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Navigation in maxillofacial and craniofacial surgery.

The standardized operational techniques available today make it possible to perform extensive surgeries for the treatment of craniofacial malformations and advanced tumors in this anatomically complex region. The new techniques of computer-assisted surgery allow us to interactively use the three-dimensional image data of the patient during surgery. Simulation of complex osteotomies in individual patients is now possible with the aid of new software developments for virtual cutting and shifting of bone segments. Intraoperative realization with navigation systems has been performed at our clinic for the past 4 years, and we have gained extensive experience from more than 100 clinical applications of mechanical and optoelectronic navigation systems. These passive localization systems supply the surgeon with direct intraoperative support while performing the surgeries. It is the primary goal of computer-assisted surgery to support the surgeon during diagnosis, operational planning, and intraoperative navigation. We can thereby achieve a reduction in operational risk and duration, which in turn results in a considerable stress reduction for the patient.

Craniofacial Abnormalities↗

Oxidation-reduction potential as a control variable for the anaerobic stage during anaerobic-aerobic p-nitrophenol degradation.

Combined anaerobic-aerobic processes are a viable alternative for the treatment of xenobiotic compounds that are difficult to treat by traditional processes. The variable nature of the sequencing batch reactors, SBR, systems allows manipulation of the selective pressure on the microorganisms. Then, the activity of the community can be dynamically adjusted to meet changing effluents conditions. To improve the response of the SBR to changing influent conditions, several efforts have been made to automate and control the duration of the sequential phases of the SBR. The objective of this work is to present and discuss the feasibility of the use of the oxidation-reduction potential, ORP, as a control variable for the determination of the anaerobic phase length in an anaerobic-aerobic SBR used to degrade p-nitrophenol, PNP. The control of the anaerobic phase of the anaerobic-aerobic reactor was achieved with software developed at the Institute of Engineering-UNAM. During the anaerobic stage, the PNP is reduced to p-aminophenol, PAP. As a consequence of the compound transformation, there is a change in the oxidation-reduction potential of the culture medium. This change was used to indicate the minimal concentration of PNP and, as a consequence, the maximal PAP concentration. The feasibility of the algorithm for using the variations in the ORP to determine on-line the length of the anaerobic stage in an anaerobic-aerobic process was demonstrated in our laboratory.

Aerobiosis↗

EEG background activity described by a large computerized database.

OBJECTIVE: To show how our newly developed software for classification and storage of visually routinely assessed EEGs are used to evaluate the general background activity (GBA) and the alpha rhythm (AR) in a large number of prospective EEGs. METHODS: EEGs from 4651 consecutive patients were visually assessed using a computerized description system connected to an EEG database. The AR and the GBA apart from the AR were described separately for frequency and amplitude. RESULTS: AR frequencies declined from the age of 45 years and slowed with increasing age independently of non-AR pathology and gender. Females had higher AR frequencies than males. EEGs with non-GBA pathology had lower GBA frequencies and higher GBA amplitudes. Higher GBA amplitudes were associated with lower GBA frequencies in normal EEGs for all age groups. EEG interpretations by 4 independent electroencephalographers showed the same trends, but differed in exact assessment of frequencies and amplitudes. CONCLUSIONS: EEG interpretations stored in a categorized database with easy access to data have successfully been used to evaluate interobserver variation and other quality control measurements. Statistical analysis of the data has at the same time produced new information regarding the development of AR and GBA throughout life.

Adolescent↗

Mathematical modeling of nicotine and cotinine as biological markers of environmental tobacco smoke exposure.

Computer software developed in our laboratory (CMATRIX) was used to design a physiological pharmacokinetic model of nicotine absorption, distribution, metabolism and excretion in man. The model accommodates inhalation of nicotine from various environmental settings and physiological conditions in man. It was also used to predict pharmacokinetic behavior of cotinine arising from nicotine metabolism. Model-predicted variations in body-fluid nicotine levels confirm that nicotine is not an acceptable quantitative marker of environmental tobacco smoke (ETS) exposure. Though cotinine provides a more stable pattern, predicted interindividual variation suggests the need for specific strict sampling and monitoring guidelines for cotinine to be a reliable quantitative marker.

Computer Simulation↗

Three-dimensional computer reconstruction of a temporal bone.

