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Software upgrading in a CT scanner. Influence on quantitative CT.

PURPOSE: In an attempt to improve field uniformity and CT number stability, the software in a CT scanner was replaced with a new version. The purpose of the present study was to investigate the influence of the software upgrading on density measurements. MATERIAL AND METHODS: The upgrading influence was investigated by means of a torso phantom (European spinal). The phantom simulates a torso which contains 3 vertebrae of different densities. RESULTS: Despite the use of a reference standard under the phantom, the software change resulted in: a) improved short-term precision; b) increased density values at 80 and 100 kVp, decreased at 130 kVp; and c) increased influence of the kVp on the values. CONCLUSION: The results of the present study suggest that conversion factors have to be used in density values for reference populations as well as in the values of patients undergoing follow-up studies.

Absorptiometry, Photon↗

An evaluation of commercial school health software for use in multisite research studies.

Multisite research studies are an ideal way to help specialty nursing organizations move toward evidence-based practice. A necessary requisite of such studies, the ability to collect data efficiently and accurately, can be addressed by adapting commercially available software to the research. This article reviews six commercial software packages designed for school nurses as to their appropriateness for use with multisite studies. The three major criteria considered were (a) whether the software is sophisticated enough to meet the demands of research, (b) whether it is user-friendly, and (c) whether it has reasonable technical specifications. The strengths, weaknesses, appropriateness, and costs of each of the products are reviewed.

Medical Records↗

Retrospective drug utilization review software systems: perspectives of state Medicaid DUR directors.

OBJECTIVE: To determine the desirability or perceived need of retrospective drug utilization review (DUR) software system characteristics. DESIGN: A 32-item questionnaire. SETTING: Ambulatory DUR directors covering more than 33 million patients. PARTICIPANTS: Medicaid DUR directors from 49 states and the District of Columbia. MAIN OUTCOME MEASURES: Five-point Likert scale measures of importance of system and vendor characteristics. RESULTS: A 100% response rate was achieved. Respondents rated the ability to change or modify criteria as very important and thought it was important to receive criteria sets from software vendors. Respondents believed cost-savings methodologies should be clearly defined and false positive DUR criteria should be minimized. CONCLUSIONS: Through the implementation of the Omnibus Budget Reconciliation Act of 1990, considerable experience in ambulatory DUR programs has been achieved. Respondents believed the ability to change DUR criteria was very important and they thought it was important to have a set of criteria supplied from software vendors. Critical issues of criteria development, cost-savings methodologies, minimizing false positive criteria, and outcomes assessment from DUR programs were important issues to DUR directors.

Drug Therapy↗

htSNPer1.0: software for haplotype block partition and htSNPs selection.

BACKGROUND: There is recently great interest in haplotype block structure and haplotype tagging SNPs (htSNPs) in the human genome for its implication on htSNPs-based association mapping strategy for complex disease. Different definitions have been used to characterize the haplotype block structure in the human genome, and several different performance criteria and algorithms have been suggested on htSNPs selection. RESULTS: A heuristic algorithm, generalized branch-and-bound algorithm, is applied to the searching of minimal set of haplotype tagging SNPs (htSNPs) according to different htSNPs performance criteria. We develop a software htSNPer1.0 to implement the algorithm, and integrate three htSNPs performance criteria and four haplotype block definitions for haplotype block partitioning. It is a software with powerful Graphical User Interface (GUI), which can be used to characterize the haplotype block structure and select htSNPs in the candidate gene or interested genomic regions. It can find the global optimization with only a fraction of the computing time consumed by exhaustive searching algorithm. CONCLUSION: htSNPer1.0 allows molecular geneticists to perform haplotype block analysis and htSNPs selection using different definitions and performance criteria. The software is a powerful tool for those focusing on association mapping based on strategy of haplotype block and htSNPs.

Algorithms↗

JColorGrid: software for the visualization of biological measurements.

