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Calculation of esophageal variceal wall tension by direct sonographic and manometric measurements.

BACKGROUND: LaPlace's law determines the wall tension of a tubular system by measuring the radius (r), wall thickness (w), and pressure gradient of a tubular structure: wall tension = pressure gradient x r/w. In theory, the determination of wall tension could provide the most accurate method of predicting the likelihood of esophageal variceal rupture. Using high-resolution endoluminal sonography, we measured the variceal wall thickness and radius. Using direct needle puncture, we measured the intravariceal pressure in three patients. We then calculated the wall tension by the LaPlace equation for each of seven varices. METHODS: A 20 MHz ultrasonographic transducer was used to image esophageal varices. Outer and inner variceal wall circumferences were measured at a cross section of each varix. The radius and wall thickness of each varix were then calculated. Pressure measurements were obtained in the esophageal lumen and variceal lumen by direct needle puncture of the varices. The pressure gradient was then calculated (esophageal lumen - variceal lumen). RESULTS: The wall tension of the varices from three patients was determined. There was a linear relation (r = 0.88) between the wall tension and pressure gradient. CONCLUSIONS: This is a novel technique by which esophageal variceal wall tension can be directly measured. Such information may be useful in the future treatment of patients with portal hypertension by which risk stratification may be determined and pharmacologic response to therapy may be measured.

Blood Pressure↗

Edge co-occurrence in natural images predicts contour grouping performance.

The human brain manages to correctly interpret almost every visual image it receives from the environment. Underlying this ability are contour grouping mechanisms that appropriately link local edge elements into global contours. Although a general view of how the brain achieves effective contour grouping has emerged, there have been a number of different specific proposals and few successes at quantitatively predicting performance. These previous proposals have been developed largely by intuition and computational trial and error. A more principled approach is to begin with an examination of the statistical properties of contours that exist in natural images, because it is these statistics that drove the evolution of the grouping mechanisms. Here we report measurements of both absolute and Bayesian edge co-occurrence statistics in natural images, as well as human performance for detecting natural-shaped contours in complex backgrounds. We find that contour detection performance is quantitatively predicted by a local grouping rule derived directly from the co-occurrence statistics, in combination with a very simple integration rule (a transitivity rule) that links the locally grouped contour elements into longer contours.

Bayes Theorem↗

The complexities of DNA computation.

Over the past few years, a handful of insightful researchers have bridged the gap between biological computing theory and actual DNA-based computation. By using ingenious encoding techniques and clever molecular-biological manipulations, simple versions of computationally complex problems have been experimentally approached or resolved. However, the technical problems revealed during the execution of these scientific set pieces make it unlikely that DNA will ever rival silicon for the solution of any real-world problem.

Algorithms↗

An integrated research tool for X-ray imaging simulation.

This paper presents a software simulation package of the entire X-ray projection radiography process including beam generation, absorber structure and composition, irradiation set up, radiation transport through the absorbing medium, image formation and dose calculation. Phantoms are created as composite objects from geometrical or voxelized primitives and can be subjected to simulated irradiation process. The acquired projection images represent the two-dimensional spatial distribution of the energy absorbed in the detector and are formed at any geometry, taking into account energy spectrum, beam geometry and detector response. This software tool is the evolution of a previously presented system, with new functionalities, user interface and an expanded range of applications. This has been achieved mainly by the use of combinatorial geometry for phantom design and the implementation of a Monte Carlo code for the simulation of the radiation interaction at the absorber and the detector.

Computer Simulation↗

The accuracy of three methods of age estimation using radiographic measurements of developing teeth.

The accuracy of age estimation using three quantitative methods of developing permanent teeth was investigated. These were Mörnstad et al. [Scand. J. Dent. Res. 102 (1994) 137], Liversidge and Molleson [J. For. Sci. 44 (1999) 917] and Carels et al. [J. Biol. Bucc. 19 (1991) 297]. The sample consisted of 145 white Caucasian children (75 girls, 70 boys) aged between 8 and 13 years. Tooth length and apex width of mandibular canine, premolars and first and second molars were measured from orthopantomographs using a digitiser. These data were substituted into equations from the three methods and estimated age was calculated and compared to chronological age. Age was under-estimated in boys and girls using all the three methods; the mean difference between chronological and estimated ages for method I was -0.83 (standard deviation +/-0.96) years for boys and -0.67 (+/-0.76) years for girls; method II -0.79 (+/-0.93) and -0.63 (+/-0.92); method III -1.03 (+/-1.48) and -1.35 (+/-1.11) for boys and girls, respectively. Further analysis of age cohorts, found the most accurate method to be method I for the age group 8.00-8.99 years where age could be predicted to 0.14+/-0.44 years (boys) and 0.10+/-0.32 years (girls). Accuracy was greater for younger children compared to older children and this decreased with age.

