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SWISS-MODEL: An automated protein homology-modeling server.

SWISS-MODEL (http://swissmodel.expasy.org) is a server for automated comparative modeling of three-dimensional (3D) protein structures. It pioneered the field of automated modeling starting in 1993 and is the most widely-used free web-based automated modeling facility today. In 2002 the server computed 120 000 user requests for 3D protein models. SWISS-MODEL provides several levels of user interaction through its World Wide Web interface: in the 'first approach mode' only an amino acid sequence of a protein is submitted to build a 3D model. Template selection, alignment and model building are done completely automated by the server. In the 'alignment mode', the modeling process is based on a user-defined target-template alignment. Complex modeling tasks can be handled with the 'project mode' using DeepView (Swiss-PdbViewer), an integrated sequence-to-structure workbench. All models are sent back via email with a detailed modeling report. WhatCheck analyses and ANOLEA evaluations are provided optionally. The reliability of SWISS-MODEL is continuously evaluated in the EVA-CM project. The SWISS-MODEL server is under constant development to improve the successful implementation of expert knowledge into an easy-to-use server.

Computer Graphics↗

The 2000 Olympic Games of protein structure prediction; fully automated programs are being evaluated vis-à-vis human teams in the protein structure prediction experiment CAFASP2.

In this commentary, we describe two new protein structure prediction experiments being run in parallel with the CASP experiment, which together may be regarded as the 2000 Olympic Games of structure prediction. The first new experiment is CAFASP, the Critical Assessment of Fully Automated Structure Prediction. In CAFASP, the participants are fully automated programs or Internet servers, and here the automated results of the programs are evaluated, without any human intervention. The second new experiment, named LiveBench, follows the CAFASP ideology in that it is aimed towards the evaluation of automatic servers only, while it runs on a large set of prediction targets and in a continuous fashion. Researchers will be watching the 2000 protein structure prediction Olympic Games, to be held in December, in order to learn about the advances in the classical 'human-plus-machine' CASP category, the fully automated CAFASP category, and the comparison between the two.

Amino Acid Sequence↗

Different approaches to synovial membrane volume determination by magnetic resonance imaging: manual versus automated segmentation.

Automated fast (5-20 min) synovial membrane volume determination by MRI, based on pre-set post-gadolinium-DTPA enhancement thresholds, was evaluated as a substitute for a time-consuming (45-120 min), previously validated, manual segmentation method. Twenty-nine knees [rheumatoid arthritis (RA) 13, osteoarthritis (OA) 16] and 17 RA wrists were examined. At enhancement thresholds between 30 and 60%, the automated volumes (Syn(x%)) were highly significantly correlated to manual volumes (SynMan) (knees: rho = 0.78-0.91, P < 10(-5) to < 10(-9); wrists: rho = 0.87-0.95, P < 10(-4) to < 10(-6)). The absolute values of the automated estimates were extremely dependent on the threshold chosen. At the optimal threshold of 45%, the median numerical difference from SynMan was 7 ml (17%) in knees and 2 ml (25%) in wrists. At this threshold, the difference was not related to diagnosis, clinical inflammation or synovial membrane volume, e.g. no systematic errors were found. The inter-MRI variation, evaluated in three knees and three wrists, was higher than by manual segmentation, particularly due to sensitivity to malalignment artefacts. Examination of test objects proved the high accuracy of the general methodology for volume determinations (maximal error 6.3%). Preceded by the determination of reproducibility and the optimal threshold at the available MR unit, automated 'threshold' segmentation appears to be acceptable when changes rather than absolute values of synovial membrane volumes are most important, e.g. in clinical trials.

Adult↗

Automated recognition of EEG changes accompanying arousal in respiratory sleep disorders.

