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A veterinary anatomy tutoring system.

A veterinary anatomy tutoring system was developed by using Knowledge Pro, an object-oriented software development tool with hypermedia capabilities, and MS Access, a relational database. Communication between them is facilitated by using the Structured Query Language (SQL). The architecture of the system is based on knowledge sets, each of which covers four different descriptions of an organ, namely gross anatomy (general description), gross anatomy (comparative features), histology, and embryology, which constitute the knowledge units. These knowledge units are linked with three global variables that define the animals, the topographies, and the system to which this organ belongs, creating three data-bases. These three data-bases are interrelated through the organ field in order to establish a relational model. This system allows versatility in the student's navigation through the information space by offering different modes for information location and presentation. These include course mode, review mode, reference mode, dissection mode, and comparison mode. In addition, the system provides a self-evaluation mode.

Anatomy, Veterinary↗

Parasitology tutoring system: a hypermedia computer-based application.

The teaching of parasitology is a basic course in all life sciences curricula, and up to now no computer-assisted tutoring system has been developed for this purpose. By using Knowledge Pro, an object-oriented software development tool, a hypermedia tutoring system for teaching parasitology to college students was developed. Generally, a tutoring system contains a domain expert, a student model, a pedagogical expert and the user interface. In this project, particular emphasis was given to the user interface design and the expert knowledge representation. The system allows access to the educational material through hypermedia and indexing at the pace of the student. The hypermedia access is facilitated through key words defined as hypertext and objects in pictures defined as hyper-areas. The indexing access is based on a list of parameters that refers to various characteristics of the parasites, e.g. taxonomy, host, organ, etc. In addition, this indexing access can be used for testing the student's level of understanding. The advantages of this system are its user-friendliness, graphical interface and ability to incorporate new educational material in the area of parasitology.

Artificial Intelligence↗

[Application of fuzzy inference to personal identification--sex determination from teeth].

Fuzzy inference has received much attention recently as a new type of computer control technology for application in various fields. In this study I applied fuzzy inference to personal identification in medical jurisprudence. Sex determination program was constructed from teeth using the fuzzy inference technique and was compared with known discriminant analysis. The materials examined were mandibular and maxillary dental plaster models of 100 adult males and females, and 80 infant males and females. For the permanent teeth, measurements were made on crown width and thickness of the mandibular and maxillary central incisors, canines, first premolars, and first molars, and of the width and length of the maxillary dental arch. For the deciduous teeth, measurements were made on crown width and thickness of all teeth. Stepwise discriminant analysis was conducted using these values. The values from 5 selected upper-ranked items were set as input objects of the fuzzy inference program and the probability of maleness obtained from the discriminant analysis was set as the output object. Finally, sex determination program for both permanent and deciduous teeth was constructed using a fuzzy inference software development tool. Each measured value was input into this program and the output results were compared with those of discriminant analysis. The percentages of correct determinations for permanent teeth were 83.0% for males and 86.0% for females using stepwise discriminant analysis, however it increased to 93.0% for males and 89.0% for females using the fuzzy inference program. The percentages of correct determinations for deciduous teeth models were 67.5% for males and 75.0% for females using stepwise discriminant analysis, and increased to 86.3% for males and 81.3% for females using the fuzzy inference program. Among samples with probabilities between 40% and 60%, 3 out of 14 males and 4 out of 13 females were misjudged using stepwise discriminant analysis in cases of permanent teeth. However using fuzzy inference program, it reduced to 0 for males and 3 for females. In case of deciduous teeth, 9 out of 20 males and 9 out of 23 females were misjudged using stepwise discriminant analysis. But it reduced to 5 for males and 4 for females using the fuzzy inference program.

Adult↗

The development of common data elements for a multi-institute prostate cancer tissue bank: the Cooperative Prostate Cancer Tissue Resource (CPCTR) experience.

