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Multitracer: a Java-based tool for anatomic delineation of grayscale volumetric images.

A Java-based tool for delineating anatomic boundaries in 8- and 16- bit grayscale volumetric images is described. Modern features implemented by the tool include the ability to simultaneously view the current cursor position and the previously delineated boundaries on three orthogonal planes, the ability to magnify images during delineation using high-quality interpolation, the ability to encode and save boundaries with subvoxel resolution, and the ability to utilize coregistered images interchangeably during delineation. Additional features facilitate use of the tool in a multiuser, multiplatform environment and provide support for the documentation of anatomic delineation protocols. In addition to providing direct estimates of structure volumes, areas, and lengths, the tool allows contoured boundaries to be exported for more sophisticated analyses. The tool also provides support for manual editing of image volumes to remove confounding structures and for manual correction of image volumes that have been inaccurately edited. In addition to its research utility, the tool also has potential value in education, allowing students to interact with volumetric data and structural boundaries in three dimensions.

Artifacts↗

Multiple sequence alignment in HTML: colored, possibly hyperlinked, compact representations.

Protein sequence alignments are widely used in protein structure prediction, protein engineering, modeling of proteins, etc. This type of representation is useful at different stages of scientific activity: looking at previous results, working on a research project, and presenting the results. There is a need to make it available through a network (intranet or WWW), in a way that allows biologists, chemists, and noncomputer specialists to look at the data and carry on research--possibly in a collaborative research. Previous methods (text-based, Java-based) are reported and their advantages are discussed. We have developed two novel approaches to represent the alignments as colored, hyper-linked HTML pages. The first method creates an HTML page that uses efficiently the image cache mechanism of a WWW browser, thereby allowing the user to browse different alignments without waiting for the images to be loaded through the network, but only for the first viewed alignment. The generated pages can be browsed with any HTML2.0-compliant browser. The second method that we propose uses W3C-CSS1-style sheets to render alignments. This new method generates pages that require recent browsers to be viewed. We implemented these methods in the Viseur program and made a WWW service available that allows a user to convert an MSF alignment file in HTML for WWW publishing. The latter service is available at http:@www.lctn.u-nancy.fr/viseur/services.htm l.

Amino Acid Sequence↗

Mathematical modelling of the human foetal cardiovascular system based on Doppler ultrasound data.

A lumped parameter model of the human foetal circulation primarily based on blood velocity data derived from the Doppler analysis was developed in this study. It consists of two major parts, the heart and the foetal vascular circulation. The heart model accounts for both ventricular and atrial contractility. The circulation was divided into 19 compliant vascular compartments in order to describe all of the clinically monitored sites. The model parameters refer to the final gestation period and were derived either from literature on foetal sheep circulation or from anatomical dimension monitoring of the human foetus. No control mechanism is incorporated into the model. The model was validated by comparing several index values of simulated velocity curves to those of the experimental Doppler waveforms. The mean and maximum percentual errors in the estimation of the experimental results by the model are 7.7% and 20.1%, respectively. Velocity and pressure tracings of the foetal circulation were investigated, as well as regional blood flow rate distribution.

Cardiovascular Physiological Phenomena↗

Representation primitives, process models and patient data in computer-interpretable clinical practice guidelines: a literature review of guideline representation models.

Representation of clinical practice guidelines in a computer-interpretable format is a critical issue for guideline development, implementation, and evaluation. We studied 11 types of guideline representation models that can be used to encode guidelines in computer-interpretable formats. We have consistently found in all reviewed models that primitives for representation of actions and decisions are necessary components of a guideline representation model. Patient states and execution states are important concepts that closely relate to each other. Scheduling constraints on representation primitives can be modeled as sequences, concurrences, alternatives, and loops in a guideline's application process. Nesting of guidelines provides multiple views to a guideline with different granularities. Integration of guidelines with electronic medical records can be facilitated by the introduction of a formal model for patient data. Data collection, decision, patient state, and intervention constitute four basic types of primitives in a guideline's logic flow. Decisions clarify our understanding on a patient's clinical state, while interventions lead to the change from one patient state to another.

Artificial Intelligence↗

An evaluation of the usefulness of two terminology models for integrating nursing diagnosis concepts into SNOMED Clinical Terms.

