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PubMed2004

Classification between normal and tumor tissues based on the pair-wise gene expression ratio.

BACKGROUND: Precise classification of cancer types is critically important for early cancer diagnosis and treatment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. However, reliable cancer-related signals are generally lacking. METHOD: Using recent datasets on colon and prostate cancer, a data transformation procedure from single gene expression to pair-wise gene expression ratio is proposed. Making use of the internal consistency of each expression profiling dataset this transformation improves the signal to noise ratio of the dataset and uncovers new relevant cancer-related signals (features). The efficiency in using the transformed dataset to perform normal/tumor classification was investigated using feature partitioning with informative features (gene annotation) as discriminating axes (single gene expression or pair-wise gene expression ratio). Classification results were compared to the original datasets for up to 10-feature model classifiers. RESULTS: 82 and 262 genes that have high correlation to tissue phenotype were selected from the colon and prostate datasets respectively. Remarkably, data transformation of the highly noisy expression data successfully led to lower the coefficient of variation (CV) for the within-class samples as well as improved the correlation with tissue phenotypes. The transformed dataset exhibited lower CV when compared to that of single gene expression. In the colon cancer set, the minimum CV decreased from 45.3% to 16.5%. In prostate cancer, comparable CV was achieved with and without transformation. This improvement in CV, coupled with the improved correlation between the pair-wise gene expression ratio and tissue phenotypes, yielded higher classification efficiency, especially with the colon dataset - from 87.1% to 93.5%. Over 90% of the top ten discriminating axes in both datasets showed significant improvement after data transformation. The high classification efficiency achieved suggested that there exist some cancer-related signals in the form of pair-wise gene expression ratio. CONCLUSION: The results from this study indicated that: 1) in the case when the pair-wise expression ratio transformation achieves lower CV and higher correlation to tissue phenotypes, a better classification of tissue type will follow. 2) the comparable classification accuracy achieved after data transformation suggested that pair-wise gene expression ratio between some pairs of genes can identify reliable markers for cancer.

Colon↗

PubMed2025

Seq2Saccharide: Discovering Oligosaccharides and Aminoglycosides Natural Products by Integrating Computational Mass Spectrometry and Genome Mining.

Natural oligosaccharides and aminoglycosides are important sources of new drug candidates, especially in the development of antibiotics. In the past, discovering novel saccharides has been time-consuming and costly. However, the rapid expansion of high-throughput data, including genomic and mass spectrometry data sets, has greatly increased opportunities for natural saccharide discovery. Yet, due to the complex biosynthesis pathways of saccharides, no existing method can predict their structures with high precision. To address this, we introduce Seq2Saccharide, a tool designed to automate saccharide natural product discovery by integrating both genomic and mass spectrometry data. To enhance accuracy, Seq2Saccharide predicts hundreds or thousands of putative structures for each gene cluster. The correct structure is then identified from these predictions using a mass spectral search. Benchmarks against saccharides in the MiBIG database show that Seq2Saccharide outperforms existing methods in predicting the structure of saccharides. Furthermore, mass spectrometry analysis indicates that the variable search module can correct mispredictions from genome mining. By searching genomic and mass spectrometry data of microbial strains, Seq2Saccharide correctly identified the biosynthetic gene cluster for the polysaccharide oligosaccharide trestatin B.

Aminoglycosides↗

PubMed2000

Clinical evaluation and follow-up results for intraoperative magnetic resonance imaging in neurosurgery.