Adolescent↗

Bagging tree classifiers for laser scanning images: a data- and simulation-based strategy.

Diagnosis based on medical image data is common in medical decision making and clinical routine. We discuss a strategy to derive a classifier with good performance on clinical image data and to justify the properties of the classifier by an adapted simulation model of image data. We focus on the problem of classifying eyes as normal or glaucomatous based on 62 routine explanatory variables derived from laser scanning images of the optic nerve head. As learning sample we use a case-control study of 98 normal and 98 glaucomatous subjects matched by age and sex. Aggregating multiple unstable classifiers allows substantial reduction of misclassification error in many applications and bench mark problems. We investigate the performance of various classifiers for the clinical learning sample as well as for a simulation model of eye morphologies. Bagged classification trees (bagged-CTREE) are compared to single classification trees and linear discriminant analysis (LDA). We additionally compare three estimators of misclassification error: 10-fold cross-validation, the 0.632+ bootstrap and the out-of-bag estimate. In summary, the application of our strategy of a knowledge-based decision support shows that bagged classification trees perform best for glaucoma classification.

Case-Control Studies↗

Quantitative MRI detects abnormalities in relatives of patients with epilepsy and malformations of cortical development.

Malformations of cortical development (MCD) are a common etiology for epilepsy. Laminar heterotopia, bilateral subependymal heterotopia, and lissencephaly have a genetic basis. No gene mutations have yet been identified in patients with focal cortical dysplasias. The aim of this study was to use quantitative morphometric tools to determine if there were gray matter abnormalities in relatives of patients with MCD. We studied 19 relatives of 13 probands with MCD and 58 healthy controls with high-resolution MRI. The relatives and controls had no neocortical abnormalities on visual inspection. MRI data were analyzed with voxel-based morphometry and autoblock analysis. Voxel-based morphometry showed significant increases of gray matter in 9 of 10 probands, 5 of 19 relatives, and 5 of 58 controls. The autoblock analysis showed significant abnormalities in 7 of 8 probands, 8 of 19 relatives, and 2 of 57 controls. This finding suggests structural abnormality in the brains of a greater number of relatives of MCD patients than would be expected, and in the context, a reasonable inference is that this reflects subtle genetically determined cerebral abnormalities, although acquired pathologies are possible and are not excluded.

Adolescent↗

Computer-assisted judgment: defining strengths and liabilities.

Clinicians often fail to recognize limitations in their own subjective judgments, make use of well-developed mechanical-prediction methods, or carefully evaluate which computer-based aids warrant their consideration. This article addresses issues regarding computer-based test interpretations (CBTIs) and computer-based decision making. Comments highlight conclusions reached by other contributors to this Special Section, additional literature bearing on these observations, and implications for consumers of computer-assisted techniques and researchers developing or evaluating these methods. The future of computer-assisted assessment depends on educating clinicians and researchers to be better consumers of existing as well as emerging technologies in this domain.

Decision Making, Computer-Assisted↗

Brain diffusion after single seizures.

PURPOSE: Diffusion-weighted magnetic resonance imaging (DWI) after focal status epilepticus has demonstrated focal alterations of the apparent diffusion coefficient (ADC) in the epileptogenic zone. We hypothesized that localized dynamic alterations of brain diffusion during the immediate postictal state will be detectable by serial DWI and correlate with the epileptogenic zone. METHODS: Nine adult patients (four men, five women) with medically intractable epilepsy were prospectively examined with a total of 25 DWI scans taken 2-210 min after a seizure. RESULTS: The interictal ADC was significantly (p < 0.05) elevated in the ictogenic hippocampus in all patients with temporal lobe epilepsy. The following postictal changes of the ADC were seen: (a) decreases by maximally 25-31%, which were most pronounced in the epileptogenic zone (n = 2); (b) generalized ADC changes after generalized seizures (n = 1) or prolonged complex partial seizures (n = 2); (c) no major changes after short-lived seizures or if the time to first DWI scan was >15 min or both (n = 3); and (d) widespread bilateral ADC increases after a flumazenil-induced seizure (n = 1). CONCLUSIONS: ADC changes seen during serial postictal DWI are complex and appear to reflect origin and spread of the preceding seizure. A delineation of the epileptogenic zone appears to be possible only in complex-partial seizures of >60 s duration that do not secondarily generalize.