BACKGROUND: Two-dimensional data colourings are an effective medium by which to represent three-dimensional data in two dimensions. Such "color-grid" representations have found increasing use in the biological sciences (e.g. microarray 'heat maps' and bioactivity data) as they are particularly suited to complex data sets and offer an alternative to the graphical representations included in traditional statistical software packages. The effectiveness of color-grids lies in their graphical design, which introduces a standard for customizable data representation. Currently, software applications capable of generating limited color-grid representations can be found only in advanced statistical packages or custom programs (e.g. micro-array analysis tools), often associated with steep learning curves and requiring expert knowledge. RESULTS: Here we describe JColorGrid, a Java library and platform independent application that renders color-grid graphics from data. The software can be used as a Java library, as a command-line application, and as a color-grid parameter interface and graphical viewer application. Data, titles, and data labels are input as tab-delimited text files or Microsoft Excel spreadsheets and the color-grid settings are specified through the graphical interface or a text configuration file. JColorGrid allows both user graphical data exploration as well as a means of automatically rendering color-grids from data as part of research pipelines. CONCLUSION: The program has been tested on Windows, Mac, and Linux operating systems, and the binary executables and source files are available for download at http://jcolorgrid.ucsf.edu.

Biology↗

MIDAS: software for analysis and visualisation of interallelic disequilibrium between multiallelic markers.

BACKGROUND: Various software tools are available for the display of pairwise linkage disequilibrium across multiple single nucleotide polymorphisms. The HapMap project also presents these graphics within their website. However, these approaches are limited in their use of data from multiallelic markers and provide limited information in a graphical form. RESULTS: We have developed a software package (MIDAS - Multiallelic Interallelic Disequilibrium Analysis Software) for the estimation and graphical display of interallelic linkage disequilibrium. Linkage disequilibrium is analysed for each allelic combination (of one allele from each of two loci), between all pairwise combinations of any type of multiallelic loci in a contig (or any set) of many loci (including single nucleotide polymorphisms, microsatellites, minisatellites and haplotypes). Data are presented graphically in a novel and informative way, and can also be exported in tabular form for other analyses. This approach facilitates visualisation of patterns of linkage disequilibrium across genomic regions, analysis of the relationships between different alleles of multiallelic markers and inferences about patterns of evolution and selection. CONCLUSION: MIDAS is a linkage disequilibrium analysis program with a comprehensive graphical user interface providing novel views of patterns of linkage disequilibrium between all types of multiallelic and biallelic markers.

Algorithms↗

Evaluation of sequence alignments and oligonucleotide probes with respect to three-dimensional structure of ribosomal RNA using ARB software package.

BACKGROUND: Availability of high-resolution RNA crystal structures for the 30S and 50S ribosomal subunits and the subsequent validation of comparative secondary structure models have prompted the biologists to use three-dimensional structure of ribosomal RNA (rRNA) for evaluating sequence alignments of rRNA genes. Furthermore, the secondary and tertiary structural features of rRNA are highly useful and successfully employed in designing rRNA targeted oligonucleotide probes intended for in situ hybridization experiments. RNA3D, a program to combine sequence alignment information with three-dimensional structure of rRNA was developed. Integration into ARB software package, which is used extensively by the scientific community for phylogenetic analysis and molecular probe designing, has substantially extended the functionality of ARB software suite with 3D environment. RESULTS: Three-dimensional structure of rRNA is visualized in OpenGL 3D environment with the abilities to change the display and overlay information onto the molecule, dynamically. Phylogenetic information derived from the multiple sequence alignments can be overlaid onto the molecule structure in a real time. Superimposition of both statistical and non-statistical sequence associated information onto the rRNA 3D structure can be done using customizable color scheme, which is also applied to a textual sequence alignment for reference. Oligonucleotide probes designed by ARB probe design tools can be mapped onto the 3D structure along with the probe accessibility models for evaluation with respect to secondary and tertiary structural conformations of rRNA. CONCLUSION: Visualization of three-dimensional structure of rRNA in an intuitive display provides the biologists with the greater possibilities to carry out structure based phylogenetic analysis. Coupled with secondary structure models of rRNA, RNA3D program aids in validating the sequence alignments of rRNA genes and evaluating probe target sites. Superimposition of the information derived from the multiple sequence alignment onto the molecule dynamically allows the researchers to observe any sequence inherited characteristics (phylogenetic information) in real-time environment. The extended ARB software package is made freely available for the scientific community via http://www.arb-home.de.