OBJECTIVE: The use of intraoperative magnetic resonance imaging (MRI) in neurosurgery has increased rapidly, and a variety of concepts have recently been presented. Although the feasibility of the procedure has been demonstrated repeatedly, no conclusive analysis of its effects on the surgical procedures, the extent of tumor removal, and outcomes, or its possible problems, has been performed. METHODS: Of 242 operations performed with intraoperative MRI, 97 procedures for supratentorial glioma treatment were analyzed with respect to intraoperative imaging results and postoperative outcomes. Analysis of the images included assessment of imaging artifacts, image quality, and extent of tumor removal. Patients were monitored to determine radiological progression, survival times, postoperative complications, and morbidity rates. RESULTS: No intraoperative complications related to the imaging procedure were observed. Image quality was good or fair in 85.5% of the cases. Different types of surgically induced imaging changes could be identified. In 56 cases, resection was continued using navigation with intraoperative MRI data sets (rereferencing accuracy, 0.9 mm). For high-grade gliomas, the percentage of cases in which residual tumor was identified by MRI could be significantly reduced from 62% intraoperatively to 33% postoperatively, which was paralleled by a significant increase in survival times for patients without residual tumor. Complication and morbidity rates were within the ranges reported for other studies. CONCLUSION: Intraoperative MRI is safe and allows reliable updating of neuronavigational data, with compensation for brain shifting. Surgically induced imaging changes, which have been identified as a possible problem with intraoperative MRI in general, necessitated comparisons with preoperative scans and require future attention. The extent of tumor removal and survival times were increased significantly. Overall, patients seemed to benefit from the method.

Adolescent↗

PubMed2006

A note on the accuracy of PAC-likelihood inference with microsatellite data.

Stephens and Donnelly have introduced a simple yet powerful importance sampling scheme for computing the likelihood in population genetic models. Fundamental to the method is an approximation to the conditional probability of the allelic type of an additional gene, given those currently in the sample. As noted by Li and Stephens, the product of these conditional probabilities for a sequence of draws that gives the frequency of allelic types in a sample is an approximation to the likelihood, and can be used directly in inference. The aim of this note is to demonstrate the high level of accuracy of "product of approximate conditionals" (PAC) likelihood when used with microsatellite data. Results obtained on simulated microsatellite data show that this strategy leads to a negligible bias over a wide range of the scaled mutation parameter theta. Furthermore, the sampling variance of likelihood estimates as well as the computation time are lower than that obtained with importance sampling on the whole range of theta. It follows that this approach represents an efficient substitute to IS algorithms in computer intensive (e.g. MCMC) inference methods in population genetics.

Gene Frequency↗

PubMed2005

Value of hydrogen peroxide enhancement of three-dimensional endoanal ultrasound in fistula-in-ano.

PURPOSE: The aim of this prospective study was to compare the accuracy of three-dimensional endoanal ultrasound with that of hydrogen peroxide enhanced three-dimensional endoanal ultrasound in diagnosing recurrent or complex fistula-in-ano. METHODS: Three-dimensional endoanal ultrasound reconstructions were performed before and after hydrogen peroxide enhancement in 19 patients with suspected recurrent or complex fistula-in-ano. Two experienced observers derived a consensus fistula classification after a blinded random review of the data sets. The accuracy of three-dimensional endoanal ultrasound and that of hydrogen peroxide-enhanced three-dimensional endoanal ultrasound were compared with a reference standard derived from surgical findings and magnetic resonance imaging and modified by outcome over a median follow-up of 13 months. RESULTS: Patients had previously undergone a median of three fistula operations. Four had Crohn's disease. There were 21 internal openings and primary tracks in 19 patients: 1 superficial, 1 intersphincteric, 18 transsphincteric, and 1 extrasphincteric. Fourteen patients had 19 secondary tracks. Both techniques detected fistula tracks in 19 of 21 (90 percent) patients. There was no significant difference between three-dimensional endoanal ultrasound and hydrogen peroxide-enhanced three-dimensional endoanal ultrasound in classifying internal openings (19/21 (90 percent) vs. 18/21 (86 percent)), primary tracks (17/21 (81 percent) vs. 15/21 (71 percent)), or secondary tracks (13/19 (68 percent) vs. 12/19 (63 percent)). Where three-dimensional endoanal ultrasound correctly detected an internal opening, gas from hydrogen peroxide enhancement was present in 8 of 18 (44 percent) studies. Similarly, gas made primary tracks more conspicuous in 6 of 19 (32 percent) and secondary tracks in 6 of 13 (46 percent) of those detected. CONCLUSIONS: In recurrent or complex fistula-in-ano, endoanal ultrasound proved more accurate for detecting primary tracks and internal openings than for detecting extensions. Hydrogen peroxide improved conspicuity of some tracks and internal openings and so may be helpful in difficult cases, although no overall diagnostic benefit was demonstrated.