The complexities of the temporal bone and the critical inter-relationships among its key structures can be simplified with three-dimensional computer-assisted reconstruction. Knowledge of the topography of these structures and their mutual relationships in essential in any surgical approach to the temporal bone. Sixty sagittal histologic sections of a normal left temporal bone were examined. Each section, 30 microns in thickness, was optically enlarged. Segments representing the facial nerve, internal carotid artery, and inner ear structures from individual slides were traced and data were entered into a computer. A personal computer was used for data processing and analysis. Graphic software developed in our laboratory generated images with x-y-z coordinates that could be rotated in any plane. The high resolution of the computer graphics system, combined with the precision of histologic sections, permitted study of the critical three-dimensional anatomic relationships among essential intratemporal bone structures. The capability of reproducing individual and joint images of the intratemporal bone structures and viewing them from all surgical angles gives skull base and otologic surgeons important topographic guidance. Accurate spatial measurements of temporal bone anatomy are now possible with the application of computer graphic technology.

Carotid Artery, Internal↗

Effects of pneumatic artificial heart driver on the rate of isovolumic pressure rise.

The aim of the research was to investigate the effects of three parameters of the artificial heart's performance on the (+) dP/dt max. Specifically, the effects of heart rate, left-sided drive pressure, and percent systole (the independent variables) on the (+) dP/dt max (the dependent variable) were examined. The study was conducted using a mock circulation which was connected to an artificial heart. Data were collected using the COMDU software developed for the computer which monitors the artificial heart. Stepwise regression analysis was used to test the three hypotheses. Hypothesis one stated the heart rate would significantly effect the (+) dP/dt max. The hypothesis was not supported. Hypothesis two stated the percent systole would significantly effect the (+) dP/dt max. Hypothesis two was also not supported. Hypothesis three stated the drive pressure would significantly effect the (+) dP/dt max. The hypothesis was supported as drive pressure accounted for 4% of the variance in (+) dP/dt max; however, the results were not clinically significant. Limitations in the study were multicollinearity among the independent variables, small sample size, and the inability of the mock circulation to represent human responses.

Heart Rate↗

MESHI: a new library of Java classes for molecular modeling.

UNLABELLED: Adapting a modular and object-oriented approach in the design of molecular modeling packages may reduce the software development barrier between ideas and their programed applications. Towards this goal we developed MESHI, a new, strictly object-oriented, molecular modeling suite written in Java. MESHI provides a comprehensive library of extendable classes for all the essential components of molecular modeling: molecular and geometry elements, energy functions and optimization methods. AVAILABILITY: MESHI and its related documentation are freely available at http://www.cs.bgu.ac.il/~meshi; the MESHI API is available at http://www.cs.bgu.ac.il/~meshi/API CONTACT: keasar@cs.bgu.ac.il SUPPLEMENTARY INFORMATION: The Supplementary information includes (1) a detailed description of several key packages and classes, and (2) a brief presentation of results achieved by using the MESHI application--Beautify--in the CASP6 experiment.

Computer Simulation↗

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Animals↗

Predication of Fhhh potential in PTA wastewater treatment.

Ebis is the intelligent environmental biotechnological informatics software developed for judging the effectiveness of the microorganism strain in the industrial wastewater treatment system(IWTS) at the optimal status. The parameter, as the objective function for the judgment, is the minimum reactor volume(Vmin) calculated by Ebis for microorganism required in wastewater treatment. The rationality and the universality of Ebis were demonstrated in the domestic sewage treatment system(DSTS) with the data published in USA and China at first,then Fhhh strain's potential for treating the purified terephthalic acid(PTA) was proved. It suggests that Ebis would be useful and universal for predicating the technique effectiveness in both DSTS and IWTS.

Forecasting↗

A new method for the automated age-at-death evaluation by tooth-cementum annulation (TCA).

A valid age at death estimation is required in historical and also forensic anthropology. Tooth cementum annulation (TCA) is a method for age at death estimation of adult individuals. The method is based on light microscope images taken from tooth-root cross sections. The age is then estimated by manually counting the cementum incremental lines and adding this to the chronological age at the assumed point of tooth eruption. Manual line counting, however, is time consuming, potentially subjective and the number of individual counts is insufficient for statistical evaluations. Software developed for the automated evaluation of TCA images, that uses Fourier analysis and algorithms for image analysis and pattern recognition is presented here. It involves "line-by-line" scanning and the counting of gray scale peaks within a selected region-of-interest (ROI). Each scanning process of a particular ROI yields up to 400 counts that are subsequently statistically evaluated. This simple and time saving program seeks to substitute manual counting and supply consistent and reproducible results as well as reduce the demand of human error by eliminating unavoidable factors such as subjectivity and fatigue.

Age Determination by Teeth↗

Prediction of the antigenic sites of the cystic fibrosis transmembrane conductance regulator protein by molecular modelling.

