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INRstar: computerised decision support software for anticoagulation management in primary care.

Computerised decision support software (CDSS) for anticoagulation management has become established practice in the UK, offering significant advantages for patients and clinicians over traditional methods of dose calculation. The New GMS Contract has been partly responsible for this shift of management from secondary to primary care, in which INRstar has been the market leader for many years. In September 2004, INRstar received the John Perry Prize, awarded by the PHCSG for excellence and innovation in medical applications of information technology.

Algorithms↗

[Theory and software of the hexapod external fixator].

Using hexapod kinematics (Stewart platform), an external fixator was developed that can be adjusted in all six spatial degrees of freedom by means of six linear adjusting elements. With such a system, any desired three-dimensional bone movements, for example, fracture reduction or deformity correction, can be effected exactly, without having temporarily to compromise any stability already achieved or to rearrange the construction during treatment. Since the introduction of the hexapod principle by Stewart in 1965, computerized control has been deemed necessary for its application. This paper describes the mathematical basis and the software developed for clinical use. Mathematical procedures are needed for the calculation of the inverse and forward kinematics of the hexapod, and for the description of three-dimensional movements.

Biomechanical Phenomena↗

Reporting cerebrospinal fluid data: knowledge base and interpretation software.

The compilation of cerebrospinal fluid (CSF) patient data together with a graphic display of immunoglobulin patterns in a single CSF report has two main advantages: analytical and clinical plausibility control of a complex set of data improves quality assessment and allows improved clinical specificity and sensitivity for recognition of disease-related "typical" data patterns. The widespread use of automated on-line evaluation programs can now be combined with knowledge-based programs for interpretation by clinical chemists and neurologists. These programs are based on knowledge of neuroimmunology, blood-CSF barrier function and dysfunction, influence of CSF flow on concentrations of blood-derived and brain-derived proteins in CSF, specific intrathecal antibody synthesis and relevance of brain proteins for differential diagnosis of degenerative diseases. The relevance of hyperbolic discrimination functions in quotient diagrams for the detection of intrathecal immunoglobulin synthesis is compared with earlier, still frequently used, linear interpretation functions. Differences found in commercially available interpretation software are discussed.

Brain↗

[A computer software system for dental caries rates: databases and statistical analysis].

A computer software system developed ICADAPLUS, is presented in order to create and tabulate data bases, calculate the DMF rate, perform statistical comparison of two populations, and calculate confidence intervals. The system offers a simplified method for health services in the area of dentistry, using dental records to carry out epidemiological surveys of tooth decay. The system's main feature is that it does not require specialists either in the area of dentistry or computing, demanding of the user only basic data-entry typing skills, since it presents simple menus, and standardized reports, with no possibility of error. The system comprises four steps: Data-entry, Processing, Reports and Utilities. In Data-entry the regions, towns and institutions supplying the data are initially registered, once only. Each record receives a code number, and it is this code which is available to the user through a Function Key, by means of which the code is transferred to the desired data field. Furthermore, there is a choice of type of dental chart: Klein and Palmer's DMF; the DMF proposed by the WHO; Klein, Palmer and Knutson's DMF surfaces; or Gruebbel's def. It is possible to include, alter and exclude records in each option. In Processing, it is necessary, first of all, to organise the indexes, totalize the data, and remit them to the data base, where no further alteration or exclusion occurs. From this stage on, reports can be prepared from the proposed indexes, grouped according to age, or age and gender. The system was validated by comparison with other methods. This comparison justifies the recommendation of its implementation.

Confidence Intervals↗

[Development and evaluation of an educational software for pediatric nursing education].

Computer Science is being introduced in education at an accelerated pace, thus forcing educators and students to become familiarized with such technology. This study aimed at the development and evaluation of the educational software "Children and medication". The program utilizes multimedia resources in four topics: the child, medication, the person who administers and administration of medication. The evaluation showed a large acceptance of the program, with most of the items being rated as excellent. We emphasize the importance of the development of teaching strategies utilizing computer resources in nursing education and in the development of nurses for the new millenium.

Evaluation Studies as Topic↗

Evaluation of the Image-Pro Plus 4.5 software for automatic counting of labeled nuclei by PCNA immunohistochemistry.

