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Expeditor: a pipeline for designing primers using human gene structure and livestock animal EST information.

We have developed software, called Expeditor, that can be used to combine known gene structure information from human and coding sequence information from farm animal species for a streamlined primer design in target farm animal species. This software has many utilities, which include PCR-based SNP discovery for identification of genes/markers associated with economically important traits in farm animals, comparative mapping analysis, and evolution studies. The use of this software helps minimize tedious manual operations and reduces the chance of errors by more conventional approaches.

Animals↗

Sequence motifs characteristic of DNA[cytosine-N4]methyltransferases: similarity to adenine and cytosine-C5 DNA-methylases.

The sequences coding for DNA[cytosine-N4]methyltransferases MvaI (from Micrococcus varians RFL19) and Cfr9I (from Citrobacter freundii RFL9) have been determined. The predicted methylases are proteins of 454 and 300 amino acids, respectively. Primary structure comparison of M.Cfr9I and another m4C-forming methylase, M.Pvu II, revealed extended regions of homology. The sequence comparison of the three DNA[cytosine-N4]-methylases using originally developed software revealed two conserved patterns, DPF-GSGT and TSPPY, which were found similar also to those of adenine and DNA[cytosine-C5]-methylases. These data provided a basis for global alignment and classification of DNA-methylase sequences. Structural considerations led us to suggest that the first region could be the binding site of AdoMet, while the second is thought to be directly involved in the modification of the exocyclic amino group.

Amino Acid Sequence↗

GOBASE: the organelle genome database.

GOBASE (http://megasun.bch.umontreal.ca/gobase/) is a network-accessible biological database, which is unique in bringing together diverse biological data on organelles with taxonomically broad coverage, and in furnishing data that have been exhaustively verified and completed by experts. So far, we have focused on mitochondrial data: GOBASE contains all published nucleotide and protein sequences encoded by mitochondrial genomes, selected RNA secondary structures of mitochondria-encoded molecules, genetic maps of completely sequenced genomes, taxonomic information for all species whose sequences are present in the database and organismal descriptions of key protistan eukaryotes. All of these data have been integrated and organized in a formal database structure to allow sophisticated biological queries using terms that are inherent in biological concepts. Most importantly, data have been validated, completed, corrected and standardized, a prerequisite of meaningful analysis. In addition, where critical data are lacking, such as genetic maps and RNA secondary structures, they are generated by the GOBASE team and collaborators, and added to the database. The database is implemented in a relational database management system, but features an object-oriented view of the biological data through a Web/Genera-generated World Wide Web interface. Finally, we have developed software for database curation (i.e. data updates, validation and correction), which will be described in some detail in this paper.

Animals↗

HyPaLib: a database of RNAs and RNA structural elements defined by hybrid patterns.

The database, called HyPaLib (for Hybrid Pattern Library), contains annotated structural elements characteristic for certain classes of structural and/or functional RNAs. These elements are described in a language specifically designed for this purpose. The language allows convenient specification of hybrid patterns, i.e. motifs consisting of sequence features and structural elements together with sequence similarity and thermodynamic constraints. We are currently developing software tools that allow a user to search sequence databases for any pattern in HyPaLib, thus providing functionality which is similar to PROSITE, but dedicated to the more complex patterns in RNA sequences. HyPaLib is available at http://bibiserv. techfak.uni-bielefeld.de/HyPa/.

Algorithms↗

A system for rapid large-area monitoring of gamma dose rates in the environment based on MCP-N (LiF:Mg,Cu,P) TL detectors.