Adolescent↗

PubMed1976

Computer detection of premature ventricular complexes: a modified approach.

The accuracy of a data reduction system for arrhythmia detection in identifying premature ventricular complexes was evaluated in continuous tape records of 30 patients in a coronary care unit. Computer analysis was performed with a Honeywell 316 digital computer. Threshold values for dominant complexes were automatically determined and recognition of premature ventricular complexes was based on differences in QRS configuration, timing and T wave configuration from the dominant complexes. Verification of the computer accuracy in detecting premature ventricular complexes was made with visual beat by beat inspection using a two channel strip chart recorder with simultaneous recording of the electrocardiogram and computer signal. This procedure allowed for exact beat to beat correlation and, thus, absolute determination of false positive and false negative identification. From 0.5 to 6 continuous hours of monitoring per patient (average 3.5 hours) were analyzed for a total of 105 monitoring hours. The basic cardiac rhythms noted were normal sinus rhythm, sinue arrhythmia, sinus tachycardia, demand pacemaker rhythm, atrial fibrillation and atrioventricular (A-V) dissociation with junctional rhythm. Premature ventricular complexes were evident in 28 tapes (93 percent) including 12 (43% with multifocal premature ventricular complexes and 3 (11 percent) with ventricular tachycardia. The visual count of premature ventricular complexes totaled 7,921. Of these, 7,542 (95 percent) were properly classified by the computer. The total computer count was 8.717, representing a 13 percent false positive and 5 percent false negative identification rate. The false positive identifications of premature ventricular complexes occurred during periods of 10 seconds or more of continuous noise artifact and in the presence of atrial premature complexes conducted aberrantly. When these sections of tape were excluded, the computer had a less than 2 percent false negative and 3 percent false positive rate of identification of premature ventricular complexes.

Arrhythmias, Cardiac↗

PubMed1997

Inferential and descriptive influences on measures of respiratory sinus arrhythmia: sampling rate, R-wave trigger accuracy, and variance estimates.

The use of respiratory sinus arrhythmia (RSA) is dependent on several quantification factors. The statistical consequences of sampling rate, R-wave trigger accuracy, and the data structure of RSA estimates were evaluated via simulations and simulated modifications. Simulations demonstrated that sampling rate determined the amplitude of the smallest oscillation that could be accurately described. When the amplitude of the oscillation was smaller in milliseconds than the sampling interval, all smaller oscillations, regardless of amplitude, were indiscriminately assigned a default value defined as 50% of the sampling interval. Also, reduced R-wave peak detection accuracy was demonstrated to influence statistical analyses. The distributional characteristics of several common methods of structuring RSA estimates were investigated, and results indicated that several methods results in asymmetrical distributions. We recommend using rapid sampling rates (i.e., 1 kHz), accurate R-wave peak detectors, and avoiding statistical trouble.

Adolescent↗

PubMed2005

Optimized normalization for antibody microarrays and application to serum-protein profiling.

The measurements of coordinated patterns of protein abundance using antibody microarrays could be used to gain insight into disease biology and to probe the use of combinations of proteins for disease classification. The correct use and interpretation of antibody microarray data requires proper normalization of the data, which has not yet been systematically studied. Therefore we undertook a study to determine the optimal normalization of data from antibody microarray profiling of proteins in human serum specimens. Forty-three serum samples collected from patients with pancreatic cancer and from control subjects were probed in triplicate on microarrays containing 48 different antibodies, using a direct labeling, two-color comparative fluorescence detection format. Seven different normalization methods representing major classes of normalization for antibody microarray data were compared by their effects on reproducibility, accuracy, and trends in the data set. Normalization with ELISA-determined concentrations of IgM resulted in the most accurate, reproducible, and reliable data. The other normalization methods were deficient in at least one of the criteria. Multiparametric classification of the samples based on the combined measurement of seven of the proteins demonstrated the potential for increased classification accuracy compared with the use of individual measurements. This study establishes reliable normalization for antibody microarray data, criteria for assessing normalization performance, and the capability of antibody microarrays for serum-protein profiling and multiparametric sample classification.