Algorithms↗

AgdbNet - antigen sequence database software for bacterial typing.

BACKGROUND: Bacterial typing schemes based on the sequences of genes encoding surface antigens require databases that provide a uniform, curated, and widely accepted nomenclature of the variants identified. Due to the differences in typing schemes, imposed by the diversity of genes targeted, creating these databases has typically required the writing of one-off code to link the database to a web interface. Here we describe agdbNet, widely applicable web database software that facilitates simultaneous BLAST querying of multiple loci using either nucleotide or peptide sequences. RESULTS: Databases are described by XML files that are parsed by a Perl CGI script. Each database can have any number of loci, which may be defined by nucleotide and/or peptide sequences. The software is currently in use on at least five public databases for the typing of Neisseria meningitidis, Campylobacter jejuni and Streptococcus equi and can be set up to query internal isolate tables or suitably-configured external isolate databases, such as those used for multilocus sequence typing. The style of the resulting website can be fully configured by modifying stylesheets and through the use of customised header and footer files that surround the output of the script. CONCLUSION: The software provides a rapid means of setting up customised Internet antigen sequence databases. The flexible configuration options enable typing schemes with differing requirements to be accommodated.

Algorithms↗

MICA: desktop software for comprehensive searching of DNA databases.

BACKGROUND: Molecular biologists work with DNA databases that often include entire genomes. A common requirement is to search a DNA database to find exact matches for a nondegenerate or partially degenerate query. The software programs available for such purposes are normally designed to run on remote servers, but an appealing alternative is to work with DNA databases stored on local computers. We describe a desktop software program termed MICA (K-Mer Indexing with Compact Arrays) that allows large DNA databases to be searched efficiently using very little memory. RESULTS: MICA rapidly indexes a DNA database. On a Macintosh G5 computer, the complete human genome could be indexed in about 5 minutes. The indexing algorithm recognizes all 15 characters of the DNA alphabet and fully captures the information in any DNA sequence, yet for a typical sequence of length L, the index occupies only about 2L bytes. The index can be searched to return a complete list of exact matches for a nondegenerate or partially degenerate query of any length. A typical search of a long DNA sequence involves reading only a small fraction of the index into memory. As a result, searches are fast even when the available RAM is limited. CONCLUSION: MICA is suitable as a search engine for desktop DNA analysis software.

Algorithms↗

BAMarraytrade mark: Java software for Bayesian analysis of variance for microarray data.

