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PubMed1985

Tensorial computer model of gaze--I. Oculomotor activity is expressed in non-orthogonal natural coordinates.

The central nervous system expresses its function in natural frames of reference. A most conspicuous feature of such frames is their non-orthogonality. Gaze stabilization and, in particular, the sensorimotor transformations performed by the vestibulo-ocular reflex, are prime examples of such general coordinate transformations between and within multidimensional non-orthogonal frames. Since such operations can be described by tensor formalisms in an abstract manner, this methodology is applied here to develop a tensorial computer model of gaze stabilization. The representation of sensorimotor transformations by a reference-frame independent method obviates the necessity to simplify the intrinsic coordinate systems either by a reduction of the dimensionality or by a presumption of orthogonality. The frames of reference intrinsic to vestibulo-ocular reflex transformation (the vestibular semicircular canals and extraocular muscles) as well as the covariant character of the sensory input and the contravariant character of the motor output are physically obvious. A model built on these intrinsic systems of coordinates first serves to quantitate the degree of non-orthogonality in the extraocular muscle system, and thus to demonstrate both the necessity and the applicability of representing them by a formalism suitable for non-orthogonal systems, such as tensor network theory. The actual non-orthogonality of the gaze-stabilization system can be quantitated on the basis of the difference of covariant and contravariant expressions as follows. Tensor network theory describes sensorimotor transformations by employing a covariant embedding procedure. This, however, yields a covariant intention-type motor vector. If the central nervous system were to transmit these sensory-type components directly to the extraocular muscle motor mechanism, an error-angle would occur since covariants do not physically compose the intended movement. The error in every direction of gaze would be zero only if the extraocular muscle system would constitute an orthogonal set of rotation axes. Otherwise, the error, called refraction angle, is a measure of non-orthogonality. The complexity of the quantitation of non-orthogonality is compounded by the fact that these rotation axes change with the moving eye. Calculation of eye movements, executed both by covariant and contravariant vectors from primary and secondary eye positions, is based on the simplest assumption that the central nervous system establishes the covariant-contravariant transformation in the retinal tangent plane.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

Three-dimensional analysis of nonhuman primate trabecular architecture using micro-computed tomography.

Until recently, detailed analyses of the architecture of nonhuman primate cancellous bone have not been possible due to a combination of methodological constraints, including poor resolution imaging or destructive protocols. The development of micro-computed tomography (microCT) and morphometric methods associated with this imaging modality offers anthropologists a new means to study the comparative architecture of cancellous bone. Specifically, microCT will allow anthropologists to investigate the relationship between locomotor behavior and trabecular structure. We conducted a preliminary study on the trabecular patterns in the proximal humerus and femur of Hylobates lar, Ateles paniscus, Macaca mulatta, and Papio anubis to investigate the quantitative differences in their trabecular architecture and evaluate the potential of microCT in anthropological inquiry. MicroCT allows the researcher to evaluate variables beyond simple two-dimensional orientations and radiographic densities. For example, this methodology facilitates the study of trabecular thickness and bone volume fraction using three-dimensional data. Results suggest that density-related parameters do not reliably differentiate suspensory-climbing species from quadrupedal species. However, preliminary results indicate that measurements of the degree of anisotropy, a measure of trabecular orientation uniformity, do distinguish suspensory-climbing taxa from more quadrupedal species. The microCT method is an advance over conventional radiography and medical CT because it can accurately resolve micron-sized struts that make up cancellous bone, and from these images a wide array of parameters that have been demonstrated to be related to cancellous bone mechanical properties can be measured. Methodological problems pertinent to any comparative microCT study of primate trabecular architecture are discussed.

Animals↗
PubMed1993

Computer-assisted qualitative research.

The use of computer technology has emerged as a significant component in qualitative research methodology. This article differentiates between mechanical and conceptual activities in qualitative analysis and discusses the interplay between them. Advantages of computer technology in the mechanical activities of data management and concerns about the use of computer programs in conceptual/analytic activities are discussed. Guidelines for the judicious application of computers in qualitative research are outlined.

Electronic Data Processing↗
PubMed1995

Computer-based screening of patients with HIV/AIDS for clinical-trial eligibility.

