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Software agents in molecular computational biology.

Progress made in applying agent systems to molecular computational biology is reviewed and strategies by which to exploit agent technology to greater advantage are investigated. Communities of software agents could play an important role in helping genome scientists design reagents for future research. The advent of genome sequencing in cattle and swine increases the complexity of data analysis required to conduct research in livestock genomics. Databases are always expanding and semantic differences among data are common. Agent platforms have been developed to deal with generic issues such as agent communication, life cycle management and advertisement of services (white and yellow pages). This frees computational biologists from the drudgery of having to re-invent the wheel on these common chores, giving them more time to focus on biology and bioinformatics. Agent platforms that comply with the Foundation for Intelligent Physical Agents (FIPA) standards are able to interoperate. In other words, agents developed on different platforms can communicate and cooperate with one another if domain-specific higher-level communication protocol details are agreed upon between different agent developers. Many software agent platforms are peer-to-peer, which means that even if some of the agents and data repositories are temporarily unavailable, a subset of the goals of the system can still be met. Past use of software agents in bioinformatics indicates that an agent approach should prove fruitful. Examination of current problems in bioinformatics indicates that existing agent platforms should be adaptable to novel situations.

Algorithms↗

Collision detection and avoidance during treatment planning.

PURPOSE: To develop computer software that assists the planner avoid potential gantry collisions with the patient or patient support assembly during the treatment planning process. METHODS AND MATERIALS: The approach uses a simulation of the therapy room with a scale model of the treatment machine. Because the dimensions of the machine and patient are known, one can calculate a priori whether any desired therapy field is possible or will result in a collision. To assist the planner, we have developed a graphical interface enabling the accurate visualization of each treatment field configuration within a "room's eye view" treatment planning window. This enables the planner to be aware of, and alleviate any potential collision hazards. To circumvent blind spots in the graphic representation, an analytical software module precomputes whether each update of the gantry or turntable position is safe. RESULTS: If a collision is detected, the module alerts the planner and suggests collision evasive actions such as either an extended distance treatment or the gantry angle of closest approach. CONCLUSIONS: The model enables the planner to experiment with unconventional noncoplanar treatment fields, and immediately test their feasibility.

Computer-Aided Design↗

Three-dimensional computer-simulated prostate models: lateral prostate biopsies increase the detection rate of prostate cancer.

OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D) computer-assisted prostate biopsy simulator based on whole-mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. METHODS: We obtained digital images of 201 step-sectioned whole-mounted radical prostatectomy specimens. 3D computer simulation software was developed to accurately depict the anatomy of the prostate and all individual tumor foci. Additional peripheral devices were incorporated into the system to perform interactive prostate biopsies. We obtained 18 biopsies of each prostate model to determine the detection rates of various biopsy protocols. RESULTS: The 10- and 12-pattern biopsy protocols had a 99.0% detection rate; the traditional sextant biopsy protocol rate was only 72.6%. The 5-region biopsy protocol had a 90.5% detection rate and the 14-pattern, which includes all the biopsies used in the patterns above, only added 1 additional positive case (99.5%). Transitional zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. Only one positive model was obtained when the transitional zone biopsies were added. The lateral sextant pattern had a detection rate of 95.5%, and the 4-pattern lateral biopsy protocol had a 93.5% detection rate. CONCLUSIONS: Our results suggest that all the biopsy protocols that use laterally placed biopsies based on the 5-region anatomic model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.

Biopsy, Needle↗

IMBA Expert: internal dosimetry made simple.