Adenocarcinoma↗

PubMed2005

A population-based study of the prenatal diagnosis of congenital malformation over 16 years.

OBJECTIVE: A population-based study of the trends in accuracy over time of prenatal diagnosis of congenital malformations. DESIGN: A prospective study of all congenital malformations. SETTING: The counties of Cleveland, Durham, North Cumbria, Northumberland and Tyne and Wear. POPULATION: All 573,471 babies born to residents at 24 weeks of gestation or more, and all terminations for fetal abnormality, occurring between 1985 and 2000. METHODS: An analysis of all congenital anomalies whether antenatally detected or diagnosed before one year of age to examine the accuracy of prenatal diagnosis and its trends over four consecutive four-year periods. MAIN OUTCOME MEASURES: The proportion of cases where a diagnosis before birth was correctly made, wrongly made or not made in a range of important structural malformations. RESULTS: There was a substantial improvement in the accuracy of prenatal diagnosis of all conditions reported here. However, the extent to which different conditions were diagnosed varied widely. It now exceeds 90% for anencephaly and for abdominal wall defects but is still less than 70% for diaphragmatic hernia, bladder outlet obstruction and many major skeletal defects. Termination of pregnancy for fetal malformation rose from 23 to 47 per 10,000 registrable births. CONCLUSION: This large prospective study provides data on the accuracy of prenatal diagnosis of a number of malformations in a geographically defined population under service conditions. Diagnostic accuracy has improved over time but may well be lower than many clinicians assume for some important conditions and may not match public expectations.

Congenital Abnormalities↗

PubMed1981

Who should abstract medical records? A study of accuracy and cost.

The accuracy of patient record data depends not only on the quality of medical record keeping but also on the accuracy of the process of abstracting patient records to produce data suitable for analysis. This article reports results comparing record abstracts produced by four classes of abstracter: physicians, tumor registrars, nurses, and fourth-year medical students. The purpose of the comparison was to determine whether or not there were differences in accuracy among the four groups and, if accuracy was approximately equal, whether there were substantial differences among the costs of employing the four groups.

Abstracting and Indexing↗

PubMedDate not supplied

Providing concept-oriented views for clinical data using a knowledge-based system: an evaluation.

OBJECTIVE: Clinical information systems typically present patient data in chronologic order, organized by the source of the information (e.g., laboratory, radiology). This study evaluates the functionality and utility of a knowledge-based system that generates concept-oriented views (organized around clinical concepts such as disease or organ system) of clinical data. DESIGN: The authors have developed a system that uses a knowledge base of interrelationships between medical concepts to infer relationships between data in electronic medical records. They use these inferences to produce summaries, or views, of the data that are relevant to a specific concept of interest. They evaluated the ability of the system to select relevant information, reduce information overload, and support physician information retrieval. MEASUREMENTS: The sensitivity and specificity of the system for identifying relevant patient information were calculated. Effect on information overload was assessed by comparing the amount of information in each view with the amount of information in the entire record. Information retrieval accuracy and cost (time) were used to measure the effect of using concept-oriented views on the efficiency and effectiveness of retrievals. RESULTS: The sensitivity and specificity of the system for identifying relevant clinical information were generally in the range of 70 to 80 percent. Concept-oriented views are effective in reducing the amount of information retrieved (over 80 percent reduction) and, compared with source-oriented views, are able to improve physician retrieval accuracy (p=0.04). CONCLUSION: Computer-generated, concept-oriented views can be used to reduce clinician information overload and improve the accuracy of clinical data retrieval.

Artificial Intelligence↗

PubMed2003

Are classification accuracy statistics underused in neuropsychological research?

