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Reliability measures for membrane protein topology prediction algorithms.

We have developed reliability scores for five widely used membrane protein topology prediction methods, and have applied them both on a test set of 92 bacterial plasma membrane proteins with experimentally determined topologies and on all predicted helix bundle membrane proteins in three fully sequenced genomes: Escherichia coli, Saccharomyces cerevisiae and Caenorhabditis elegans. We show that the reliability scores work well for the TMHMM and MEMSAT methods, and that they allow the probability that the predicted topology is correct to be estimated for any protein. We further show that the available test set is biased towards high-scoring proteins when compared to the genome-wide data sets, and provide estimates for the expected prediction accuracy of TMHMM across the three genomes. Finally, we show that the performance of TMHMM is considerably better when limited experimental information (such as the in/out location of a protein's C terminus) is available, and estimate that at least ten percentage points in overall accuracy in whole-genome predictions can be gained in this way.

Algorithms↗

Measurement and interpretation of QT dispersion.

QT dispersion was proposed as an index of the spatial inhomogeneity of ventricular recovery times. The results of studies that found significant correlation between dispersion of ventricular recovery times measured with monophasic action potentials and QT dispersion were interpreted as proof of the direct link between QT dispersion and the dispersion of ventricular recovery times. Later it was shown that QT dispersion is not a direct reflection of the spatial variation of the recovery times and cannot be used for quantification of this variation. The interlead variability of the QT intervals is a result of different projections of the spatial T-wave loop into the various electrocardiographic leads. The reliability of both manual and automatic measurement of QT dispersion is low and is often of the order of the differences of Qt dispersion between different patient groups. The measurement reliability is influenced by intrinsic factors (e.g., amplitude of the T wave) and extrinsic factors (e.g., noise, paper speed of recording, instruments for manual measurements, and type of algorithm and interalgorithmic settings for automatic measurement). There is very little to choose between the different indices of expression of QT dispersion, as well as between the different lead configurations used for its measurement. QT dispersion is not simply a result of measurement error, but a crude measure of abnormalities during the whole course of repolarization. Only grossly prolonged QT dispersion (e.g., > or =100 ms), must be interpreted simply as a sign of the abnormal course of the repolarization, and inferences about the actual dispersion of the ventricular recovery times should not be made. Newer concepts of assessment of the morphology of the T wave are already emerging and will probably be of higher clinical value.

Electrocardiography↗

Automatic construction of gene relation networks using text mining and gene expression data.

Microarray gene expression analysis is a powerful high-throughput technique that enables researchers to monitor the expression of thousands of genes simultaneously. Using this methodology huge amounts of data are produced which have to be analysed. Clustering algorithms are used to group genes together based on a predefined distance measure. However, clustering algorithms do not necessarily group the genes in a biological meaningful way. Additional information is needed to improve the identification of disease relevant genes. The primary objective of our project is to support the analysis of microarray gene expression data by construction of gene relation networks (GRNs). Required information can not be found in a structured representation like a database. In contrast, a large number of relations are described in biomedical literature. The main outcome of this project is the implementation of a software system that provides clinicians and researchers with a tool that supports the analysis of microarray gene expression data by mapping known relationships from the biomedical literature to local gene expression experiments.

Abbreviations as Topic↗

Volumetric quantification of coronary artery calcifications using dual-slice spiral CT scanner: improved reproducibility of measurements with 180 degrees linear interpolation algorithm.

PURPOSE: The purpose of this work was to determine the reproducibility of coronary total calcium score (TCS) with dual-slice helical CT and compare three acquisition protocols. METHOD: Fifty patients (59 +/- 10 years old) underwent dual-slice helical CT (collimation = 2 x 2.5 mm) and coronary angiography. Two successive scans were performed, resulting in three sets of images: pitch = 1, 360 degrees linear interpolation (LI) (A360); pitch = 1, 180 degrees LI (A180); and pitch = 1.5, 180 degrees LI (B180). TCS values, calculated using a volumetric method with a threshold of 90 HU, were compared, and the interscan variation was determined. Diagnostic performances were compared with receiver operating characteristic curves. RESULTS: Protocol A360 provided significantly lower TCS than protocols A180 and B180 (p < 0.0001). No statistical difference was seen between A180 and B180, which provided the lowest interscan variation (40 +/- 58%). However, no significant clinical impact of the observed interscan variations was found. CONCLUSION: Reproducibility of TCS with dual-slice helical CT is improved by the 180 LI algorithm. However, dual-slice helical CT is not sufficiently reproducible to allow serial quantification of TCS over time.

