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Computer based program for rapid canine rabies diagnosis.

Rabies post exposure treatment and rapid diagnosis in an endemic area requires skillful and an experienced medical staff and veterinary specialists. A software program was introduced in 2000 as a tool to diagnose rabies based on clinical symptoms and signs of suspicious dogs where veterinarian service and other laboratory diagnostic options are not immediately available. It is easily accessed from the website: www.soonak.com/rabies.

Algorithms↗

Laboratory information system test environment: validate upgrades, prevent disasters, and assist training.

A laboratory information system (LIS) test environment allows the laboratory to run and test programs without affecting the current production environment. This is essential for successfully introducing system enhancements and upgrades because it allows the LIS manager to uncover software errors before introducing them into the actual LIS system. A test environment is also a useful tool for training employees. In addition, a test environment enables laboratories to validate software before use in the live environment, which will probably be required by the Food and Drug Administration and the Health Care Financing Administration inspectors now that LISs are considered medical devices. This article examines the benefits, uses, and limitations of an LIS test environment; discusses the computer resources required; and explores the process of installing and validating a software release.

Clinical Laboratory Information Systems↗

Multimodality image registration quality assurance for conformal three-dimensional treatment planning.

PURPOSE: We present a quality assurance methodology to determine the accuracy of multimodality image registration and fusion for the purpose of conformal three-dimensional and intensity-modulated radiation therapy treatment planning. Registration and fusion accuracy between any combination of computed tomography (CT), magnetic resonance (MR), and positron emission computed tomography (PET) imaging studies can be evaluated. METHODS AND MATERIALS: A commercial anthropomorphic head phantom filled with water and containing CT, MR, and PET visible targets was modified to evaluate the accuracy of multimodality image registration and fusion software. For MR and PET imaging, the water inside the phantom was doped with CuNO(3) and 18F-fluorodeoxyglucose (18F-FDG), respectively. Targets consisting of plastic spheres and pins were distributed throughout the cranium section of the phantom. Each target sphere had a conical-shaped bore with its apex at the center of the sphere. The pins had a conical extension or indentation at the free end. The contours of the spheres, sphere centers, and pin tips were used as anatomic landmark models for image registration, which was performed using affine coordinate-transformation tools provided in a commercial multimodality image registration/fusion software package. Four sets of phantom image studies were obtained: primary CT, secondary CT with different phantom immobilization, MR, and PET study. A novel CT, MR, and PET external fiducial marking system was also tested. RESULTS: The registration of CT/CT, CT/MR, and CT/PET images allowed correlation of anatomic landmarks to within 2 mm, verifying the accuracy of the registration software and spatial fidelity of the four multimodality image sets. CONCLUSIONS: This straightforward phantom-based quality assurance of the image registration and fusion process can be used in a routine clinical setting or for providing a working image set for development of the image registration and fusion process and new software.

Head and Neck Neoplasms↗

MAVIS: an interactive visualization tool for computational chemistry calculations in a distributed networked environment.

This paper describes the software package, MAVIS (Molecular Animation and VI-sualization System), which was developed as a collaborative project between the University of Manchester Department of Chemistry and the Manchester Visualization Centre as a tool for the visualization of chemical systems and their properties and for the generation, submission, monitoring and study of results from calculations in a networked computing environment. MAVIS has been developed using AVS, a general visualization environment, as a suite of modules which can be extended with relative ease. Using the AVS system gives the application the power and flexibility of a general system with no requirement for the programmer to understand many of the complexities involved in modern image rendering systems and allowing them to concentrate upon the features of the functionality and the user interface. It also allows the code to be as portable between platforms as the AVS package itself and so it is available on a wide range of systems.

Chemistry, Organic↗

PBAT: a comprehensive software package for genome-wide association analysis of complex family-based studies.