BACKGROUND: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a consortium of four geographically dispersed institutions that are funded by the U.S. National Cancer Institute (NCI) to provide clinically annotated prostate cancer tissue samples to researchers. To facilitate this effort, it was critical to arrive at agreed upon common data elements (CDEs) that could be used to collect demographic, pathologic, treatment and clinical outcome data. METHODS: The CPCTR investigators convened a CDE curation subcommittee to develop and implement CDEs for the annotation of collected prostate tissues. The draft CDEs were refined and progressively annotated to make them ISO 11179 compliant. The CDEs were implemented in the CPCTR database and tested using software query tools developed by the investigators. RESULTS: By collaborative consensus the CPCTR CDE subcommittee developed 145 data elements to annotate the tissue samples collected. These included for each case: 1) demographic data, 2) clinical history, 3) pathology specimen level elements to describe the staging, grading and other characteristics of individual surgical pathology cases, 4) tissue block level annotation critical to managing a virtual inventory of cases and facilitating case selection, and 5) clinical outcome data including treatment, recurrence and vital status. These elements have been used successfully to respond to over 60 requests by end-users for tissue, including paraffin blocks from cases with 5 to 10 years of follow up, tissue microarrays (TMAs), as well as frozen tissue collected prospectively for genomic profiling and genetic studies. The CPCTR CDEs have been fully implemented in two major tissue banks and have been shared with dozens of other tissue banking efforts. CONCLUSION: The freely available CDEs developed by the CPCTR are robust, based on "best practices" for tissue resources, and are ISO 11179 compliant. The process for CDE development described in this manuscript provides a framework model for other organ sites and has been used as a model for breast and melanoma tissue banking efforts.

Computational Biology↗

CASE tools and UML: state of the ART.

With increasing need for automated tools to assist complex systems development, software design methods are becoming popular. This article analyzes the state of art in computer-aided software engineering (CASE) tools and unified modeling language (UML), focusing on their evolution, merits, and industry usage. It identifies managerial issues for the tools' adoption and recommends an action plan to select and implement them. While CASE and UML offer inherent advantages like cheaper, shorter, and efficient development cycles, they suffer from poor user satisfaction. The critical success factors for their implementation include, among others, management and staff commitment, proper corporate infrastructure, and user training.

Computer-Aided Design↗

COMKAT: compartment model kinetic analysis tool.

UNLABELLED: Compartment models are the basis for most physiologically based quantification of nuclear medicine data. Although some software packages are available for this purpose, many are expensive, run on relatively few types of computers or are of limited capability, and cannot be extended because of the unavailability of source code. Consequently, institutions with modeling expertise often develop software for themselves, which has the disadvantages of lack of standardization and possible replication of effort. Therefore, general-purpose compartment-modeling software distributed with source code would be a welcome resource for the nuclear medicine community. METHODS: We formulated a mathematic framework within which compartment models containing unimolecular and bimolecular (receptor saturation) kinetics can be described. We implemented this framework within MATLAB and call the resultant software COMKAT (Compartment Model Kinetic Analysis Tool). RESULTS: COMKAT simplifies the process of defining and solving standard blood flow, 18F-FDG, and receptor models as well as models of a user's own design. In particular, COMKAT automatically defines and implements state, analytic sensitivity, and Jacobian equations. Given these, COMKAT can perform simulations in which model outputs are solved for specified parameter values, thereby allowing the user to predict how sensitive data are to these parameters. In addition, COMKAT can be used to estimate values for the parameters by fitting model output to experimental data. COMKAT is equipped with command-line and graphic user interfaces from which the user can access these features. Examples of these applications are presented along with validation and performance summaries. CONCLUSION: COMKAT is a useful software tool and is available without cost to researchers, at www.nuclear.uhrad.com/comkat.

Computer Simulation↗

ProbID: a probabilistic algorithm to identify peptides through sequence database searching using tandem mass spectral data.

With the recent quick expansion of DNA and protein sequence databases, intensive efforts are underway to interpret the linear genetic information of DNA in terms of function, structure, and control of biological processes. The systematic identification and quantification of expressed proteins has proven particularly powerful in this regard. Large-scale protein identification is usually achieved by automated liquid chromatography-tandem mass spectrometry of complex peptide mixtures and sequence database searching of the resulting spectra [Aebersold and Goodlett, Chem. Rev. 2001, 101, 269-295]. As generating large numbers of sequence-specific mass spectra (collision-induced dissociation/CID) spectra has become a routine operation, research has shifted from the generation of sequence database search results to their validation. Here we describe in detail a novel probabilistic model and score function that ranks the quality of the match between tandem mass spectral data and a peptide sequence in a database. We document the performance of the algorithm on a reference data set and in comparison with another sequence database search tool. The software is publicly available for use and evaluation at http://www.systemsbiology.org/research/software/proteomics/ProbID.

Algorithms↗

Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling.

