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BIAS: Bioinformatics Integrated Application Software.

MOTIVATION: We introduce a development platform especially tailored to Bioinformatics research and software development. BIAS (Bioinformatics Integrated Application Software) provides the tools necessary for carrying out integrative Bioinformatics research requiring multiple datasets and analysis tools. It follows an object-relational strategy for providing persistent objects, allows third-party tools to be easily incorporated within the system and supports standards and data-exchange protocols common to Bioinformatics. AVAILABILITY: BIAS is an OpenSource project and is freely available to all interested users at http://www.mcb.mcgill.ca/~bias/. This website also contains a paper containing a more detailed description of BIAS and a sample implementation of a Bayesian network approach for the simultaneous prediction of gene regulation events and of mRNA expression from combinations of gene regulation events. CONTACT: hallett@mcb.mcgill.ca.

Computational Biology↗

Development and adoption of a simple nonpoint source pollution model for Port Phillip Bay, Australia.

New computing tools and approaches allow tailored development of software to meet the needs of environmental managers. The processes required for such tailoring fit well with adaptive management concepts where, as knowledge and system understanding develop among managers, the software can be developed or replaced to match. This paper reports on development and adoption of a simple nonpoint source pollution modeling tool, including technical aspects of data support for modeling and social aspects of software design. The software, named FILTER, used a unit load model to generate expected pollutant loads from subcatchments of Port Phillip Bay, Australia. Monitoring data were used for calibration to modify the delivery of generated pollutants to receiving waters. Spatial, tabular, and charting software components were used to provide alternative forms of output visualization. FILTER was developed using a process that resulted in manager-stakeholders taking responsibility for setting of model parameter values and operation of the user interface, thereby encouraging uptake. The inclusive development process, tailoring of the software to manager needs and styles of usage, and matching of model complexity to data and knowledge, resulted in a successful application that has become the current agreed system representation among disparate stakeholder organizations.

Australia↗

Development of a controlled vocabulary and software application to analyze fruit shape variation in tomato and other plant species.

The domestication and improvement of fruit-bearing crops resulted in a large diversity of fruit form. To facilitate consistent terminology pertaining to shape, a controlled vocabulary focusing specifically on fruit shape traits was developed. Mathematical equations were established for the attributes so that objective, quantitative measurements of fruit shape could be conducted. The controlled vocabulary and equations were integrated into a newly developed software application, Tomato Analyzer, which conducts semiautomatic phenotypic measurements. To demonstrate the utility of Tomato Analyzer in the detection of shape variation, fruit from two F2 populations of tomato (Solanum spp.) were analyzed. Principal components analysis was used to identify the traits that best described shape variation within as well as between the two populations. The three principal components were analyzed as traits, and several significant quantitative trait loci (QTL) were identified in both populations. The usefulness and flexibility of the software was further demonstrated by analyzing the distal fruit end angle of fruit at various user-defined settings. Results of the QTL analyses indicated that significance levels of detected QTL were greatly improved by selecting the setting that maximized phenotypic variation in a given population. Tomato Analyzer was also applied to conduct phenotypic analyses of fruit from several other species, demonstrating that many of the algorithms developed for tomato could be readily applied to other plants. The controlled vocabulary, algorithms, and software application presented herein will provide plant scientists with novel tools to consistently, accurately, and efficiently describe two-dimensional fruit shapes.

Algorithms↗

The coming commoditization of processes.

Despite the much-ballyhooed increase in outsourcing, most companies are in do-it-yourself mode for the bulk of their processes, in large part because there's no way to compare outside organizations' capabilities with those of internal functions. Given the lack of comparability, it's almost surprising that anyone outsources today. But it's not surprising that cost is by far companies' primary criterion for evaluating outsourcers or that many companies are dissatisfied with their outsourcing relationships. A new world is coming, says the author, and it will lead to dramatic changes in the shape and structure of corporations. A broad set of process standards will soon make it easy to determine whether a business capability can be improved by outsourcing it. Such standards will also help businesses compare service providers and evaluate the costs versus the benefits of outsourcing. Eventually these costs and benefits will be so visible to buyers that outsourced processes will become a commodity, and prices will drop significantly. The low costs and low risk of outsourcing will accelerate the flow of jobs offshore, force companies to reassess their strategies, and change the basis of competition. The speed with which some businesses have already adopted process standards suggests that many previously unscrutinized areas are ripe for change. In the field of technology, for instance, the Carnegie Mellon Software Engineering Institute has developed a global standard for software development processes, called the Capability Maturity Model (CMM). For companies that don't have process standards in place, it makes sense for them to create standards by working with customers, competitors, software providers, businesses that processes may be outsourced to, and objective researchers and standard-setters. Setting standards is likely to lead to the improvement of both internal and outsourced processes.

