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PubMed2003

Whole-genome microarrays of fission yeast: characteristics, accuracy, reproducibility, and processing of array data.

BACKGROUND: The genome of the fission yeast Schizosaccharomyces pombe has recently been sequenced, setting the stage for the post-genomic era of this increasingly popular model organism. We have built fission yeast microarrays, optimised protocols to improve array performance, and carried out experiments to assess various characteristics of microarrays. RESULTS: We designed PCR primers to amplify specific probes (180-500 bp) for all known and predicted fission yeast genes, which are printed in duplicate onto separate regions of glass slides together with control elements (approximately 13,000 spots/slide). Fluorescence signal intensities depended on the size and intragenic position of the array elements, whereas the signal ratios were largely independent of element properties. Only the coding strand is covalently linked to the slides, and our array elements can discriminate transcriptional direction. The microarrays can distinguish sequences with up to 70% identity, above which cross-hybridisation contributes to the signal intensity. We tested the accuracy of signal ratios and measured the reproducibility of array data caused by biological and technical factors. Because the technical variability is lower, it is best to use samples prepared from independent biological experiments to obtain repeated measurements with swapping of fluorochromes to prevent dye bias. We also developed a script that discards unreliable data and performs a normalization to correct spatial artefacts. CONCLUSIONS: This paper provides data for several microarray properties that are rarely measured. The results define critical parameters for microarray design and experiments and provide a framework to optimise and interpret array data. Our arrays give reproducible and accurate expression ratios with high sensitivity. The scripts for primer design and initial data processing as well as primer sequences and detailed protocols are available from our website.

DNA Primers↗
PubMed1992

Differentiation between transmembrane helices and peripheral helices by the deconvolution of circular dichroism spectra of membrane proteins.

The interpretation of the circular dichroism (CD) spectra of proteins to date requires additional secondary structural information of the proteins to be analyzed, such as X-ray or NMR data. Therefore, these methods are inappropriate for a CD database whose secondary structures are unknown, as in the case of the membrane proteins. The convex constraint analysis algorithm (Perczel, A., Hollósi, M., Tusnády, G., & Fasman, G. D., 1991, Protein Eng. 4, 669-679), on the other hand, operates only on a collection of spectral data to extract the common spectral components with their spectral weights. The linear combinations of these derived "pure" CD curves can reconstruct the original data set with great accuracy. For a membrane protein data set, the five-component spectra so obtained from the deconvolution consisted of two different types of alpha helices (the alpha helix in the soluble domain and the alpha T helix, for the transmembrane alpha helix), a beta-pleated sheet, a class C-like spectrum related to beta turns, and a spectrum correlated with the unordered conformation. The deconvoluted CD spectrum for the alpha T helix was characterized by a positive red-shifted band in the range 195-200 nm (+95,000 deg cm2 dmol-1), with the intensity of the negative band at 208 nm being slightly less negative than that of the 222-nm band (-50,000 and -60,000 deg cm2 dmol-1, respectively) in comparison with the regular alpha helix, with a positive band at 190 nm and two negative bands at 208 and 222 nm with magnitudes of +70,000, -30,000, and -30,000 deg cm2 dmol-1, respectively.

Adenosine Triphosphatases↗
PubMed2006

Accurate and unbiased estimation of power-law exponents from single-emitter blinking data.

Single emitter blinking with a power-law distribution for the on and off times has been observed on a variety of systems including semiconductor nanocrystals, conjugated polymers, fluorescent proteins, and organic fluorophores. The origin of this behavior is still under debate. Reliable estimation of power exponents from experimental data is crucial in validating the various models under consideration. We derive a maximum likelihood estimator for power-law distributed data and analyze its accuracy as a function of data set size and power exponent both analytically and numerically. Results are compared to least-squares fitting of the double logarithmically transformed probability density. We demonstrate that least-squares fitting introduces a severe bias in the estimation result and that the maximum likelihood procedure is superior in retrieving the correct exponent and reducing the statistical error. For a data set as small as 50 data points, the error margins of the maximum likelihood estimator are already below 7%, giving the possibility to quantify blinking behavior when data set size is limited, e.g., due to photobleaching.