Adult↗

[Stimulation parameters for automatic examination of color vision].

PURPOSE: We have developed a polyvalent computer controlled instrument, which uses the "two equation method" (Rayleigh and Moreland equations) to measure human colour vision. This "colorimeter" (or anomaloscope) was used to determine the influence of some important stimulation parameters. METHODS: The influence of stimulus exposure time, observation field size, absolute stimulus luminance, saturation and luminance mismatches between mixture and reference stimuli were measured on our computer controlled colorimeter. All subjects were normal observers. RESULTS: 1) An exposure time of 2s was found to be optimal for clinical work. 2) The Moreland equation on a 7 degrees observation field yields results in which population variability is comparable to a Rayleigh equation on a 2 degrees field. 3) A retinal illuminance between 40 and 1000 trolands can be used for automated Moreland matches. 4) The saturation of the reference field for the Moreland match can be preset to a fixed value. 5) It is important to vary automatically the radiance of the reference field to provide an approximate luminance match as the ratio of primaries in the mixture field is changed. CONCLUSION: These measurements allows us to determine optimal conditions for automated colour vision examinations and to make recommendations for an international standard.

Color Perception Tests↗

Distributional regimes for the number of k-word matches between two random sequences.

When comparing two sequences, a natural approach is to count the number of k-letter words the two sequences have in common. No positional information is used in the count, but it has the virtue that the comparison time is linear with sequence length. For this reason this statistic D(2) and certain transformations of D(2) are used for EST sequence database searches. In this paper we begin the rigorous study of the statistical distribution of D(2). Using an independence model of DNA sequences, we derive limiting distributions by means of the Stein and Chen-Stein methods and identify three asymptotic regimes, including compound Poisson and normal. The compound Poisson distribution arises when the word size k is large and word matches are rare. The normal distribution arises when the word size is small and matches are common. Explicit expressions for what is meant by large and small word sizes are given in the paper. However, when word size is small and the letters are uniformly distributed, the anticipated limiting normal distribution does not always occur. In this situation the uniform distribution provides the exception to other letter distributions. Therefore a naive, one distribution fits all, approach to D(2) statistics could easily create serious errors in estimating significance.

Computer Simulation↗

Modeling DNA hydration: comparison of calculated and experimental hydration properties of nuclic acid bases.

Hydration properties of individual nucleic acid bases were calculated and compared with the available experimental data. Three sets of classical potential functions (PF) used in simulations of nucleic acid hydration were juxtaposed: (i) the PF developed by Poltev and Malenkov (PM), (ii) the PF of Weiner and Kollman (WK), which together with Jorgensen's TIP3P water model are widely used in the AMBER program, and (iii) OPLS (optimized potentials for liquid simulations) developed by Jorgensen (J). The global minima of interaction energy of single water molecules with all the natural nucleic acid bases correspond to the formation of two water-base hydrogen bonds (water bridging of two hydrophilic atoms of the base). The energy values of these minima calculated via PM potentials are in somewhat better conformity with mass-spectrometric data than the values calculated via WK PF. OPLS gave much weaker water-base interactions for all compounds considered, thus these PF were not used in further computations. Monte Carlo simulations of the hydration of 9-methyladenine, 1-methyluracil and 1-methylthymine were performed in systems with 400 water molecules and periodic boundary conditions. Results of simulations with PM potentials give better agreement with experimental data on hydration energies than WK PF. Computations with PM PF of the hydration energy of keto and enol tautomers of 9-methylguanine can account for the shift in the tautomeric equilibrium of guanine in aqueous media to a dominance of the keto form in spite of nearly equal intrinsic stability of keto and enol tautomers. The results of guanine hydration computations are discussed in relation to mechanisms of base mispairing errors in nucleic acid biosynthesis. The data presented in this paper along with previous results on simulation of hydration shell structures in DNA duplex grooves provide ample evidence for the advantages of PM PF in studies of nucleic-acid hydration.