In 1997, a collaboration between British Nuclear Fuels plc (BNFL), Westlakes Research Institute and NRPB started, with the aim of producing IMBA (Integrated Modules for Bioassay Analysis), a suite of software modules that implement the new ICRP models for estimation of intakes and doses. This was partly in response to new UK regulations, and partly due to the requirement for a unified approach in estimating intakes and doses from bioassay measurements within the UK. Over the past 5 years, the IMBA modules have been developed further, have gone through extensive quality assurance, and are now used for routine dose assessment by approved dosimetry services throughout the UK. More recently, interest in the IMBA methodology has been shown by the United States Department of Energy (USDOE), and in 2001 an ambitious project to develop a software package (IMBA Expert USDOE Edition) which would meet the requirements of all of the major USDOE sites began. Interest in IMBA Expert is now being expressed in many other countries. The aim of this paper is to outline the origin and evolution of the IMBA modules (the past); to describe the full capabilities of the current IMBA Expert system (the present) and to indicate possible future directions in terms of capabilities and availability (the future).

Computer Simulation↗

Improving the fit of press-fit hip stems.

The implant-bone fit is critical to the longevity of press-fit total hips. Maximum contact on the internal cortical bone surface, especially proximally, produces more normal strain values and reduces micromotion and sinkage. Stem design computer software was developed to design both individualized hip stems that maximize implant-bone contact for a unique anatomy, and average anatomic hip stems in which the mean error of fit is minimized for many patients. Cadaver femurs were used to test the following two hypotheses: (1) Average anatomic stems, designed using the optimal-fit software for an average femoral geometry, improve implant-bone fit when compared with standard stems; and (2) Individualized optimal-fit stems provide an even better fit than average anatomic stems. Results showed that the average anatomical stems fit better than the standard stems. However, the individualized hip stems, designed from individual three-dimensional geometry data, fit the best.

Aged↗

Computer assisted monitoring in intensive medicine.

Intensive Medicine is always associated with the problem of handling the mass and assuring the quality of information on vital signs, fluid and blood balance, laboratory data, physiological calculations, etc., required in patient care. A computer based monitoring system for intensive care was introduced in 1973 at the Academic Hospital in Leuven. The basic software was developed at the Peter Bent Brigham Hospital of the Harvard Medical School and the medical division of the Hewlett Packard Company; the computer used was a H.P. 2100 central processor with 32K of core memory. Initially, the program allowed mainly acquisition, storage and retrieval of bedside monitored and manual data of cardiac and circulatory function. Very soon however, the software was extended and modified by the division of "Medical Informatics" in order to meet new or different requirements. In the present situation our vision on the use of computer-assisted monitoring has changed and our present program has been extended as follows : 1. On-line collection and retrieval of bedside monitored data including heart rate, arterial blood pressure (systolic-diastolic-mean) left atrial pressure, central venous pressure, pulmonary artery pressure, intracranial pressure. Trend analysis of those data, with calculation of mean values, standard variation and corresponding t-tests. 2. Computer assistance in performing time consuming calculations on off-line data such as : -- clearance-values (renal function), -- temperature-correction of blood-gasvalues, -- hour-to-hour fluid balance, including calculation of in-sensible losses, -- blood-balance. 3. Data transmission of laboratory results as soon as available in the central laboratory through a direct link between laboratory and I.T.U. 4. Computer assisted E.C.G. analysis. The three first objectives are realised, on-line E.C.G.-analysis is being developed. The same computer serves the remotely located medical and coronary care units and one bed in the emergency department. An assessment of computer assistance in intensive therapy, on nursing labor and on quality of patient care is made.

Clinical Laboratory Techniques↗

HIVbase: a PC/Windows-based software offering storage and querying power for locally held HIV-1 genetic, experimental and clinical data.

BACKGROUND: Human immunodeficiency virus (HIV) research involves ongoing, repetitious sequencing of the HIV genome and the massive accumulation of associated investigational data. As a result, the storage of annotated DNA and/or protein sequences, as well as information retrieval, have become increasingly difficult tasks, with scientists extracting less information from their collected data than they should. OBJECTIVES: Our objective was to design and develop a software package to aid researchers in the storage, analysis and exploration of their HIV-associated data. RESULTS: HIVbase contains familiar, easy-to-use interfaces and functionality for integrating many types of disparate data. The software contains tools that allow for the mass import of raw genetic data, eliminate repetitious sequence translations, have the ability to identify automatically and store HIV regions of interest from nucleic acid or protein sequences, allow for the export of data in commonly used analysis-ready formats, and for unique querying approaches.