Computer Simulation↗
PubMedDate not supplied

Triage accuracy at a multiple casualty incident disaster drill: the Emergency Medical Service, Fire Department of New York City experience.

We sought to evaluate the accuracy and speed for the triage of multiple patients during a disaster drill by Emergency Medical Service (EMS) personnel. During a disaster drill (train collision with blast injury and chemical release), the accuracy and speed of triage of 130 patient-actors by the Fire Department of New York City (FDNY) EMS personnel was evaluated using the Simple Triage and Rapid Treatment (START) triage system. All EMS personnel had been previously trained in START, but refresher training was not administered before the drill. Overall triage accuracy was 78%. In patients that had additional changes in their status during the triage process (injects), 62% were retriaged appropriately. Because of security and decontamination procedures, triage at the triage/treatment area began 40 minutes after the drill commenced. It took 2 hours and 38 minutes to completely clear the scene of all patients. On average, the time from the start of triage to transport was 1 hour and 2 minutes. Despite the fact that triage is a skill practiced by every EMS system in the country on a daily basis, few studies regarding triage accuracy are available. Limited data suggest that the triage accuracy rates using different triage strategy algorithms are approximately 45% to 55%. During this drill, FDNY-EMS triage accuracy using the START system exceeded these expectations. This study provides insight as to the triage experience of a large urban EMS system operating at a disaster drill.

Algorithms↗
PubMed2006

Automated in-silico detection of cell populations in flow cytometry readouts and its application to leukemia disease monitoring.

BACKGROUND: Identification of minor cell populations, e.g. leukemic blasts within blood samples, has become increasingly important in therapeutic disease monitoring. Modern flow cytometers enable researchers to reliably measure six and more variables, describing cellular size, granularity and expression of cell-surface and intracellular proteins, for thousands of cells per second. Currently, analysis of cytometry readouts relies on visual inspection and manual gating of one- or two-dimensional projections of the data. This procedure, however, is labor-intensive and misses potential characteristic patterns in higher dimensions. RESULTS: Leukemic samples from patients with acute lymphoblastic leukemia at initial diagnosis and during induction therapy have been investigated by 4-color flow cytometry. We have utilized multivariate classification techniques, Support Vector Machines (SVM), to automate leukemic cell detection in cytometry. Classifiers were built on conventionally diagnosed training data. We assessed the detection accuracy on independent test data and analyzed marker expression of incongruently classified cells. SVM classification can recover manually gated leukemic cells with 99.78% sensitivity and 98.87% specificity. CONCLUSION: Multivariate classification techniques allow for automating cell population detection in cytometry readouts for diagnostic purposes. They potentially reduce time, costs and arbitrariness associated with these procedures. Due to their multivariate classification rules, they also allow for the reliable detection of small cell populations.

Computational Biology↗
PubMed2006

Prediction of one repetition maximum strength from multiple repetition maximum testing and anthropometry.

The purpose of this study was to quantify the decrease in the load lifted from 1 to 5, 10, and 20 repetitions to failure for the flat barbell bench press (chest press; CP) and plate-loaded leg press (LP). Furthermore, we developed prediction equations for 1 repetition maximum (RM) strength from the multiple RM tests, including anthropometric data, gender, age, and resistance training volume. Seventy subjects (34 men, 36 women), 18-69 years of age, completed 1, 5, 10, and 20RM testing for each of the CPs and LPs. Regression analyses of mean data revealed a nonlinear decrease in load with increasing repetition number (CP: linear S(y.x) = 2.6 kg, nonlinear S(y.x) = 0.2 kg; LP: linear S(y.x) = 11.0 kg, nonlinear S(y.x) = 2.6 kg, respectively). Multiple regression analyses revealed that the 5RM data produced the greatest prediction accuracy, with R(2) data for 5, 10, and 20RM conditions being LP: 0.974, 0.933, 0.915; CP: 0.993, 0.976, and 0.955, respectively. The regression prediction equations for 1RM strength from 5RM data were LP: 1RM = 1.0970 x (5RM weight [kg]) + 14.2546, S(y.x) = 16.16 kg, R(2) = 0.974; CP: 1RM = 1.1307 x (5RM weight) + 0.6999, S(y.x) = 2.98 kg, R(2) = 0.993. Dynamic muscular strength (1RM) can be accurately estimated from multiple repetition testing. Data reveal that no more than 10 repetitions should be used in linear equations to estimate 1RM for the LP and CP actions.