The prevalence of classification accuracy statistics was calculated in five prominent neuropsychology journals and five leading neurology journals for the years 2000 and 2001. Only 29% of neuropsychological articles judged to be appropriate for classification accuracy statistics presented sufficient data to calculate a full range of such analyses. Moreover, classification accuracy statistics were significantly less prevalent in neuropsychology journal articles than in studies published in neurology journals during the same time period. Various indices of sensitivity and/or specificity were present in 31% of neuropsychology articles, whereas fewer than 3% reported predictive values or risk ratios. These findings indicate that classification accuracy statistics, most notably predictive values and risk ratios, are potentially underused in neuropsychology. Investigators and research consumers are encouraged to consider the applicability of classification accuracy statistics as a means of evaluating the clinical relevance of neuropsychological research findings.

Bibliometrics↗

PubMed1995

Agreement between self-reported early cancer detection practices and medical audits among Hispanic and non-Hispanic white health plan members in northern California.

BACKGROUND: Using the medical records of a large, prepaid health plan, our purpose was to assess the accuracy of self-reported data on cancer detection practices and to evaluate any differences in accuracy between Hispanics and non-Hispanic whites. METHODS: Data were collected on six procedures: mammography, clinical breast examination, Pap smear, sigmoidoscopy, fecal occult blood tests, and digital rectal examination. We audited the medical records of 815 randomly selected Hispanic and 483 non-Hispanic white members of the Kaiser Permanente Medical Care Program in Northern California. All responded to a telephone survey. Using a standardized form, we recorded any of the six target examinations that had been performed within 5 years of the telephone interview. We then compared the times of the most recent screening tests as reported in the telephone survey with those in the medical record. RESULTS: For the 2 years before the telephone interview, self-reports for screening tests overestimated the actual rates at which these tests were performed as documented in the medical records. Lack of agreement between self-report and medical record audits was substantial for all screening procedures except sigmoidoscopy. Hispanic members had fewer procedures done for most tests, but the differences were not statistically significant. Overestimates in self-reported screening rates did not differ substantially between Hispanics and non-Hispanic whites. CONCLUSIONS: Self-reported data on early cancer detection procedures can substantially overestimate their occurrence among both non-Hispanic white and Hispanic populations. These findings confirm earlier findings for Pap smear and affect decisions on cancer prevention procedures that rely on the accuracy of self-reported data.

Breast Neoplasms↗

PubMed2004

Rasch model estimation: further topics.

Building on Wright and Masters (1982), several Rasch estimation methods are briefly described, including Marginal Maximum Likelihood Estimation (MMLE) and minimum chi-square methods. General attributes of Rasch estimation algorithms are discussed, including the handling of missing data, precision and accuracy, estimate consistency, bias and symmetry. Reasons for, and the implications of, measure misestimation are explained, including the effect of loose convergence criteria, and failure of Newton-Raphson iteration to converge. Alternative parameterizations of rating scales broaden the scope of Rasch measurement methodology.

Algorithms↗

PubMed2006

New coil concept for endoluminal MR imaging: initial results in staging of gastric carcinoma in correlation with histopathology.

Our aim was to conduct a prospective study to evaluate staging accuracy of a new coil concept for endoluminal magnetic resonance imaging (MRI) on ex vivo gastric carcinomas. Twenty-eight consecutive patients referred to surgery with a clinically proven primary gastric malignancy were included. Surgical specimens were examined with a foldable and self-expanding loop coil (8-cm diameter) at 1.5 Tesla immediately after total gastrectomy. T1- and T2-weighted and opposed-phase sequences (axial, frontal sections; 3- to 4-mm slice thickness) were acquired. Investigators blinded to any patient information analyzed signal intensity of normal gastric wall, gastric tumor, and lymph nodes. Findings were compared with histopathological staging. On surgical specimens, 2-5 gastric wall layers could be visualized. All gastric tumors (26 carcinomas, two lymphomas) were identified on endoluminal MR data (100%). Overall accuracy for T staging was 75% (18/24); sensitivity to detect serosal involvement was 80% and specificity 89%. N staging correlated in 58% (14/24) with histopathology (N+ versus N-). The endoluminal coil concept is feasible and applicable for an ex vivo setting. Endoluminal MR data provided sufficient detail for gastric wall layer differentiation, and therefore, identification of T stages in gastric carcinoma is possible. Further investigations in in vivo settings should explore the potential of our coil concept for endoluminal MR imaging.