OBJECTIVE: To assess the potential effect of a computer-based system on accrual to clinical trials, we have developed methodology to identify retrospectively and prospectively patients who are eligible or potentially eligible for protocols. DESIGN: Retrospective chart abstraction with computer screening of data for potential protocol eligibility. SETTING: A county-operated clinic serving human immunodeficiency virus (HIV) positive patients with or without acquired immune deficiency syndrome (AIDS). PATIENTS: A randomly selected group of 60 patients who were HIV-infected, 30 of whom had an AIDS-defining diagnosis. DESIGN: Using a computer-based eligibility screening system, for each clinic visit and hospitalization, patients were categorized as eligible, potentially eligible, or ineligible for each of the 17 protocols active during the 7-month study period. Reasons for ineligibility were categorized. RESULTS: None of the patients was enrolled on a clinical trial during the 7-month period. Thirteen patients were identified as eligible for protocol; three patients were eligible for two different protocols; and one patient was eligible for the same protocol during two different time intervals. Fifty-four patients were identified as potentially eligible for a total of 165 accrual opportunities, but important information, such as the result of a required laboratory test, was missing, so that eligibility could not be determined unequivocally. Ineligibility for protocol was determined in 414 (35%) potential opportunities based only on conditions that were amenable to modification, such as the use of concurrent medications; 194 (17%) failed only laboratory tests or subjective determinations not routinely performed; and 346 (29%) failed only routine laboratory tests. CONCLUSIONS: There are substantial numbers of eligible and potentially eligible patients who are not enrolled or evaluated for enrollment in prospective clinical trials. Computer-based eligibility screening when coupled with a computer-based medical record offers the potential to identify patients eligible or potentially eligible for clinical trial, to assist in the selection of protocol eligibility criteria, and to make accrual estimates.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Direct relationship between hormone sensitivity level and growth pattern. Evidence in 18 gastrointestinal neoplastic cell lines.

OBJECTIVE: We investigated whether a relationship exists in terms of growth pattern and hormone sensitivity in 18 gastrointestinal neoplastic cell lines. Hormones studied included gastrin, epidermal growth factor, estradiol and luteinizing hormone-releasing hormone. STUDY DESIGN: The growth patterns were assessed by means of computer-assisted microscope analysis of Feulgen-stained nuclei combined with the mathematical Delaunay triangulation and Voronoi paving techniques. This methodology enabled four variables characterizing the cell colony patterns to be computed. The information contributed by these variables was analyzed by means of discriminant analysis and the decision tree technique. RESULTS: Each phenotype (sensitivity level) exhibited distinct growth pattern (or cell colony) characteristics in the case of each hormone and/or growth factor under study. Furthermore, the sensitivity of the gastrointestinal cell lines to a given hormone (or growth factor) appeared to be peculiar to the hormone (or growth factor). CONCLUSION: A direct relationship seems to exist between growth pattern and hormone sensitivity levels in gastrointestinal cancers, particularly colorectal.

Cell Count↗
PubMed2001

Artificial neural network-based predictive model for bacterial growth in a simulated medium of modified-atmosphere-packed cooked meat products.

The data of Devilieghere et al. (Int. J. Food Microbiol. 1999, 46, 57--70) on bacterial growth in a simulated medium of modified-atmosphere-packed cooked meat products was processed for estimating maximum specific growth rate mu(max) and lag phase lambda of Lactobacillus sake using artificial neural networks-based model (ANNM) computation. The comparison between ANNM and response surface methodology (RSM) model showed that the accuracy of ANNM prediction was higher than that of RSM. Two-dimensional and three-dimensional plots of the response surfaces revealed that the relationships of water activity a(w), temperature T, and dissolved CO(2) concentration with mu(max) and lambda were complicated, not just linear or second-order relations. Furthermore, it was possible to compute the sensitivity of the model outputs against each input parameter by using ANNM. The results showed that mu(max) was most sensitive to a(w), T, and dissolved CO(2) in this order; whereas lambda was sensitive to T the most, followed by a(w), and dissolved CO(2) concentrations.

Animals↗
PubMed1998

Measures of complexity for cancellous bone.

The problem of quantifying the structure of cancellous bone has been addressed in the past by histomorphometry and more recently by imaging techniques using X-ray attenuation. The current approaches compute and describe parts of the construction of the trabecular net. We developed a new technique which quantifies cancellous bone of human lumbar vertebrae as a whole. The interactions, transactions, and interrelationships of all parts of the structural composition of the trabeculae are accounted for and quantified. The method is based on the concept of structural complexity within the framework of nonlinear dynamics. The methodology was developed by using axial high resolution computed tomography images. The technique was transferred to quantitative computed tomography images and is based on the non-invasive assessment of 50 human L3 specimens. The value of Houndsfield units per pixel representing trabecular bone of the vertebrae was transformed into color-encoded and alphabet-encoded symbols. The procedure of transformation of the X-ray attenuation pixels into symbols was necessary as a basis on which measures of complexity were introduced to assess the composition of symbols within the images. The development of a generalization of symbolic dynamics, a mathematical method, to work with two-dimensional images was a prerequisite. The results of this study demonstrate that the structural composition of cancellous bone declines more rapidly than bone mineral density during the loss of bone. This outcome strongly suggests an exponential relationship between bone mineral density and the architectural composition of cancellous bone. Normal trabecular bone has a complex ordered structure. The structural composition during the osteopenic phase of bone loss is characterized by lower structural complexity and a significantly higher level of architectural disorder. A high grade of osteoporosis leads again to an ordered structure, although its structural complexity is minimal.

