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Evaluation of a data collection tool (TELEform) for palliative care research.

INTRODUCTION: The Alberta Cancer Board Palliative Care Research Initiative (ACBPCRI) encourages province-wide collaboration on palliative care research projects. Because of geographic differences in information system infrastructure, it is necessary to evaluate and adopt a data collection tool that will span the variability in system hardware and software. We assessed TELEform (Cardiff Sofware Inc., Vista CA), an optical recognition-based technology that scans data collection paper forms and exports data to a computer database. We examined work place suitability, data quality, and effective resource utilization (time and cost) during the data collection tool evaluation. METHODS: Two hospices and two hospitals from the cities of Edmonton and Calgary participated in the revised Edmonton Staging System (rESS) project that used TELEform as its data collection tool. The evaluation was conducted over a period of 7 months. Data source such as e-mail and summary notes collected primarily through meetings and discussions with management, caregivers, researchers, and clerical staff was used to assess work practice and resource utilization. Descriptive statistics was employed to examine data quality and resource utilization. RESULTS: One hundred seventy eight patients were recruited during the 7-month trial. The costs and time involved in staff training, logistic support, and equipment startup were found to be reasonable. Data error and missing data were 0.4% and 0.6%, respectively. We initially encountered several problems with TELEform. The optical recognition tool could not easily pick up handwritten data. Furthermore, it was unforgiving in the sense that an error was not correctable by an eraser on the paper form. Data collectors found TELEform usage to be easy and simple because it retained the familiarity of paper-based recording. CONCLUSION: It is important to develop an information infrastructure to support research project data collection for different health settings across health regions. The TELEform based on optical recognition was able to respond to the need for current information processing. We believe that TELEform is a useful tool in terms of work practice, data quality, and resource utilization.

Data Collection↗

Using hypertext and the Internet for structure and management of observational studies.

The evolution of computer and communications systems in the past decade brings new opportunities for increased efficiency and accuracy of observational studies. In ongoing, large scale research studies, the problem of bridging organizational and analytical methods of the past to modern methods of data structure and control can consume considerable effort. A model for information flow in an observational study is sketched, and the flow is found inherently complex. This complexity and corresponding managerial demands are compounded by database file proliferation and by evolution of system hardware and software. Interactive, network-based database mapping and documentation tools are described as currently implemented in an SAS-based system for the management and analysis of several large epidemiologic studies.

Computer Communication Networks↗

Fast interactive real-time volume rendering of real-time three-dimensional echocardiography: an implementation for low-end computers.

Real-time three-dimensional echocardiography (RT3DE) is an innovative cardiac imaging modality. However, partly due to lack of user-friendly software, RT3DE has not been widely accepted as a clinical tool. The object of this study was to develop and implement a fast and interactive volume renderer of RT3DE datasets designed for a clinical environment where speed and simplicity are not secondary to accuracy. Thirty-six patients (20 regurgitation, 8 normal, 8 cardiomyopathy) were imaged using RT3DE. Using our newly developed software, all 3D data sets were rendered in real-time throughout the cardiac cycle and assessment of cardiac function and pathology was performed for each case. The real-time interactive volume visualization system is user friendly and instantly provides consistent and reliable 3D images without expensive workstations or dedicated hardware. We believe that this novel tool can be used clinically for dynamic visualization of cardiac anatomy.

Artifacts↗

XNBC: a simulation tool. Application to the study of neural coding using hybrid networks.

XNBC is a software package for simulating biological neural networks. Two neuron models are available, a leaky integrator model and an ion-conductance model. Inputs to the simulated neurons can be provided by experimental data stored in files, allowing the creation of 'hybrid' networks. Graphic tools are used to describe the modeled neurons as well as the network. Neuron and network parameters can be modified during the simulation, to mimic electrical stimulations and drugs action. The temporal evolution of the network and of selected neurons can be visualized. A point process, frequency or dynamic analysis of the simulator output can be performed. The successive stages of the creation of a hybrid network are explained.