The PBAT software package (v2.5) provides a unique set of tools for complex family-based association analysis at a genome-wide level. PBAT can handle nuclear families with missing parental genotypes, extended pedigrees with missing genotypic information, analysis of single nucleotide polymorphisms (SNPs), haplotype analysis, quantitative traits, multivariate/longitudinal data and time to onset phenotypes. The data analysis can be adjusted for covariates and gene/environment interactions. Haplotype-based features include sliding windows and the reconstruction of the haplotypes of the probands. PBAT's screening tools allow the user successfully to handle the multiple comparisons problem at a genome-wide level, even for 100,000 SNPs and more. Moreover, PBAT is computationally fast. A genome scan of 300,000 SNPs in 2,000 trios takes 4 central processing unit (CPU)-days. PBAT is available for Linux, Sun Solaris and Windows XP.

Family↗

Animated simulation: a valuable decision support tool for practice improvement.

Animated computer simulation is a powerful tool for healthcare operation improvement. As a decision support tool, it offers a systematic method to compare alternative approaches to healthcare operations. Because staff interaction is encouraged by this tool, simulation projects facilitate staff team building and process change ownership. Information that is not used as applied knowledge for the purpose of improvement is worthless. Simulation offers management detailed knowledge of processes, enabling management to make better-informed decisions by providing performance data, such as resource usage rates, patient wait times, capacity rates, and process performance information. Alternatives under consideration can be compared and modified without high financial, personal, and customer costs to the healthcare operation. The knowledge gained from each alternative's simulation response variables can be evaluated against set criteria, the status quo, and each other to determine the best option. Current automation systems and software products allow decision makers to use this tool without investing resources in errant options. A simulation project strategy with examples and a case study of change and renovation of a family practice clinic are provided.

Community Health Services↗

Construction of integrated case environments.

The main goal of Computer-Aided Software Engineering (CASE) technology is to improve the entire software system development process. The CASE approach is not merely a technology; it involves a fundamental change in the process of software development. The tendency of the CASE approach, technically speaking, is the integration of tools that assist in the application of specific methods. In this sense, the environment architecture, which includes the platform and the system's hardware and software, constitutes the base of the CASE environment. The problem of tools integration has been proposed for two decades. Current integration efforts emphasize the interoperability of tools, especially in distributed environments. In this work we use the Brown approach. The environment resulting from the application of this model is called a federative environment, focusing on the fact that this architecture pays special attention to the connections among the components of the environment. This approach is now being used in component-based design. This paper describes a concrete experience in civil engineering and architecture fields, for the construction of an integrated CASE environment. A generic architectural framework based on an intermediary architectural pattern is applied to achieve the integration of the different tools. This intermediary represents the control perspective of the PAC (Presentation-Abstraction-Control) style, which has been implemented as a Mediator pattern and it has been used in the interactive systems domain. In addition, a process is given to construct the integrated CASE.

Journal Article↗

Evaluating protein structures determined by structural genomics consortia.

Structural genomics projects are providing large quantities of new 3D structural data for proteins. To monitor the quality of these data, we have developed the protein structure validation software suite (PSVS), for assessment of protein structures generated by NMR or X-ray crystallographic methods. PSVS is broadly applicable for structure quality assessment in structural biology projects. The software integrates under a single interface analyses from several widely-used structure quality evaluation tools, including PROCHECK (Laskowski et al., J Appl Crystallog 1993;26:283-291), MolProbity (Lovell et al., Proteins 2003;50:437-450), Verify3D (Luthy et al., Nature 1992;356:83-85), ProsaII (Sippl, Proteins 1993;17: 355-362), the PDB validation software, and various structure-validation tools developed in our own laboratory. PSVS provides standard constraint analyses, statistics on goodness-of-fit between structures and experimental data, and knowledge-based structure quality scores in standardized format suitable for database integration. The analysis provides both global and site-specific measures of protein structure quality. Global quality measures are reported as Z scores, based on calibration with a set of high-resolution X-ray crystal structures. PSVS is particularly useful in assessing protein structures determined by NMR methods, but is also valuable for assessing X-ray crystal structures or homology models. Using these tools, we assessed protein structures generated by the Northeast Structural Genomics Consortium and other international structural genomics projects, over a 5-year period. Protein structures produced from structural genomics projects exhibit quality score distributions similar to those of structures produced in traditional structural biology projects during the same time period. However, while some NMR structures have structure quality scores similar to those seen in higher-resolution X-ray crystal structures, the majority of NMR structures have lower scores. Potential reasons for this "structure quality score gap" between NMR and X-ray crystal structures are discussed.