BACKGROUND: DNA microarrays open up a new horizon for studying the genetic determinants of disease. The high throughput nature of these arrays creates an enormous wealth of information, but also poses a challenge to data analysis. Inferential problems become even more pronounced as experimental designs used to collect data become more complex. An important example is multigroup data collected over different experimental groups, such as data collected from distinct stages of a disease process. We have developed a method specifically addressing these issues termed Bayesian ANOVA for microarrays (BAM). The BAM approach uses a special inferential regularization known as spike-and-slab shrinkage that provides an optimal balance between total false detections and total false non-detections. This translates into more reproducible differential calls. Spike and slab shrinkage is a form of regularization achieved by using information across all genes and groups simultaneously. RESULTS: BAMarray is a graphically oriented Java-based software package that implements the BAM method for detecting differentially expressing genes in multigroup microarray experiments (up to 256 experimental groups can be analyzed). Drop-down menus allow the user to easily select between different models and to choose various run options. BAMarraycan also be operated in a fully automated mode with preselected run options. Tuning parameters have been preset at theoretically optimal values freeing the user from such specifications. BAMarray provides estimates for gene differential effects and automatically estimates data adaptive, optimal cutoff values for classifying genes into biological patterns of differential activity across experimental groups. A graphical suite is a core feature of the product and includes diagnostic plots for assessing model assumptions and interactive plots that enable tracking of prespecified gene lists to study such things as biological pathway perturbations. The user can zoom in and lasso genes of interest that can then be saved for downstream analyses. CONCLUSION: BAMarray is user friendly platform independent software that effectively and efficiently implements the BAM methodology. Classifying patterns of differential activity is greatly facilitated by a data adaptive cutoff rule and a graphical suite. BAMarray is licensed software freely available to academic institutions. More information can be found at http://www.bamarray.com.

Algorithms↗

JMATING: a software for the analysis of sexual selection and sexual isolation effects from mating frequency data.

BACKGROUND: Many different sexual isolation and sexual selection statistics have been proposed in the past. However, there is no available software that implements all these statistical estimators and their corresponding tests for the study of mating behaviour. RESULTS: JMATING is an easy-to-use program developed in Java for the analysis of mating frequency data to study sexual selection and sexual isolation effects from laboratory experiments as well as descriptive studies accomplished in the wild. The software allows the re-organization of the data previous to the analysis, the estimation of the most important estimators, and a battery of complementary statistical tests. CONCLUSION: JMATING is the first complete and versatile software for the analyses of mating frequency data. It is available at http://www.uvigo.es/webs/c03/webc03/XENETICA/XB2/JMsoft.htm and requires the Java runtime environment.

Animals↗

Software for optimization of SNP and PCR-RFLP genotyping to discriminate many genomes with the fewest assays.

BACKGROUND: Microbial forensics is important in tracking the source of a pathogen, whether the disease is a naturally occurring outbreak or part of a criminal investigation. RESULTS: A method and SPR Opt (SNP and PCR-RFLP Optimization) software to perform a comprehensive, whole-genome analysis to forensically discriminate multiple sequences is presented. Tools for the optimization of forensic typing using Single Nucleotide Polymorphism (SNP) and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses across multiple isolate sequences of a species are described. The PCR-RFLP analysis includes prediction and selection of optimal primers and restriction enzymes to enable maximum isolate discrimination based on sequence information. SPR Opt calculates all SNP or PCR-RFLP variations present in the sequences, groups them into haplotypes according to their co-segregation across those sequences, and performs combinatoric analyses to determine which sets of haplotypes provide maximal discrimination among all the input sequences. Those set combinations requiring that membership in the fewest haplotypes be queried (i.e. the fewest assays be performed) are found. These analyses highlight variable regions based on existing sequence data. These markers may be heterogeneous among unsequenced isolates as well, and thus may be useful for characterizing the relationships among unsequenced as well as sequenced isolates. The predictions are multi-locus. Analyses of mumps and SARS viruses are summarized. Phylogenetic trees created based on SNPs, PCR-RFLPs, and full genomes are compared for SARS virus, illustrating that purported phylogenies based only on SNP or PCR-RFLP variations do not match those based on multiple sequence alignment of the full genomes. CONCLUSION: This is the first software to optimize the selection of forensic markers to maximize information gained from the fewest assays, accepting whole or partial genome sequence data as input. As more sequence data becomes available for multiple strains and isolates of a species, automated, computational approaches such as those described here will be essential to make sense of large amounts of information, and to guide and optimize efforts in the laboratory. The software and source code for SPR Opt is publicly available and free for non-profit use at http://www.llnl.gov/IPandC/technology/software/softwaretitles/spropt.php.