Computer Graphics↗

Conservative extraction of over-represented extensible motifs.

MOTIVATION: The discovery of motifs in biosequences is frequently torn between the rigidity of the model on the one hand and the abundance of candidates on the other. In particular, the variety of motifs described by strings that include 'don't care' (dot) patterns escalates exponentially with the length of the motif, and this gets only worse if a dot is allowed to stretch up to some prescribed maximum length. This circumstance tends to generate daunting computational burdens, and often gives rise to tables that are impossible to visualize and digest. This is unfortunate, as it seems to preclude precisely those massive analyses that have become conceivable with the increasing availability of massive genomic and protein data. Although a part of the problem is endemic, another part of it seems rooted in the various characterizations offered for the notion of a motif, that are typically based either on syntax or on statistics alone. It seems worthwhile to consider alternatives that result from a prudent combination of these two aspects in the model. RESULTS: We introduce and study a notion of extensible motif in a sequence which tightly combines the structure of the motif pattern, as described by its syntactic specification, with the statistical measure of its occurrence count. We show that a combination of appropriate saturation conditions (expressed in terms of minimum number of dots compatible with a given list of occurrences) and the monotonicity of probabilistic scores over regions of constant frequency afford us significant parsimony in the generation and testing of candidate over-represented motifs. The merits of the method are documented by the results obtained in implementation, which specifically targeted protein sequence families. In all cases tested, the motif reported in PROSITE as the most important in terms of functional/structural relevance emerges among the top 30 extensible motifs returned by our algorithm, often right at the top. Of equal importance seems the fact that the sets of all surprising motifs returned in each experiment are extracted faster and come in much more manageable sizes than would be obtained in the absence of saturation constrains. AVAILABILITY: This software will be available for use with the suite of tools at www.research.ibm.com/bioinformatics.

Algorithms↗

MedDietScore: a computer program that evaluates the adherence to the Mediterranean dietary pattern and its relation to cardiovascular disease risk.

Mediterranean dietary traditions have long been associated with lower mortality rates and better health status. The Mediterranean dietary pattern has become customary to be represented in the form of a pyramid, the base of which refers to foods which are suggested to be consumed most frequently and the top of the pyramid to those foods consumed rarely. Recently, an index (diet score) that estimates the adherence level to Mediterranean diet was developed and associated with cardiovascular disease risk and biomarkers. In this work we present a computer program that can easily calculate this diet score, as well as its association with cardiovascular disease risk. The application of this software to the general public might be a useful tool for the reduction of the disease burden related with nutritional habits at population level.

Biomarkers↗

Patchy interspecific sequence similarities efficiently identify positive cis-regulatory elements in the sea urchin.

We demonstrate that interspecific sequence conservation can provide a systematic guide to the identification of functional cis-regulatory elements within a large expanse of genomic DNA. The test was carried out on the otx gene of Strongylocentrotus purpuratus. This gene plays a major role in the gene regulatory network that underlies endomesoderm specification in the embryo. The cis-regulatory organization of the otx gene is expected to be complex, because the gene has three different start sites (X. Li, C.-K. Chuang, C.-A. Mao, L. M. Angerer, and W. H. Klein, 1997, Dev. Biol. 187, 253-266), and it is expressed in many different spatial domains of the embryo. BAC recombinants containing the otx gene were isolated from Strongylocentrotus purpuratus and Lytechinus variegatus libraries, and the ordered sequence of these BACs was obtained and annotated. Sixty kilobases of DNA flanking the gene, and included in the BAC sequence from both species, were scanned computationally for short conserved sequence elements. For this purpose, we used a newly constructed software package assembled in our laboratory, "FamilyRelations." This tool allows detection of sequence similarities above a chosen criterion within sliding windows set at 20-50 bp. Seventeen partially conserved regions, most a few hundred base pairs long, were amplified from the S. purpuratus BAC DNA by PCR, inserted in an expression vector driving a CAT reporter, and tested for cis-regulatory activity by injection into fertilized S. purpuratus eggs. The regulatory activity of these constructs was assessed by whole-mount in situ hybridization (WMISH) using a probe against CAT mRNA. Of the 17 constructs, 11 constructs displayed spatially restricted regulatory activity, and 6 were inactive in this test. The domains within which the cis-regulatory constructs were expressed are approximately consistent with results from a WMISH study on otx expression in the embryo, in which we used probes specific for the mRNAs generated from each of the three transcription start sites. Four separate cis-regulatory elements that specifically produce endomesodermal expression were identified, as well as ubiquitously active elements, and ectoderm-specific elements. We confirm predictions from other work with respect to target sites for specific transcription factors within the elements that express in the endoderm.