Antibodies are powerful tools for studying the in situ localization and physiology of proteins. The prediction of epitopes by molecular modelling has been used successfully for the papilloma virus, and valuable antibodies have been raised [Müller et al. (1990) J. Gen. Virol., 71, 2709-2717]. We have improved the modelling approach to allow us to predict epitopes from the primary sequences of the cystic fibrosis transmembrane conductance regulator. The procedure involves searching for fragments of primary sequences likely to make amphipathic secondary structures, which are hydrophilic enough to be at the surface of the folded protein and thus accessible to antibodies. Amphipathic helices were predicted using the methods of Berzofsky, Eisenberg and Jähnig. Their hydrophobic-hydrophilic interface was calculated and drawn, and used to predict the orientation of the helices at the surface of the native protein. Amino acids involved in turns were selected using the algorithm of Eisenberg. Tertiary structures were calculated using 'FOLDING', a software developed by R. Brasseur for the prediction of small protein structures [Brasseur (1995) J. Mol. Graphics, in press]. We selected sequences that folded as turns with at least five protruding polar residues. One important property of antibodies is selectivity. To optimize the selectivity of the raised antibodies, each sequence was screened for similarity (FASTA) to the protein sequence from several databanks. Ubiquitous sequences were discarded. This approach led to the identification of 13 potential epitopes in the cystic fibrosis transmembrane conductance regulator: seven helices and six loops.

Algorithms↗

A computer-assisted system for reconstructing and interpreting the dynamic three-dimensional relationships of the outer surface, nucleus and pseudopods of crawling cells.

Newly developed software additions to the three-dimensional dynamic image analysis system, 3D-DIAS, are described for simultaneously reconstructing and motion analyzing in three dimensions the outer surface, nucleus and pseudopods of living, crawling cells. This new system is then used to describe for the first time a nuclear behavior cycle in translocating Dictyostelium discoideum amoebae and to investigate the role of pseudopod extension in this process. The nuclear behavior cycle is tuned to the two phases of the general cell behavior cycle [Wessels et al., 1994], and includes nuclear migration both in the z- and in the x,y-axes from the proximal border of the prior anterior pseudopod to the proximal border of a newly expanding anterior pseudopod. Nuclear migration is cued by pseudopod-substratum contact, achieves velocities in excess of 50 microm/min, and is accompanied by characteristic changes in nuclear shape. The rules and characteristics of nuclear behavior are demonstrated to be intact in two mutants affecting pseudopod formation, a myosin IB null mutant (myoB-) and a myosin II heavy chain phosphorylation mutant (3XALA). The rules and characteristics of nuclear migration, however, are disrupted upon dissolution of microtubules by colcemid. Together the above results demonstrate that the newly developed 3D-DIAS system can be used to gain new insights into the dynamic changes in the intracellular 3D architecture associated with cellular translocation.

Animals↗

A customisable framework for the assessment of therapies in the solution of therapy decision tasks.

In current medical research, a growing interest can be observed in the definition of a global therapy-evaluation framework which integrates considerations such as patients preferences and quality-of-life results. In this article, we propose the use of the research results in this domain as a source of knowledge in the design of support systems for therapy decision analysis, in particular with a view to application in oncology. We discuss the incorporation of these considerations in the definition of the therapy-assessment methods involved in the solution of a generic therapy decision task, described in the context of AI software development methodologies such as CommonKADS. The goal of the therapy decision task is to identify the ideal therapy, for a given patient, in accordance with a set of objectives of a diverse nature. The assessment methods applied are based either on data obtained from statistics or on the specific idiosyncrasies of each patient, as identified from their responses to a suite of psychological tests. In the analysis of the therapy decision task we emphasise the importance, from a methodological perspective, of using a rigorous approach to the modelling of domain ontologies and domain-specific data. To this aim we make extensive use of the semi-formal object oriented analysis notation UML to describe the domain level.

Artificial Intelligence↗

Modification of the OMED nomenclature: a system approach based on the SISCOPE data model.

The OMED nomenclature represented a turning point in endoscopic computer systems by supplying software developers with an internationally recognized scientific document on which prototypes could be based. The main pitfalls of the OMED system are related to its hierarchical structure, probably not the most effective design to represent endoscopic findings. Based on our experience during the development of SISCOPE, an integrated data management system for endoscopy, an alternative scheme is proposed: Endoscopic descriptions are modeled as a set of objects represented by a data structure whose elements are location, morphology, associated lesions and hemorrhage. 72 objects appear to be sufficient for an accurate representation of all endoscopic scenes and a consistent data model could be created with this approach. Efforts should be made to decrease redundancy in the OMED nomenclature, but extension to other endoscopic data types, such as clinical and pathological diagnosis, is more urgently required. Furthermore, if data exchange between systems is desired, the definition of an Endoscopy Metafile is an absolute requirement.