Alterations in transcription, RNA editing, translation, protein processing, and clearance are a consistent feature of Alzheimer's disease (AD) brain. To extend our initial study (Alzheimer Reports [2000] 3:161-167), RNA samples isolated from control and AD hippocampal cornu ammonis 1 (CA1) were analyzed for 12633 gene and expressed sequence tag (EST) expression levels using DNA microarrays (HG-U95Av2 Genechips; Affymetrix, Santa Clara, CA). Hippocampal CA1 tissues were carefully selected from several hundred potential specimens obtained from domestic and international brain banks. To minimize the effects of individual differences in gene expression, RNA of high spectral quality (A(260/280) > or= 1.9) was pooled from CA1 of six control or six AD subjects. Results were compared as a group; individual gene expression patterns for the most-changed RNA message levels were also profiled. There were no significant differences in age, postmortem interval (mean < or = 2.1 hr) nor tissue pH (range 6.6-6.9) between the two brain groups. AD tissues were derived from subjects clinically classified as CDR 2-3 (CERAD/NIA). Expression data were analyzed using GeneSpring (Silicon Genetics, Redwood City, CA) and Microarray Data Mining Tool (Affymetrix) software. Compared to controls and 354 background/alignment markers, AD brain showed a generalized depression in brain gene transcription, including decreases in RNA encoding transcription factors (TFs), neurotrophic factors, signaling elements involved in synaptic plasticity such as synaptophysin, metallothionein III, and metal regulatory factor-1. Three- or morefold increases in RNAs encoding DAXX, cPLA(2), CDP5, NF-kappaBp52/p100, FAS, betaAPP, DPP1, NFIL6, IL precursor, B94, HB15, COX-2, and CEX-1 signals were strikingly apparent. These data support the hypothesis of widespread transcriptional alterations, misregulation of RNAs involved in metal ion homeostasis, TF signaling deficits, decreases in neurotrophic support and activated apoptotic and neuroinflammatory signaling in moderately affected AD hippocampal CA1.

Aged↗

Volume changes of experimental carotid sidewall aneurysms due to embolization with liquid embolic agents: a multidetector CT angiography study.

Iodine-containing polyvinyl alcohol polymer (I-PVAL) is a novel precipitating liquid embolic that allows for artifact-free evaluation of CT angiography (CTA). As accurate aneurysm volumetry can be performed with multidetector CTA, we determined volumes of experimental aneurysms before, immediately after, and 4 weeks after embolization of 14 porcine experimental carotid sidewall aneurysms with this liquid embolic. An automated three-dimensional software measurement tool was used for volumetric analysis of volume-rendering CTA data. Furthermore, intra-aneurysmal pressure changes during liquid embolization were measured in four silicone aneurysms and potential polymer volume changes within 4 weeks were assessed in vitro. Liquid embolic injection was performed during temporary balloon occlusion of the aneurysm neck, resulting in a mean occlusion rate of 98.3%. Aneurysms enlarged significantly during embolization by 61.1 +/- 28.9%, whereas a significant shrinkage of 5.6 +/- 2.7% was observed within the follow-up period. Histologic analysis revealed an inflammatory foreign body reaction with partial polymer degradation. In silicone aneurysm models, intra-aneurysmal pressure remained unchanged during liquid embolic injection, whereas balloon inflation resulted in a mean pressure increase of 31.2 +/- 0.7%. No polymer shrinkage was observed in vitro. The aneurysm enlargement noted was presumably due to pressure elevation after balloon inflation, which resulted in dilatation of the weak venous wall of the newly constructed aneurysm--another shortcoming of this experimental aneurysm model. The volume decrease after 4 weeks expressed partial polymer degradation.

Angiography, Digital Subtraction↗

Mapping the phrenic nerve motor point: the key to a successful laparoscopic diaphragm pacing system in the first human series.