Algorithms↗
PubMed2003

Dynamical and integrative cell signaling: challenges for the new biology.

Years of careful experimental analysis have revealed that signaling molecules are organized into complex networks of biochemical reactions exquisitely regulated in time and space to provide a cell with high-fidelity information about an extremely noisy and volatile environment. A new view of signaling networks as systems consisting of multiple complex elements interacting in a multifarious fashion is emerging, a view that conflicts with the single-gene or protein-centric approach common in biological research. The postgenomic era has brought about a different, network-centric methodology of analysis, suddenly forcing researchers toward the opposite extreme of complexity, where the networks being explored are, to a certain extent, intractable and uninterpretable. Both the cartoons of simple pathways and the very large "hair-ball" diagrams of large intracellular networks are also representations of static worlds, superficially devoid of dynamics and chemistry. These representations are often viewed as being analogous to stably linked computer and neural networks rather than dynamically changing networks of chemical interactions, where the notions of concentration, compartmentalization, and diffusion may be the primary determinants of connectivity. Arguably, the systems biology approach, relying on computational modeling coupled with various experimental techniques and methodologies, will be an essential component of analysis of the behavior of signal transduction pathways. Combining the dynamical view of rapidly evolving responses and the structural view arising from high-throughput analyses of the interacting species will be the best approach toward efforts toward greater understanding of intracellular signaling processes.

Cell Communication↗
PubMed1991

Dose-volume histograms.

A plot of a cumulative dose-volume frequency distribution, commonly known as a dose-volume histogram (DVH), graphically summarizes the simulated radiation distribution within a volume of interest of a patient which would result from a proposed radiation treatment plan. DVHs show promise as tools for comparing rival treatment plans for a specific patient by clearly presenting the uniformity of dose in the target volume and any hot spots in adjacent normal organs or tissues. However, because of the loss of positional information in the volume(s) under consideration, it should not be the sole criterion for plan evaluation. DVHs can also be used as input data to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). The sensitivity of TCP and NTCP calculations to small changes in the DVH shape points to the need for an accurate method for computing DVHs. We present a discussion of the methodology for generating and plotting the DVHs, some caveats, limitations on their use and the general experience of four hospitals using DVHs.

Humans↗
PubMed2004

New methods for assessing cartilage contact stress after articular fracture.

Progress in reducing the incidence and severity of posttraumatic arthritis depends in part on avoiding deleterious stress levels at residual local incongruities. Systematic efforts to elucidate factors adversely influencing cartilage's mechanical environment in turn depend on the availability of suitable modalities to assess intraarticular contact stresses. This has been and remains a challenging biomechanical problem. Technologic approaches used in the past have included mathematical analyses and indwelling physical sensors, each with advantages and limitations. Two emerging, mutually complementary capabilities show promise of dramatically altering the state of the art in this important field. The first of these methodologies, voxel-based contact finite element analysis, provides accurate computational estimates of cartilage stress on a patient-specific basis, and does so while accommodating arbitrarily idiosyncratic patterns of local articular incongruity. The second methodology, instrumentational, involves transient pressure distribution recordings using specially designed piezoresistive array sensors. Operational considerations for both of these new assessment technologies are described, and promising directions for future development are outlined.

Biomechanical Phenomena↗
PubMed2006

Efficient computation of partial expected value of sample information using Bayesian approximation.

We describe a novel process for transforming the efficiency of partial expected value of sample information (EVSI) computation in decision models. Traditional EVSI computation begins with Monte Carlo sampling to produce new simulated data-sets with a specified sample size. Each data-set is synthesised with prior information to give posterior distributions for model parameters, either via analytic formulae or a further Markov Chain Monte Carlo (MCMC) simulation. A further 'inner level' Monte Carlo sampling then quantifies the effect of the simulated data on the decision. This paper describes a novel form of Bayesian Laplace approximation, which can be replace both the Bayesian updating and the inner Monte Carlo sampling to compute the posterior expectation of a function. We compare the accuracy of EVSI estimates in two case study cost-effectiveness models using 1st and 2nd order versions of our approximation formula, the approximation of Tierney and Kadane, and traditional Monte Carlo. Computational efficiency gains depend on the complexity of the net benefit functions, the number of inner level Monte Carlo samples used, and the requirement or otherwise for MCMC methods to produce the posterior distributions. This methodology provides a new and valuable approach for EVSI computation in health economic decision models and potential wider benefits in many fields requiring Bayesian approximation.