Computational Biology↗

Computer-assisted teaching and learning in medicine.

Induced mainly by the increased spreading of personal computers in the last few years computer-assisted instruction (CAI) systems for medicine have been developed on a large scale. Proven structure principles are above all the simulation of patient management in a problem-orientated approach, the mathematical simulation of (patho-) physiological functions independent of particular patients and the separation of educational mode and scoring mode. There exists already a large choice in programs dealing with topics of internal medicine--especially cardiology--while operative disciplines are less represented so far. Programs accredited in the US for continuing medical education (CME) are usually of high quality as to medical contents. Other important quality criteria to be mentioned concerning simulation programs are algorithms of medical decision making, completeness and refinement of the medical knowledge base, software design and user interface. CAI is a unique tool to enhance clinical problem solving skills although--of course--it can by no means replace bedside teaching.

Computer-Assisted Instruction↗

Precision of periprosthetic bone mineral density measurements using Hologic Windows versus DOS-based analysis software.

Dual energy X-ray absorptiometry (DXA) is a precise tool for measuring bone mineral density (BMD) around total joint prostheses. The Hologic "metal-removal hip" analysis package (Hologic Inc., Waltham, MA) is a Microsoft DOS-based analysis platform that has undergone a change in the operating platform to a Microsoft Windows-based system that has also incorporated changes to DXA image manipulation on-screen. We evaluated the impact of these changes on instrument precision by analysis of sequential DXA scans taken on the same day using the Hologic QDR-4500A fan beam densitometer (Hologic Inc.) in 29 subjects after total hip arthroplasty. The coefficient of variation percentage (CV%) for the net pelvic region was 3.04 for Windows versus 2.36 for DOS (p>0.05). The CV% for the net femoral region was 1.75 for Windows versus 1.51 for DOS (p>0.05). Absolute BMD values for the net pelvic and net femoral regions were similar (Bland-Altman, Windows minus DOS; pelvic region mean=-1.0%; femoral region mean=1.3%; p>0.05 for both comparisons). Our results suggest that scans analyzed using each platform may be used interchangeably without the need for a calibration correction.

Absorptiometry, Photon↗

MD@: a physician-friendly decision analysis tool.

The cost-effective use of medical resources is increasingly important in justifying strategies for medical diagnosis and management. Although some software is available to help with decision analysis, it can be difficult to use these tools for medical applications. We have developed a prototype package for modeling various medical decision strategies, which can be used with a Macintosh or Windows-based personal computer. The system is graphically based, intuitive, and user-friendly. The user constructs decision trees for comparing alternative strategies for diagnosis and management. Selecting blocks from a library, the user sets mean values for variables such as prevalence, sensitivity, specificity, cost, morbidity, and mortality. The system then generates the probabilities of various pathways, using Bayesian analysis, without requiring the user to enter equations. It displays the best strategy in terms of a particular criterion and, when appropriate, performs sensitivity analysis.

Decision Support Techniques↗

The reengineering of a software system for glaucoma analysis.