Commerce↗

Investigation of transfusion reactions through microcomputer education software.

The purpose of this study was to develop educational software to simulate laboratory investigation of transfusion reactions. An interactive, branching-style program was developed using a 256K Personal Computer (International Business Machines, Boca Raton, FL). Over 75 institutions in the United States and Canada are currently using the software in preprofessional and continuing professional education programs.

Journal Article↗

Evaluation of educational software.

Evaluation is an important component of developing educational software. Ideally, such evaluation quantifies and qualifies the effects of a new educational intervention on the learning process and outcomes. Conducting meaningful and rigorous educational evaluation is difficult, however. Challenges include defining and measuring educational outcomes, accounting for media effects, coping with practical problems in designing studies, and asking the right research questions. Practical considerations that make the design of evaluation studies difficult include confounding, potentially small effect sizes, contamination effects, and ethics. Two distinct approaches to evaluation are objectivist and subjectivist. These two complement each other in describing the whole range of effects a new educational program can have. Objectivist demonstration studies should be preceded by measurement studies that assess the reliability and validity of the evaluation instrument(s) used. Many evaluation studies compare the performance of learners who are exposed to either the new program or a more traditional approach. However, this method is problematic because test or exam performance is often a weak indicator of competence and may fail to capture important nuances in outcomes. Subjectivist studies are more qualitative in nature and may provide insights complementary to those gained with objectivist studies. Several published examples are used in this article to illustrate different evaluation methods. Readers are encouraged to contemplate a wide range of evaluation study designs and explore increasingly complex questions when evaluating educational software.

Computer Simulation↗

Development of a non-radiographic cephalometric system.

The purpose of the present study was to develop a three-dimensional (3D) non-radiographic cephalometric system based on Simon's three planes. In pursuit of cephalometry without irradiation of patients, readiness of data and simplicity of the system, a portable 3D computer-aided, contact-method cephalometric system, equipped with newly developed cephalometric software for chairside use, was developed. The feasibility of its clinical use was examined based on comparison of the measurements obtained with those from conventional radiographic cephalometry on a human dry skull, as well as on three living subjects. From a total of nine measurements, a statistically significant difference was seen in six measurements: FMPA, U1/FH, FMIA, ANB, IMPA, and A-Np for the dry skull; in four measurements: FPA, FMPA, U1/FH, and Pog-Np for subject A; in five measurements: FMPA, U1/FH, FMIA, AN/FH, and A-Np for subject B; and in seven measurements: FMA, FMPA, U1/FH, FMIA, ANB, IMPA, and AN/FH for subject C. A clinically significant difference was found only in one measurement, U1/FH for the dry skull, in four measurements FPA, FMPA, U1/FH, and Pog-Np for subject A, in one measurement AN/FH for subject B, and in three measurements U1/FH, FMIA, and AN/FH for subject C. While demonstrating workability as a chairside tool and whilst there is a need for further refinement in measurement accuracy, this newly developed cephalometric system shows potential applicability, not only in the clinic as an auxiliary to or as a substitute for existing radiographic cephalometry, but also outside the clinic as an epidemiological tool.

Algorithms↗

The SPOCC (Selective Procedures, Operative Cases, and Consults) program as an advance in orthopaedic resident record keeping.

This paper outlines the development and use of a software package developed at the University of New Mexico that allows residents to use a simple menu driven program for record keeping. Selective Procedures, Operative Cases, and Consults (SPOCC) was developed for recording data in individually arranged formats and searching on a number of input parameters. As Residency Review Committees become more stringent in their demand for documentation of activities, this program will give residents the ability to quickly recall any number of selective procedures, consults or operative cases, along with case specific data to enable them to review cases, study results in relation to future follow-up, generate statistics, and stimulate research ideas. SPOCC can be run on any dual floppy or hard disk personal computer that uses MS-DOS or PC-DOS 2.0 or greater. It requires 256 kilobytes of free memory, and a color or monochrome monitor. A printer is optional.