Bayes Theorem↗
PubMed1996

Biochemical markers of myocardial damage for early diagnosis and prognosis in patients with acute coronary syndromes. Minireview based on a doctorial thesis.

In patients with suspected AMI. Monitoring of a combination of myoglobin and CK-MB or tn-T allowed ruling-in AMI within 2-3 hours and ruling-out AMI within 3-6 hours in almost all patients admitted with chest pain and a nondiagnostic ECG. This might have a large impact on the early handling and treatment of these patients. The neural network methodology, with monitoring of myoglobin, CK-MB and tn-T allowed, within the first three hours, reliable diagnosis/exclusion of AMI/MMD and prediction of infarct size in patients admitted with suspicion of AMI. The computer system was faster than clinicians. Thus, neural network methodology might be a useful support for the early assessment of patients with suspected myocardial infarction. In patients with unstable CAD. The risk of subsequent cardiac events is increased by increasing maximal levels of tn-T obtained during the initial 24 hours. Thereby a normal, a slightly elevated and a clearly elevated tn-T level identified a low, intermediate and high risk group, respectively, for MI or death. The tn-T level was an independent prognostic variable for MI or death in a multivariate analysis comparing other early available risk indicators. Furthermore, tn-T seemed to be superior to CK-MB (mass) for risk stratification. In patients able to perform a predischarge ET both the tn-T level and the ET response were independent prognostic indicators for MI or death. The combination of tn-T and the ET response allowed a further improved risk stratification. In patients with tn-T elevation at inclusion, prolonged dalteparin treatment was beneficial. However, in patients without tn-T elevation, long term dalteparin treatment had no protective effect. Thus, tn-T determination provides independent and important prognostic information in unstable CAD. In the selection of treatment strategy for the individual patient, this simple, inexpensive and early available biochemical test might be useful.

Aged↗
PubMed1993

Infertility treatment: from cookery to science. The epidemiology of randomised controlled trials.

OBJECTIVES: To review the epidemiology of published randomised controlled trials in infertility treatment over the last 25 years, with special emphasis on the number and quality of trials. DESIGN: Computer literature review by MEDLINE backed up by a manual search of 41 journals. Each trial was classified according to the methodology described and quality criteria. The results were recorded in a computer database. Odds ratios (OR) and confidence intervals (CI) were calculated where the data were sufficient. SUBJECTS: Couples suffering from primary or secondary infertility. The trials studied 33,761 patients overall. SETTING: Institute of Epidemiology and Health Services Research, Leeds. RESULTS: Five hundred and one randomised trials in male and female infertility treatment were identified between 1966 and 1990. Pregnancy was an outcome in 291 (58%) and these were the subject of detailed analysis. Two hundred and twenty-four (77%) and 67 (23%) 'pregnancy trials' were concerned, respectively, with female and male infertility. Four per cent of the trials were preceded by a sample size calculation, and the average sample size was 96 patients (range 5-933); 700 patients per group would be required to demonstrate plausible success rates for most treatments. The method of randomisation was unstated or pseudo-randomised in 206 (71%) of trials where pregnancy was an outcome. Only 29 (5.8%) of studies were multicentre. The method of confirmation of pregnancy was omitted for 70% of papers. Cross-over design was used in 103 (21%) of cases. Meta-analysis is possible for selected topics such as the use of anti-oestrogens in idiopathic oligospermia and unexplained female infertility. Eight cases of double reporting were identified. CONCLUSIONS: Trials using randomised methodology were relatively few in comparison with other branches of medicine, although their use is important in the evaluation of treatment for infertility as treatment-independent pregnancy is common. It was encouraging to note that an exponential increase in the use of this methodology occurred during the last three years, especially in association with assisted conception techniques, and meta-analysis has become possible for selected topics. However, many trials suffer from an unrealistically small sample size, inappropriate use of cross-over design or pseudo-randomisation. The trend towards properly controlled studies should be encouraged but these studies should be of improved quality and organised on a multicentre or even international basis.

Female↗
PubMed2004

The Global Error Assessment (GEA) model for the selection of differentially expressed genes in microarray data.

