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Data acquisition and analysis system for intracellular neuronal signals.

A comprehensive system for the acquisition and analysis of neurophysiological data is described, with a focus on intracellular data. The software comprising the system will evaluate a number of neuronal signals, including intracellular as well as extracellular recordings from neurons, evoked potentials and computer simulation data. Significant enhancements enable sampling at high resolution (50 kHz throughput to disk; +/- 15 bit or 96 db), concurrent with extensive on-line analysis capabilities and display. Modifications of existing software and development of new types of input and output devices and analysis can be incorporated as needed, using a binary digital database as the primary storage for the experimental signals and device-independent graphics.

Cell Communication↗

Development and application of reflexodent in the quantitative functional evaluation of chewing control in patients with temporomandibular joint dysfunction and a control group.

BACKGROUND: There has been controversy with respect to the diagnostic value of the inhibitory masseteric reflex in temporomandibular joint dysfunction (TMJD) because the whole reflex response was not considered. The purpose of this study was to characterize the reflex changes that occur in patients with different levels of TMJD and in a control group. METHODS: Eighty-nine patients (ages 31.14 +/- 12.74 years) divided into three groups were studied and compared. The control group was without TMJD (n = 30), with moderate symptoms (n = 30), and with severe symptoms (n = 29). Using an instrument and a software program developed by our group (Reflexodent), the masseteric inhibitory reflex was studied. The electromyography record (EMG) was captured with surface electrodes and the inhibitory reflex was produced by tapping the chin. The EMG signal was processed, filtered, and averaged with the Reflexodent. Twenty series of records were applied to each patient. The faulty inhibitory area, the area's relation (potentiation/inhibition) regarding the values of healthy subjects previously characterized, and the bilateral symmetry were measured. RESULTS: Discriminate analysis showed a statistically significant correlation between clinical groups and electromyographic findings. Statistical function explained 91.8% of the discrimination among groups (canonical correlation = 0.918, chi(2) = 164.435, p <0.001). CONCLUSIONS: The study of whole inhibitory masseteric reflex and the Reflexodent technique are useful as a diagnostic tool to evaluate TMJ illness in the dental clinic.

Adult↗

CTRD: a fast applet for computing signed translocation distance between genomes.

CTRD is a software for computing translocation distance between genomes. It takes two genomes as its input and tests whether one genome can be transformed into the other. If possible, it computes the translocation distance between two genomes, and gives the translocation operation serial. We adopt the fastest known O(n(2)log n) algorithm. Our contributions include (1) give a necessary and sufficient condition to ensure that one genome can be transformed into the other for translocation operations, and (2) develop a software using the fastest known O(n(2)log n) algorithm.

Algorithms↗

Real-time 12-lead high-frequency QRS electrocardiography for enhanced detection of myocardial ischemia and coronary artery disease.

Several studies have shown that diminution of the high-frequency (HF; 150-250 Hz) components present within the central portion of the QRS complex of an electrocardiogram (ECG) is a more sensitive indicator for the presence of myocardial ischemia than are changes in the ST segments of the conventional low-frequency ECG. However, until now, no device has been capable of displaying, in real time on a beat-to-beat basis, changes in these HF QRS ECG components in a continuously monitored patient. Although several software programs have been designed to acquire the HF components over the entire QRS interval, such programs have involved laborious off-line calculations and postprocessing, limiting their clinical utility. We describe a personal computer-based ECG software program developed recently at the National Aeronautics and Space Administration (NASA) that acquires, analyzes, and displays HF QRS components in each of the 12 conventional ECG leads in real time. The system also updates these signals and their related derived parameters in real time on a beat-to-beat basis for any chosen monitoring period and simultaneously displays the diagnostic information from the conventional (low-frequency) 12-lead ECG. The real-time NASA HF QRS ECG software is being evaluated currently in multiple clinical settings in North America. We describe its potential usefulness in the diagnosis of myocardial ischemia and coronary artery disease.

Adult↗

Anterior cingulate cortex: an MRI-based parcellation method.