Adolescent↗
PubMed2006

Automated identification of cancerous smears using various competitive intelligent techniques.

In this study the performance of various intelligent methodologies is compared in the task of pap-smear diagnosis. The selected intelligent methodologies are briefly described and explained, and then, the acquired results are presented and discussed for their comprehensibility and usefulness to medical staff, either for fault diagnosis tasks, or for the construction of automated computer-assisted classification of smears. The intelligent methodologies used for the construction of pap-smear classifiers, are different clustering approaches, feature selection, neuro-fuzzy systems, inductive machine learning, genetic programming, and second order neural networks. Acquired results reveal the power of most intelligent techniques to obtain high quality solutions in this difficult problem of medical diagnosis. Some of the methods obtain almost perfect diagnostic accuracy in test data, but the outcome lacks comprehensibility. On the other hand, results scoring high in terms of comprehensibility are acquired from some methods, but with the drawback of achieving lower diagnostic accuracy. The experimental data used in this study were collected at a previous stage, for the purpose of combining intelligent diagnostic methodologies with other existing computer imaging technologies towards the construction of an automated smear cell classification device.

Artificial Intelligence↗
PubMed1993

Distinguishing transmembrane helices from peripheral helices by circular dichrosim.

The interpretation of the circular dichroism (c.d.) spectra of proteins to date requires additional secondary structural information of the proteins to be analysed (e.g., X-ray or n.m.r. data). Therefore these methods are inappropriate for a c.d. database whose secondary structures are unknown, as in the case of the membrane proteins. The Convex Constraint Analysis algorithm [Perczel, Hollósi, Tusnady, and Fasman (1991) Convex constraint analysis: a natural deconvolution of circular dichroism curves of proteins. Protein Eng. 4, 669-679] operates on a collection of c.d. spectral data to extract the common spectral components with their spectral weights. The linear combinations of these derived 'pure' c.d. curves can reconstruct the original data set with great accuracy. For a membrane protein data set, the five-component spectra so obtained from the deconvolution consisted of two different types of alpha-helices (the alpha-helix in the soluble domain and the alpha1-helix, for the transmembrane alpha-helix), a beta-pleated sheet, a class-C-like spectrum related to beta-turns and a spectrum correlated with the unordered conformation. The deconvoluted c.d. spectrum for the alpha1-helix was characterized by a positive red-shifted band in the range 195-200 nm (+95,000 degrees.cm2-dmol-1), with the intensity of the negative band at 208 nm being slightly less negative than that of the 222 nm band (-50,000 and -60,000 degrees.cm2.dmol-1 respectively) in comparison with the regular alpha-helix, with a positive band at 190 nm and two negative bands at 208 and 222 nm with magnitudes of +70,000, -30,000 and -30,000 degrees.cm2.dmol-1 respectively.

Animals↗
PubMed1983

The value of clinical, biochemical, ultrasound and liver biopsy data in assessing patients with liver disease.