MOTIVATION: Microarray technology has become a powerful research tool in many fields of study; however, the cost of microarrays often results in the use of a low number of replicates (k). Under circumstances where k is low, it becomes difficult to perform standard statistical tests to extract the most biologically significant experimental results. Other more advanced statistical tests have been developed; however, their use and interpretation often remain difficult to implement in routine biological research. The present work outlines a method that achieves sufficient statistical power for selecting differentially expressed genes under conditions of low k, while remaining as an intuitive and computationally efficient procedure. RESULTS: The present study describes a Global Error Assessment (GEA) methodology to select differentially expressed genes in microarray datasets, and was developed using an in vitro experiment that compared control and interferon-gamma treated skin cells. In this experiment, up to nine replicates were used to confidently estimate error, thereby enabling methods of different statistical power to be compared. Gene expression results of a similar absolute expression are binned, so as to enable a highly accurate local estimate of the mean squared error within conditions. The model then relates variability of gene expression in each bin to absolute expression levels and uses this in a test derived from the classical ANOVA. The GEA selection method is compared with both the classical and permutational ANOVA tests, and demonstrates an increased stability, robustness and confidence in gene selection. A subset of the selected genes were validated by real-time reverse transcription-polymerase chain reaction (RT-PCR). All these results suggest that GEA methodology is (i) suitable for selection of differentially expressed genes in microarray data, (ii) intuitive and computationally efficient and (iii) especially advantageous under conditions of low k. AVAILABILITY: The GEA code for R software is freely available upon request to authors.

Algorithms↗
PubMed2005

Tailoring transition metal complexes for nonlinear optics applications. 2. A theoretical investigation of the second-order nonlinear optical properties of M(CO)(5)L complexes (M = Cr, W; L = Py, PyCHO, Pyz, PyzBF(3), BPE, BPEBF(3)).

In this work, we report an ab initio investigation of second-order nonlinear optical (NLO) properties and absorption electronic spectra of push-pull transition metal chromophores of the formula [M(CO)(5)L] (M = Cr, W; L = pyridine (Py), 4-formyl-pyridine (PyCHO), pyrazine (Pyz), trans-1,2-bis(4-pyridyl)ethylene (BPE)). Pyz and BPE are considered either with one nitrogen atom free or interacting with the strong acceptor BF(3). All of the molecular properties have been calculated using two different and methodologically independent approaches: the time dependent and coupled perturbed density functional theories (TDDFT and CPDFT) and the sum-over-states (SOS) approach, where the excited states are obtained via the single configuration interaction (SCI) ab initio method. DFT results are in acceptable agreement with the experimental energy values of electronic transitions (with the exception of chromophores with the large pi-delocalization, like BPE); SCI calculations overestimate excitation energies and produce an inversion in the order of d(M) --> pi(L) and d(M) --> pi(CO) transitions. The SCI-SOS approach gives first-order hyperpolarizabilities, basically in agreement as trend and values with the experiments and seems to be a tool generally suitable for the evaluation of these properties also for transition metal complexes. On the other hand, the first-order hyperpolarizabilities computed using the CPDFT approach are consistently overestimated in comparison with the experimental results, especially in the case of a ligand with large pi-delocalization. We also show that the "two-level" approximation taking into account only the lowest energy charge transfer excitation (e.g., d(M) --> pi(L)) is not applicable to chromophores with the extended pi-delocalized ligand (BPE) coordinated to a transition metal, due to significant contributions originating from intraligand pi(L) --> pi(L) transitions. This study reports a detailed analysis and comparison of electronic NLO effects of transition metal complexes computed with DFT and ab initio SCI-SOS methodology.

Chromium↗
PubMed1995

[Manufacture of computer-based testing and analyzing system for measuring step-through performance].

The computer-Based Testing and Analysing System for measuring Step-Through (avoiding darkness) performance (CTASS) has been developed. The system is based on the infrared beams which transfer actions of mice inside the boxes into signals of voltage. The signals are fed into the computer through A/D converter to computer for software processing. The functions which have been realized include, but not limited to: signal sampling and data curve displaying; intelligent identification and elimination of jamming signal; auto-calculation of number of errors (No) in all channels, latent period (LP) of entering into the light chamber, total time of mice staying in the light chamber (safty place Tl) and dark chamber (error place Td); hardcopy of screen graphics and resulting output by various printers. The CATSS system was applied to test normal mice and the cognition-deficient mice induced by anisodine, a M-Cholinergic antagonist at a dose of 1-10 mg/kg i.p. The data collected by the system were compared and proved to be consistent with those acquired by manual labour. The system has produced refined and accurate information refined to a maximum extent and guaranteed scientifically sound experimental results. It is foreseable that introducing the computer into pharmacological researches will update and advance their methodology.

Animals↗