OBJECTIVE: The anterior cingulate cortex (ACC) is an important part of the limbic system involved in emotions, cognition and executive function. The ACC has structurally distinct subregions, both microscopically and functionally, that have been implicated in several major psychiatric disorders. However, a structural analysis of these subregions with magnetic resonance imaging (MRI) has not been done. Our main purpose was to develop an MRI-based parcellation method of the ACC that permits us to explore plausible abnormalities in 4 functionally relevant subregions: dorsal, rostral, subcallosal and subgenual. METHODS: The reliability study for gray matter volume and surface area of each subregion was performed on 14 randomly selected MR scans by 3 different raters. Our method posits to conserve the topographic uniqueness of individual brains and is based on our ability to visualize both the 3-dimensional rendered brain and the 3 orthogonal planes simultaneously with BRAINS2 software. We developed rules to hand-trace regions of interest (ROI) to surround contiguous areas of gray matter for dorsal, rostral, subcallosal and subgenual regions. The ACC was then parcellated into these 4 distinct subregions (8 when both right and left hemispheres were measured). RESULTS AND DISCUSSION: The intraclass R coefficients for gray matter volume of each subregion ranged between 0.85 and 0.93. The current study describes a new highly reliable and reproducible topography-based parcellation method of the ACC into its dorsal, rostral, subcallosal and subgenual regions. CONCLUSIONS: This new parcellation method provides a new means of exploring the role of the functionally and structurally distinct subregions of the ACC in schizophrenia, depression and various other brain illnesses.

Cerebral Cortex↗

Elite system: recording of condylar movements using a modified computerized technique.

BACKGROUND: The aim was to develop a method to measure condylar movements using a computerized system. The Elite system is a computerized device for the graphic recording of mandibular movements by processing images of marks recorded with two video cameras. The Elite system has traditionally been used to measure mandibular movements; it was modified to record condylar movements as well. METHODS: The position of the markers was altered to enable 3-D recording not only of mandibular movements but also of condylar movements. New software was developed. Ten subjects (young adults; good complete dentition; no temporo-mandibular disorders; no orthodontic treatment) underwent recording with traditional and then with modified Elite system. The subjects were asked to perform the following movements: maximum opening and closing; protrusive and retrusive movements; border movements on the frontal plane. The sequence of movements was repeated three times on three different days. Data processing was effected using the Spline-smoothing method. RESULTS: The modified Elite system technique records condylar movements with extreme reliability, reproducibility and the resulting graphics are comparable. CONCLUSIONS: This method provides the chance to obtain more information about condylar movements in healthy subjects with good dentition, but also in patients with joint dysfunction.

Adult↗

Improved detection of differentially expressed genes in microarray experiments through multiple scanning and image integration.

The variability of results in microarray technology is in part due to the fact that independent scans of a single hybridised microarray give spot images that are not quite the same. To solve this problem and turn it to our advantage, we introduced the approach of multiple scanning and of image integration of microarrays. To this end, we have developed specific software that creates a virtual image that statistically summarises a series of consecutive scans of a microarray. We provide evidence that the use of multiple imaging (i) enhances the detection of differentially expressed genes; (ii) increases the image homogeneity; and (iii) reveals false-positive results such as differentially expressed genes that are detected by a single scan but not confirmed by successive scanning replicates. The increase in the final number of differentially expressed genes detected in a microarray experiment with this approach is remarkable; 50% more for microarrays hybridised with targets labelled by reverse transcriptase, and 200% more for microarrays developed with the tyramide signal amplification (TSA) technique. The results have been confirmed by semi-quantitative RT-PCR tests.

False Negative Reactions↗

APEX disease gene resequencing: mutations in exon 7 of the p53 tumor suppressor gene.

Detection of mutations in disease genes will be a significant application of genomic research. Methods for detecting mutations at the single nucleotide level are required in highly mutated genes such as the tumor suppressor p53. Resequencing of an individual patient's DNA by conventional Sanger methods is impractical, calling for novel methods for sequence analysis. Toward this end, an arrayed primer extension (APEX) method for identifying sequence alterations in primary DNA structure was developed. A two-dimensional array of immobilized primers (DNA chip) was fabricated to scan p53 exon 7 by single bases. Primers were immobilized with 200 microm spacing on a glass support. Oligonucleotide templates of length 72 were used to study individual APEX resequencing reactions. A template-dependent DNA polymerase extension was performed on the chip using fluorescein-labeled dideoxynucleotides (ddNTPs). Labeled primers were evanescently excited and the induced fluorescence was imaged by CCD. The average signal-to-noise ratio (S/N) observed was 30:1. Software was developed to analyze high-density DNA chips for sequence alterations. Deletion, insertion, and substitution mutations were detected. APEX can be used to scan for any mutation (up to two-base insertions) in a known region of DNA by fabricating a DNA chip comprising complementary primers addressing each nucleotide in the wild-type sequence. Since APEX is a parallel method for determining DNA sequence, the time required to assay a region is independent of its length. APEX has a high level of accuracy, is sequence-based, and can be miniaturized to analyze a large DNA region with minimal reagents.