Algorithms↗

Non-invasive assessment of cardiovascular mechanics using a new, user-friendly software application.

Currently, in most non-invasive imaging laboratories, echocardiographic tracings are interpreted by "eyeballing" M-mode and 2-dimensional echocardiographic recordings. This subjective method of data analysis severely hampers the possibility of serial assessment of physiological interventions on cardiovascular disease states. Moreover, acquisition of important cardiovascular physiological data usually requires recordings of instantaneous aortic pressure and flow data that, until recently, could only be acquired invasively in the cardiac catheterization laboratory. Recently, our laboratory has developed and validated new "non-invasive" methods for the acquisition of aortic pressure and flow using calibrated subclavian pulse tracings and continuous wave aortic Doppler, respectively. With these limitations and new developments in mind, we developed new software that enables simultaneous non-invasive acquisition of left ventricular (LV) chamber geometry and aortic pressure and flow data. This new, user-friendly software in conjunction with other non-invasive tools allows non-invasive quantification of multiple cardiovascular physiological parameters. More importantly, the new software enables objective and serial assessment of multiple pharmacological interventions on various patients' disease states.

Aged↗

MRI quality control: six imagers studied using eleven unified image quality parameters.

Quality control of the magnetic resonance imagers of different vendors in the clinical environment is non-harmonised, and comparing the performance is difficult. The purpose of this study was to develop and apply a harmonised long-term quality control protocol for the six imagers in our organisation in order to assure that they fulfil the same basic image quality requirements. The same Eurospin phantom set and identical imaging parameters were used with each imager. Values of 11 comparable parameters describing the image quality were measured. Automatic image analysis software was developed to objectively analyse the images. The results proved that the imagers were operating at a performance level adequate for clinical imaging. Some deficiencies were detected in image uniformity and geometry. The automated analysis of the Eurospin phantom images was successful. The measurements were successfully repeated after 2 weeks on one imager and after half a year on all imagers. As an objective way of examining the image quality, this kind of comparable and objective quality control of different imagers is considered as an essential step towards harmonisation of the clinical MRI studies through a large hospital organisation.

Algorithms↗

Laser burn intensity and the risk for choroidal neovascularization in the CNVPT Fellow Eye Study.

OBJECTIVE: To explore the relationship between laser burn intensity and the subsequent risk for development of choroidal neovascularization (CNV) in eyes assigned to the treatment group of the Fellow Eye Study (FES) of the Choroidal Neovascularization Prevention Trial (CNVPT), using computerized methods for laser burn quantitation, and to examine the association between laser burn intensity and (1) drusen reduction and (2) visual acuity. METHODS: Color fundus images before and immediately after laser treatment in the CNVPT FES were available for 53 of 59 eyes. Prelaser and postlaser treatment images were analyzed using custom-developed computer software, allowing for laser burn identification and quantitation. As measures of laser burn intensity, we derived integrated burn rating (IBR) (the integral of the normalized intensity difference divided by the burn pixels), and the maximum burn intensity (MAX). We identified CNV using fluorescein angiography. A Cox proportional hazards model was fit to the time to development of CNV. Baseline and 6-month color photographs were used to determine reduction in drusen. Visual acuity was measured using a standardized protocol. RESULTS: The IBR and MAX spanned 4.5 logarithm units. After adjusting for smoking history and predominant drusen size, the risk ratio for CNV per logarithm unit of increasing laser burn intensity for each measure was 2.0 (P =.05) for MAX and 1.7 (P =.07) for IBR. When patients were divided into high- and low-intensity treatment groups of equal size, the high-intensity group had more drusen reduction (57% vs 32%; P =.14). There was no effect of laser intensity on change in visual acuity at 6 months. CONCLUSION: Higher-intensity prophylactic laser applications appear to be associated with a greater risk for development of CNV and with more extensive drusen reduction.

Choroidal Neovascularization↗

An adjustable fetal weight standard.