Daytime sleepiness and impaired cognitive function can be a consequence of recurrent transient arousal from sleep, associated with abrupt changes in the electroencephalogram (EEG). EEG is normally assessed by trained observers from paper records, but automation offers the advantages of speed and objectivity. We assessed 10 automated indices of EEG activity as potential indicators of arousal. Arousals from light, slow wave and rapid eye movement sleep were studied in 30 subjects. Segments of EEG recorded immediately before and after each arousal were analyzed by automated measurement of 10 EEG indices using a personal computer. We investigated the ability of each index to recognize arousal while rejecting change due to variability during sleep. Nine of the 10 indices showed significant changes with arousal (p < 0.001); the better indices were related to EEG frequency, and 3 were chosen for further study. In these indices, the mean changes with arousal were 3.8 Hz (ZeroCross), 1.7 Hz (Hjorth's Mobility) and 1.2 Hz (FrqMean, an index of central EEG frequency). With none of these three indices were significant differences in performance due to base sleep stage or subject group found. We conclude that detection of arousal is feasible using automated methods that measure simple indices related to the frequency of the EEG waveform.

Adult↗

Automated echocardiographic analysis. Examination of serial intraoperative measurements.

BACKGROUND: Although transesophageal echocardiography allows continuous intraoperative cardiac monitoring, the technique has been limited by the lack of a method for realtime, quantitative assessment of cardiac chamber size and systolic function. Automated border detection (ABD), based on an analysis of integrated backscatter, is a new technique that is purported to provide real-time, quantitative assessment of left ventricular (LV) areas and fractional area change (FAC). A prospective investigation was designed to assess the accuracy and trending capability of ABD during continuous intraoperative monitoring. METHODS: In 16 patients monitored throughout noncardiac surgical procedures, serial real-time estimates of LV end-diastolic area (EDA), end-systolic area (ESA), and FAC by ABD were compared with paired off-line manual measurements made by two experiences echocardiographers. RESULTS: There was a high correlation between real-time ABD estimates of LV ESA (r = 0.93), EDA (r = 0.89), and FAC (r = 0.90) to those of the off-line technique. The automated technique systematically underestimated both EDA and ESA, resulting in a small underestimation of FAC. The automated technique demonstrated an accuracy rate of 96% in tracking serial changes in LV area. The technique performed with an 83% sensitivity and 85% specificity for detecting acute changes in LV area. CONCLUSIONS: This analysis of serial intraoperative echocardiograms demonstrates the accuracy of ABD to estimate LV area in real time and to track serial changes in cardiac area during surgery. Although ABD is an automated technique, application by personnel experienced in its operation and an echocardiographic system that includes lateral-gain adjustment controls are recommended for its optimal performance.

Adult↗

Comparison between radionuclide ejection fraction and fractional area changes derived from transesophageal echocardiography using automated border detection.

BACKGROUND: Left ventricular fractional area changes (FAC) can be derived from transesophageal echocardiography using an automated border detection system. However, FAC has not yet been compared to left ventricular ejection fraction (EF) evaluated by a reference technique. The aim of this study was to correlate transesophageal echocardiography automated FAC to EF derived from radionuclide angiography to obtain a quantifying method of global left ventricular systolic function at the bedside. METHODS: Ten critically ill patients, whose lungs were mechanically ventilated, were included in this prospective study. Patients were scheduled for radionuclide EF evaluation when at least 75% of the endocardium was clearly visualized on transesophageal echocardiography. Patients with esophageal pathology or cardiac dysrhythmia were excluded. Ejection fraction derived from radionuclide angiography was measured using technetium 99m. Echocardiographic data were obtained using an ultrasound system with automated border capabilities. Simultaneous measurements of left ventricular EF and FAC were obtained for each patient, both before and after starting a dobutamine intravenous infusion to modify left ventricular contractility. RESULTS: Mean values for radionuclide EF and transesophageal echocardiography FAC were, respectively: 55% +/- 19% (range 19-89%) and 46% +/- 18% (range 17-80%). Left ventricular EF and FAC were significantly correlated (r = 0.85, SEE = 9.6%). Variations of EF and FAC, induced by dobutamine, were also correlated (r = 0.70, SEE = 4.9%). CONCLUSIONS: Fractional area changes determined by transesophageal echocardiography using automated border detection correlate well with radionuclide EF and may be used at the bedside to quantify left ventricular function in selected intensive care unit patients.

Echocardiography, Transesophageal↗

Evaluation of an automated procedure for scoring patient notes as part of a clinical skills examination.