Base Composition↗

Theoretical studies using an ab initio and molecular modelling combination method on the binding of sequence recognition altered bis-benzimidazoles to the minor groove of DNA.

Ab initio calculations (Hartree-Fock) using the 3-21G and the STO-3G Gaussian basis sets were performed on synthetic analogues of the minor groove binding bis-benzimidazole Hoechst 33258 designed to exhibit altered sequence recognition. Geometry optimized conformations, energies and distribution of electrostatic charges within the molecule were derived. The binding of the optimized conformations of the drug to both alternating and non-alternating (AT)n and (GC)n sequences were studied.

Binding Sites↗

Molecular dynamics and continuum solvent studies of the stability of polyG-polyC and polyA-polyT DNA duplexes in solution.

Molecular dynamics simulation in explicit solvent and continuum solvent models are applied to investigate the relative stability of A- and B-form helices for two DNA sequences, dA10-dT10 and dG10-dC10 in three structural forms. One structural form is based on an unrestrained molecular dynamics (MD) trajectory starting from a canonical B-DNA structure, the second is based on a MD trajectory starting in a canonical B-DNA structure with the sugars constrained to be C2'-endo and the third simulation started from a canonical A-DNA structure with the sugars constrained to C3'-endo puckers. For the energetic analysis, structures were taken as snapshots from nanosecond length molecular dynamics simulations computed in a consistent fashion in explicit solvent, applying the particle mesh Ewald method and the Cornell et al. force field. The electrostatic contributions to solvation free energies are computed using both a finite-difference Poisson-Boltzmann model and a pairwise Generalized Born model. The non-electrostatic contributions to the solvation free energies are estimated with a solvent accessible surface area dependent term. To estimate the gas phase component of the relative free energy between the various structures, the mean solute internal energies (determined with the Cornell et al. molecular mechanics potential including all pairwise interactions within the solute) and estimates of the solute entropy (using a harmonic approximation) were used. Consistent with experiment, the polyG-polyC (GC) structures are found to be much more A-phillic than the polyA-polyT (AT) structures, the latter being quite A-phobic. The dominant energy components responsible for this difference comes from the internal and van der Waal energies. A perhaps less appreciated difference between the GC and AT rich sequences is suggested by the calculated salt dependence which demonstrates a significantly enhanced ability to drive GC rich sequences towards an A-form structure compared to AT rich sequences. In addition to being A-phobic, the AT structure also has a noticably larger helical repeat than GC and other mixed sequence duplexes, consistent with experiment. Analysis of the average solvent density from the trajectories shows hydration patterns in qualitative agreement with experiment and previous theoretical treatments.

Computer Simulation↗

Image analysis of comet assay measurements.

In the last decade the 'comet assay' or 'single cell gel electrophoresis assay' has been established as a sensitive method for the detection of DNA damage and the measurement of its recovery. The results published in the literature have often been obtained with different methods for comet structure measurement. In most cases these data are not comparable with each other. Even when using similar systems for the analysis, it is difficult to obtain matching data. This presentation will describe some technical aspects of our measurement equipment and evaluation software. It focuses on necessary experimental conditions to minimize errors in obtaining such data. The software developed here allows the rapid analysis of the microscopic samples (< 2 s per image). The image analysis was designed with respect to the morphological shapes of comet cells, which were investigated with a confocal laser microscope. The system is built with standard components which are commercially available. As a measure of the amount of DNA damage the ratio of fluorescence intensity was used inside the comet tail and the fluorescence intensity of the comet head. Other parameters such as DNA content, comet area, head radius, tail length and tail moment are also determined. The reproducibility of the system has been evaluated in several experiments over a period of 5 years.

Ataxia Telangiectasia↗

Optimal sampling times in bioequivalence tests.

In bioequivalence studies, drug formulations are compared in terms of bioavailability parameters such as the area under the concentration-time curve (AUC), the maximum concentration (Cmax), and the time to maximum concentration (t(max)). Accuracy in measuring these parameters directly affects the accuracy of bioequivalence tests. Because the number of blood draws per patient is limited, the blood collection times must be spaced so that concentration-time curve measurements can produce accurate bioavailability parameter estimates. This paper describes an optimization approach for calculating optimal time designs for one-compartment models, but is sufficiently general for other compartmental models. Simulation indicates that the optimal design improves the accuracy of AUC estimation.

Area Under Curve↗