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Computer-based analysis of continuous non-invasive blood pressure and heart rate variability-methodology and normal values during wakefulness and sleep.

Polysomnographic recordings were made in 10 healthy male adult subjects (mean age 25.1 +/- 2.8 years). Parameters were obtained from continuous non-invasive measurement of blood pressure and from heart rate spectra analysed both in the waking state and during sleep (stage 4). The total heart rate variability (mean +/- SE) was not significantly diminished (p < 0.2; paired t-test) during stage 4 sleep (6.2 +/- 0.5%) as compared with the waking state (7.1 +/- 0.5%). The relative heart rate variability coefficient within the frequency band HRV-II ((3-9)/min) was, however, significantly higher (p < 0.001) during slow-wave sleep (0.55 +/- 0.04) than during wakefulness (0.34 +/- 0.04). This fact is in accordance with results concerning an estimated value of the baroreflex sensitivity, which was also significantly higher (p < 0.001) during sleep stage 4 (7.0 +/- 0.8 ms/mmHg vs. 10.4 +/- 1.4 mmHg).

Adult↗

Methodology and tools for source term assessment in case of emergency.

By looking at the power plant state of fission product barriers and critical safety systems, the magnitude of a potential radioactive release could be predicted in a timely manner to allow emergency response to be executed even before the occurrence of a release. This is the perspective in which the development of ASTRID methodology and tool is performed. The methodology maps out, for several reactor types as well as reactor containments, relevant process parameters and indicators, what and how to calculate and a structured way to summarise and conclude on potential source term and likely time projections. A computer tool is proposed to support the methodology, to suite different user situations, both on-site and off-site as well as size of staff, priority and work order. The output from such an assessment is intended to, first, give bases for decisions on necessary urgent protective actions pre-release, and, second, an input for the sophisticated dispersion calculation codes.

Computer Simulation↗

Bayesian analysis of prevalence with covariates using simulation-based techniques: applications to HIV screening.

Ignoring the limited precision of medical diagnostic tests can incur serious bias in prevalence estimation. Conversely, treating the values of sensitivity and specificity as constants, as in most studies, inevitably underestimates the variability of prevalence estimates. Bayesian inference provides a natural framework with which to integrate the variability in the estimates of sensitivity and specificity with estimation of prevalence. However, the resulting model becomes quite complicated and presents a computational challenge. Recently, Mendoza-Blanco et al. proposed a missing-data approach with simulation-based techniques to deal with the computational difficulties. Although their approach is quite effective in reducing the computational complexity into manageable tasks, their developed methodology is not general enough for modelling the effects of covariates in prevalence estimation. In this paper, we extend their work in this direction by combining their missing-data approach with a latent variable technique for modelling discrete data. The present work also generalizes the methods of Albert and Chib for Bayesian analysis of binary response data with errors in the response. We illustrate the methodology with several real data examples extracted from the literature.

AIDS Serodiagnosis↗

Nursing faculty members competence of Web-based course development systems directly influences students' satisfaction.

Nursing faculty are compelled to use and implement computer assisted instruction to meet the technological needs of a diverse student population. Much of the current trend of nursing faculty and nursing curricula design encompasses a traditional face-to-face instruction mode and teaching methodology. Although faculty are using and implementing computer assisted instruction, the format is not personalized to the student. The goal of enhancing and maintaining continued student satisfaction will depend on the efficient nature of the faculty in the development of their individual technological competencies, nursing content area mastery and available university-wide technological support systems and resources.

Attitude of Health Personnel↗

Methods for improving the repeatability of automated ECG analysis.

Statistically-based smoothing techniques are described which have been applied to the existing framework of the Glasgow ECG Analysis program. These methods have been designed with the aim of improving repeatability in the computer interpretation of ECGs which have been recorded either several minutes or 24 hours apart from patients in a clinically stable condition. With respect to the ECG diagnosis of Left Ventricular Hypertrophy (LVH), these flexible methods have the effect to reducing the number of inconsistent day-to-day interpretations by 36% from 33 to 21 in 330 pairs of ECGs recorded one day apart. Similarly, when comparing agreement in the diagnosis of LVH in 249 pairs of ECGs which were recorded several minutes apart, the number of discordant computer interpretations was 6 using the new methodology, compared with 13 using conventional criteria, i.e. there was a 54% reduction in disagreements.

Computer Graphics↗

Future in biomolecular computation.