PROBLEM STATEMENT AND BACKGROUND: The purpose of the present study was to examine the extent to which an automated scoring procedure that emulates expert ratings with latent semantic analysis could be used to score the written patient note component of the proposed clinical skills examination (CSE). METHOD: Human ratings for four CSE cases collected in 2002 were compared to automated holistic scores and to regression-based scores based on automated holistic and component scores. RESULTS AND CONCLUSIONS: Regression-based scores account for approximately half of the variance in the human ratings and are more highly correlated with the ratings than the scores produced from the automated algorithm. Implications of this study and suggestions for follow-up research are discussed.

Algorithms↗

Automated sensory nerve conduction testing using fuzzy logic.

Nerve conduction studies continue to be an important tool in the evaluation of peripheral nerve disorders but have come under increased scrutiny because of heightened cost control in health care service delivery. In selected clinical settings, automated nerve conduction studies may be a useful clinical tool replacing conventional testing, but existing instruments are limited and have not generally been accepted into clinical practice. Further advancements in nerve conduction automation may be possible by incorporating expert system approaches into nerve conduction measurement and control algorithms. Using fuzzy logic techniques to duplicate the reasoning strategies of experienced electrodiagnostic clinicians, a software controller was developed to automatically perform sensory nerve conduction studies. The fuzzy logic system successfully performed 88% of 97 sensory studies in a mixed group of normal and patient populations. Sensory nerve action potential latency and amplitude measures obtained with automated testing were the same as determined by clinicians. Failures were related to design limitations of the controller, noise, and artifact. The high negative predictive value and sensitivity of fuzzy logic based testing suggest that its utility is in minimizing the need for unnecessary conventional electrodiagnostic studies in patients with normal nerve function. Fuzzy logic appears to be a useful approach to nerve conduction automation that can model expert reasoning and judgment.

Action Potentials↗

Expanding automatic external defibrillators to include automated detection of cardiac, respiratory, and cardiorespiratory arrest.

The new Guidelines of the American Heart Association state that lay rescuers can no longer rely on the manual pulse check to confirm cardiac arrest in an unresponsive patient. We were therefore prompted to develop a method for automated determination of the presence or absence of cardiac contraction and breathing. The technique was designed to be incorporated into conventional automated external defibrillators and to work in conjunction with the information derived from rhythm analyses by the automated defibrillator. Using conventional electrocardiographic sensing and defibrillation electrodes, the transthoracic impedance was measured by passing a constant amplitude alternating current of 5 mA through the thorax at a frequency of 35 kHz. In five anesthetized male domestic swine, we observed pulses that were coincident with cardiac contraction documented by esophageal echocardiography. In addition, we observed larger signals of lower frequency that were time related to ventilation and documented by capnography. Both signals disappeared after inducing ventricular fibrillation. The impedance measurement identified respiratory arrest in anesthetized animals and primary cardiac arrest after ventricular fibrillation was induced. The cardiac arrest detector is therefore likely to augment the current information provided by automated defibrillators and to allow for more precise verbal prompting of lay rescuers.

Animals↗

Automated short-axis cardiac magnetic resonance image acquisitions: accuracy of left ventricular dimension measurements in normal subjects and patients.

RATIONALE AND OBJECTIVE: This study investigates the use of an automated observer-independent planning system for short-axis cardiovascular magnetic resonance (MR) acquisitions in the clinical environment. The capacity of the automated method to produce accurate measurements of left ventricular dimensions and function was quantitatively assessed in normal subjects and patients. METHODS: Fourteen healthy volunteers and 8 patients underwent cardiovascular MR (CMR) acquisitions for ventricular function assessment. Short-axis datasets of the left ventricle (LV) were acquired in 2 ways: manually planned and generated in an automatic fashion. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and left ventricular mass (LVM) were derived from the 2 datasets. The agreement between the manual and automatic planning methods was assessed. RESULTS: The mean differences between the manual and automated CMR planning methods for the normal subjects and patients were 5.89 mL and 1.93 mL (EDV), 1.14 mL and -0.41 mL (ESV), 0.81% and 0.89% (EF), and 4.35 g and 3.88 g (LVM), respectively. There was no significant difference in ESV and EF. LVM significantly differed in both groups, whereas EDV was significantly different in the normal subjects and insignificantly different in the patients. The variability coefficients were 2.8 and 3.59 (EDV), 3.3 and 5.03 (ESV), 1.79 and 2.65 (EF), and 4.36 and 2.27 (LVM) for the normal subjects and patients, respectively. The mean angular deviation of the LV axes turned out to be 8.58 +/- 5.76 degrees for the normal subjects and 8.35 +/- 5.15 degrees for the patients. CONCLUSIONS: Automated CMR planning method can provide accurate measurements of LV dimensions in normal subjects and patients, and therefore, can be used in the clinical environment for functional assessment of the human cardiovascular system.