DNA Mutational Analysis↗

Radiation oncology residents' computer workstation.

We are investigating the feasibility of using the Macintosh computer as a workstation platform for radiation oncology residents because of its ease of use, graphics capability, and low cost. Hypercard was chosen as the programming environment because it easily mixes graphics, text, and control functions in an integrated screen display. Furthermore, it results in a system that can be relatively easily extended and customized by individual users with varying degrees of computer skills. We have developed several software modules in order to test the ability of this environment to support the demands of such a workstation. Modules created thus far include various clinical physics aids and tutorials, treatment planning guides, oncology databases, and others. The software runs on all Macintosh configurations, but calculation speeds are improved when a 68020 or greater processor is used. In general, we have been pleased with the implementation thus far. Graphics display capability is good, but design and entry of graphics have proved labor-intensive. Searching is fast and text is easily entered and manipulated. Finished modules can be customized with minimal computer training, but implementing complex new functions requires familiarity with Hypercard's programming language. New modules, once developed, are easily integrated into the workstation universe, suggesting that cooperative development of the workstation by multiple contributors is realistically achievable.

Computer Graphics↗

Simulation of the biomechanical behavior of the skin in virtual surgical applications by finite element method.

The objective of this study was to develop a software application that is able to support plastic surgeons interested in applying simulations and soft tissue modeling during presurgical planning activities. By using our user-friendly interface and force-displacement graphs, users can analyze scalp skin behaviors when subjected to stress. Users can 1) determine the dynamic of a general point of scalp skin after the application of a specific force, 2) predict the force needed for displacement of a point, and 3) study the deformation of all the points of the entire scalp based on the force applied. Results showed how users are able to manipulate and analyze mechanical behaviors on a mechanical model rather than on a pure geometric qualitative physiological model. The entire application was developed on a Silicon Graphics workstation.

Animals↗

Development of an underwater weighing system for determining body composition.

A system was developed to reduce some of the difficulties associated with hydrostatic (underwater) weighing, specifically the need for complete exhalation and the subjective approximation of weighing scale measurements. The exhalation portion of the weighing protocol is particularly difficult for many disabled individuals and has contributed to the lack of available body composition information for this population. The components of our system include a computer system, load cell, spirometer, breathing tube, logic and signal conditioning circuitry specially constructed for this system, and a software package developed for this project. In a preliminary test, the body fat percentages of fourteen subjects (six males and eight females, ages 21-32 years) were determined both with the standard method and with our system. A correlation of r = 0.967 was found between the two methods, with our system's precision ranging from 1.0 to 1.3 body fat percentage points. The system could be used, for example, in developing a database for monitoring an individual's fitness or for making comparisons between groups (such as athlete to non-athlete).

Adult↗

On the use of EPID-based implanted marker tracking for 4D radiotherapy.

Four-dimensional (4D) radiotherapy delivery to dynamically moving tumors requires a real-time signal of the tumor position as a function of time so that the radiation beam can continuously track the tumor during the respiration cycle. The aim of this study was to develop and evaluate an electronic portal imaging device (EPID)-based marker-tracking system that can be used for real-time tumor targeting, or 4D radiotherapy. Three gold cylinders, 3 mm in length and 1 mm in diameter, were implanted in a dynamic lung phantom. The phantom range of motion was 4 cm with a 3-s "breathing" period. EPID image acquisition parameters were modified, allowing image acquisition in 0.1 s. Images of the stationary and moving phantom were acquired. Software was developed to segment automatically the marker positions from the EPID images. Images acquired in 0.1 s displayed higher noise and a lower signal-noise ratio than those obtained using regular (> 1 s) acquisition settings. However, the markers were still clearly visible on the 0.1-s images. The motion of the phantom blurred the images of the markers and further reduced the signal-noise ratio, though they could still be successfully segmented from the images in 10-30 ms of computation time. The positions of gold markers placed in the lung phantom were detected successfully, even for phantom velocities substantially higher than those observed for typical lung tumors. This study shows that using EPID-based marker tracking for 4D radiotherapy is feasible, however, changes in linear accelerator technology and EPID-based image acquisition as well as patient studies are required before this method can be implemented clinically.