OBJECTIVES: We evaluated the usefulness of two models for integrating nursing diagnosis concepts into SNOMED Clinical Terms (CT). METHODS: First, we dissected nursing diagnosis term phrases from two source terminologies (North American Nursing Diagnosis Association Taxonomy 1 (NANDA) and Omaha System) into the semantic categories of the European Committee for Standardization (CEN) categorical structure and ISO reference terminology model (RTM). Second, we critically analyzed the similarities between the semantic links in the CEN and ISO models and the semantic links used to formally define diagnostic concepts in SNOMED CT. RESULTS: Our findings demonstrated that focus, bearer/subject of information, and judgment were present in 100% of the NANDA and Omaha term phrases. The Omaha term phrases contained no additional descriptors beyond those considered mandatory in the CEN and ISO models. The comparison among the semantic links showed that SNOMED CT currently contains all but one of the semantic links needed to model the two source terminologies for integration. In conclusion, our findings support the potential utility of the CEN and ISO models for integrating nursing diagnostic concepts into SNOMED CT.

Classification↗

Adaptive user interface customization through browsing knowledge capitalization.

Hypermedia data browsing is a mean for improving information access. However, the overload and the heterogeneity of medical information, as well as the multitude of possible navigational paths, turn the consultation of data into a difficult task. We present in this paper a solution for the development of adaptive user interfaces in a hypermedia data browsing environment. It is based on the capitalization of the users knowledge in the decision-making process, expressed in terms of navigational paths and of data presentation modes that are customized to the user's preferences and practice. This capitalization offers the user a way to automatically store and reuse the experience accumulated in browsing through patient records. We illustrate our approach with the implementation of HEMA, a clinical workstation prototype that we have specialized for the cardiology domain.

Artificial Intelligence↗

Healthcare teams over the Internet: programming a certificate-based approach.

Healthcare environments are a representative case of collaborative environments since individuals (e.g. doctors) in many cases collaborate in order to provide care to patients in a more proficient way. At the same time modern healthcare institutions are increasingly interested in sharing access of their information resources in the networked environment. Healthcare applications over the Internet offer an attractive communication infrastructure at worldwide level but with a noticeably great factor of risk. Security has, therefore, become a major concern. However, although an adequate level of security can be relied upon digital certificates, if an appropriate security model is used, additional security considerations are needed in order to deal efficiently with the above team-work concerns. The already known Hybrid Access Control (HAC) security model supports and handles efficiently healthcare teams with active security capabilities and is capable to exploit the benefits of certificate technology. In this paper we present the way for encoding the appropriate authoritative information in various types of certificates, as well as the overall operational architecture of the implemented access control system for healthcare collaborative environments over the Internet. A pilot implementation of the proposed methodology in a major Greek hospital has shown the applicability of the proposals and the flexibility of the access control provided.

Certification↗

Developing a virtual patient record using XML and web-based workflow technologies.

Virtual patient records (VPR) provide a means for integrated access to patient information that may be scattered around different healthcare settings. Within the boundaries of a health district providing all levels of care, this concept can be implemented in a corporate Intranet environment to support longitudinal patient care activities across the participating healthcare providers. In this context, a VPR implementation enables autonomous healthcare providers to operate in a cooperative working environment and apply continuity of care. Workflow systems bring this collaboration and cooperation into effect by automatically routing the medical information needed by authorized actors in a healthcare process. This paper presents a VPR framework that allows integrating geographically dispersed medical information within a health district and enhancing collaboration and coordination of authorized workgroups by means of a web-based workflow system. An implementation of the proposed framework is also presented.

Delivery of Health Care, Integrated↗

Active X based standards for healthcare integration.

With cost pressures brought to the forefront by the growth of managed care, the integration of healthcare information systems is more important than ever. Providers of healthcare information are under increasing pressure to provide timely information to end users in a cost effective manner. Organizations have had to decide between the strong functionality that a multi-vendor 'best of breed' architecture provides and the strong integration provided by a single-vendor solution. As connectivity between systems increased, these interfaces were migrated to work across serial and eventually, network, connections. In addition, the content of the information became standardized through efforts like HL7 and ANSI X12 and Edifact. Although content-based standards go a long way towards facilitating interoperability, there is also quite a bit of work required to connect two systems even when they both adhere to the standard. A key to accomplishing this goal is increasing the connectivity between disparate systems in the healthcare environment. Microsoft is working with healthcare organizations and independent software vendors to bring Microsoft's powerful enterprise object technology, ActiveX, to the healthcare industry. Whilst object orientation has been heralded as the 'next big thing' in computer applications development, Microsoft believe that, in fact, component software is the technology which will provide the greatest benefit to end users.