Adult↗

Utilization of an automated multiphasic health testing system for performing prehospitalization examinations.

Various impacts of performing prehospitalization examinations (of elective surgical patients) by utilizing automated multiphasic screening technology were evaluated. Compared to the conventional way of conducting such examinations (in the concerned health care organization) the automated system was found to be more efficient (results were available earlier, in a more complete and convenient format), saved considerable time to patients and resulted in a shorter average hospital (postoperative) stay, suggesting that the automated technology is also cost effective. Postoperative stay was reduced by 20 per cent (1.8 days) in the group of patients who undertook the automated multiphasic testing, as compared to a similar group of patients who performed the required tests in the conventional way. Possible explanations for this finding are discussed.

Adolescent↗

Automation of the homogeneous substrate-labeled fluorescent immunoassay for theophylline in serum: application to the determination of phenytoin and phenobarbital in serum.

A substrate labeled fluorescent immunoassay procedure for serum theophylline has been automated. The method uses the Ames (SLFIA) substrate-labeled fluorescent immunoassay reagents and Technicon AutoAnalyzer equipment. Forty-seven sera analyzed for theophylline by the automated Ames SLFIA procedure and by the Syva EMIT method yielded the regression equation y (Ames) = 0.92x (Syva) + 0.47, SE, sy.x = 1.67, and correlation coefficient r = 0.934. Recoveries ranged from 94.6 to 100% by the automated SLFIA method. Within-run mean and SD for a sample in and above the therapeutic range was 14.5 +/- 0.37 and 22.7 +/- 1.0 mg/L, respectively. Day-to-day reproducibility was 13.4 +/- 0.92 and 24.7 +/- 1.71 mg/L for a sample in and above the therapeutic range, respectively. The automated SLFIA procedure analyzes serum for theophylline at the rate of 40 per hour and gives results comparable to the Syva EMIT method. The same equipment was also used for the SLFIA determination of phenytoin and phenobarbital and yielded reliable results. The manifold and equipment were the same. The only change was the substitution of the Ames phenytoin and phenobarbital reagents for the theophylline reagent.

Autoanalysis↗

Totally automated analysis by robotized PrepStation and liquid chromatography: direct-sample analysis of felbamate.

A totally automated analysis of felbamate was developed by using a robotized PrepStation for extraction, followed by automated liquid chromatographic (LC) analysis and data reduction. This is one of the newer direct-sample analysis approaches by LC. Felbamate was a previously approved antiepileptic agent used to treat partial seizures with and without generalization and to treat Lennox-Gastaut syndrome in pediatric patients. However, due to the reported incidences of aplastic anemia, its clinical application was recently restricted to the treatment of the latter syndrome. The automated assay using Bench Supervisor, PrepStation, and LC, based on a previously developed manual method, used 200 microliters of serum standards, quality control, or patients' plasma. These were mixed with 600 microliters of internal standard (IS) W509 dissolved in acetonitrile for protein precipitation. After axial centrifugation and standing, aliquots of the clear supernatant were transferred and washed with hexane. Aliquots of the supernatant were transferred and injected into a high-performance liquid chromatograph (HPLC). HPLC parameters included an mu Bondapak C-18 column, phosphate/acetonitrile (8:2) as mobile phase, and detection at 214 nm. Retention times were 2.9 and 4.2 min for felbamate and IS, respectively. Calibration was linear for concentrations from 10 to 200 mg/L with r > 0.994. Precision studies showed coefficients of variation ranging from 2.7% to 8.8%. Correlation with the manual method showed that r = 0.934, slope = 1.048, intercept = -2.642, and n = 21. Phenobarbital coeluted with the IS. This study demonstrated the feasibility of using a robotized, automated method for monitoring felbamate, readily extended to monitoring other antiepileptic drugs with minimal modification.

