for persons with idiopathic CN exhibit no significant kurtosis. Moreover, neither group of subjects exhibits significant kurtosis for refractive errors in the vertical meridian, which corresponds to the retinal-image orientation with the least motion smear during horizontal nystagmus. The absence of significant leptokurtosis in the refractive-error distributions of young-adult albinos and persons with idiopathic CN suggests that the presence of nystagmus may interfere with normal refractive development.
The primary rationale for the use of phylogenetically based statistical methods is that phylogenetic signal, the tendency for related species to resemble each other, is ubiquitous. Whether this assertion is true for a given trait in a given lineage is an empirical question, but general tools for detecting and quantifying phylogenetic signal are inadequately developed. We present new methods for continuous-valued characters that can be implemented with either phylogenetically independent contrasts or generalized least-squares models. First, a simple randomization procedure allows one to test the null hypothesis of no pattern of similarity among relatives. The test demonstrates correct Type I error rate at a nominal alpha = 0.05 and good power (0.8) for simulated datasets with 20 or more species. Second, we derive a descriptive statistic, K, which allows valid comparisons of the amount of phylogenetic signal across traits and trees. Third, we provide two biologically motivated branch-length transformations, one based on the Ornstein-Uhlenbeck (OU) model of stabilizing selection, the other based on a new model in which character evolution can accelerate or decelerate (ACDC) in rate (e.g., as may occur during or after an adaptive radiation). Maximum likelihood estimation of the OU (d) and ACDC (g) parameters can serve as tests for phylogenetic signal because an estimate of d or g near zero implies that a phylogeny with little hierarchical structure (a star) offers a good fit to the data. Transformations that improve the fit of a tree to comparative data will increase power to detect phylogenetic signal and may also be preferable for further comparative analyses, such as of correlated character evolution. Application of the methods to data from the literature revealed that, for trees with 20 or more species, 92% of traits exhibited significant phylogenetic signal (randomization test), including behavioral and ecological ones that are thought to be relatively evolutionarily malleable (e.g., highly adaptive) and/or subject to relatively strong environmental (nongenetic) effects or high levels of measurement error. Irrespective of sample size, most traits (but not body size, on average) showed less signal than expected given the topology, branch lengths, and a Brownian motion model of evolution (i.e., K was less than one), which may be attributed to adaptation and/or measurement error in the broad sense (including errors in estimates of phenotypes, branch lengths, and topology). Analysis of variance of log K for all 121 traits (from 35 trees) indicated that behavioral traits exhibit lower signal than body size, morphological, life-history, or physiological traits. In addition, physiological traits (corrected for body size) showed less signal than did body size itself. For trees with 20 or more species, the estimated OU (25% of traits) and/or ACDC (40%) transformation parameter differed significantly from both zero and unity, indicating that a hierarchical tree with less (or occasionally more) structure than the original better fit the data and so could be preferred for comparative analyses.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Undetected genotyping errors pose a problem in genetic epidemiological studies, as they may invalidate statistical analysis or reduce its power. Haplotype analysis requires an improved standard of the data, because a haplotype can be inferred correctly only if the genotypes of all its markers are correct. Here, we present a method that identifies probable genotyping errors in trio samples with the help of the estimated haplotype frequency distribution of the sample. If the likelihood of the most likely haplotype explanation depends strongly on just one genotype, in the sense that setting the genotype to be missing leads to a much more likely haplotype explanation, this genotype is considered as a potential genotyping error. We describe a method that systematically searches the whole data set for such potential errors. Based on the haplotype distribution of a real data set, we carry out a simulation study to estimate the sensitivity and specificity of the method. In addition, we apply our approach to the real data set itself. Potentially erroneous genotypes are re-determined via sequencing. The results of both the simulation study and of the application to the real data set show that a considerable proportion of true genotyping errors is detected and that the number of false-positive signals is acceptable. We conclude that it is indeed possible to identify probable genotyping errors by considering haplotypes. The method described here will be part of the next release of our FAMHAP software.
Explore the source record for details and available documents.
The histopathological diagnosis is the bedrock of modern oncology, and plays a major role in the treatment of many other types of disease. Errors in these reports can critically affect patient care and may become the subject of media concern. This article considers how audit in histopathology can provide information about errors and inconsistencies in the diagnosis of surgical specimens. The use of audit to generate information about the background level of errors in pathology reports is reviewed, along with findings about the nature of these errors and the types of specimens more commonly affected. Generic audit strategies that can be used to minimize the risk of errors in reports are discussed, together with the use of audit to evaluate diagnostic criteria and pathological scoring or grading systems. The role of audit in determining the informational content of reports is included, and there is consideration of the relationship between sample size and error rates. The limited extent to which audit can be used to assess the performance of individual pathologists is also covered.