One lesson learned from the Chernobyl accident was that the spatial distribution of far-field contamination was strongly non-uniform due to local variation of atmospheric conditions, such as wind direction, rain etc. An environmental monitoring system using highly sensitive thermoluminescent LiF:Mg,Cu,P (MCP-N) detectors has been completed and field-tested. The system consists of 3000 MCP-N detectors in 1000 TLD cards (three TLDs per card), two Mikrolab automatic TL readers, heating ovens, and specially developed software which includes a database for rapid evaluation of results. The main dosimetric parameters of MCP-N dosemeters, such as thermally-induced fading, light sensitivity, minimum detectable dose, self-dose, zero-dose, energy response up to 6-7 MeV, influence of annealing and readout conditions on detector stability, have been tested. About 100 locations over an area of about 15,000 km2 in the south of Poland were selected for measurements lasting from 4 days to 3 months. The kerma rates measured over a 4 day screening period agree well with kerma rates determined over a 75 day monitoring period. Results from short- and long-term exposure periods agree well with those performed using MTS-N (LiF:Mg,Ti) over southern Poland in 1985, before the Chernobyl accident. Thus, using the system based on MCP-N detectors, one is able simultaneously to monitor environmental radiation kerma rates at a large number of locations over periods of four days or less. Provided natural background kerma rates at selected monitoring points are available prior to the accident, the system can be applied to assess kerma rates rapidly in the environment, following a nuclear accident.

Calcium↗

Application of new imaging and calculation techniques to activity and dose assessment in the case of a 106Ru contaminated wound.

The aim of this paper is to describe the dosimetric evaluation of a point contamination that occurred in a laboratory during the examination of an irradiated sample. The incident led to point contamination of the operator's finger due to the presence of mainly 106Ru, with its progeny, 106Rh. The paper reports on the activity and dose assessment, performed using several methods. The measured activity was obtained using a conventional device based on a germanium detector and confirmed using software developed at IRSN, based on reconstruction of voxel phantom associated with the Monte Carlo N-Particle code (MCNP) for in vivo measurement. Two dose assessment calculations were performed using both analytical and Monte Carlo methods, applying the same approach as for activity assessment based on the personal computational phantom of the finger. The results are compared, followed by a discussion on the suitability of the tools described in this study.

Computer Simulation↗

Space dosimetry with the application of a 3D silicon detector telescope: response function and inverse algorithm.

One of the many risks of long-duration space flights is the excessive exposure to cosmic radiation, which has great importance particularly during solar flares and higher sun activity. Monitoring of the cosmic radiation on board space vehicles is carried out on the basis of wide international co-operation. Since space radiation consists mainly of charged heavy particles (protons, alpha and heavier particles), the equivalent dose differs significantly from the absorbed dose. A radiation weighting factor (w(R)) is used to convert absorbed dose (Gy) to equivalent dose (Sv). w(R) is a function of the linear energy transfer of the radiation. Recently used equipment is suitable for measuring certain radiation field parameters changing in space and over time, so a combination of different measurements and calculations is required to characterise the radiation field in terms of dose equivalent. The objectives of this project are to develop and manufacture a three-axis silicon detector telescope, called Tritel, and to develop software for data evaluation of the measured energy deposition spectra. The device will be able to determine absorbed dose and dose equivalent of the space radiation.

Algorithms↗

Description, validation, and performance characteristics of a new computer-automated sperm motility analysis system.