Large-scale computations for biomolecules are dominated by three levels of theory: rigorous quantum mechanical calculations for molecules with up to about 30 atoms, semi-empirical quantum mechanical calculations for systems with up to several hundred atoms, and force-field molecular dynamics studies of biomacromolecules with 10,000 atoms and more including surrounding solvent molecules. It can be anticipated that increased computational power will allow the treatment of larger systems of ever growing complexity. Due to the scaling of the computational requirements with increasing number of atoms, the force-field approaches will benefit the most from increased computational power. On the other hand, progress in methodologies such as density functional theory will enable us to treat larger systems on a fully quantum mechanical level and a combination of molecular dynamics and quantum mechanics can be envisioned. One of the greatest challenges in biomolecular computation is the protein folding problem. It is unclear at this point, if an approach with current methodologies will lead to a satisfactory answer or if unconventional, new approaches will be necessary. In any event, due to the complexity of biomolecular systems, a hierarchy of approaches will have to be established and used in order to capture the wide ranges of length-scales and time-scales involved in biological processes. In terms of hardware development, speed and power of computers will increase while the price/performance ratio will become more and more favorable. Parallelism can be anticipated to become an integral architectural feature in a range of computers.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

Fast finite element modeling for surgical simulation.

Given the geometric complexity of anatomical structures, realistic real-time deformation of graphical reconstructions is prohibitively computationally intensive. Instead, real-time deformation of virtual anatomy is roughly approximated through simpler methodologies. Since the graphical interpolations and simple spring models commonly used in these simulations are not based on the biomechanical properties of tissue structures, these "quick and dirty" methods typically do not accurately represent the complex deformations and force-feedback interactions that can take place during surgery. Finite element (FE) analysis is widely regarded as the most appropriate alternative to these methods. Extensive research has been directed toward applying the method to modeling a wide range of biological structures, and a few simple FE models have been incorporated into surgical simulations. However, because of the highly computational nature of the FE method, its direct application to real-time force-feedback and visualization of tissue deformation has not been practical for most simulations. This limitation is primarily due to the overabundance of information provided by the standard FE approaches. If the mathematics is optimized to yield only the information essential for the surgical task, computation time can be drastically reduced. Parallel computation and preprocessing of the model before the simulation begins can also reduce the size of the problem and greatly increase computation speed. Such methodologies are being developed in a combined effort between the Human Interface Technology Laboratory (HIT Lab) and the Mechanical Engineering Department of the University of Washington. We have created computer demonstrations which support real-time interaction with simple finite element soft tissue models. In collaboration with the Division of Dermatology, a real-time skin surgery simulator is being developed using these fast FE methods.

Computer Simulation↗

Considering clustering: a methodological review of clinical decision support system studies.

Computer-based clinical decision support systems (CDSSs) are often implemented at a cluster level, but standard statistical methods for sample estimation and analysis may not be appropriate for such studies. This review aims to determine whether the design and analysis methods of cluster-based studies were adequately addressed in reports of CDSS studies. We retrieved 61 reports of the CDSS controlled trials and identified 24 studies meeting our inclusion criteria. Of these, none included sample size calculations that allowed for clustering, while 14 (58%) took account of clustering in the analysis. Although there is increasing recognition of the methodological issues associated with cluster design in health care, many medical informaticians are still not aware of these issues. Investigators should publish estimates of the intracluster correlation coefficients and variance components in their reports to guide the planning of the future studies.

Cluster Analysis↗

Computer modelling of processes in ecosystems--general principles.

Concept of the mathematical modelling of ecosystems is presented, starting with a set of variables and a set of relations. Examples are given for the models of plant populations in terrestrial ecosystems. The differences between well-structured and ill-structured problems are shown with some methodological consequences for strategy of applications of computer models.

Computer Simulation↗

Toward unification of taxonomy databases in a distributed computer environment.

All the taxonomy databases constructed with the DNA databases of the international DNA data banks are powerful electronic dictionaries which aid in biological research by computer. The taxonomy databases are, however not consistently unified with a relational format. If we can achieve consistent unification of the taxonomy databases, it will be useful in comparing many research results, and investigating future research directions from existent research results. In particular, it will be useful in comparing relationships between phylogenetic trees inferred from molecular data and those constructed from morphological data. The goal of the present study is to unify the existent taxonomy databases and eliminate inconsistencies (errors) that are present in them. Inconsistencies occur particularly in the restructuring of the existent taxonomy databases, since classification rules for constructing the taxonomy have rapidly changed with biological advancements. A repair system is needed to remove inconsistencies in each data bank and mismatches among data banks. This paper describes a new methodology for removing both inconsistencies and mismatches from the databases on a distributed computer environment. The methodology is implemented in a relational database management system, SYBASE.