Documentation↗

Recent developments in the PHENIX software for automated crystallographic structure determination.

A new software system called PHENIX (Python-based Hierarchical ENvironment for Integrated Xtallography) is being developed for the automation of crystallographic structure solution. This will provide the necessary algorithms to proceed from reduced intensity data to a refined molecular model, and facilitate structure solution for both the novice and expert crystallographer. Here, the features of PHENIXare reviewed and the recent advances in infrastructure and algorithms are briefly described.

Algorithms↗

Analyzing irregular working hours: lessons learned in the development of RAS 1.0--The Representation and Analysis Software.

Actual working hours of employees vary widely, especially in the transportation industry. We developed a tool, the RAS (Representation and Analysis Software), to ease the assessment of such irregular hours and the transfer of existing knowledge of proper schedule design to the problem of irregular hours. This article discusses several critical design questions that were addressed during software development in order for it to assess irregular work patterns, including the (1) importance, in spite of a lack of established definitions, of basic concepts like, e.g., night shift, (2) difficulty of modeling and adapting existing knowledge on proper design, and (3) large number of analytical methods and additional data beyond company schedule that are necessary to meet the needs of various research groups. This article describes how the RAS addresses these three issues by illustrating its application to the work schedule of a train driver involved in the Hinton train disaster.

Employment↗

PET/CT: panacea, redundancy, or something in between?

In the past decade, the integration of anatomic imaging and functional imaging has emerged as a new and promising diagnostic tool. Developments in software provided methods to integrate various modalities, such as PET, CT, MRI, and MR spectroscopy. The introduction of combined PET/CT scanners has boosted image fusion in this specific field and raised high expectations. Image fusion can be performed at 3 different levels: visual fusion, software fusion, and hardware fusion, each having strengths, weaknesses, and issues inherent to technique. Visual fusion is the traditional side-by-side reviewing of 2 separate modalities. Software image fusion provides evaluation of 2 modalities in 1 integrated image set. True hardware fusion of PET and CT does not exist at present. Currently, hardware fusion refers to a PET/CT scanner that consists of separate scanners, which positioned in line at a fixed distance, with projection of the PET image over the CT image. The suggested superiority of hardware fusion with these so-called hybrid PET/CT scanners over software fusion has sparked debate. Because scientific data that unequivocally show that state-of-the-art software fusion is less accurate than hardware fusion (as provided in hybrid PET/CT scanners) are unavailable, the primacy of a combined PET/CT scanner over stand-alone PET and CT is more a matter of belief than of science. Further research comparing the overall performance of PET/CT scanners with that of separate scanners with software for image fusion is much needed. The continuous development of better software for image fusion and respiratory and cardiac gating is also needed, not only for PET and CT imaging but also for fusion of PET with MRI and CT with MRI.

Artifacts↗

A new plug-in software architecture applied for a portable molecular structure browser.

A new software configuration method using plug-in style components was established for the tool with the incremental development of software used in protein structural study. Our memory database provides the interface of data and functions among plug-in modules and its host program. A molecular structure browser program was developed together with several plug-in modules on our programming library that maintains graphics portability and user interfaces. This plug-in software architecture is generally useful for large-scale software development and for prototyping parts of the system.

Computer Graphics↗

[A software program for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) with oxygen-sensitive (3)He-MRI].

PURPOSE: To develop a software tool for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) as well as its time course during apnea. MATERIAL AND METHODS: T (1)-relaxation times of hyperpolarized (3)He are reduced by paramagnetic oxygen rendering (3)He-MRI sensitive to oxygen and thus allowing the assessment of the local oxygen partial pressure in the pulmonary airspaces. Oxygen-related relaxation and loss of polarization by RF-excitation can be discriminated by acquiring two image series with varying interscan delay and/or flip angles. Software was developed to calculate the p(A)O(2) and the decay rate in user-defined regions of interest (ROIs) automatically. Moreover, parameter maps can be calculated. In addition to the analysis of 2-dimensional data sets, the software allows the evaluation of 3-dimensional measurements for the first time. Artifacts due to lung motion were reduced by implementing a motion correction algorithm. RESULTS: The software was successfully applied to data sets from healthy volunteers and from patients with various lung diseases. The parameter maps demonstrated a more homogeneous distribution of p(A)O(2) for the volunteers than for the patients. A regional increase in p(A)O(2) was found in a few patients. CONCLUSION: The described software allows the absolute quantification of p(A)O(2) as well as its variation over time. In the future, therefore, the software may gain importance for detecting mismatches between ventilation and perfusion, e. g., in patients with pulmonary embolism or chronic obstructive lung diseases.