Adult↗

Will mercury manometers soon be obsolete?

After a century of clinical use, the mercury sphygmomanometric technique of blood pressure (BP) measurement is under threat. There are three reasons for this: mercury is likely to be banned from hospital use because of the danger of toxicity, accurate automated devices are now available to replace the mercury sphygmomanometer and with the advent of 24 h ambulatory BP measurement into clinical practice, more reliance is being placed on BP behaviour rather than on casual measurements. The passing of the mercury sphygmomanometer from clinical practice raises two issues that merit deliberation. Without the mercury standard with which to compare measurements generated by algorithmic interpretation of BP, the clinician is dependent on the consistency and accuracy of such algorithms. If the millimetre of mercury is no longer the unit of measurement for BP, it will soon be replaced by the kilopascal thereby introducing, at least temporarily, the potential for uncertainty in clinical judgment.

Blood Pressure↗

A modified SPIHT algorithm for image coding with a joint MSE and classification distortion measure.

The set partitioning in hierarchical trees (SPIHT) algorithm is an efficient wavelet-based progressive image-compression technique, designed to minimize the mean-squared error (MSE) between the original and decoded imagery. However, the MSE-based distortion measure is not in general well correlated with image-recognition quality, especially at low bit rates. Specifically, low-amplitude wavelet coefficients that may be important for classification are given low priority by conventional SPIHT. In this paper, we use the kernel matching pursuits (KMP) method to autonomously estimate the importance of each wavelet subband for distinguishing between different textures, with textural segmentation first performed via a hidden Markov tree. Based on subband importance determined via KMP, we scale the wavelet coefficients prior to SPIHT coding, with the goal of minimizing a Lagrangian distortion based jointly on the MSE and classification error. For comparison we consider Bayes tree-structured vector quantization (B-TSVQ), also designed to obtain a tradeoff between MSE and classification error. The performances of the original SPIHT, the modified SPIHT, and B-TSVQ are compared.

Algorithms↗

Auditory filters and the benefit measured from spectral enhancement.

Algorithms designed to improve speech intelligibility for those with sensorineural hearing loss (SNHL) by enhancing peaks in a spectrum have had limited success. Since testing of such algorithms cannot separate the theory of the design from the implementation itself, the contribution of each of these potentially limiting factors is not clear. Therefore, psychophysical paradigms were used to test subjects with either normal hearing or SNHL in detection tasks using well controlled stimuli to predict and assess the limits in performance gain from a spectrally enhancing algorithm. A group of normal-hearing (NH) and hearing-impaired (HI) subjects listened in two experiments: auditory filter measurements and detection of incremented harmonics in a harmonic spectrum. The results show that NH and HI subjects have an improved ability to detect incremented harmonics when there are spectral decrements surrounding the increment. Various decrement widths and depths were compared against subjects' equivalent rectangular bandwidths (ERBs). NH subjects effectively used the available energy cue in their auditory filters. Some HI subjects, while showing significant improvements, underutilized the energy reduction in their auditory filters.

Acoustic Stimulation↗

A neural mass model for the simulation of cortical activity estimated from high resolution EEG during cognitive or motor tasks.