Animals↗

Active-site-directed 3D database searching: pharmacophore extraction and validation of hits.

Two new computational tools, PRO_PHARMEX and PRO_SCOPE, for use in active-site-directed searching of 3D databases are described. PRO_PHARMEX is a flexible, graphics-based program facilitating the extraction of pharmacophores from the active site of a target macromolecule. These pharmacophores can then be used to search a variety of databases for novel lead compounds. Such searches can often generate many 'hits' of varying quality. To aid the user in setting priorities for purchase, synthesis or testing, PRO_SCOPE can be used to dock molecules rapidly back into the active site and to assign them a score using an empirical scoring function correlated to the free energy of binding. To illustrate how these tools can add value to existing 3D database software, their use in the design of novel thrombin inhibitors is described.

Binding Sites↗

A knowledge based interpretation system for EMG abnormalities.

The conventional method of diagnosis in electromyography is complex and time consuming, not only due to the large number of parameters, to be considered for diagnosis, but also because of the usual procedure of evaluating the different parameters of EMG signal by visual scanning of the plotted signal. So there is a clear need to make use of computer aided decision support system. In the present work an attempt has been made in the direction of integration into one automated system, the qualitative knowledge of the physician, with possibly sophisticated signal analysis tools which must replace the visual scanning. A software program (in Turbo-C) on a PC-AT has been developed to evaluate the different parameters of MUAP's (motor unit action potential) in a EMG signal. Then an Expert system (in Turbo-Prolog) has been implemented for diagnostic purposes of different muscular abnormalities by making a knowledge base from the different parameters involved in the decision making procedure of clinical electromyography. A hybrid model of rule and frame based Expert system is implemented. An attempt has been made for making a complete system, i.e., for recording, analysis and decision making for diagnosis.

Diagnosis, Computer-Assisted↗

Quantitative analysis of images in erythropoietin doping control.

The software system GASepo has been developed as a tool to visualise and analyse doping (searching for performance-enhancing drugs in sports) with recombinant erythropoietin (rEpo). Digital images derived from the separation of Epo isoforms in gels by iso-electric focusing followed by double blotting and chemiluminescence detection contain spots (bands) of characteristic shape and positions. For Epo doping control, these have to be analysed and evaluated. A relevant element of the analysis is calculation of the reference cutoff-line (COL) to which the doping positivity criterion is related. Based on analysis of the previous method used, a novel method for the COL calculation was developed and validated. The methodology was based on generation of a partition of the image (lane) being processed into a system of adjacent subimages (blocks) and quantitative characterisation of intensity variability within these blocks by a suitably defined measure. The coordinate of the proper COL position, separating the image part with recombinant Epo bands from the homogeneous background, was calculated by minimisation of the difference function of the measures for two adjacent image blocks. The proposed method was tested on real Epo images and validated on a synthetic phantom of the Epo image. The deviations of the COL position are limited by a 7 pixel-wide corridor. For the cases of noise with standard deviations 2300 and 2600, the deviations did not exceed 2 pixels over the whole range of the lane width values. Testing the method on 50 real Epo images originating from different doping-control laboratories worldwide showed its robust behaviour in Epo images.