Database Management Systems↗

Implementation of talairach atlas based automated brain segmentation for radiation therapy dosimetry.

Radiotherapy for brain cancer inevitably results in irradiation of uninvolved brain. While it has been demonstrated that irradiation of the brain can result in cognitive deficits, dose-volume relationships are not well established. There is little work correlating a particular cognitive deficit with dose received by the region of the brain responsible for the specific cognitive function. One obstacle to such studies is that identification of brain anatomy is both labor intensive and dependent on the individual performing the segmentation. Automatic segmentation has the potential to be both efficient and consistent. Brains2 is a software package developed by the University of Iowa for MRI volumetric studies. It utilizes MR images, the Talairach atlas, and an artificial neural network (ANN) to segment brain images into substructures in a standardized manner. We have developed a software package, Brains2DICOM, that converts the regions of interest identified by Brains2 into a DICOM radiotherapy structure set. The structure set can be imported into a treatment planning system for dosimetry. We demonstrated the utility of Brains2DICOM using a test case, a 34-year-old man with diffuse astrocytoma treated with three-dimensional conformal radiotherapy. Brains2 successfully applied the Talairach atlas to identify the right and left frontal, parietal, temporal, occipital, subcortical, and cerebellum regions. Brains2 was not successful in applying the ANN to identify small structures, such as the hippocampus and caudate. Further work is necessary to revise the ANN or to develop new methods for identification of small structures in the presence of disease and radiation induced changes. The segmented regions-of-interest were transferred to our commercial treatment planning system using DICOM and dose-volume histograms were constructed. This method will facilitate the acquisition of data necessary for the development of normal tissue complication probability (NTCP) models that assess the probability of cognitive complications secondary to radiotherapy for intracranial and head and neck neoplasms.

Adult↗

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↗

Local photorelease of caged thymosin beta4 in locomoting keratocytes causes cell turning.

The broad aim of this work was to explore the feasibility of using light-directed perturbation techniques to study cell locomotion. Specifically, a caged form of thymosin beta4 (Tbeta4) was photoactivated in a defined local region of locomoting fish scale keratocytes and the resulting perturbation of locomotion was studied. Purified Tbeta4 was produced in an inactive form by "caging" with ([n-nitroveratryl]oxy)chlorocarbamate. In vitro spectrophotofluorometric assays indicated that caged Tbeta4 did not change the normal actin polymerization kinetics, whereas photoactivated Tbeta4 significantly inhibited actin polymerization. With an a priori knowledge of the cytoplasmic diffusion coefficient of Tbeta4 as measured by fluorescence recovery after photobleaching experiments, the rapid sequestration of actin monomers by uncaged Tbeta4 and the consequent reduction in the diffusional spread of the Tbeta4-actin complex were predicted using Virtual Cell software (developed at the Center for Biomedical Imaging Technology, University of Connecticut Health Center). These simulations demonstrated that locally photoactivating Tbeta4 in keratocytes could potentially elicit a regional locomotory response. Indeed, when caged Tbeta4 was locally photoactivated at the wings of locomoting keratocytes, specific turning about the irradiated region was observed, whereas various controls were negative. Additionally, loading of exogenous Tbeta4 into both keratocytes and fibroblasts caused very rapid disassembly of actin filaments and reduction of cellular contractility. Based on these results, a mechanical model is proposed for the turning behavior of keratocytes in response to photoreleased Tbeta4.

3T3 Cells↗

[Computer-assisted evaluation of aortic aneurysm morphology for choosing the method of therapy].

Computer aided surgery planning software for AAA is a industry-standard software development for viewing patient-specific data on a personal computer through a unique approach, which improve visualization, navigation, and decision support capabilities for both open and endovascular surgery. Raw scan data is extracted from CT scans, and rendered into a three-dimensional format. This 3D modeling technology and user interface provides a patient-specific model with a rapid visual access to the full range of information, including accurate 3D assessment of AAA morphology and pathology, interactive multiplanar reconstructions, measurements, and views to assist the surgeon in understanding of complex 3D relationships. It provides an optimal system for patient evaluation and selection for endovascular repair of AAA and in the post-operative evaluation of stent deployment and/or complications, such as endoleaks.

Aortic Aneurysm↗