The objective of this study was to create and evaluate a routine (macro) using Image-Pro Plus 4.5 software (Media Cybernetics, Silver Spring, USA) for automatic counting of labeled nuclei by proliferating cell nuclear antigen (PCNA) immunohistochemistry. A total of 154 digital color images were obtained from eleven sections of reticular oral lichen planus stained by PCNA immunohistochemistry. Mean density (gray-level), red density, green density, blue density, area, minor axis, perimeter rate and roundness were parameters used for PCNA labeled nuclei discrimination, followed by their outlined presentation and counting in each image by the macro. Mean density and area thresholds were automatically defined based, respectively, on mean density and mean area of PCNA labeled nuclei in the assessed image. The reference method consisted in visual counting of manually outlined labeled nuclei. Statistical analysis of macro results versus reference countings showed a very significant correlation (rs = 0.964, p < 0.001) for general results and a high level (89.8 +/- 3.8%) of correctly counted labeled nuclei. We conclude that the main parameters associated with a high correlation between macro and reference results were mean density (gray-level) and area thresholds based on image profiles; and that Image-Pro Plus 4.5 using a routine with automatic definition of mean density and area thresholds can be considered a valid alternative to visual counting of PCNA labeled nuclei.

Cell Count↗

Evaluation of the performance of drug-drug interaction screening software in community and hospital pharmacies.

BACKGROUND: Computerized drug-drug interaction (DDI) screening is widely used to identify potentially harmful drug combinations in the inpatient and outpatient setting. OBJECTIVE: To evaluate the performance of drug-drug interaction (DDI) screening software in identifying select clinically significant DDIs in pharmacy computer systems in community and hospital pharmacies. METHODS: Ten community pharmacies and 10 hospital pharmacies in the Tucson metropolitan area were invited to participate in the study in 2004. To test the performance of each of the systems used by the pharmacies, 25 medications were used to create 6 mock patient profiles containing 37 drug-drug pairs, 16 of which are clinically meaningful DDIs that pose a potential risk to patient safety. Each profile was entered into the computer pharmacy system, and the system response in terms of the presence or absence of a DDI alert was recorded for each drug pair. The percentage of correct responses and the sensitivity, specificity, positive predictive value, and negative predictive value of each system to correctly classify each drug pair as a DDI or not was calculated. Summary statistics of these measures were calculated separately for community and hospital pharmacies. RESULTS: Eight community pharmacies and 5 hospital pharmacies in the Tucson metropolitan area agreed to participate in the study. The median sensitivity and median specificity for community pharmacies was 0.88 (range, 0.81-0.94) and 0.91 (range, 0.67-1.00), respectively. For hospital pharmacies, the median sensitivity and median specificity was 0.38 (range, 0.15-0.94) and 0.95 (range, 0.81-0.95), respectively. CONCLUSION: Based on this convenience sample of 8 community pharmacies and 5 hospital pharmacies in 1 metropolitan area, the performance of community pharmacy computer systems in screening DDIs appears to have improved over the last several years compared with research published previously in 2001. However, significant variation remains in the performance of hospital pharmacy computer systems, even among systems manufactured by the same vendor. Future research should focus on improving the performance of these systems in accurately and precisely identifying DDIs with a high probability of resulting in true potential adverse effects on clinical outcomes and creating a low .noise. ratio associated with false-positive alerts.

Clinical Pharmacy Information Systems↗

Genotools SNP manager: a new software for automated high-throughput MALDI-TOF mass spectrometry SNP genotyping.

Analysis of single nucleotide polymorphisms (SNPs) is a rapidly growing field of research that provides insights into the most common type of differences between individual genomes. The resulting information has a strong impact in the fields of pharmacogenomics, drug development, forensic medicine, and diagnostics of specific disease markers. The technique of matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) has been shown to be a highly suitable tool for the analysis of DNA. It supplies a very versatile method for addressing a high-throughput SNP genotyping approach. Here, we present the Bruker genotools SNP MANAGER, a new software tool suitable for highly automated MALDI-TOF MS SNP genotyping. The genotools SNP MANAGER administers the sample preparation data, calculates masses of allele-specific primer extension products, performs genotyping analysis, and displays the results. In the current study, we have used the genotools SNP MANAGER to perform an automated duplex SNP analysis of two biallelic markers from the promoter of the gene encoding the inflammatory mediator interleukin-6.

DNA↗

Publication-quality labeling of gels using transparency-mounted photographs and word processing software.

Obtaining a high quality nucleic acid or protein gel may be an easier and less daunting task than labeling the gel for publication. Techniques for adding information and identifiers to gels range from laboriously applying lettering or labels on gel photographs to computerized approaches that work directly with digitized gel images and produce photographic-quality output. The computerized approach may require specialized software and a considerable investment in a photographic-quality output device, like a dye sublimation printer. It can be argued that electronically processed gel images do not actually achieve the quality readily obtained photographically. We describe an approach that uses photographic gel images that are quickly and easily labeled using the drawing-lettering capability of a commercial word processor in widespread use (Microsoft Word for Windows Version 6).