Artifacts↗

A software application that answers the need for an enterprise budgeting tool.

A prototype software application developed for the Vanderbilt University School of Medicine answered our need for an enterprise budgeting tool--one that has application across the entire organization. This application, built on Microsoft Access, provides a flexible user interface without requiring sophisticated technical support.

Academic Medical Centers↗

Introduction of handheld computing to a family practice residency program.

BACKGROUND: Handheld computers are valuable practice tools. It is important for residency programs to introduce their trainees and faculty to this technology. This article describes a formal strategy to introduce handheld computing to a family practice residency program. METHODS: Objectives were selected for the handheld computer training program that reflected skills physicians would find useful in practice. TRGpro handheld computers preloaded with a suite of medical reference programs, a medical calculator, and a database program were supplied to participants. Training consisted of four 1-hour modules each with a written evaluation quiz. Participants completed a self-assessment questionnaire after the program to determine their ability to meet each objective. RESULTS: Sixty of the 62 participants successfully completed the training program. The mean composite score on quizzes was 36 of 40 (90%), with no significant differences by level of residency training. The mean self-ratings of participants across all objectives was 3.31 of 4.00. Third-year residents had higher mean self-ratings than others (mean of group, 3.62). Participants were very comfortable with practical skills, such as using drug reference software, and less comfortable with theory, such as knowing the different types of handheld computers available. CONCLUSION: Structured training is a successful strategy for introducing handheld computing to a residency program.

Attitude to Computers↗

Development of an opto-electronic positioning device for serial direct digital images of oral structures.

The aim of this study was to develop and test in vitro an opto-electronic positioning device for serial direct digital images of oral structures, i.e. to associate direct digital imaging with the principles of computer-aided surgery. This system registered positions of infrared light emitting diodes (LED) on carriers, establishing local coordinate systems. With LED markers attached on the sensor holder, the X-ray tube and a fix reference, the opto-electronic camera (Optotrak) registered the geometric source/detector relation. A specially designed tracking and guidance software was developed which enabled the operator to reposition the X-ray source. A graphical user interface guided the operator in aligning 2 circles to the reference axis, one indicating the origin of the beam, the other its tip. In addition, depth control was provided. An in vitro calibration was performed. A sensor holder/bite block carried the Sens-A-Ray sensor with a hair-cross. In front of the object a second hair-cross was fixed. A steel ball fixed to the center of the X-ray cone allowed to verify the alignment. The mean angulation error in the vertical plane was 0.06 degrees and 0.04 degrees in the horizontal one. Translation mean errors were small and ranged between -0.02 mm and 0.37 mm. The translation in the Z axis is negligible. This resulted in pairs of images suitable for digital subtraction. Although still in an experimental state, the results showed that opto-electronic navigation was useful to standardize projection geometry without any mechanical link and to achieve digital subtraction images based on direct digital imaging.

Equipment Design↗

Towards clustering of incomplete microarray data without the use of imputation.