Certification↗

Robot printing of reverse dot blot arrays for human mutation detection.

We report on a generally useful, partially automated, human mutation detection method based upon printing moderate density oligonucleotide arrays using a biorobot on activated nylon membranes. The Beckman Biomek 2000 was adapted to this task through fabrication of aluminum membrane filter holders and the development of an addressable Tool Command Language (Tcl) program, which can be invoked through BioScript. During program execution, a robot arm is moved along the x, y, and z axes to expel liquid, without dripping, from disposable barrier pipette tips and then to touch the drops on preactivated membranes. Printed arrays consist of alternating rows of oligonucleotides containing normal and mutant sequences. Hybridization of biotin labeled polymerase chain reaction products derived from human patient genomic DNA samples are visualized using chemiluminescent or chromogenic indicators. This technique allows unequivocal genotyping of 32 mutations at the beta-thalassemia locus (11p15.5) and of 34 mutations and one polymorphism at the cystic fibrosis transconductance membrane regulator locus (7p35).

Chromosomes, Human, Pair 11↗

Computer model of the maintenance and selection of genetic heterogeneity in polygamous helminths.

A stochastic simulation model of the transmission and maintenance of genetic heterogeneity in the absence and presence of external selection pressures is presented for polygamous intestinal helminths such as Ascaris. The model assumes that the density distribution of the adult parasites is highly aggregated and that density-dependent effects on fecundity are important. The model gives rise to stable infection rates in the host. Where the parasite population contains genetic heterogeneity, with the exception of stochastic fluctuations which models genetic drift, the ratio of the different alleles remained constant over extended periods of time. This result contrasts with that of an earlier analytical model (Anderson, R.M., May, M.R. & Gutpa S. (1989) Parasitology 99, S59-S79), in which uneven mating probabilities for the different combinations of worm possible in a host was postulated to inevitably lead to fixation of the most abundant allele. New results suggest that in spite of the restricted choice of mating available to a worm in the confines of a host, selection pressure always leads to enrichment of the parasites carrying resistant alleles.

Animals↗

Development of a bioartificial nerve graft. I. Design based on a reaction-diffusion model.

A simple reaction-diffusion model has been developed to describe the mass transport of nutrients and nerve growth factor within a bioartificial nerve graft (BNG). The BNG consists of a porous polymer conduit that is preseeded with Schwann cells in its lumen. The Schwann cells produce growth factors to stimulate nerve regeneration within the lumen of the conduit. The model can predict the wall thickness, porosity, and Schwann cell seeding density needed to maximize the axon extension rate while ensuring that sufficient nutrients, especially oxygen, are made available to the neurons until the formation of the neovasculature. The model predicts a sixteen-fold increase in the levels of nerve growth factor by dropping the porosity from 95 to 55% but only at the expense of reducing the oxygen concentration. At higher porosities, increasing the wall thickness and increasing the Schwann cell seeding density both have the same effect of increasing the concentration of nerve growth factor within the lumen of the conduit. This model provides a simple tool for evaluating various conduit designs before continuing with experimental studies in vivo.

Animals↗

ARTS: a flexible laboratory instrument control language.

A generalized computer program, ARTS (Analytical Robot Telecommunications Software), has been developed to give the research scientist more flexible control of laboratory robots and instruments. As a stand-alone program, ARTS is a complete laboratory control language. ARTS can also be an extension of other software in either a master or slave mode. As master, ARTS can call on other software to perform certain tasks. In a slave mode, ARTS can act as a sensory extension of the calling software. ARTS is a flexible laboratory control language capable of adapting to changing laboratory requirements.

Laboratories↗

Spline-fitting with a genetic algorithm: a method for developing classification structure-activity relationships.