Cluster Analysis↗

Development and validation of MIX: comprehensive free software for meta-analysis of causal research data.

BACKGROUND: Meta-analysis has become a well-known method for synthesis of quantitative data from previously conducted research in applied health sciences. So far, meta-analysis has been particularly useful in evaluating and comparing therapies and in assessing causes of disease. Consequently, the number of software packages that can perform meta-analysis has increased over the years. Unfortunately, it can take a substantial amount of time to get acquainted with some of these programs and most contain little or no interactive educational material. We set out to create and validate an easy-to-use and comprehensive meta-analysis package that would be simple enough programming-wise to remain available as a free download. We specifically aimed at students and researchers who are new to meta-analysis, with important parts of the development oriented towards creating internal interactive tutoring tools and designing features that would facilitate usage of the software as a companion to existing books on meta-analysis. RESULTS: We took an unconventional approach and created a program that uses Excel as a calculation and programming platform. The main programming language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for Applications in Excel 2000 and higher. The development took approximately two years and resulted in the 'MIX' program, which can be downloaded from the program's website free of charge. Next, we set out to validate the MIX output with two major software packages as reference standards, namely STATA (metan, metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta-analyses that had been published in major journals were used as data sources. All numerical and graphical results from analyses with MIX were identical to their counterparts in STATA and CMA. The MIX program distinguishes itself from most other programs by the extensive graphical output, the click-and-go (Excel) interface, and the educational features. CONCLUSION: The MIX program is a valid tool for performing meta-analysis and may be particularly useful in educational environments. It can be downloaded free of charge via http://www.mix-for-meta-analysis.info or http://sourceforge.net/projects/meta-analysis.

Causality↗

The caCORE Software Development Kit: streamlining construction of interoperable biomedical information services.

BACKGROUND: Robust, programmatically accessible biomedical information services that syntactically and semantically interoperate with other resources are challenging to construct. Such systems require the adoption of common information models, data representations and terminology standards as well as documented application programming interfaces (APIs). The National Cancer Institute (NCI) developed the cancer common ontologic representation environment (caCORE) to provide the infrastructure necessary to achieve interoperability across the systems it develops or sponsors. The caCORE Software Development Kit (SDK) was designed to provide developers both within and outside the NCI with the tools needed to construct such interoperable software systems. RESULTS: The caCORE SDK requires a Unified Modeling Language (UML) tool to begin the development workflow with the construction of a domain information model in the form of a UML Class Diagram. Models are annotated with concepts and definitions from a description logic terminology source using the Semantic Connector component. The annotated model is registered in the Cancer Data Standards Repository (caDSR) using the UML Loader component. System software is automatically generated using the Codegen component, which produces middleware that runs on an application server. The caCORE SDK was initially tested and validated using a seven-class UML model, and has been used to generate the caCORE production system, which includes models with dozens of classes. The deployed system supports access through object-oriented APIs with consistent syntax for retrieval of any type of data object across all classes in the original UML model. The caCORE SDK is currently being used by several development teams, including by participants in the cancer biomedical informatics grid (caBIG) program, to create compatible data services. caBIG compatibility standards are based upon caCORE resources, and thus the caCORE SDK has emerged as a key enabling technology for caBIG. CONCLUSION: The caCORE SDK substantially lowers the barrier to implementing systems that are syntactically and semantically interoperable by providing workflow and automation tools that standardize and expedite modeling, development, and deployment. It has gained acceptance among developers in the caBIG program, and is expected to provide a common mechanism for creating data service nodes on the data grid that is under development.

Humans↗

Java Web Start based software for automated quantitative nuclear analysis of prostate cancer and benign prostate hyperplasia.