MOTIVATION: Clustering technique is used to find groups of genes that show similar expression patterns under multiple experimental conditions. Nonetheless, the results obtained by cluster analysis are influenced by the existence of missing values that commonly arise in microarray experiments. Because a clustering method requires a complete data matrix as an input, previous studies have estimated the missing values using an imputation method in the preprocessing step of clustering. However, a common limitation of these conventional approaches is that once the estimates of missing values are fixed in the preprocessing step, they are not changed during subsequent processes of clustering; badly estimated missing values obtained in data preprocessing are likely to deteriorate the quality and reliability of clustering results. Thus, a new clustering method is required for improving missing values during iterative clustering process. RESULTS: We present a method for Clustering Incomplete data using Alternating Optimization (CIAO) in which a prior imputation method is not required. To reduce the influence of imputation in preprocessing, we take an alternative optimization approach to find better estimates during iterative clustering process. This method improves the estimates of missing values by exploiting the cluster information such as cluster centroids and all available non-missing values in each iteration. To test the performance of the CIAO, we applied the CIAO and conventional imputation-based clustering methods, e.g. k-means based on KNNimpute, for clustering two yeast incomplete data sets, and compared the clustering result of each method using the Saccharomyces Genome Database annotations. The clustering results of the CIAO method are more significantly relevant to the biological gene annotations than those of other methods, indicating its effectiveness and potential for clustering incomplete gene expression data. AVAILABILITY: The software was developed using Java language, and can be executed on the platforms that JVM (Java Virtual Machine) is running. It is available from the authors upon request.

Algorithms↗

Quantitative relationship between synonymous codon usage bias and GC composition across unicellular genomes.

BACKGROUND: Codon usage bias has been widely reported to correlate with GC composition. However, the quantitative relationship between codon usage bias and GC composition across species has not been reported. RESULTS: Based on an informatics method (SCUO) we developed previously using Shannon informational theory and maximum entropy theory, we investigated the quantitative relationship between codon usage bias and GC composition. The regression based on 70 bacterial and 16 archaeal genomes showed that in bacteria, SCUO = -2.06 * GC3 + 2.05*(GC3)2 + 0.65, r = 0.91, and that in archaea, SCUO = -1.79 * GC3 + 1.85*(GC3)2 + 0.56, r = 0.89. We developed an analytical model to quantify synonymous codon usage bias by GC compositions based on SCUO. The parameters within this model were inferred by inspecting the relationship between codon usage bias and GC composition across 70 bacterial and 16 archaeal genomes. We further simplified this relationship using only GC3. This simple model was supported by computational simulation. CONCLUSIONS: The synonymous codon usage bias could be simply expressed as 1+ (p/2)log2(p/2) + ((1-p)/2)log2((l-p)/2), where p = GC3. The software we developed for measuring SCUO (codonO) is available at http://digbio.missouri.edu/~wanx/cu/codonO.

Base Composition↗

Assessment of left ventricular parameters using 16-MDCT and new software for endocardial and epicardial border delineation.

OBJECTIVE: The purpose of our study was to quantify left ventricular function and mass derived from retrospectively ECG-gated 16-MDCT coronary angiography data sets using a new analysis software based on automatic contour detection in comparison to corresponding standard of reference measurements acquired with MRI. SUBJECTS AND METHODS: Multiplanar reformations in the short-axis orientation were calculated from axial contrast-enhanced CT images in 18 patients (men, 15; women, three; age range, 38-70 years; mean, 57.4 +/- 10.2 [SD] years) who were referred for CT coronary angiography. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and left ventricular mass (LVM) were analyzed with a recently developed imaging software using an automated contour detection algorithm of left ventricular endo- and epicardial contours and by manual tracing. The data were compared with similar measurements on MRI as the standard of reference. RESULTS: EDV, ESV, EF, and LVM derived from an automated contour detection algorithm were not statistically significantly different from manual tracing (CT(auto) vs CT(manual): EDV = 137.1 +/- 45.7 mL vs 134.2 +/- 39.9 mL, ESV = 58.8 +/- 34.2 mL vs 58.1 +/-30.1 mL, EF = 59.2% +/- 13.7% vs 58.1% +/- 12.0%, LVM = 130.9 +/- 29.1 g vs 133.7 +/- 33.2 g; p > 0.05). However, EDV (118.7 +/- 43.6 mL), ESV (50.1 +/- 33.5 mL), and LVM (142.8 +/-38.4 g) as calculated on MR data sets were statistically significantly different from those calculated on CT (p < 0.05), whereas MRI-based EF (59.9% +/- 14.4%) did not differ statistically significantly from those based on both CT algorithms (p > 0.05). CONCLUSION: Automatic and manual analysis of data acquired during CT coronary angiography using a 16-MDCT scanner allows a reliable assessment of left ventricular ejection fraction and a rough estimation of left ventricular volumes and mass.

Adult↗