Computational Biology↗

Automatic gene collection system for genome-scale overview of G-protein coupled receptors in eukaryotes.

We have developed an automatic system for identifying GPCR (G-protein coupled receptor) genes from various kinds of genomes, which is finally deposited in the SEVENS database (http://sevens.cbrc.jp/), by integrating such software as a gene finder, a sequence alignment tool, a motif and domain assignment tool, and a transmembrane helix predictor. SEVENS enables us to perform a genome-scale overview of the "GPCR universe" using sequences that are identified with high accuracy (99.4% sensitivity and 96.6% specificity). Using this system, we surveyed the complete genomes of 7 eukaryotes and 224 prokaryotes, and found that there are 4 to 1016 GPCR genes in the 7 eukaryotes, and only a total of 16 GPCR genes in all the prokaryotes. Our preliminary results indicate that 11 subfamilies of the Class A family, the Class 2(B) family, the Class 3(C) family and the fz/smo family are commonly found among human, fly, and nematode genomes. We also analyzed the chromosomal locations of the GPCR genes with the Kolmogorov-Smirnov test, and found that species-specific families, such as olfactory, taste, and chemokine receptors in human and nematode chemoreceptor in worm, tend to form clusters extensively, whereas no significant clusters were detected in fly and plant genomes.

Animals↗

A model approach to sharing electronic medical records between and within the state hospitals in Turkey.

It has always been a research interest to solve hospital management problems with systematic approach by using modern management tools. Almost all the Hospital Information System (HIS) software packages in Turkey keep track of local transactions in administrative activities and material flow. In state hospitals in Turkey, very little medical information is processed and most of the records are still kept manually and archived on papers. In this paper, a cost-effective, flexible and easy-to-use Hospital Information System model is proposed in order to give better diagnostic and treatment services. It is also demonstrated that this model makes it possible to exchange information between and within the hospitals over Transmission Control Protocol/Internet Protocol (TCP/IP) network. User needs are taken into consideration during model development and the benefits of model implementation to the hospital administration are stated. According to the model proposed in this paper, only a single health care record number (HCRN) is required for a patient to access all her/his medical records stored in different locations, from any state hospital in Turkey.

Computer Simulation↗

HEART: an automated beat-to-beat cardiovascular analysis package using Matlab.

A computer program is described for beat-to-beat analysis of cardiovascular parameters from high-fidelity pressure and flow waveforms. The Hemodynamic Estimation and Analysis Research Tool (HEART) is a post-processing analysis software package developed in Matlab that enables scientists and clinicians to document, load, view, calibrate, and analyze experimental data that have been digitally saved in ascii or binary format. Analysis routines include traditional hemodynamic parameter estimates as well as more sophisticated analyses such as lumped arterial model parameter estimation and vascular impedance frequency spectra. Cardiovascular parameter values of all analyzed beats can be viewed and statistically analyzed. An attractive feature of the HEART program is the ability to analyze data with visual quality assurance throughout the process, thus establishing a framework toward which Good Laboratory Practice (GLP) compliance can be obtained. Additionally, the development of HEART on the Matlab platform provides users with the flexibility to adapt or create study specific analysis files according to their specific needs.

Algorithms↗

Computer-generated graphical presentations: use of multimedia to enhance communication.

Personal computers may be used to create, store, and deliver graphical presentations. With computer-generated combinations of the five media (text, images, sound, video, and animation)--that is, multimedia presentations--the effectiveness of message delivery can be greatly increased. The basic tools are (1) a personal computer; (2) presentation software; and (3) a projector to enlarge the monitor images for audience viewing. Use of this new method has grown rapidly in the business-conference world, but has yet to gain widespread acceptance at medical meetings. We review herein the rationale for multimedia presentations in medicine (vis-à-vis traditional slide shows) as an improved means for increasing audience attention, comprehension, and retention. The evolution of multimedia is traced from earliest times to the present. The steps involved in making a multimedia presentation are summarized, emphasizing advances in technology that bring the new method within practical reach of busy physicians. Specific attention is given to software, digital image processing, storage devices, and delivery methods. Our development of a urology multimedia presentation--delivered May 4, 1996, before the Society for Urology and Engineering and now Internet-accessible at http://www.usrf.org--was the impetus for this work.