Neural mass models have been used for many years to study the macroscopic dynamics of neural populations in a simple and computationally inexpensive way. In this paper, we modified a model proposed by Wendling et al. [Wendling F, Bartolomei F, Bellanger JJ, Chauvel P. Epileptic fast activity can be explained by a model of impaired GABAergic dendritic inhibition. Eur J Neurosci 2002;15:1499-508] to simulate EEG power spectral density (PSD) in some regions of interest (ROIs) during simple tasks (finger movement or working memory tests). The work consists of two subsequent stages: (1) in the first we evaluated the role of some model parameters (i.e., average gain of synapses and their time constants) in affecting power spectral density. This analysis confirmed the possibility to simulate various EEG rhythms (in the alpha, beta and gamma frequency ranges) by modifying just the time constants of the synapses. The position of the individual rhythms (i.e., the corresponding peaks in the PSD) can be finely tuned acting on the average gain of fast inhibitory synapses. This analysis suggested that a single neural mass model produces a unimodal spectrum, which can be finely adjusted, but cannot mimic the overall complexity of EEG in an entire cortical area. (2) Hence, in the second stage we built a model of a ROI by combining three neural mass models arranged in parallel. With this model, and using an automatic fitting procedure, we carefully reproduced the PSD of cortical EEG in several ROIs during finger movement, and their temporal changes during a working memory task, by estimating nine parameters. The estimated parameters represent the excitation of each population (mean value and variance of exogenous input noise) and the average gain of fast inhibitory synapses. Cortical EEGs were computed with an inverse propagation algorithm, starting from measurement performed with a high number of electrodes on the scalp (46-96). Results show that the proposed model is able to mimic PSD of cortical activity acting on a few parameters, which represent external activation and short-time synaptic changes. This information may be exploited to reach a quantitative summary of electrical activity in ROIs during a task, and to derive information on connectivity, starting from non-invasive EEG measurements.

Algorithms↗

Electron pencil-beam redefinition algorithm dose calculations in the presence of heterogeneities.

The electron pencil-beam redefinition algorithm (PBRA) is currently being refined and evaluated for clinical use. The purpose of this work was to evaluate the accuracy of PBRA-calculated dose in the presence of heterogeneities and to benchmark PBRA dose accuracy for future improvements to the algorithm. The PBRA was evaluated using a measured electron beam dose algorithm verification data set developed at The University of Texas M. D. Anderson Cancer Center. The data set consists of measurements made using 9 and 20 MeV beams in a water phantom with air gaps, internal air and bone heterogeneities, and irregular surfaces. Refinements to the PBRA have enhanced the speed of the dose calculations by a factor of approximately 7 compared to speeds previously reported in published data; a 20 MeV, 15 x 15 cm2 field electron-beam dose distribution took approximately 10 minutes to calculate. The PBRA showed better than 4% accuracy in most experiments. However, experiments involving the low-energy (9 MeV) electron beam and irregular surfaces showed dose differences as great as 22%, in albeit a small fractional region. The geometries used in this study, particularly those in the irregular surface experiments, were extreme in the sense that they are not seen clinically. A more appropriate clinical evaluation in the future will involve comparisons to Monte Carlo generated patient dose distributions using actual computed tomography scan data. The present data also serve as a benchmark against which future enhancements to the PBRA can be evaluated.

Algorithms↗

Impact of active versus usual algorithmic titration of basal insulin and point-of-care versus laboratory measurement of HbA1c on glycemic control in patients with type 2 diabetes: the Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) trial.