An external quality assessment (EQA) survey on 14 fresh-frozen, single-donation sera assigned with reference measurement procedure (RMP) values revealed a mean bias of + 5.2% and + 3.7% for the cholesterol oxidase and the photometric glucose oxidase procedure groups, respectively. Conversely, on lyophilized sera, the same procedure groups showed almost bias-free results, the differences from the RMP values being only -0.8% for cholesterol and + 0.7% for glucose. These data, which are in fairly good agreement with the literature, suggest the existence of artificial matrix effects in processed materials. Therefore they indicate that, currently, assessment of trueness is hampered in many European EQA schemes, as most of them use lyophilized sera. This approach may give a false impression about the trueness of laboratory results as well as carrying the risk that laboratories calibrated on the RMP values of the survey samples could make errors in patient testing. Consequently, if European EQA is willing to fulfil a post-market vigilance function of the performance of in vitro diagnostic medical devices, then the time has come to tackle the problem of the quality of the survey samples. EQA organizers urgently need to make an effort to seek out materials that analytically behave like authentic clinical specimens. In the meantime, alternative approaches should be used. Although not ideal, the special survey described in this article is one of the possibilities. Naturally, it implies logistic problems and increased costs for the individual EQA schemes. However, both can be overcome with the cooperation of the predominantly nationally organized schemes.
The "normal" physiological taurine status in human plasma and whole blood was evaluated for day-to-day variation. Because plasma taurine concentrations can vary by greater than or equal to 100% because of sampling and analytical techniques, various blood-collecting and -handling procedures were compared to ascertain the most reliable method for measuring plasma taurine. Blood collection into EDTA-wetted plastic syringes at room temperature proved most reliable. Plasma and whole-blood taurine concentrations were determined in the same 13 women and 11 men three times within a 10-d period. The normal plasma taurine concentration was 44 +/- 9 mumol/L (mean +/- SD; n = 40) in fasting subjects and 42 +/- 7 mumol/L (n = 30) in semi-fasted individuals, with an intraindividual variation of 9 +/- 5%. Whole-blood taurine concentrations ranged from 164 to 318 mumol/L and had an intraindividual variation of 11 +/- 5%. Inter-individual variation averaged 12 +/- 7% for plasma and 7 +/- 6% for whole blood taurine. Because plasma and whole-blood taurine concentrations were not correlated, assessment of both would provide the most accurate estimate of taurine status. Short of that, whole-blood taurine would appear to be the best single measure.
High-resolution melting techniques are a simple and cost-effective alternative to other closed-tube genotyping methods. Here, we genotyped human platelet antigens (HPAs) 1 to 6 and 15 by high-resolution melting methods that did not require labeled probes. Conventional melting analysis with hybridization probes (HybProbes) was also performed at each locus. HybProbe assays were performed individually, whereas amplicon melting (HPAs 1 to 5 and 16) and unlabeled probe (HPA 6) assays were duplexed when possible. At all loci for each method, both homozygous and heterozygous genotypes were easily identified. We analyzed 100 blinded clinical samples (33 amniotic fluid, 12 cultured amniocytes, and 55 blood samples) for all 7 single-nucleotide polymorphisms (SNPs) by each method. Genotype assignments could be made in 99.0% of the SNPs by high-resolution melting and in 98.7% of the SNPs with HybProbes with an overall genotype concordance of 98.8%. Errors included two sample misidentifications and six incorrect assignments that were all resolved by repeating the analysis. Advantages of high-resolution melting include rapid assay development and execution, no need for modified oligonucleotides, and similar accuracy in genotyping compared with other closed-tube melting methods.
OBJECTIVE: To determine how commonly articles are retracted on the basis of unintentional mistakes, and whether these articles differ from those retracted for scientific misconduct in authorship, funding, type of study, publication, and time to retraction. DATA SOURCE AND STUDY SELECTION: All retractions of English language publications indexed in MEDLINE between 1982 and 2002 were extracted. DATA EXTRACTION: Two reviewers categorised the reasons for retraction of each article as misconduct (falsification, fabrication, or plagiarism) or unintentional error (mistakes in sampling, procedures, or data analysis; failure to reproduce findings; accidental omission of information about methods or data analysis). DATA SYNTHESIS: Of the 395 articles retracted between 1982 and 2002, 107 (27.1%) were retracted because of scientific misconduct, 244 (61.8%) because of unintentional errors, and 44 (11.1%) could not be categorised. Compared with articles retracted because of misconduct, articles with unintentional mistakes were more likely to have multiple authors, no reported funding source, and to be published in frequently cited journals. They were more likely to be retracted by the author(s) of the article, and the retraction was more likely to occur more promptly (mean, 2.0 years; 95% CI, 1.8-2.2) than articles withdrawn because of misconduct (mean, 3.3 years; 95% CI, 2.7-3.9) (P < 0.05 for all comparisons). CONCLUSIONS: Retractions in the biomedical literature were more than twice as likely to result from unintentional mistakes than from scientific misconduct. The different characteristics of articles retracted for misconduct and for mistakes reflect distinct causes and, potentially, distinct solutions.