To determine the value of clinical, biochemical, ultrasound and liver biopsy data in the management of patients with liver disease, eight doctors each assessed 75 case histories. With clinical and biochemical data alone, the predictive accuracy was significantly higher when identifying patients as 'medical' rather than 'surgical' (97 compared with 79%, p less than 0.001). However, when making a specific diagnosis as opposed to classifying into medical and surgical categories, clinical and biochemical information resulted in a much lower predictive accuracy for both medical (67%) and surgical (56%) patients. With ultrasound data the predictive accuracy increased to 91% when identifying patients as 'surgical'; with liver biopsy it increased to 99% when identifying patients as 'medical'. The value of the different data assessed involves more than an evaluation of diagnostic accuracy, and in this study the relative worth of each test was therefore assessed on a five point scale based on the effect of the information on the doctors. This included a willingness to give specific treatment and make a specific diagnosis, as well as classifying patients into medical and surgical categories and the confidence they felt in their diagnoses. After clinical, biochemical and ultrasound information the doctors were only prepared to give specific treatment to 11.9% of the medical and 9.3% of the surgical patients. After liver biopsy data, however, they were willing to give specific treatment to an additional 66.6% of the medical patients and 25% of the surgical patients. Further evidence of the value of liver biopsy information came from an analysis of the changes in the doctors' confidence in a diagnosis. Thus, 96 patients were assigned a correct specific diagnosis with clinical and biochemical data alone but none were considered as 'definitive' by the doctors; when liver biopsy information was provided 59 (61%) were placed in this category.

Biopsy↗
PubMed2003

Competency in interpretation of 12-lead electrocardiograms: a summary and appraisal of published evidence.

BACKGROUND: There have been many proposals for objective standards designed to optimize training, testing, and maintaining competency in interpretation of electrocardiograms (ECGs). However, most of these recommendations are consensus based and are not derived from clinical trials that include patient outcomes. PURPOSE: To critically review the available data on training, accuracy, and outcomes of computer and physician interpretation of 12-lead resting ECGs. DATA SOURCES: English-language articles were retrieved by searching MEDLINE (1966 to 2002), EMBASE (1974 to 2002), and the Cochrane Controlled Trials Register (1975-2002). The references in articles selected for analysis were also reviewed for relevance. STUDY SELECTION: All articles on training, accuracy, and outcomes of ECG interpretations were analyzed. DATA EXTRACTION: Study design and results were summarized in evidence tables. Information on physician interpretation compared to a "gold standard," typically a consensus panel of expert electrocardiographers, was extracted. The clinical context of and outcomes related to the ECG interpretation were obtained whenever possible. DATA SYNTHESIS: Physicians of all specialties and levels of training, as well as computer software for interpreting ECGs, frequently made errors in interpreting ECGs when compared to expert electrocardiographers. There was also substantial disagreement on interpretations among cardiologists. Adverse patient outcomes occurred infrequently when ECGs were incorrectly interpreted. CONCLUSIONS: There is no evidence-based minimum number of ECG interpretations that is ideal for attaining or maintaining competency in ECG interpretation skills. Further research is needed to clarify the optimal way to build and maintain ECG interpretation skills based on patient outcomes.

Cardiology↗
PubMed2007

Comparison of the diagnostic accuracy of the Cognitive Performance Scale (Minimum Data Set) and the Mini-Mental State Exam for the detection of cognitive impairment in nursing home residents.

OBJECTIVE: To compare the diagnostic accuracy of an outcome measurement scale of the Minimum Data Set of the Resident Assessment Instrument for nursing homes (MDS/RAI-NH), the Cognitive Performance Scale (CPS) and the Mini-Mental State Exam (MMSE) for the detection of cognitive impairment. The Cambridge Examination for Mental Disorders of the Elderly--Revised (CAMDEX-R) was used as the reference standard. STUDY DESIGN AND SETTING: This study was part of a larger prospective study (QUALIDEM) involving a diagnostic procedure and two-year follow-up on the quality of primary care for demented patients. CAMDEX-R and MDS/RAI-NH were administered to 198 residents, aged 65 or more, living in 42 low and high care institutions for aged people. MAIN OUTCOME MEASURES: Indicators of diagnostic accuracy: sensitivity, specificity, predictive values, likelihood ratios, odds ratio and area under receiver operating characteristics curve (AUC). RESULTS: The CAMDEX-based prevalence of cognitive impairment was 75%. The diagnostic values of a CPS score of two or more for the detection of cognitive impairment were: sensitivity = 0.81; specificity = 0.80; PPV = 0.92; NPV = 0.57. The diagnostic values of a MMSE score of less than or equal 23 were: sensitivity = 0.97; specificity = 0.59; PPV = 0.88; NPV = 0.85. For CPS, the area under the receiver operating characteristic (ROC) curve was 0.87 (95% CI, 0.81-0.91), and not significantly different (p = 0.63) from the MMSE score, 0.88 (0.83-0.93). CONCLUSIONS: CPS and MMSE demonstrated similar performance to detect cognitive impairment in nursing home residents.