OBJECTIVE: The objective of this study was to assess the impact of active versus usual monitoring of algorithmic insulin titration and point-of-care (POC) versus laboratory HbA1c (A1C) measurement on glycemic control in primary care. RESEARCH DESIGN AND METHODS: The Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) study was a 24-week, randomized, parallel-group, four-arm, open-label study of 7,893 adults with type 2 diabetes uncontrolled by oral antidiabetic agents and requiring insulin. Patients were randomly assigned by investigators from 2,164 sites in the U.S. to insulin glargine with either 1) usual (no unsolicited contact between visits) insulin titration using a simple algorithm with laboratory A1C testing, 2) usual titration with POC A1C testing, 3) active (weekly monitored) titration with laboratory A1C testing, or 4) active titration with POC A1C testing. Outcome measures included a change in A1C and fasting self-monitoring of blood glucose (SMBG) levels, percentage of patients achieving A1C <7.0%, and hypoglycemia frequency. RESULTS: Significant A1C and SMBG reductions were observed in all arms (P < 0.0001). Compared with usual insulin titration, active titration achieved greater A1C reduction (1.5 vs. 1.3%; P < 0.0001), SMBG reduction (88 vs. 79 mg/dl; P < 0.0001), and proportion of patients achieving A1C <7.0% (38 vs. 30%; P < 0.0001). Among patients receiving active titration, POC A1C testing was associated with an increase in the proportion achieving an A1C <7.0% (41% for POC vs. 36% for laboratory; P < 0.0001). Hypoglycemia rates were low (usual vs. active groups: 3.7 vs. 6.0 all confirmed episodes/patient-year [P < 0.001]; 0.09 vs. 0.14 severe episodes/patient-year [NS]). CONCLUSIONS: In a predominantly primary care setting, addition of insulin glargine using a simple algorithm achieved significant improvements in glycemic control in patients with type 2 diabetes in all four study arms. Active titration resulted in significant incremental improvements in glycemic control, and, among patients receiving active titration, POC A1C testing resulted in a greater portion achieving A1C <7.0%.

Administration, Oral↗

Catching up on health outcomes: the Texas Medication Algorithm Project.

OBJECTIVE: To develop a statistic measuring the impact of algorithm-driven disease management programs on outcomes for patients with chronic mental illness that allowed for treatment-as-usual controls to "catch up" to early gains of treated patients. DATA SOURCES/STUDY SETTING: Statistical power was estimated from simulated samples representing effect sizes that grew, remained constant, or declined following an initial improvement. Estimates were based on the Texas Medication Algorithm Project on adult patients (age > or = 18) with bipolar disorder (n = 267) who received care between 1998 and 2000 at 1 of 11 clinics across Texas. STUDY DESIGN: Study patients were assessed at baseline and three-month follow-up for a minimum of one year. Program tracks were assigned by clinic. DATA COLLECTION/EXTRACTION METHODS: Hierarchical linear modeling was modified to account for declining-effects. Outcomes were based on 30-item Inventory for Depression Symptomatology-Clinician Version. PRINCIPAL FINDINGS: Declining-effect analyses had significantly greater power detecting program differences than traditional growth models in constant and declining-effects cases. Bipolar patients with severe depressive symptoms in an algorithm-driven, disease management program reported fewer symptoms after three months, with treatment-as-usual controls "catching up" within one year. CONCLUSIONS: In addition to psychometric properties, data collection design, and power, investigators should consider how outcomes unfold over time when selecting an appropriate statistic to evaluate service interventions. Declining-effect analyses may be applicable to a wide range of treatment and intervention trials.

Adult↗

Age differences in dynamic measures of EEG.

Eighteen older adults and 18 younger adults were compared on two quantitative measures describing changes over time in the spatial distribution of running EEG. EEG was collected from 128 electrodes under resting eyes-open and eyes-closed conditions and during performance of a 13 minute sustained attention task. One EEG measure, the recrudescence rate, represented the number of changes in the location of the highest squared voltage per second. A second EEG measure consisted of the algorithmic complexity of changes in the location of the highest squared voltage over time. Regardless of the task condition, older adults had significantly higher scores than younger adults on both the recrudescence rate and the measure of algorithmic complexity. The implications of the results for neurologically-based theories of performance declines in older adults are discussed.

Adolescent↗

Spiral interpolation algorithms for multislice spiral CT--part II: measurement and evaluation of slice sensitivity profiles and noise at a clinical multislice system.