A computer-automated sperm motility assay (CASMA) system has been developed that provides a rapid and accurate analysis of multiple sperm movement parameters and a new measure of linearity, the linear deviation angle. CASMA provides objective, unbiased sampling and accurate quantitation of the movement characteristics of 200 sperm cells in 20 min. It consists of a microscope-mounted video camera, a high-resolution video disk recorder, a video digitizer/memory board mounted in an IBM 9000 microcomputer, and newly developed software. After manual recording, at 60 frames/s, of the video sequences (takes) of sperm suspensions, each take is automatically played back frame by frame, digitized, and stored in video memory. The software searches each frame, recognizes sperm cells, randomly selects a preset number for analysis, and traces each cell through the sequence to generate sperm "tracks" that are then stored in disk memory. This process is repeated for each take. Analysis of the stored tracks of each take yields the mean +/- SEM of the standard sperm motility parameters: percent motile (%M), curvilinear velocity (VC), net velocity (Vn), position-averaged velocity (Va), linear index (Vn/Va), progressiveness ration (Vn/Vc), and curvilinear progressiveness ratio (Va/Vc). Additionally, CASMA allows measurement of the linear deviation angle, a more direct measure of the linearity of sperm movement. For statistical comparisons, multiple takes can be considered either as replicates or separate experimental determinations. Finally, for more detailed analysis, each individually stored track, with its associated parameters, or histogram distributions of all sperm for each parameter can be displayed and printed. The performance of CASMA was evaluated by comparison of CASMA-determined movement parameters with manually determined values derived from the same sperm cells in the same video sequence and by comparison with published values determined using microcinematographic techniques. In each case, the CASMA values were essentially identical to those determined by manual measurements. Finally, CASMA accurately quantitates the linearity of sperm movement, a characteristic previously determined only by much more time-consuming methods. CASMA is a rapid and accurate system for measuring washed bull sperm motility and has reliably analyzed monkey and elephant sperm. The system has the potential to quantitate motility equally well with sperm from any species that have similar sperm head size.

Animals↗

Perfusion and function assessment by nuclear cardiology techniques.

This review focuses on the currently available nuclear cardiology techniques for assessing simultaneously myocardial perfusion and left-ventricular function information. The ability to obtain both types of information in the same patient has been considered impractical because of logistics restraints. New software development now permits ventricular function and myocardial perfusion information to be obtained by electrocardiogram-gated images of the perfused myocardium. These images permit analysis of wall motion as well as measurements of ejection fraction. New advances in the past decade such as the development of technetium-labeled perfusion tracers and portable compact multicrystal gamma cameras have provided the ability to perform single-photon emission computed tomography (SPECT) imaging and first-pass radionuclide angiography during a single exercise test. This particular technique offers the advantage of performing all three tests--exercise treadmill, radionuclide angiocardiography, and myocardial perfusion imaging--during a single exercise session. Preliminary data regarding the current clinical role of these studies in the diagnosis, prognosis, and assessment of viability in patients with coronary artery disease also is addressed.

Coronary Circulation↗

The dual-isotope ProstaScint imaging procedure: clinical experience and staging results in 145 patients.

PURPOSE: Whole-body, regional planar, and SPECT imaging using the In-111-labeled monoclonal antibody capromab pendetide (In-111 MAb; ProstaScint) has been shown to increase the detection of early disease spread in patients with prostate cancer. However, recognition of metastatic tumor sites can be difficult, especially if the involved nodes are near blood vessels. We have developed an alternate approach to the identification of metastatic sites that is based on a single simultaneous In-111 MAb and Tc-99m RBC SPECT acquisition of the pelvis and abdomen on day 5 after injection. We have also developed software that dynamically subtracts the Tc-99m RBC data set (vascular component) from the In-111 MAb data set (prostate and lymph node component), which allows for easier identification of metastatic sites. METHODS: We evaluated the effectiveness of ProstaScint for staging 145 patients with prostate cancer, 19 newly diagnosed and 126 with recurrence, using these two modifications. RESULTS: With clinical follow-up in 13 of 19 (68%) patients with primary disease, 10 of 13 (78%) had organ-confined disease. With follow-up in 64 of 126 (51%) patients with possible recurrent disease, 49 of 64 (77%) were found to have prostatic fossa activity only. Disease stage was deemed more advanced in 3 of 13 (22%) patients with primary cancer and in 13 of 64 (20%) of those with recurrent disease based on ProstaScint findings when all other imaging tests were inconclusive. Six patients with recurrent disease had negative results of their scans. In the 16 patients with more advanced disease, 3 of 59 lesions (5%) were documented as false positive, and there were no reported cases of false-negative findings. CONCLUSIONS: Using both the dual-isotope procedure and the subtraction analysis software with the ProstaScint examination provides additional information for staging primary and possibly recurrent prostate cancer compared with standard imaging techniques.