Adult↗

MEGA2: molecular evolutionary genetics analysis software.

UNLABELLED: We have developed a new software package, Molecular Evolutionary Genetics Analysis version 2 (MEGA2), for exploring and analyzing aligned DNA or protein sequences from an evolutionary perspective. MEGA2 vastly extends the capabilities of MEGA version 1 by: (1) facilitating analyses of large datasets; (2) enabling creation and analyses of groups of sequences; (3) enabling specification of domains and genes; (4) expanding the repertoire of statistical methods for molecular evolutionary studies; and (5) adding new modules for visual representation of input data and output results on the Microsoft Windows platform. AVAILABILITY: http://www.megasoftware.net. CONTACT: s.kumar@asu.edu

DNA↗

A modular software system for computer-aided surgery and its first application in oral implantology.

Development of complex software applications in image guided therapy (IGT) is often complicated by the fact that providing basic functionality for image processing and user interaction from a graphical user interfaces (GUI) requires considerable manpower for software development. We present a programming environment that combines the high-level image processing library AVW, in-house developed patient-to-image registration procedures, and an interface to position measurement hardware. A specific application can be developed by using Tcl/Tk, a simple platform-independent scripting language, for GUI development. This environment was applied to developing VISIT, a navigation system for computer-aided implant dentistry. VISIT is presented as a result of this paper. Parts of the development environment were made accessible to the public. Future work includes the implementation of video input for connecting ultrasound or fluoroscopy units. We conclude that our approach is well suited to accelerate the development of exploratory new applications of IGT.

Dental Implantation↗

Multiple spatially distributed stimulators and timing programs for entrainment of activation during ventricular fibrillation.

Activation sequences during ventricular fibrillation (VF) display complex pattern and fast rate. Recent evidence suggests that even during VF an excitable gap may exist. Existence of excitable gap lead us to hypothesize that it should be possible to entrain activation patterns during VF by using spatially distributed and temporally phased pacing strength stimuli. We describe here the electronics hardware and software that were developed to test our hypothesis. Eight biphasic stimulators were designed and fabricated, each addressable via a TTL input and thus independently triggered. To minimize electrical interference from stimulus pulses the stimulators were optically isolated. A program written in C was used to deliver TTL inputs to time the sequence of stimulation. The parameters that could be varied were, pulse intensity, polarity, and duration, inter pulse interval and activation pattern cycle length. Restitution's of action potential duration, conduction velocity, and complex activation patterns make the timing of stimulators complex. To aid in optimal timing of these stimulators, we used a Luo-Rudy ionic model of cellular activation to simulate VF in a matrix of 400 x 400 cells. Entrainment of activation was verified using animated displays of activation sequences. Using results of simulation we verified the function of our stimulators experimentally using electrically induced VF in canines and by using electrograms recorded from 121-electrode patch. Our results show that the developed hardware and software can be used to deliver distributed stimuli in a flexible and effective pattern, which may aid in development of approaches for treatment of VF.

Animals↗

Quantitative image analysis: software systems in drug development trials.

Multi-dimensional image analysis is being used increasingly to arrive at surrogate end-points for drug development trials. Various imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound are used to analyze treatments for diseases such as cancer, multiple sclerosis, osteoarthritis, and Alzheimer's disease. However, extracting information from images can be tedious and is prone to high user variability. The medical image analysis community is moving towards advanced software systems specifically designed for drug development trials. These systems can automatically identify the anatomy of interest in medical images (segmentation methods), can compare the anatomy over time or between patients (registration methods) and allow the quantitative extraction of anatomical features and the integration of the data and results into a database management system, automatically tracking the changes made to the data (audit trail generation). In this article, we present a case study using a prototype system that is used for quantifying multiple sclerosis lesions from multivariate MRI.

Clinical Trials as Topic↗