The recently introduced multislice data acquisition for computed tomography (CT) is based on multirow detector design, increased rotation speed, and advanced z-interpolation and z-filtering algorithms. We evaluated slice sensitivity profiles (SSPs) and noise of a clinical multislice spiral CT (MSCT) scanner with M = 4 simultaneously acquired slices and adaptive axial interpolator (AAI) reconstruction software. SSPs were measured with a small gold disk of 50 microm thickness and 2-mm diameter located at the center of rotation (COR) and 100 mm off center. The standard deviation of CT values within a 20-cm water phantom was used as a measure of image noise. With a detector slice collimation of S = 1.0 mm, we varied spiral pitch p from 0.25 to 2.0 in steps of 0.025. Nominal reconstructed slice thicknesses were 1.25, 1.5, and 2.0 mm. For all possible pitch values, we found the full-width at half maximum (FWHM) of the respective sensitivity profile at the COR equivalent to the selected nominal slice thickness. The profiles at 100 mm off center are broadened less than 7 % on the average compared with the FWHM at the COR. In addition, variation of the full-width at tenth maximum (FWTM) at the COR was below 10% for p < or = 1.75. Within this range, image noise varied less than 10% with respect to the mean noise level. The slight increase in measured slice-width above p = 1.75 for nominal slice-widths of 1.25 and 1.50 mm is accompanied by a decrease of noise according to the inverse square root relationship. The MSCT system that we scrutinized provides reconstructed slice-widths and image noise, which can be regarded as constant within a wide range of table speeds. With respect to this, MSCT is superior to single-slice spiral CT. These facts can be made use of when defining and optimizing clinical protocols: the spiral pitch can be selected almost freely, and scan protocols can follow the diagnostic requirements without technical restrictions. In summary, MSCT offers constant image quality while scan times are reduced drastically. Volume scans with three-dimensional (3-D) isotropic resolution are routinely feasible for complete anatomical regions.

Algorithms↗

Monte Carlo-based dosimetry of head-and-neck patients treated with SIB-IMRT.

PURPOSE: To evaluate the accuracy of previously reported superposition/convolution (SC) dosimetric results by comparing with Monte Carlo (MC) dose calculations for head-and-neck intensity-modulated radiation therapy (IMRT) patients treated with the simultaneous integrated boost technique. METHODS AND MATERIALS: Thirty-one plans from 24 patients previously treated on a phase I/II head-and-neck squamous cell carcinoma simultaneous integrated boost IMRT protocol were used. Clinical dose distributions, computed with an SC algorithm, were recomputed using an EGS4-based MC algorithm. Phantom-based dosimetry quantified the fluence prediction accuracy of each algorithm. Dose-volume indices were used to compare patient dose distributions. RESULTS AND DISCUSSION: The MC algorithm predicts flat-phantom measurements better than the SC algorithm. Average patient dose indices agreed within 2.5% of the local dose for targets; 5.0% for parotids; and 1.9% for cord and brainstem. However, only 1 of 31 plans agreed within 3% for all indices; 4 of 31 agreed within 5%. In terms of the prescription dose, 4 of 31 plans agreed within 3% for all indices, whereas 28 of 31 agreed within 5%. CONCLUSIONS: Average SC-computed doses agreed with MC results in the patient geometry; however deviations >5% were common. The fluence modulation prediction is likely the major source of the dose discrepancy. The observed dose deviations can impact dose escalation protocols, because they would result in shifting patients to higher dose levels.

Algorithms↗

Discrimination of ventricular tachycardia from supraventricular tachycardia by a downloaded wavelet-transform morphology algorithm: a paradigm for development of implantable cardioverter defibrillator detection algorithms.