Antibodies, Monoclonal↗

Morphology of corneal Basal epithelial cells by in vivo slit-scanning confocal microscopy.

PURPOSE: To determine corneal basal epithelial cell density and morphology in a group of normal corneas and corneas with various conditions. METHODS: The central corneas of a group of 20 normal patients and 27 other patients who either had refractive surgery or had documented corneal pathology were examined with an in vivo slit-scanning confocal microscope. For all these patients in whom a well-defined basal epithelial layer was visualized, the basal cell density, area, and number of sides per cell were determined using customized software. RESULTS: The average basal cell density was 5,274 +/- 575 cells/mm2, the average cell area was 192 +/- 19.6 microm2, and the average number of cell sides was 5.5 +/- 0.1 sides for the group of normal controls. There were no statistically significant differences between basal cell density, cell area, or number of sides between the normal group and any of the other groups in which there were four or more patients. Corneas examined from patients with Fuchs' endothelial dystrophy or bullous keratopathy had hyperreflective basal epithelial cell borders. The measurement of the number of cell sides is not reliable using software developed for endothelial cell counting. CONCLUSION: Corneal basal epithelial cell density and area were found to be remarkably consistent in the variety of corneal disorders that we examined. This finding is further evidence that this aspect of corneal epithelial cell differentiation and maturation is tightly controlled with little variability between individuals even if a corneal condition is present.

Adult↗

Using cost/risk procedures to establish recovery criteria following a nuclear reactor accident.

In the event of a major accidental release of radionuclides at a nuclear power plant, large populated areas could become seriously contaminated. Local officials would be responsible for establishing radiation recovery criteria that would permit the evacuated population to return safely to their jobs and homes. The range of acceptable criteria could imply variations in property losses in the billions of dollars. Given the likely public concern over the health consequences and the enormity of the potential property losses, a cost/risk analysis can provide important input to establishing the recovery criteria. This paper describes procedures for conducting a cost/risk analysis of a site radiologically contaminated by a nuclear power plant accident. The procedures are illustrated by analyzing a hypothetically contaminated site, using software developed for determining the property and health effects of major reactor accidents.

Accidents↗

"ASAP": a microcomputer-based automated safety & performance testing system.

An HP-85 microcomputer programmed in BASIC was interfaced to a PEI 2000 safety analyzer via an HP-6942A Multiprogrammer and appropriate interface cards. This configuration allows automated safety and performance testing as well as report generation. The system is operated by means of a menu displayed on a built-in CRT and the keyboard. Data are displayed and then stored on the built-in cassette unit. Additional testing features are easily added with minimal software development, since all programming is in BASIC and all interface drivers are part of the hardware.

Biomedical Engineering↗

Artifacts and thresholding in X-ray CT of a cortical bone and titanium composite.

PURPOSE: X-Ray CT has the potential to provide precise and accurate data from which the mechanical properties of bone can be calculated. Such data would be useful in understanding the response of bone tissue to implants. Various artifacts can, however, degrade accuracy of the data. The aim of this study was to measure the artifactual errors produced in CT of a simulated femoral bone-titanium composite and to propose a method to correct for them. METHOD: A composite phantom that simulates cortical bone and a titanium implant was designed and constructed. The phantom was scanned and the image data were analyzed over a range of thresholds with image analysis software developed for this study. The outer (OD) and inner (ID) diameter and the CT number of the cortical bone, with and without titanium, were measured over a range of cortical thicknesses. RESULTS: While ID can be accurately measured by choosing the proper threshold (800 HU), OD, even at optimal threshold, will be underestimated by approximately 2%. If a proper threshold is selected, CT number can also be accurately determined. Errors of up to 5%, however, are produced by titanium unless corrected by proper threshold selection. CONCLUSION: Intramedullary titanium is not a deterrent to obtaining accurate measurements of cortical bone dimensions and properties. Proper choice of thresholds for image analysis of CT scan data can yield accuracy and precision of < or = 2%.