BACKGROUND: Androgen acts via androgen receptor (AR) and accurate measurement of the levels of AR protein expression is critical for prostate research. The expression of AR in paired specimens of benign prostate and prostate cancer from 20 African and 20 Caucasian Americans was compared to demonstrate an application of this system. METHODS: A set of 200 immunopositive and 200 immunonegative nuclei were collected from the images using a macro developed in Image Pro Plus. Linear Discriminant and Logistic Regression analyses were performed on the data to generate classification coefficients. Classification coefficients render the automated image analysis software independent of the type of immunostaining or image acquisition system used. The image analysis software performs local segmentation and uses nuclear shape and size to detect prostatic epithelial nuclei. AR expression is described by (a) percentage of immunopositive nuclei; (b) percentage of immunopositive nuclear area; and (c) intensity of AR expression among immunopositive nuclei or areas. RESULTS: The percent positive nuclei and percent nuclear area were similar by race in both benign prostate hyperplasia and prostate cancer. In prostate cancer epithelial nuclei, African Americans exhibited 38% higher levels of AR immunostaining than Caucasian Americans (two sided Student's t-tests; P < 0.05). Intensity of AR immunostaining was similar between races in benign prostate. CONCLUSION: The differences measured in the intensity of AR expression in prostate cancer were consistent with previous studies. Classification coefficients are required due to non-standardized immunostaining and image collection methods across medical institutions and research laboratories and helps customize the software for the specimen under study. The availability of a free, automated system creates new opportunities for testing, evaluation and use of this image analysis system by many research groups who study nuclear protein expression.

Algorithms↗

Software for quantitative trait analysis.

This paper provides a brief overview of software currently available for the genetic analysis of quantitative traits in humans. Programs that implement variance components, Markov Chain Monte Carlo (MCMC), Haseman-Elston (H-E) and penetrance model-based linkage analyses are discussed, as are programs for measured genotype association analyses and quantitative trait transmission disequilibrium tests. The software compared includes LINKAGE, FASTLINK, PAP, SOLAR, SEGPATH, ACT, Mx, MERLIN, GENEHUNTER, Loki, Mendel, SAGE, QTDT and FBAT. Where possible, the paper provides URLs for acquiring these programs through the internet, details of the platforms for which the software is available and the types of analyses performed.

Chromosome Mapping↗

Video-based eye tracking: our experience with Advanced Stimuli Design for Eye Tracking software.

We present an independent, flexible, and easily programmable software program for generating a wide set of visual stimuli paradigms in eye-movement studies. The software, called ASTIDET (Advanced Stimuli Design for Eye Tracking), has been interfaced in real time with a high speed video-based eye tracking system in order to obtain a reliable measurement of saccades. Two saccadic paradigms have been tested (gap and memory guided tasks) in 10 normal subjects. The preliminary results confirm that ASTIDET is a user-friendly software and can be interfaced with a video-based eye-tracking device in order to obtain reliable measurement of saccades.

Equipment Design↗

Development and application of computer software for cell culture laboratory management.

Prototype computer software for a Cell Culture Laboratory Management System (CCLMS) has been developed to relieve cell culture specialists of the burden of manual recordkeeping. Conventional data archives in cell culture laboratories are prone to error and expensive to maintain. The reliance upon cell culture to provide models for biochemical and molecular biological research serves to magnify errors at great expense. The CCLMS prototype encapsulates a modular software application that manages the many aspects of cell culture laboratory recordkeeping. A transaction-based database stores detailed information on subcultures, freezes and thaws, prints waterproof labels for culture vessels, and provides for immediate historical trace-back of any cultured cell line. Linked database files store information specific to an individual culture flask while removing redundancy between similar groups of flasks. A frozen cell log maintains locations of all vials within any type of cryogenic storage unit, locates spaces for newly frozen cell lines, and generates alphabetical or numerical reports. Finally, modules for maintaining cell counts, user records, and culture vessel specifications to support a comprehensive automation process are incorporated within this software. The developed CCLMS prototype has been demonstrated to be an adaptable, reliable tool for improving training, efficiency, and historical rigor for two independent cell culture facilities.

Animals↗