The monitoring of fetal weight is an important aspect of antenatal care. To construct an individually adjustable standard, we developed a model to link the predicted birth weight to a fetal weight curve which outlines how this weight is to be reached in an uncomplicated pregnancy. A formula was derived which describes the median fetal weight at each gestation as a proportion of the optimal term weight, and also defines the 90th and 10th centile curves as normal limits. We analyzed a birth weight database of 38,114 singleton, routine ultrasound-dated pregnancies resulting in term deliveries. By stepwise multiple regression analysis, we derived coefficients for the factors that act as variables on term birth weight in our population. Apart from gestational age and sex, the maternal height, weight at first visit, ethnic group, parity and smoking all have significant and independent effects on birth weight. The variation due to ethnic group appears to be physiological in this population. Smoking is associated with a reduction in birth weight, which is independent of maternal physique and related to the number of cigarettes per day as reported at the first visit. We have developed a software program which calculates, on the basis of pregnancy variables entered at the first visit, an adjusted normal range for fetal size. This can be printed out as a chart and used for antenatal surveillance of growth.

Birth Weight↗

Application of the new ISO 2631-5 to health hazard assessment of repeated shocks in U.S. Army vehicles.

The U.S. Army Aeromedical Research Laboratory conducted a research program to develop a new methodology for health hazard assessment of tactical ground vehicle rides. This paper describes the new method and compares the health risk prediction using the new multiple shocks standard International Standards Organization (ISO 2631-5) to predictions by the current whole-body vibration (WBV) standard (ISO 2631-1). This article also describes the software tool developed to implement both parts of ISO 2631, as well as Army Regulation 40-10. The comparison shows the new standard to be more sensitive to cross-country terrain than other standards. Data analysis demonstrates the applicability of the new ISO 2631-5 standard to tactical ground vehicles, especially in the vertical axis.

Automobile Driving↗

A versatile, inexpensive, intuitive and simple system for computer-assisted instruction in radiology.

A system for constructing courseware in Radiology is described. It uses widely available, inexpensive hardware and software to produce material that is versatile and easy to use. The computer-naive student readily interacts with both text and images. We briefly describe the hardware, the software, the development process, and the different prototype applications developed at this time.

Computer Graphics↗

Gene structure prediction and alternative splicing analysis using genomically aligned ESTs.

With the availability of a nearly complete sequence of the human genome, aligning expressed sequence tags (EST) to the genomic sequence has become a practical and powerful strategy for gene prediction. Elucidating gene structure is a complex problem requiring the identification of splice junctions, gene boundaries, and alternative splicing variants. We have developed a software tool, Transcript Assembly Program (TAP), to delineate gene structures using genomically aligned EST sequences. TAP assembles the joint gene structure of the entire genomic region from individual splice junction pairs, using a novel algorithm that uses the EST-encoded connectivity and redundancy information to sort out the complex alternative splicing patterns. A method called polyadenylation site scan (PASS) has been developed to detect poly-A sites in the genome. TAP uses these predictions to identify gene boundaries by segmenting the joint gene structure at polyadenylated terminal exons. Reconstructing 1007 known transcripts, TAP scored a sensitivity (Sn) of 60% and a specificity (Sp) of 92% at the exon level. The gene boundary identification process was found to be accurate 78% of the time. also reports alternative splicing patterns in EST alignments. An analysis of alternative splicing in 1124 genic regions suggested that more than half of human genes undergo alternative splicing. Surprisingly, we saw an absolute majority of the detected alternative splicing events affect the coding region. Furthermore, the evolutionary conservation of alternative splicing between human and mouse was analyzed using an EST-based approach. (See http://stl.wustl.edu/~zkan/TAP/)

Alternative Splicing↗

Automation and system integration of scanning tomographic acoustic microscope.