Audiovisual Aids↗

Analysis of differential display RT-PCR products using fluorescent primers and GENESCAN software.

Differential display reverse transcription PCR (DDRT-PCR) is a procedure used to identify the induction or repression of gene expression. In most DDRT-PCR protocols, radioisotopes are incorporated during PCR and the cDNA products are detected by autoradiography. This report describes the fluorescent labeling of cDNAs and their detection on automated sequencers from PE Applied Biosystems. A fluorescent tag can be incorporated into the PCR product by using either a labeled primer or a labeled dUTP. The fluorescent signals are analyzed by GENESCAN software. Fluorescent DDRT-PCR increases throughput and obviates the handling of hazardous radioisotopes. A PCR cycling profile, expected to give improved reproducibility, is also described. Because amplified cDNAs can't be recovered from the automated sequencer gel, suggestions are given for the identification and recovery of differentially expressed cDNAs.

Animals↗

User-friendly and versatile software for analysis of protein hydrophobicity.

We have developed a simple and flexible program to analyze regional hydrophobicity of a protein from its amino acid (aa) sequence. This program runs as a Microsoft Excel document into which aa sequence can be copied from any Windows-compatible or Macintosh word processor. The program returns the hydrophobicity index of each aa residue and other analyses that can be used to predict transmembrane domains, amphiphilic alpha helices and putative antigenic epitopes in a protein using established algorithms. The program can also be easily modified to test user-defined algorithms and to accommodate non-conventional aa residues or ambiguities in the aa sequence. Simple modification of the program allows direct use of nucleic acid sequence information for various analyses. Graphic visualization of the results is readily achieved using the graphics function of Microsoft Excel. Alternatively, the data can be imported into other graphics software for preparation of publication-quality figures. By running as a document in Microsoft Excel, which can be found in virtually all personal computers, this program provides easy access even to the computer novice.

Amino Acid Sequence↗

WinGene/WinPep: user-friendly software for the analysis of amino acid sequences.

WinGene1.0/WinPep1.2 is a pair of Microsoft Windows programs designed to read nucleotide or amino acid sequence data. These versatile programs have the following capabilities: (i) searches for open reading frames and their translation, (ii) assisting the design of primers for PCR and (iii) calculation of molecular weight, isoelectric point and molar absorbtion coefficients of polypeptides. Furthermore, hydropathic plots and helical wheel displays are easily produced. The programs run with an intuitive Windows interface, contain a comprehensive help file and enable data exchange with other applications by means of the Copy&Paste command. The software is free for academic and noncommercial users.

Amino Acid Sequence↗

REF Select: expert system software for selecting restriction endonucleases for restriction endonuclease fingerprinting.

REF Select, expert system software, has been developed to assist in the selection of optimal restriction endonucleases for restriction endonuclease fingerprinting (REF), a method for rapid and sensitive mutation screening of long DNA segments (1-2 kb). The REF method typically involves six separate digestions with up to two restriction endnonucleases used in each digestion. If done manually, performing a comprehensive review of the large number of possible sets of restriction endonucleases that could be used (over 10(19) in the example presented here) and making an optimal choice is not feasible. Furthermore, the typical nonoptimal manual selection takes approximately 8 h by someone experienced with REF. REF Select enables a comprehensive review of the possible sets and a consistent, objective and fast selection of an optimal set by using a two-step strategy: the selection of sets that meet specific constraints, which is followed by a ranking of those sets by an optimality score. Based on our experience with REF, we chose default selection and ranking parameters to help the user get started quickly. These parameters form a knowledge base that can be customized and then saved by the user. In conclusion, REF Select facilitates the general application of REF by serving as an expert system for the selection of optimal restriction endonucleases. We demonstrated REF Select using an example segment from the human p53 gene.

Algorithms↗

Spreadsheet software for thermodynamic melting point prediction of oligonucleotide hybridization with and without mismatches.