Animals↗

[Data display and reduction in computer-assisted EEG analysis in the time domain].

Analysis of EEG frequency spectra leads in two fields to problems demanding optimal data reduction methods: especially if topological aspects have to be considered, it is likely that the rather limited memory capacity of laboratory computer systems will be exceeded; furthermore severe methodological problems arise in statistical analysis of combined data sets, including frequency spectra, other physiological, and non-physiological data. Three data reduction methods are discussed: the classification with respect to frequency bands, the search for prominent frequencies, and the computation of quartiles of the frequency spectra. There is some evidence in favour of the method of prominent frequencies. This method seems to preserve much of the differential information of the frequency spectra.

Computers↗

Issues in the statistical analysis of small area health data.

The availability of geographically indexed health and population data, with advances in computing, geographical information systems and statistical methodology, have opened the way for serious exploration of small area health statistics based on routine data. Such analyses may be used to address specific questions concerning health in relation to sources of pollution, to investigate clustering of disease or for hypothesis generation. We distinguish four types of analysis: disease mapping; geographic correlation studies; the assessment of risk in relation to a prespecified point or line source, and cluster detection and disease clustering. A general framework for the statistical analysis of small area studies will be considered. This framework assumes that populations at risk arise from inhomogeneous Poisson processes. Disease cases are then realizations of a thinned Poisson process where the risk of disease depends on the characteristics of the person, time and spatial location. Difficulties of analysis and interpretation due to data inaccuracies and aggregation will be addressed with particular reference to ecological bias and confounding. The use of errors-in-variables modelling in small area analyses will be discussed.

Bayes Theorem↗

Modulation of gene expression as a biomarker in colon.

Computer-driven scanning and image processing methodology has demonstrated that genetic inheritance of risk for colorectal cancer in familial polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) families is associated with highly pleiotropic effects on patterns of gene expression in the flat colonic mucosa. The mitochondrial (mt) gene encoding subunit 3 of cytochrome oxidase (COXIII) is one of a panel of cloned sequences which characterize genetic risk. Expression of COXIII decreased in progression of, and risk for, colonic tumors in vivo. Further, metabolizable, unbranched, short-chain fatty acids (SCFAs) elevated expression of mtCOXIII, as well as mtCOXI, in HT29 cells and also elevated mtCOX enzymatic activity. However, expression of nuclear encoded COX subunits were unaffected. These changes may be related to documented alterations in mitochondria structure and function in transformed colonic epithelial cells. SCFAs produced when colonic microflora causes fermentation of fiber are the principle energy source for normal colonic epithelial cells; SCFAs also induce a more differentiated phenotype both in vitro and in vivo. Therefore, a mechanistic link may exist between molecular events in inherited risk and a dietary factor (fiber) which may modulate such risk. In a preliminary intervention trial in collaboration with M. Lipkin, high risk HNPCC patients received daily supplements of 1500 mg CaCO3 per day, which may be protective for development of colorectal tumors. Elevations in COXIII expression were seen in 7 of 12 patients within the first 7 months, followed by complex changes in expression of this sequence.

Adenomatous Polyposis Coli↗

High-resolution episcopic microscopy: a rapid technique for high detailed 3D analysis of gene activity in the context of tissue architecture and morphology.

We describe a new methodology for rapid 2D and 3D computer analysis and visualisation of gene expression and gene product pattern in the context of anatomy and tissue architecture. It is based on episcopic imaging of embryos and tissue samples, as they are physically sectioned, thereby producing inherently aligned digital image series and volume data sets, which immediately permit the generation of 3D computer representations. The technique uses resin as embedding medium, eosin for unspecific tissue staining, and colour reactions (beta-galactosidase/Xgal or BCIP/NBT) for specific labelling of gene activity and mRNA pattern. We tested the potential of the method for producing high-resolution volume data sets of adult human and porcine tissue samples and of specifically and unspecifically stained mouse, chick, quail, frog, and zebrafish embryos. The quality of the episcopic images resembles the quality of digital images of true histological sections with respect to resolution and contrast. Specifically labelled structures can be extracted using simple thresholding algorithms. Thus, the method is capable of quickly and precisely detecting molecular signals simultaneously with anatomical details and tissue architecture. It has no tissue restrictions and can be applied for analysis of human tissue samples as well as for analysis of all developmental stages of embryos of a wide variety of biomedically relevant species.