BACKGROUND: For patients with high spinal cord injury and chronic respiratory insufficiency, electrically induced diaphragm pacing is an alternative to long-term positive pressure ventilation. The goal of this study was to laparoscopically assess the phrenic nerve motor point of the diaphragm and then implant electrodes to produce chronic negative pressure ventilation. METHODS: Patients undergoing elective laparoscopic procedures (volunteer patient group) underwent a series of electrical stimuli (2 to 24 mA at 100-microsecond pulse widths) with a mapping probe to identify the motor point through qualitative visualization of diaphragm motion and quantitative measurement of the abdominal pressure to assess the strength of the contraction. After Food and Drug Administration and Institutional Review Board approval, tetraplegic patients (spinal cord injured patient group) who were ventilator dependent underwent mapping and implantation of electrodes for pacing in both diaphragms. RESULTS: In the volunteer group, 28 patients underwent 3 to 50 stimulations per diaphragm to identify the motor points. Throughout this series the surgical tools and software were improved to allow rapid motor point location with a grid-mapping algorithm. In the spinal cord injured group, 5 of 6 patients had electrodes successfully implanted at the motor point to produce adequate tidal volumes. The one failure caused a change in our inclusion criteria to include fluoroscopic confirmation of diaphragm movement during surface nerve stimulation. Three patients are completely free of the ventilator, and the other 2 are progressively increasing their time off the ventilator with conditioning. CONCLUSIONS: Mapping and implantation of the electrodes can be done laparoscopically, providing for a low-risk, cost-effective, outpatient, diaphragm pacing system that will support the respiratory needs of patients.

Adult↗

Three years' experience with an all-digital nuclear medicine department.

We describe our all-digital, filmless, department of nuclear medicine, which has been fully operational for 3 years. The approach to the design and implementation of a nuclear medicine picture archiving and communication system (PACS) is discussed, as well as enhancements found to be necessary or desirable during our 3 years of experience using the system. Studies are initially viewed on remote monitors in the reading room, and transferred from multiple vendor's computers to the PACS by floppy disc network. Scans are analyzed on networked image workstations using a variety of software imaging tools. Reports are dictated into a digital voice storage system, allowing the referring physician immediate telephone access. The dictated report is typed into a computer, electronically edited, reviewed, billed, and printed for appropriate distribution on an integrated medical information system. The final report is stored on the PACS, along with the scan image and other patient information on 1-gigabyte removable optical discs. Two networked optical disc drives allow us to have approximately 3 years of our department's studies available instantly, allowing recall of previous studies for comparison with the current scan. Emergency night and weekend studies are sent via modern over normal phone lines to the on-call physician, who has a similar image workstation at home. Digital image storage allows for easy manipulation of the data, such as gray scale manipulation and cine (movie) display. Cost analysis shows significant savings compared with a film-based department. We conclude that an all-digital nuclear medicine department is practical, cost effective, and beneficial to both patients and staff.

Analog-Digital Conversion↗

Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling.

Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n = 40), normal lung specimens (n = 4), normal pleura specimens (n = 5), and MPM and SV40-immortalized mesothelial cell lines (n = 5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma that correlated loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (ie, software) to create and explore complex physiological pathways. Combined, all of these data may advance our understanding of mesothelioma tumorigenesis, pathobiology, or both.

Blotting, Western↗

Distinguishing plant and fungal sequences in ESTs from infected plant tissues.

Expressed sequence tags (ESTs) from fungal-infected plant tissues are composed of a mixture of plant and fungal sequences. Using freely available software and tools, a novel procedure is described for distinguishing plant and fungal DNA sequences. Although the GenBank non-redundant (NR) database is larger and therefore one would presume that BLASTX analysis of it would be more accurate, superior resolution of 700 randomly selected fungal ESTs was found with Standalone TBLASTX analyses with a local matching database composed of a plant and a fungal genome. Standalone TBLASTX analyses of 3,983 ESTs from nine different fungal-infected plant EST libraries also proved to be superior in identifying the origin of sequences as either plant or fungal compared to GenBank BLASTX analysis. Standalone TBLASTX with a matching database comprised of a single plant and a single fungal genome appears to be a faster and more accurate method than BLASTX searches of the GenBank non-redundant database to distinguish fungal and plant sequences in mixed EST collections.

DNA, Fungal↗

Design and implementation of a PC-based image-guided surgical system.

In interactive, image-guided surgery, current physical space position in the operating room is displayed on various sets of medical images used for surgical navigation. We have developed a PC-based surgical guidance system (ORION) which synchronously displays surgical position on up to four image sets and updates them in real time. There are three essential components which must be developed for this system: (1) accurately tracked instruments; (2) accurate registration techniques to map physical space to image space; and (3) methods to display and update the image sets on a computer monitor. For each of these components, we have developed a set of dynamic link libraries in MS Visual C++ 6.0 supporting various hardware tools and software techniques. Surgical instruments are tracked in physical space using an active optical tracking system. Several of the different registration algorithms were developed with a library of robust math kernel functions, and the accuracy of all registration techniques was thoroughly investigated. Our display was developed using the Win32 API for windows management and tomographic visualization, a frame grabber for live video capture, and OpenGL for visualization of surface renderings. We have begun to use this current implementation of our system for several surgical procedures, including open and minimally invasive liver surgery.