Glaucoma is a destructive eye disease that causes blindness in individuals displaying little or no symptoms. There is no cure as yet though there are treatments that can arrest its effects or slow its development. The earlier the disease is detected, the more likely the treatment will be successful; however early detection of the disease can be difficult. This highlights the importance of ophthalmologists having access to tools that can assist in accurately diagnosing glaucoma and other retinal diseases as early as possible. The stereo optic disc analyser (SODA) software package is a tool intended to be used by ophthalmologists, to aid in the accurate detection of retinal diseases. SODA will use stereoscopy and three-dimensional image analysis to assist in accurately detecting changes in the retina, caused by diseases such as glaucoma. This paper will focus on the reengineering and redesign of the SODA software package to overcome the shortcomings inherent in its prototype implementation and develop a package that can be commercialised. Software Engineering principles and the software development lifecycle, along with principles of object-orientation and usability, have been used to establish a framework for SODA, improve its accuracy, enhance its usability and to redevelop the product into an implementation that can later be commercialised.

Color↗

The UMD-LDLR database: additions to the software and 490 new entries to the database.

Mutations in the LDL receptor gene (LDLR) cause familial hypercholesterolemia (FH), one of the most frequent hereditary dominant disorders. The protein defect was identified in 1973, the gene was localized by in situ hybridization in 1985, and since, a growing number of mutations have been reported. The UMD-LDLR database is customized software that has been developed to list all mutations, and also to provide means to analyze them at the nucleotide and protein levels. The database has been recently modified to fulfill the recommendations of the Nomenclature Working Group for human gene mutations. However, in the current version, both the nomenclature and usual LDLR gene mutation names are reported since the latter are more commonly used. The software has also been modified to accommodate the splicing mutations and alleles that carry two nucleotide variations. The current version of UMD-LDLR contains 840 entries, of which 490 are new entries. Point mutations account for 90% of all mutations in the LDLR gene; the remaining are mostly major rearrangements, due to the presence of Alu sequences. Three new routines have been implemented in the software, thus giving users access to 13 sorting tools. In addition to the database, a Web site containing information about polymorphisms, major rearrangements, and promoter mutations is available. Both are accessible to the scientific community (www.umd.necker.fr) and should help groups working on LDLR to check their mutations and identify new ones, and greatly facilitate the understanding of functional classes/genotype relationships and of genotype/phenotype correlations.

Databases, Genetic↗

Analyze: a comprehensive, operator-interactive software package for multidimensional medical image display and analysis.

A comprehensive software package, called ANALYZE, has been developed (1) which permits detailed investigation and evaluation of multidimensional biomedical images. ANALYZE can be used with 3-D imaging modalities based on x-ray computed tomography, radionuclide emission tomography, ultrasound tomography, and magnetic resonance imaging. The software is written entirely in "C" and runs on standard UNIX workstations. The ANALYZE package features integrated, complimentary tools for fully interactive display, manipulation and measurement of multidimensional image data. The software architecture permits systematic enhancements and upgrades which has fostered development of a readily expandable package. It provides an effective shell for custom software prototyping and turnkey applications. This paper provides a general description of this software as well as specific details on the methodology employed to develop it, both conceptual and technical. Applications of the software are illustrated.

Image Processing, Computer-Assisted↗

MASQOT-GUI: spot quality assessment for the two-channel microarray platform.

UNLABELLED: MASQOT-GUI provides an open-source, platform-independent software pipeline for two-channel microarray spot quality control. This includes gridding, segmentation, quantification, quality assessment and data visualization. It hosts a set of independent applications, with interactions between the tools as well as import and export support for external software. The implementation of automated multivariate quality control assessment, which is a unique feature of MASQOT-GUI, is based on the previously documented and evaluated MASQOT methodology. Further abilities of the application are outlined and illustrated. AVAILABILITY: MASQOT-GUI is Java-based and licensed under the GNU LGPL. Source code and installation files are available for download at http://masqot-gui.sourceforge.net/

Computer Graphics↗

Modeling and modification of medical 3D objects. The benefit of using a haptic modeling tool.