Animals↗

The qualitative approach in investigating the role of species interactions on stability of natural communities.

Community models with competition and mutualism are qualitatively analyzed using the methodology of loop analysis combined with computer stochastic simulation. The concept of "moving equilibrium" in the growth rate of the species is discussed in 14 "tables of predictions", presented as analytical tools that can help to shed light on controversial ecological issues such as direct versus indirect interaction and positive feedback effects on stability. While the stochastic simulation shows that only little or no difference exists in probability of stability between models with competition and models with mutualism, the related tables of predictions show that the networks among links are able to activate indirect interactions, with both negative and positive effects, between any pair of species. This phenomenon makes it difficult to determine how much stability is related to the direct interactions.

Biological Evolution↗

Quick estimation of heats of detonation of aromatic energetic compounds from structural parameters.

In this paper, a simple procedure is introduced for a quick and reliable estimation of detonation heats of aromatic energetic compounds without considering heats of formation of energetic compounds. This method does not use any experimental or computed data of energetic materials. The methodology assumes that the heat of detonation of an energetic compound with composition of C(a)H(b)N(c)O(d) can be obtained from the number of nitrogens, ratios of oxygen to carbon and hydrogen to oxygen as well as the contribution of some specific functional groups. There is no need to use any assumed decomposition products to calculate heats of detonation for energetic compounds. Predicted heats of detonation of pure energetic compounds with the product H(2)O in the liquid state for 31 aromatic energetic compounds have a root mean square (rms) of deviation of 0.32 kJ/g from experiment. The new method gives good results with respect to two empirical methods which use measured heats of formation of explosives with two sets of decomposition gases.

Explosive Agents↗

On the analysis of protein self-association by sedimentation velocity analytical ultracentrifugation.

Analytical ultracentrifugation is one of the classical techniques for the study of protein interactions and protein self-association. Recent instrumental and computational developments have significantly enhanced this methodology. In this paper, new tools for the analysis of protein self-association by sedimentation velocity are developed, their statistical properties are examined, and considerations for optimal experimental design are discussed. A traditional strategy is the analysis of the isotherm of weight-average sedimentation coefficients s(w) as a function of protein concentration. From theoretical considerations, it is shown that integration of any differential sedimentation coefficient distribution c(s), ls-g(*)(s), or g(s(*)) can give a thermodynamically well-defined isotherm, as long as it provides a good model for the sedimentation profiles. To test this condition for the g(s(*)) distribution, a back-transform into the original data space is proposed. Deconvoluting diffusion in the sedimentation coefficient distribution c(s) can be advantageous to identify species that do not participate in the association. Because of the large number of scans that can be analyzed in the c(s) approach, its s(w) values are very precise and allow extension of the isotherm to very low concentrations. For all differential sedimentation coefficients, corrections are derived for the slowing of the sedimentation boundaries caused by radial dilution. As an alternative to the interpretation of the isotherm of the weight-average s value, direct global modeling of several sedimentation experiments with Lamm equation solutions was studied. For this purpose, a new software SEDPHAT is introduced, allowing the global analysis of several sedimentation velocity and equilibrium experiments. In this approach, information from the shape of the sedimentation profiles is exploited, which permits the identification of the association scheme and requires fewer experiments to precisely characterize the association. Further, under suitable conditions, fractions of incompetent material that are not part of the reversible equilibrium can be detected.

Algorithms↗

An improved function for fitting sedimentation velocity data for low-molecular-weight solutes.

Many traditional approaches to the analysis of sedimentation velocity data work poorly with data for low-molecular-weight solutes, which have sedimentation boundaries that are severely broadened by diffusion. An approach that has previously had some success is to directly fit these broad boundaries to approximate solutions of the Lamm equation that directly account for the high diffusion. However, none of the available approximate solutions work well at times both early and late in the run, or give boundary shapes that are highly accurate, especially for species of molecular weight < 10,000. An improved fitting function has been developed to overcome some of these limitations. The new function adds two correction terms to the Fujita-MacCosham solution. The optimum coefficients for these new correction terms were determined by a least-squares approach. The accuracy and limitations of fitting with this new function were tested against synthetic data sets obtained by finite-element methods, for analysis of samples containing either single species or several noninteracting species. We also compare the strengths and weaknesses of this method of analysis, and its ability to work with noisy data, relative to recently developed time-derivative methodologies.

Computer Simulation↗