Algorithms↗

Designing and implementing E-health Applications in the UK's National Health Service.

Telemedicine/e-health applications have the potential to play an important role in Britain's National Health Service (NHS), including the NHS in Scotland. The Scottish Telemedicine Action Forum (STAF) was established by the Scottish Executive Department of Health in 1999 to take a range of applications, targeted on national priorities, into routine service. In the process it has provided insights into how advanced information and communication technologies (ICTs) can be moved from the research stage into routine service. In this article four of the projects are described and analysed focusing on the key issues that have emerged as critical for carrying projects successfully through to implementation in service as follows: 1. A multisite videoconferencing network linking 15 minor injury units to the main accident and emergency (A&E) centre. 2. A single-site neonatal intensive care "cotside" laptop system to assist communication between parents and clinical staff. 3. A single-site outpatient chronic disease management system. 4. A multisite software audit tool to support the care of cleft lip and palate patients from birth onward.

Humans↗

From a phylogenetic tree to a reticulated network.

In many phylogenetic problems, assuming that species have evolved from a common ancestor by a simple branching process is unrealistic. Reticulate phylogenetic models, however, have been largely neglected because the concept of reticulate evolution have not been supported by using appropriate analytical tools and software. The reticulate model can adequately describe such complicated mechanisms as hybridization between species or lateral gene transfer in bacteria. In this paper, we describe a new algorithm for inferring reticulate phylogenies from evolutionary distances among species. The algorithm is capable of detecting contradictory signals encompassed in a phylogenetic tree and identifying possible reticulate events that may have occurred during evolution. The algorithm produces a reticulate phylogeny by gradually improving upon the initial solution provided by a phylogenetic tree model. The new algorithm is compared to the popular SplitsGraph method in a reanalysis of the evolution of photosynthetic organisms. A computer program to construct and visualize reticulate phylogenies, called T-Rex (Tree and Reticulogram Reconstruction), is available to researchers at the following URL: www.fas.umontreal.ca/biol/casgrain/en/labo/t-rex.

Algorithms↗

HAGR: the Human Ageing Genomic Resources.

The Human Ageing Genomic Resources (HAGR) is a collection of online resources for studying the biology of human ageing. HAGR features two main databases: GenAge and AnAge. GenAge is a curated database of genes related to human ageing. Entries were primarily selected based on genetic perturbations in animal models and human diseases as well as an extensive literature review. Each entry includes a variety of automated and manually curated information, including, where available, protein-protein interactions, the relevant literature, and a description of the gene and how it relates to human ageing. The goal of GenAge is to provide the most complete and comprehensive database of genes related to human ageing on the Internet as well as render an overview of the genetics of human ageing. AnAge is an integrative database describing the ageing process in several organisms and featuring, if available, maximum life span, taxonomy, developmental schedules and metabolic rate, making AnAge a unique resource for the comparative biology of ageing. Associated with the databases are data-mining tools and software designed to investigate the role of genes and proteins in the human ageing process as well as analyse ageing across different taxa. HAGR is freely available to the academic community at http://genomics.senescence.info.

Aging↗

Visualizing plant development and gene expression in three dimensions using optical projection tomography.

A deeper understanding of the mechanisms that underlie plant growth and development requires quantitative data on three-dimensional (3D) morphology and gene activity at a variety of stages and scales. To address this, we have explored the use of optical projection tomography (OPT) as a method for capturing 3D data from plant specimens. We show that OPT can be conveniently applied to a wide variety of plant material at a range of scales, including seedlings, leaves, flowers, roots, seeds, embryos, and meristems. At the highest resolution, large individual cells can be seen in the context of the surrounding plant structure. For naturally semitransparent structures, such as roots, live 3D imaging using OPT is also possible. 3D domains of gene expression can be visualized using either marker genes, such as beta-glucuronidase, or more directly by whole-mount in situ hybridization. We also describe tools and software that allow the 3D data to be readily quantified and visualized interactively in different ways.

Flowers↗