INTRODUCTION: Present implantable cardioverter defibrillators (ICDs) have algorithms that discriminate supraventricular tachycardia (SVT) from ventricular tachycardia (VT). One type of algorithm is based on differences in morphology of ventricular electrograms during VT and SVT. Prior SVT-VT discrimination algorithms have not undergone real-time evaluation in ambulatory patients until they were incorporated permanently into ICDs. This approach may result in incomplete testing of electrogram morphology algorithms because they are influenced by posture, activity, and electrogram maturation. We downloaded software into implanted ICDs to study a novel algorithm that compares morphologies of baseline and tachycardia electrograms based on differences between corresponding coefficients of their wavelet transforms. This comparison is expressed as a match-percent score. METHODS AND RESULTS: In 23 patients, we downloaded the wavelet algorithm into implanted ICDs to assess the temporal and postural stability of baseline electrograms as measured by this algorithm and its accuracy for SVT-VT discrimination. Median follow-up was 6 months. Software was downloaded into all ICDs without altering other device functions. With few exceptions, percent template match in baseline rhythm was stable with changes in body position, rest versus walking, isometric exercise, and over time (1 and 3 months). Using the nominal match-percent threshold of 70%, sensitivity for detection of 38 VTs was 100%. Specificity for rejection of 65 SVTs was 78%. SVTs were rejected for a total of 2.7 hours. Inappropriate detections of SVT as VT were caused by electrogram truncation, myopotential interference with low-amplitude electrograms, waveform alignment error, and rate-dependent aberrancy. The first three accounted for 69% of inappropriate detections and could have been prevented by optimal programming. The optimal match-percent threshold was 60% to 70% based on a receiver-operator characteristic curve. After shocks, the median time for baseline electrogram morphology to normalize was 85 seconds. CONCLUSION: The wavelet morphology algorithm has high sensitivity for VT detection. Inappropriate detections of SVT as VT may be reduced by optimal programming. Downloadable software permits evaluation of new algorithms in implanted ICDs.

Aged↗

Light fields for minimal invasive surgery using an endoscope positioning robot.

OBJECTIVES: To generate a fast and robust 3-D visualization of the operation site during minimal invasive surgery. METHODS: Light fields are used to model and visualize the 3-D operation site during minimal invasive surgery. An endoscope positioning robot provides the position and orientation of the endoscope. The a priori un-known transformation from the endoscope plug to the endoscope tip (hand-eye transformation) can either be determined by a three-step algorithm, which includes measuring the endoscope length by hand or by using an automatic hand-eye calibration algorithm. Both methods are described in this paper and their respective computation times and accuracies are compared. RESULTS: Light fields were generated during real operations and in the laboratory. The comparison of the two methods to determine the unknown hand-eye transformation was done in the laboratory. The results which are being presented in this paper are: rendered images from the generated light fields, the calculated extrinsic camera parameters and their accuracies with respect to the applied hand-eye calibration method, and computation times. CONCLUSION: Using an endoscope positioning robot and knowing the hand-eye transformation, the fast and robust generation of light fields for minimal invasive surgery is possible.

Algorithms↗

Clinical detection of optic nerve damage: measuring changes in cup steepness with use of a new image alignment algorithm.

The purpose of this study was to study the effect of a subpixel image alignment algorithm on the standard deviation (SD) of mean topography images obtained by laser scanning tomography and to evaluate changes of the cup shape measure parameter (CSM) over time based upon the individual parameter variability using the new algorithm. Triple measurements from optic nerve heads of 132 eyes of 132 subjects were obtained using the Heidelberg Retina Tomograph HRT. To calculate a mean topography image from three single topography images, alignment of the raw optical section image data was performed with the standard software and again with a new subpixel-based image alignment algorithm. The effect on the averaged (SD) of the mean topography images was evaluated. CSM was evaluated in 15 eyes of 15 normal subjects (N) and 28 eyes of 14 glaucoma patients (G) over a period of 28.6 +/- 4.6 months (N) and 28.56 +/- 5.2 months (G) respectively. A change in the CSM value over time was considered significant if CSM measurements exceeded two standard deviations of this variable determined for the individual eye. Mean-topography image SD was 22.86 +/- 8.2 microns (min. 9.5 microm; max. 47.8 microm) with the standard alignment procedure and 15.46 +/- 6.8 microm (min. 6.8 microm; max. 42.8 microm) with the new algorithm. The average SD improvement was 7.46 +/- 3.9 microns (min. -8.1 microm; max. 28.7 microm). The coefficient of correlation of both methods was R(2) = 0.77 (p < 0.0001). No control group eye demonstrated significant changes of CSM in the follow-up period. The CSM indicated an increase in cup steepness in 4 eyes of 4 glaucoma patients. In one of these four eyes, a deterioration of the visual field was identified by white on white perimetry. The new image alignment algorithm significantly reduces the SD of mean topography images calculated from identical raw data. If topometric variables are evaluated over time, the individual variability of data should be taken into account.

Adult↗