Aged↗
PubMed2004

The accuracy of risk scores in predicting preterm birth--a systematic review.

This review aims to determine the accuracy with which published risk scores predict spontaneous preterm birth in pregnant women. Studies were identified without language restrictions through nine different databases (up to June 2002), and manual searching of bibliographies of known primary and review articles. Two reviewers selected studies independently and extracted data on their characteristics, quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables of the results of risk scoring with spontaneous preterm birth as the reference standard. Heterogeneity was assessed and its reasons were explored. Summary estimates of accuracy were produced within clinically appropriate subgroups. There were 19 primary accuracy articles that met the selection criteria, including a total of 67390 women. There are 12 different risk-scoring systems, the one developed by Creasy being the most commonly evaluated. Quality features of an ideal study, such as blinding and consecutive enrolment, were frequently missing from the included studies, no study fulfilled all criteria for high quality study, and there was heterogeneity between their accuracy estimates. The reference standard most often used was birth before 37 weeks' gestation. The point estimates for the likelihood ratios (LRs) varied widely among the studies. LRs for an abnormal score (LR+) ranged from 1.0 (95% confidence interval (CI) 0.6-1.4) to 38.8 (95% CI 23.5-63.9) while that for a normal score (LR-) ranged from 0.1 (95% CI 0.02-0.6) to 1.2 (95% CI 0.9-1.6). In otherwise asymptomatic women, risk scoring in early pregnancy has a wide range of accuracy in predicting spontaneous preterm birth before 37 weeks' gestation. The evidence is of a relatively poor quality and lacks clinically important reference standards.

Female↗
PubMed2000

Methods to improve diagnostic accuracy in a community mental health setting.

OBJECTIVE: This study determined the extent to which adding structured procedures improved diagnostic accuracy for outpatients with severe mental illness in a community mental health setting. METHOD: The Structured Clinical Interview for DSM-III-R (SCID) was used to interview 200 psychiatric outpatients. A research nurse reviewed medical records and amended the SCID diagnoses accordingly. A research psychiatrist or psychologist reviewed the diagnostic data and interviewed each patient to verify or further modify the previous findings. Diagnostic outcomes at each step of the procedure were compared to determine whether adding additional data improved diagnostic accuracy. The additional time required for each element of the diagnostic procedure was also assessed. RESULTS: Kappa comparisons of the different diagnostic levels showed that adding additional data significantly improved accuracy. Diagnoses rendered by combining the SCID and review of the medical record were the most accurate, followed by the SCID alone, and then diagnoses made by psychiatrists during routine care. In addition, the SCID alone identified five times as many current and past secondary diagnoses as were documented routinely in patients' charts. CONCLUSIONS: Combining structured interviewing with a review of the medical record appears to produce more accurate primary diagnoses and to identify more secondary diagnoses than routine clinical methods. The patients' knowledge of their diagnoses was limited, suggesting a need for patient education in this setting. Whether use of structured interviewing in routine practice improves patient outcomes deserves further study.

Adolescent↗
PubMed1990

The effects of data entry error: an analysis of partial verification.

Modern data entry technology has greatly reduced entry errors by building quality control mechanisms such as cross-field and range edits directly into data entry programs. In many application areas the increased accuracy of modern data entry techniques has made 100% verification unnecessary to assure high standards of data quality. Verification of randomly selected forms combined with 100% verification of critical fields provides a cost efficient alternative to 100% verification of all fields. This paper analyzes the effects of data entry error on study findings and provides a basis for designing a partial verification scheme for achieving quality control goals in a cost efficient manner.