Classification methods allow for the development of structure-activity relationship models when the target property is categorical rather than continuous. We describe a classification method which fits descriptor splines to activities, with descriptors selected using a genetic algorithm. This method, which we identify as SFGA, is compared to the well-established techniques of recursive partitioning (RP) and soft independent modeling by class analogy (SIMCA) using five series of compounds: cyclooxygenase-2 (COX-2) inhibitors, benzodiazepine receptor (BZR) ligands, estrogen receptor (ER) ligands, dihydrofolate reductase (DHFR) inhibitors, and monoamine oxidase (MAO) inhibitors. Only 1-D and 2-D descriptors were used. Approximately 40% of compounds in each series were assigned to a test set, "cherry-picked" from the complete set such that they lie outside the training set as much as possible. SFGA produced models that were more predictive for all but the DHFR set, for which SIMCA was most predictive. RP gave the least predictive models for all but the MAO set. A similar trend was observed when using training and test sets to which compounds were randomly assigned and when gradually eliminating compounds from the (designed) training set. The stability of models was examined for the random and reduced sets, where stability means that classification statistics and the selected descriptors are similar for models derived from different sets. Here, SIMCA produced the most stable models, followed by SFGA and RP. We show that a consensus approach that combines all three methods outperforms the single best model for all data sets.

Algorithms↗

NIPALSTREE: a new hierarchical clustering approach for large compound libraries and its application to virtual screening.

A hierarchical clustering algorithm--NIPALSTREE--was developed that is able to analyze large data sets in high-dimensional space. The result can be displayed as a dendrogram. At each tree level the algorithm projects a data set via principle component analysis onto one dimension. The data set is sorted according to this one dimension and split at the median position. To avoid distortion of clusters at the median position, the algorithm identifies a potentially more suited split point left or right of the median. The procedure is recursively applied on the resulting subsets until the maximal distance between cluster members exceeds a user-defined threshold. The approach was validated in a retrospective screening study for angiotensin converting enzyme (ACE) inhibitors. The resulting clusters were assessed for their purity and enrichment in actives belonging to this ligand class. Enrichment was observed in individual branches of the dendrogram. In further retrospective virtual screening studies employing the MDL Drug Data Report (MDDR), COBRA, and the SPECS catalog, NIPALSTREE was compared with the hierarchical k-means clustering approach. Results show that both algorithms can be used in the context of virtual screening. Intersecting the result lists obtained with both algorithms improved enrichment factors while losing only few chemotypes.

Algorithms↗

Chemoinformatics-based classification of prohibited substances employed for doping in sport.

Representative molecules from 10 classes of prohibited substances were taken from the World Anti-Doping Agency (WADA) list, augmented by molecules from corresponding activity classes found in the MDDR database. Together with some explicitly allowed compounds, these formed a set of 5245 molecules. Five types of fingerprints were calculated for these substances. The random forest classification method was used to predict membership of each prohibited class on the basis of each type of fingerprint, using 5-fold cross-validation. We also used a k-nearest neighbors (kNN) approach, which worked well for the smallest values of k. The most successful classifiers are based on Unity 2D fingerprints and give very similar Matthews correlation coefficients of 0.836 (kNN) and 0.829 (random forest). The kNN classifiers tend to give a higher recall of positives at the expense of lower precision. A naïve Bayesian classifier, however, lies much further toward the extreme of high recall and low precision. Our results suggest that it will be possible to produce a reliable and quantitative assignment of membership or otherwise of each class of prohibited substances. This should aid the fight against the use of bioactive novel compounds as doping agents, while also protecting athletes against unjust disqualification.

Algorithms↗

Algorithm for exhaustive and nonredundant organic stereoisomer generation.

Generation of organic stereoisomers with R/S, Z/E, and/or M/P configurations that may contain heteroatoms, multiple bonds, and any kind of cycle (isolated, spiro, condensed, and nested) is described. Inputs for processing are molecular structures in a N_tuple format resident on an automatic (canonical) or manual (non canonical) generated file which are processed by doing internal molecular graph construction, a weighted bipartite tree construction for all atoms and bonds to detect stereocenters, and symmetrical atom groups (SAG) with some specific SAG parameters that constitute a novel way for redundancy elimination of meso structures. Finally, determination of ligand CIP priorities allows for writing the output N_tuples with stereoisomer description. Several examples showing application of this methology to a wide number of structures are also presented.

Algorithms↗

Distributions of distances in information strings.

Distances between identical symbols in information strings (biological, language, computer programs (*.exe files) are described with a different precision with four distributions: exponential, Weibull, log-normal and negative binomial. The correlations are sometimes highly significant.

Amino Acid Sequence↗