The Scanning Tomographic Acoustic Microscope (STAM) is an instrument capable of performing subsurface imaging of microscopic specimens. Designed around the Scanning Laser Acoustic Microscope (SLAM), the STAM incorporates numerous hardware and software advances which allow automated imaging of the acoustic properties of thick specimens at high resolution. With these modifications the STAM is shown to be capable of image formation for tissue characterization and nondestructive evaluation (NDE) of microscopic specimens. This paper describes the design and operation of the STAM hardware, and software algorithms developed to permit high resolution imaging. Examples are provided to demonstrate the capability of multiple angle and multiple frequency tomographic reconstructions.

Acoustics↗

Development and evaluation of a pictorial-based analogical problem-solving programme for people with traumatic brain injury.

BACKGROUND: People with traumatic brain injury (TBI) must often deal with cognitive problems, including social problem-solving. The study reported herein evaluated the effectiveness of a newly developed pictorial-based analogical problem-solving skills training programme. It is hypothesized that the programme can help people with TBI to learn better problem-solving skills through systematic, theoretically driven learning strategies. METHOD: Based on the instrumental enrichment model and the hierarchy of daily problem-solving as suggested by Holloran and Bressler, analogical problem-solving training software was developed. Thirty subjects with TBI then attended a 20-session interactive analogical problem-solving skills training programme. Another 20 subjects with TBI and of similar demographics formed the control group. The outcome measures included session-based quizzes on analogical problem-solving, the Category Test of the Halstead Reitan Test Battery (HRTB) and the Lawton IADL Scale. FINDINGS: The analogical problem-solving training strategies were found to be effective in improving problem-solving skills. The subjects generally demonstrated a selective improvement in their functional and overall problem-solving skills, but not in their basic problem-solving skills. The subjects in the control group showed stable problem-solving skills over a 4-week interval (no statistically significant changes). The findings indicated the therapeutic significance of the training programme. CONCLUSIONS: The results of the study suggested that innovative cognitive rehabilitation programmes can be customized to match the needs of clients with TBI. The applicability and implications of the interactive pictorial-based analogical problem-solving skill-training programme that was used in the study and possibilities for future study in this research area are also discussed.

Adolescent↗

Integration of a knowledge-based system and a clinical documentation system via a data dictionary.

This paper describes the design and realisation of a knowledge-based system and a clinical documentation system linked via a data dictionary. The software was developed as a shell with object oriented methods and C++ for IBM-compatible PC's and WINDOWS 3.1/95. The data dictionary covers terminology and document objects with relations to external classifications. It controls the terminology in the documentation program with form-based entry of clinical documents and in the knowledge-based system with scores and rules. The software was applied to the clinical field of acute abdominal pain by implementing a data dictionary with 580 terminology objects, 501 document objects, and 2136 links; a documentation module with 8 clinical documents and a knowledge-based system with 10 scores and 7 sets of rules.

Abdominal Pain↗

Flexible ex vivo phantoms for validation of diffusion tensor tractography on a clinical scanner.

PURPOSE: The aim of this study was to develop ex vivo diffusion tensor (DT) flexible phantoms. MATERIALS AND METHODS: Materials were bundles of textile threads of cotton, monofilament nylon, rayon, and polyester bunched with spiral wrapping bands and immersed in water. DT images were acquired on a 1.5-Tesla clinical magnetic resonance scanner using echo planar imaging sequences with 15 motion probing gradient directions. DT tractography with seeding and a line-tracking method was carried out by software originally developed on a PC-based workstation. RESULTS: We observed relatively high fractional anisotropy on the polyester phantom and were able to reconstruct tractography. Straight tracts along the bundle were displayed when it was arranged linearly. It was easy to bend arcuately or bifurcate at one end; and tracts followed the course of the bundle, whether it was curved or branched and had good agreement with direct visual observation. Tractography with the other fibers was unsuccessful. CONCLUSION: The polyester phantom revealed a diffusion anisotropic structure according to its shape and would be utilizable repeatedly under the same conditions, differently from living central neuronal system. It would be useful to validate DT sequences and to optimize an algorithm or parameters of DT tractography software. Additionally, the flexibility of the phantom would enable us to model human axonal projections.

Anisotropy↗