Anticonvulsants↗

Automated colorimetric in situ hybridization (CISH) detection of immunoglobulin (Ig) light chain mRNA expression in plasma cell (PC) dyscrasias and non-Hodgkin lymphoma.

Immunohistochemistry (IHC) is frequently used to detect plasma cell (PC) or B cell monoclonality in histologic sections, but its interpretation is often confounded by background staining. We evaluated a new automated method for colorimetric in situ hybridization (CISH) detection of clonality in PC dyscrasias and small B cell lymphomas. Cases of PC dyscrasia included multiple myeloma (MM; 31 cases), plasmacytoma (seven cases), or amyloidosis (one case), while cases of lymphoma included small lymphocytic (three cases), marginal zone (four cases), lymphoplasmacytic (three cases), and mantle cell lymphomas (three cases). Tissue sections were stained for kappa and lambda light chains by IHC and for light chain mRNA by automated CISH using haptenated probes. Twenty-eight of 31 MM cases had detectable light chain restriction by IHC. Thirty of 31 MM cases demonstrated light chain restriction by CISH, including 2 cases with uninterpretable IHC and one case of nonsecretory myeloma, which was negative for light chains by IHC. Seven of 7 plasmacytoma cases had detectable light chain restriction by CISH, including one case of nonsecretory plasmacytoma in which IHC was noninformative. Automated CISH demonstrated monoclonality in 9 of 13 cases of B cell non-Hodgkin lymphoma and had a slightly higher sensitivity than IHC (6 of 13 cases), especially in cases of lymphoplasmacytic and marginal zone lymphoma. Overall, there were no discrepancies in light chain restriction results between IHC, CISH, or serum paraprotein analysis. Automated CISH is useful in detecting light chain expression in paraffin sections and appeared superior to IHC for light chain detection in PC dyscrasias and B cell non-Hodgkin lymphomas, predominantly due to lack of background staining.

Bone Marrow Cells↗

Recent developments in automated perimetry in glaucoma diagnosis and management.

Recently, there have been several new developments in automated perimetry that have contributed to enhanced diagnosis and management of glaucoma. This paper will briefly review four of the latest advances in automated perimetry: (1) efficient test strategies that reduce the testing time and variability of automated perimetric testing, in particular, the Swedish Interactive Threshold Algorithm (SITA) and Tendency Oriented Perimetry (TOP) test strategies will be described; (2) Frequency Doubling Technology (FDT) perimetry, which has been shown to be a rapid, effective method of detecting glaucomatous visual field loss; (3) Short Wavelength Automated Perimetry (SWAP), which has demonstrated the ability to predict the onset and progression of glaucomatous visual field deficits; (4) The Multifocal Electroretinogram (mfERG) and the Multifocal Visual Evoked Potential (mfVEP), which provide an objective measurement of the visual field. Each of these techniques has presented distinct advantages for the diagnosis and management of glaucoma.

Glaucoma↗

Accuracy of an automated method to measure rotations of vertebrae from computerized tomography data.

STUDY DESIGN: In this phantom study, rotations of a vertebral body calculated from computerized tomography (CT) were compared to the actual rotations provided by a specially designed device incorporating a reduction gear. OBJECTIVE: The objective was to measure the accuracy of the CT and an automated software program to calculate rotations of lumbar vertebral bodies. BACKGROUND: Rotations of individual vertebrae secondary to a change in position or load can be measured in select patients by roentgen stereophotogrammetry or by using CT and a specially constructed table that creates the rotation of the torso. The purpose of this study was to measure the precision and accuracy of rotation measurements made with a CT scanner and an automated program to calculate rotation. METHODS: We constructed a phantom with a lumbar vertebra that can be rotated within a CT scanner. CT of the vertebra were obtained at angular positions of 0, 0.360 degrees , 1.080 degrees , 2.520 degrees , 5.400 degrees , 11.160 degrees , 29.160 degrees , 29.340 degrees , 29.520 degrees , 29.610 degrees , 29.700 degrees , 29.790 degrees , 29.880 degrees , and 29.889 degrees . With an automated program based on a pixel-shift algorithm, we calculated rotations of the vertebra between pairs of images. Accuracy was calculated as mean difference between the actual and the calculated rotation, and precision was calculated as the standard deviation of the differences. RESULTS: Differences between actual and calculated rotations varied from -0.083 degrees to 0.132 degrees . For rotations less than 15 degrees , mean error (accuracy) was -0.039 degrees , and the standard deviation (precision) was 0.029 degrees . For rotations greater than 15 degrees , the accuracy was 0.086 degrees , and the precision was 0.023 degrees . CONCLUSIONS: This study shows that rotations of lumbar vertebrae may be measured with CT, and an automated program to an accuracy and precision better than 0.1 degrees , comparable to that of roentgen stereophotogrammetry.