Adenocarcinoma↗

PubMed1995

Dual-energy X-ray absorptiometry measurements of body composition: effects of depth and tissue thickness, including comparisons with direct analysis.

1. There are few data regarding the accuracy of Hologic QDR-1000W dual-energy X-ray absorptiometry for the measurement of body composition. In two studies, one in an in vitro experimental system using oil and water mixtures and the other in samples of pork meat, the effect of depth and tissue thickness on the measured composition was assessed. In the latter study the measured fat mass was compared with that measured by direct analysis. 2. All data indicated a trend in the measured fat mass with depth, such that more fat was measured at extremes of depth (< 10 cm and > 25 cm) than at intermediate depths. 3. In samples of meat weighing approximately 55 kg, dual X-ray absorptiometry significantly under-estimated the absolute fat mass compared with direct analysis (mean 20.4 +/- 1.65%) by 5-8% or 1-4 kg of fat. 4. These findings are of direct relevance to both clinical and research work using this technique to measure body composition, in particular in circumstances in which changes in body composition and/or tissue thickness are anticipated.

Absorptiometry, Photon↗

PubMed1983

Influence of physiological noise and the occlusion effect on the measurement of real-ear attenuation at threshold.

The most commonly alleged experimental artifact associated with real-ear attenuation at threshold (REAT) measurements of hearing protection devices (HPDs) was examined: Masking of the protected thresholds due to physiological noise amplified by the occlusion effect. An ear canal mounted subminiature microphone was used to obtain objective measures of physiological noise in occluded and unoccluded test conditions and of the insertion loss (IL) of insert, semi-aural, supra-aural and circumaural HPDs when exposed to broadband noise with a sound pressure level of 93 dB. Measurements spanned 1/3 octave bands from 125 Hz to 2 kHz. Attenuation was also measured via a subjective REAT procedure and the magnitude of the occlusion effect was examined via bone conduction audiometry. The IL data confirmed the accuracy of the REAT results except at the lowest frequencies tested, where the degree to which the REAT values were spuriously inflated was quantified and found to be device related. Furthermore, the magnitude of the error (which never exceeded 5 dB) could be predicted by measuring the physiological noise in the occluded ear and calculating how much this would mask the occluded threshold. It was noted that no evidence was found in the data to suggest a dependency of HPD attenuation on sound level.

Adult↗

PubMed1984

Immunoradiometric assay for quantitation of Dirofilaria immitis antigen in dogs with heartworm infections.

An immunoradiometric assay (IRMA) was developed, optimized, and validated for detection of parasite-specific antigen in sera from hosts with filarial infections, using Dirofilaria immitis in dogs as a model. The precision, reproducibility, and parallelism of the IRMA were examined, using precision profile analysis. The IRMA had acceptable precision and reproducibility [less than 15% intra-assay coefficient of variation (CV)] over a working range of 10 to 2,000 ng of D immitis-antigen (AG)/ml. The IRMA parallelism (agreement between dilutions) was acceptable (less than 10% interdilutional CV) with laboratory-spiked D immitis AG sera containing no D immitis-antibody (AB). However, it was not acceptable (greater than 20% interdilutional CV) for analysis of sera from naturally infected dogs containing D immitis AB, probably due to dissociation of immune-complexed AG with increasing serum dilution. Nonparallelism limited the accuracy of binding data interpolation from the standard curve. Specificity of the IRMA was enhanced by preabsorption of the radiolabeled detection antibody with Toxocara canis AG before use. Varying amounts of D immitis AG (22 to 1,000 ng/ml) were detected in 42% (20/48) of microfilaremic dogs. The presence of AG-specific AB at concentrations as low as 1 microgram/ml reduced the ability of the IRMA to detect D immitis AG. Factors that influence the accuracy and sensitivity of immunoassays for circulating filarial antigens are discussed.

Animals↗