Communication↗

Harvesting chemical information from the Internet using a distributed approach: ChemXtreme.

The Internet is a comprehensive resource of chemical information which is at the same time largely unstructured. It provides a wealth of scientific information such as experimental data and requires a suitable automated data mining and analysis tool for its meaningful exploration. The Java based software presented here, ChemXtreme, is developed for harvesting chemical information from the Internet employing the Google API in combination with a distributed client/server text analysis architecture based on JavaRMI. It represents the first and until now the only toolkit for automated structured data retrieval from the Internet which is itself open source. ChemXtreme employs the "search the search engine" strategy, where the URLs returned from the search engine are analyzed further via textual pattern analysis. This process resembles the manual analysis of the hit list, where relevant data are captured and, by means of human intervention, are mined into a format suitable for further analysis. ChemXtreme on the other hand transforms chemical information automatically into a structured format suitable for storage in databases and further analysis and also provides links to the original information source. The query data retrieved from the search engine by the server is encoded, encrypted, and compressed and then sent to all the participating active clients in the network for parsing. Relevant information identified by the clients on the retrieved Web sites is sent back to the server, verified, and added to the database for data mining and further analysis. The distributed further analysis of URLs in a client/server architecture scales very favorably, thus producing only minimal overhead.

Chemistry↗

Open computing grid for molecular science and engineering.

Grid is an emerging infrastructure for distributed computing that provides secure and scalable mechanisms for discovering and accessing remote software and data resources. Applications built on this infrastructure have great potential for addressing and solving large scale chemical, pharmaceutical, and material science problems. The article describes the concept behind grid computing and will present the OpenMolGRID system that is an open computing grid for molecular science and engineering. This system provides grid enabled components, such as a data warehouse for chemical data, software for building QSPR/QSAR models, and molecular engineering tools for generating compounds with predefined chemical properties or biological activities. The article also provides an overview about the availability of chemical applications in the grid.

Journal Article↗

LEA3D: a computer-aided ligand design for structure-based drug design.

We present an improved version of the program LEA developed to design organic molecules. Rational drug design involves finding solutions to large combinatorial problems for which an exhaustive search is impractical. Genetic algorithms provide a tool for the investigation of such problems. New software, called LEA3D, is now able to conceive organic molecules by combining 3D fragments. Fragments were extracted from both biological compounds and known drugs. A fitness function guides the search process in optimizing the molecules toward an optimal value of the properties. The fitness function is build up by combining several independent property evaluations, including the score provided by the FlexX docking program. One application in de novo drug design is described. The example makes use of the structure of Mycobacterium tuberculosis thymidine monophosphate kinase to generate analogues of one of its natural substrates. Among 22 tested compounds, 17 show inhibitory activity in the micromolar range.

Algorithms↗

Exploring prokaryotic taxonomy.

Techniques drawn from exploratory data analysis, using tools found in the S-Plus statistical software package, have been used to inspect and maintain the Bergey's Taxonomic Outline and to move towards an automated and community-based means of working on the outline. These techniques can be used to classify sequences from unnamed and uncultured organisms, to visualize errors in the taxonomy or in the curation of the sequences, to suggest emendations to the taxonomy or to the classification of extant species and to complement the visualization of phylogenies based on treeing methods. A dataset of more than 9200 aligned small-subunit rRNA sequences was analysed in the context of the current taxonomic outline. The use of the algorithm in exploring and modifying the taxonomy is illustrated with an example drawn from the family Comamonadaceae.

Bacteria↗