Humans↗

Human factors impact successful lay person automated external defibrillator use during simulated cardiac arrest.

OBJECTIVE: With the dissemination of automated external defibrillators in the community, there is increasing lay person use, along with less formal automated external defibrillator training and retraining. Therefore, the "ease of use" factors related to the human-device interface may be vital for successful use. We sought to determine whether human factor differences would result in differences in parameters of successful or safe use by lay persons in the setting of simulated cardiac arrest. METHODS: We measured parameters of successful and safe use with two automated external defibrillator devices among two groups of volunteers, those trained with a brief video tape and those without any training (completely naive). Both devices (the Philips FR2 or the HS1) are used in public access defibrillator settings. Volunteers entered a mock cardiac arrest scenario after randomization to either the naive (untrained) group or to a video-trained group. RESULTS: Both the FR2 and HS1 were found to be completely safe when used by video-trained and by naive groups of participants, with no adverse events observed (total, n = 256). For both devices, video-trained participants demonstrated high rates of successful defibrillation in the simulated testing (86% for FR2 and 89% for HS1). With the FR2, video-trained participants were significantly more successful compared with naive, untrained participants (86% vs. 48% successful use; p < .001). However, for the HS1, there was no significant difference in success rates for the video-trained vs. naive, untrained groups (89% vs. 87%; p = .79). CONCLUSIONS: Both devices are safe with either video-trained or naive users. The successful use of each device is high when participants view the training videotape designed for the device. An important difference in successful use was observed for naive users where the HS1 showed improved successful use compared with the FR2. Because defibrillation in the community may increasingly be attempted by lay persons whose training is remote or who have not been trained at all, the "naive" scenario may be increasingly relevant to automated external defibrillator use. Collectively, these data support the notion that human factors associated with ease of use may play a critical factor in survival rates achieved by specific devices.

Adult↗

Automated quantification of 99mTc sestamibi myocardial perfusion compared with visual analysis.

OBJECTIVES: The visual interpretation of 99mTc sestamibi single photon emission computed tomography (SPECT) myocardial perfusion images can be challenging due to the quantity of scan information generated, the large number of normal variants, attenuation artifacts and gender differences. The development of automated, computer derived, quantitative indices of perfusion can assist in this interpretation by providing an objective measure. It is important to verify that similar results can be obtained when the software is used in centres outside those where the algorithms were initially developed. Our objective was to assess the degree of concordance between the visual and automated diagnostic assessments of 99mTc sestamibi SPECT. METHODS: We studied 718 patients referred for 99mTc sestamibi SPECT myocardial perfusion imaging. The SPECT studies were initially interpreted visually without benefit of computer based analysis, and were then subjected to blinded reprocessing to extract quantitative indices of perfusion. RESULTS: There was very good agreement between the visual and quantitative diagnostic classifications. When a visual abnormality was taken to be the reference standard, the automated summed stress score (SSS) showed agreement (SSS>3) in 80% (kappa 0.60, P<0.0001). The area under the receiver operating characteristic (ROC) curve was 0.89 (95% confidence interval (CI), 0.86-0.91). Concordance was greater in those with previous myocardial infarction or severe perfusion defects, but was not affected by age, prior revascularization, stress procedure or heart rate. Concordance over the presence or absence of visual reversibility and the summed difference score (SDS) in abnormal scans was slightly lower (overall agreement 73% (kappa 0.36, P<0.00001) and ROC area 0.84 (95% CI, 0.77-0.90)). CONCLUSION: Automated quantification of 99mTc sestamibi SPECT myocardial perfusion with the SSS and SDS provides objective diagnostic information and concordance when compared with conventional visual image interpretation.

Algorithms↗