Data Collection↗
PubMed1993

Beyond Utstein: implementation of a multisource uniform data base for prehospital cardiac arrest research.

This article is an overview of the issues affecting the use of a multisource uniform data base for prehospital cardiac arrest research. The goals of data base standardization include improved communication between emergency medical services (EMS) systems and between EMS physicians and the lay public; improved quantification of EMS system performance and documentation of benefit; in-depth analysis of factors that contribute to outcome; and development of EMS system models that will enhance system planning. Challenges to developing a multisource research data base include establishing a concensus approach to data base development; enlisting EMS system cooperation; verifying the accuracy of the data collected; coordinating data storage and analysis; and obtaining fiscal support for such a project. One illustrative approach to initiating multisource data base research is outlined. The iterative nature of data base development, use, expansion, and refinement is emphasized. Future reports addressing the methodology of multisource data base development and application in EMS systems should build on these concepts.

Databases, Factual↗
PubMedDate not supplied

Identification of protein modifications using MS/MS de novo sequencing and the OpenSea alignment algorithm.

Algorithms that can robustly identify post-translational protein modifications from mass spectrometry data are needed for data-mining and furthering biological interpretations. In this study, we determined that a mass-based alignment algorithm (OpenSea) for de novo sequencing results could identify post-translationally modified peptides in a high-throughput environment. A complex digest of proteins from human cataractous lens, a tissue containing a high abundance of modified proteins, was analyzed using two-dimensional liquid chromatography, and data was collected on both high and low mass accuracy instruments. The data were analyzed using automated de novo sequencing followed by OpenSea mass-based sequence alignment. A total of 80 modifications were detected, 36 of which were previously unreported in the lens. This demonstrates the potential to identify large numbers of known and previously unknown protein modifications in a given tissue using automated data processing algorithms such as OpenSea.

Aged↗
PubMed1999

Magnetoencephalographic mapping of the language-specific cortex.

OBJECT: In this paper the authors introduce a novel use of magnetoencephalography (MEG) for noninvasive mapping of language-specific cortex in individual patients and in healthy volunteers. METHODS: The authors describe a series of six experiments in which normative MEG data were collected and the reliability, validity, and topographical accuracy of the data were assessed in patients who had also undergone the Wada procedure or language mapping through intraoperative cortical stimulation. CONCLUSIONS: Findings include: 1) receptive language-specific areas can be reliably activated by simple language tasks and this activation can be readily recorded in short MEG sessions; 2) MEG-derived maps of each individual are reliable because they remain stable over time and are independent of whether auditory or visual stimuli are used to activate the brain; and 3) these maps are also valid because they concur with results of the Wada procedure in assessing hemispheric dominance for language and with the results of cortical stimulation in identifying the precise topography of receptive language regions within the dominant hemisphere. Although the MEG mapping technique should be further refined, it has been shown to be efficacious by correctly identifying the language-dominant hemisphere and specific language-related regions within this hemisphere. Further development of the technique may render it a valuable adjunct for routine presurgical planning in many patients who harbor tumors or have epilepsy.

Acoustic Stimulation↗
PubMedDate not supplied

Safety, permanency, and in-home services: applying administrative data.

This article describes the construction and use of safety and permanency indicators, two aspects of a full set of indicators that also includes child well-being and family functioning. The indicators were constructed from Philadelphia's Family and Child Tracking System and were used to examine the city's Services to Children in their Own Home (SCOH) program. Cohort datasets were constructed through the use of extract files, and two independent data file construction algorithms were employed to calibrate the accuracy of the data construction process. The primary unit of analysis was the "family" spell in SCOH services. Contextual variables included family structure, race, and service intensity. The indicators associated with SCOH spells included reports of maltreatment after service, founded maltreatment after service, and out-of-home placement after service. Event history techniques were used to conduct the data analysis. Baseline indicator data for Philadelphia are presented, and future uses for such data are discussed.

Child↗