Artifacts↗

Cardiovascular magnetic resonance in the quantitative assessment of left ventricular mass, volumes and contractile function.

Cardiovascular magnetic resonance is a well validated, highly accurate and reproducible technique for the assessment of ventricular volumes, function and mass. State of the art cardiovascular magnetic resonance practice is capable of a ventricular assessment that includes not only systolic but also diastolic function. Thus, it provides an insight into the complex changes in ventricular morphology, physiology and function in cardiovascular disease. This has produced great interest not only in its clinical utilization but also as an important research tool. As refinement of the technique continues to incorporate hardware and software developments, the technique becomes quicker, more accurate and easier to analyse. Here, we review recent developments and current practice.

Cardiovascular System↗

Trends in drinking among Americans age 18 and younger: 1975-2002.

BACKGROUND: Although changes over time in the prevalence of drinking by youth under 18 have been previously reported, we present results based on data from multiple surveys, using recently developed software for trend analyses. In this study, we applied joinpoint statistical methodology to three national data sets to analyze trends in drinking by youth, age 18 and under, for the period 1975 to 2002. METHODS: Information was obtained from three national data sets, Monitoring the Future for the years 1975 to 2002, the Youth Risk Behavior Survey for the years 1991 to 2001, and the National Household Survey on Drug Abuse for 1979, 1985, and 1991 to 2001. Approximately 80,000 persons between 12 and 18 were included in the most recent survey years. The alcohol consumption measures examined over time were any use of alcohol, consumption of five or more drinks on one occasion, and daily consumption. RESULTS: Alcohol consumption by 8th, 10th and 12th graders decreased substantially since the 1970s according to joinpoint trend analyses. It remains disturbingly high, however, according to data from three national surveys (e.g., 12.4% of 8 and 28.6% of 12th graders drinking five or more drinks in a row in the past 2 weeks), although prevalence rates have been relatively stable for the last 5 to 10 years. CONCLUSIONS: Since the early 1990s, rates of drinking by youth under 18 remained relatively stable according to the Youth Risk Behavior Survey and National Household Survey on Drug Abuse and moved up and then down according to Monitoring the Future, underscoring the need for continued surveillance and enhanced understanding of this long-standing problem.

Adolescent↗

National Burn Repository 2005: a ten-year review.

In the early 1990s, the American Burn Association (ABA) started its first burn registry development initiatives. The impetus for the registry development software originated from several directions, including the following: (1) the recognition that national registries were widespread and of proven benefit; (2) growing demands from accrediting institutions, payers, and patient advocacy groups for objective and verifiable data regarding patient costs, treatments, and outcomes; and (3) the shift toward "evidence-based" medicine and the ongoing analysis of treatment effectiveness. The ABA has issued three calls for burn registry data for its National Burn Repository (NBR): 1994, 2002, and 2005. In 1994, 28 burn centers contributed data for more than 6,400 patients treated from 1991 to 1993. The ABA announced its second call for data in 2001 and distributed the published results of more than 54,000 acute burn admissions treated from 1974 to 2002 at the Association's 2002 Annual Meeting. The third ABA call for data was issued in the Fall of 2005. The results are detailed in this report, which provides a summary of more than a quarter million acute burn admissions from 1995 to 2005, representing 70 hospitals from 30 states plus the District of Columbia. Statistics are presented in chart and table format to illustrate such key factors as patient age, burn size group, types of injuries, mortality rates, and average hospital charges by etiology and length of hospital stay. The data presented herein should help stimulate quality improvement programs in burn care, as burn centers compare their performance with the national data and as research is expanded using the NBR. The NBR will be published annually and, with continued refinements to the registry software, should become of increasing importance to clinicians, payers, researchers, and the public.

Adolescent↗