The Computer Laboratory of the medical faculty in Goteborg (Mednet) has since the end of 1998 been one of a limited numbers of participants in the development of a new modeling tool together with SensAble Technologies Inc [http:¿www.sensable.com/]. The software called SensAble FreeForm was officially released at Siggraph September 1999. Briefly, the software mimics the modeling techniques traditionally used by clay artists. An imported model or a user defined block of "clay" can be modified using different tools such as a ball, square block, scrape etc via the use of a SensAble Technologies PHANToM haptic arm. The model will deform in 3D as a result of touching the "clay" with any selected tool and the amount of deformation is linear to the force applied. By getting instantaneous haptic as well as visual feedback, precise and intuitive changes are easily made. While SensAble FreeForm lacks several of the features normally associated with a 3D modeling program (such as text handling, application of surface and bumpmaps, high-end rendering engines, etc) it's strength lies in the ability to rapidly create non-geometric 3D models. For medical use, very few anatomically correct models are created from scratch. However, FreeForm features tools enable advanced modification of reconstructed or 3D scanned models. One of the main problems with 3D laserscanning of medical specimens is that the technique usually leaves holes or gaps in the dataset corresponding to areas in shadows such as orifices, deep grooves etc. By using FreeForms different tools, these defects are easily corrected and gaps are filled out. Similarly, traditional 3D reconstruction (based on serial sections etc) often shows artifacts as a result of the triangulation and/or tessellation processes. These artifacts usually manifest as unnatural ridges or uneven areas ("the accordion effect"). FreeForm contains a smoothing algorithm that enables the user to select an area to be modified and subsequently apply any given amount of smoothing to the object. While the final objects need to be exported for further 3D graphic manipulation, FreeForm addresses one of the most time consuming problems of 3D modeling: modification and creation of non-geometric 3D objects.

Computer Simulation↗

Distant collaboration in drug discovery: the LINK3D project.

The work describes the development of novel software supporting synchronous distant collaboration between scientists involved in drug discovery and development projects. The program allows to visualize and share data as well as to interact in real time using standard intranets and Internet resources. Direct visualization of 2D and 3D molecular structures is supported and original tools for facilitating remote discussion have been integrated. The software is multiplatform (MS-Windows, SGI-IRIX, Linux), allowing for a seamless integration of heterogeneous working environments. The project aims to support collaboration both within and between academic and industrial institutions. Since confidentiality is very important in some scenarios, special attention has been paid to security aspects. The article presents the research carried out to gather the requirements of collaborative software in the field of drug discovery and development and describes the features of the first fully functional prototype obtained. Real-world testing activities carried out on this prototype in order to guarantee its adequacy in diverse environments are also described and discussed.

Computer Graphics↗

An interactive power analysis tool for microarray hypothesis testing and generation.

MOTIVATION: Human clinical projects typically require a priori statistical power analyses. Towards this end, we sought to build a flexible and interactive power analysis tool for microarray studies integrated into our public domain HCE 3.5 software package. We then sought to determine if probe set algorithms or organism type strongly influenced power analysis results. RESULTS: The HCE 3.5 power analysis tool was designed to import any pre-existing Affymetrix microarray project, and interactively test the effects of user-defined definitions of alpha (significance), beta (1-power), sample size and effect size. The tool generates a filter for all probe sets or more focused ontology-based subsets, with or without noise filters that can be used to limit analyses of a future project to appropriately powered probe sets. We studied projects from three organisms (Arabidopsis, rat, human), and three probe set algorithms (MAS5.0, RMA, dChip PM/MM). We found large differences in power results based on probe set algorithm selection and noise filters. RMA provided high sensitivity for low numbers of arrays, but this came at a cost of high false positive results (24% false positive in the human project studied). Our data suggest that a priori power calculations are important for both experimental design in hypothesis testing and hypothesis generation, as well as for the selection of optimized data analysis parameters. AVAILABILITY: The Hierarchical Clustering Explorer 3.5 with the interactive power analysis functions is available at www.cs.umd.edu/hcil/hce or www.cnmcresearch.org/bioinformatics. CONTACT: jseo@cnmcresearch.org

Algorithms↗