The use of thermodynamic parameters for the calculation of oligonucleotide duplex stability provides the best estimates of oligonucleotide melting temperatures (Tm). Such estimates can be used for evidence-based design of molecular biological experiments in which oligonucleotide melting behavior is a critical issue, such as temperature or denaturing gradient gel electrophoreses, Southern blotting or hybridization probe assays on the LightCycler. We have developed a user friendly program for Tm calculation of matched and mismatched probes using the spreadsheet software Microsoft Excel. The most recently published values for entropy and enthalpy of Watson-Crick paris are used, and salt and oligonucleotide concentrations are considered. The 5' and 3' end stability is calculated for the estimation of primer specificity. In addition, the influence of all possible mutations under a given probe can be calculated automatically. The experimental evaluation of predicted Tm with the LightCycler, based on 14 hybridization probes for different gene loci, showed an excellent fit between measured results and values predicted with the thermodynamic model in 14 matched, 25 single mismatched and 8 two-point mismatched assays (r = 0.98; Sy. x = 0.90; y = 1.01 x -0.38). This program is extremely useful for the design of oligonucleotide probes because the use of probes that do not discriminate with a reasonable Tm difference between wild-type and mutation can be avoided in advance.

Base Pair Mismatch↗

Pharmacokinetic software for the health sciences: choosing the right package for teaching purposes.

Computer assisted learning has an important role in the teaching of pharmacokinetics to health sciences students because it transfers the emphasis from the purely mathematical domain to an 'experiential' domain in which graphical and symbolic representations of actions and their consequences form the major focus for learning. Basic pharmacokinetic concepts can be taught by experimenting with the interplay between dose and dosage interval with drug absorption (e.g. absorption rate, bioavailability), drug distribution (e.g. volume of distribution, protein binding) and drug elimination (e.g. clearance) on drug concentrations using library ('canned') pharmacokinetic models. Such 'what if' approaches are found in calculator-simulators such as PharmaCalc, Practical Pharmacokinetics and PK Solutions. Others such as SAAM II, ModelMaker, and Stella represent the 'systems dynamics' genre, which requires the user to conceptualise a problem and formulate the model on-screen using symbols, icons, and directional arrows. The choice of software should be determined by the aims of the subject/course, the experience and background of the students in pharmacokinetics, and institutional factors including price and networking capabilities of the package(s). Enhanced learning may result if the computer teaching of pharmacokinetics is supported by tutorials, especially where the techniques are applied to solving problems in which the link with healthcare practices is clearly established.

Computer Simulation↗

MultiPrimer: software for multiplex primer design.

This study presents a novel application, MultiPrimer, to assist users to design multiplex PCR primers. MultiPrimer adopts an algorithm based on a genetic algorithm and can efficiently solve the multi-objective optimisation problem. A match pattern model is proposed to speed up examination of the specificity constraint. MultiPrimer is able to find a set of primer pairs simultaneously for a set of gene family sequences and multiple targets for a single cDNA sequence. A public version of the MultiPrimer software is available from http://edith.cse.nsysu.edu.tw/new/software/MultiPrimer.htm.

Algorithms↗

MetaBasis: a web-based database containing metadata on software tools and databases in the field of bioinformatics.

UNLABELLED: We have developed an integrated web-based relational database information system, which offers an extensive search functionality of validated entries containing available bioinformatics computing resources. This system, called MetaBasis, aims to provide the bioinformatics community, and especially newcomers to the field, with easy access to reliable bioinformatics databases and tools. MetaBasis is focused on non-commercial and open-source software tools. AVAILABILITY: http://metabasis.bioacademy.gr/

Computational Biology↗

Software for automating analysis of encoded combinatorial libraries.

This paper describes the applications which are used to automate the analysis of encoded combinatorial libraries. Commercial packages from MDL, Oracle and Agilent are linked with application software written in C/C++, in Microsoft Access and in ChemStation macro language. Encoding correspondence lists for each of up to three synthetic steps are conveniently associated with building block lists using the first application, CodeGen. The second application Decode allows the user to identify the individual beads picked onto a 96-well plate and the pool number for each bead. The decoding chromatography data for each well is then loaded into the program. The chromatography data is used to identify the tags used in the synthesis. Along with the building block information from ISIS/Host, the building block used in each step of the synthesis can be identified. A third routine, Code-to-Structure, takes the coded library building blocks and creates the connection table in ISIS for each structure found by the decode program. For quality control of encoded library synthesis, the decoded structures on a set of beads is compared to the LC/UV/MS data for the ligand cleaved from the same bead. CAPTURE, a GlaxoSmithKline proprietary application, is used to display and analyze the decoded structures and associated mass spectral data. This application uses simple isotopic composition and electrospray ionization rule sets to predict mass spectra and judge the concordance of a structure- mass spectrum data set. An ancillary program, EIC, is used to extract predicted single ion chromatograms from the full scan LC/MS data.

Combinatorial Chemistry Techniques↗