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A formal method to resolve temporal mismatches in clinical databases.

Overcoming data heterogeneity is essential to the transfer of decision-support programs to legacy databases and to the integration of data in clinical repositories. Prior methods have focused primarily on problems of differences in terminology and patient identifiers, and have not addressed formally the problem of temporal data heterogeneity, even though time is a necessary element in storing, manipulating, and reasoning about clinical data. In this paper, we present a method to resolve temporal mismatches present in clinical databases. This method is based on a foundational model of time that can formalize various temporal representations. We use this temporal model to define a novel set of twelve operators that can map heterogeneous time-stamped data into a uniform temporal scheme. We present an algorithm that uses these mapping operators, and we discuss our implementation and evaluation of the method as a software program called Synchronus.

Algorithms↗

Integrated power controllers and RF data transmitters for totally implantable telemetry.

Data transmitters and power/source controllers are common elements in all totally implantable instrumentation systems. Two custom-designed integrated circuits have been developed for these elements and have significant impact on the realization of compact reliable telemetry packages. The first is an elapsed-time power switch that can remotely turn on implanted battery-powered systems with a short RF burst; to prevent accidental battery drainage, it will automatically turn off after a preprogrammed time (1-5 min). The second is a precision RF transmitter capable of operation up to 125 MHz in either FM or pulse-coded format and requires only two nonintegrated inductors. These IC systems are basic building blocks for a large number of totally implantable telemetry applications.

Electric Power Supplies↗

Life cycle of a data warehousing project in healthcare.

Hill Physicians Medical Group (and its medical management firm, PriMed Management) early on recognized the need for a data warehouse. Management demanded that data from many sources be integrated, cleansed, and formatted. As a first step, an operational data store (ODS) was built and populated with data from the main transactional system; encounter data were added. The ODS has served its purpose well and has whetted management's appetite for more information and faster, more reliable access, all in one location. PriMed hired Annams Systems Consulting (Annams) for this effort. A team was formed, made up of consultants from Annams and members of PriMed's information services (IS) team. The "classical" approach is being taken: enhancing the ODS, which is largely normalized in structure, and integrating data from various sources, along with enforcing business rules. The team is designing and implementing data marts and a "star schema" style of data modeling--a useful tool for management to evaluate results before investing further.

California↗

Trans-activation and stable integration of the maize transposable element Ds cotransfected with the Ac transposase gene in transgenic rice plants.

To develop an efficient gene tagging system in rice, a plasmid was constructed carrying a non-autonomous maize Ds element in the untranslated leader sequence of a hygromycin B resistance gene fused with the 35S promoter of cauliflower mosaic virus. This plasmid was cotransfected by electroporation into rice protoplasts together with a plasmid containing the maize Ac transposase gene transcribed from the 35S promoter. Five lines of evidence obtained from the analyses of hygromycin B-resistant calli, regenerated plants and their progeny showed that the introduced Ds was trans-activated by the Ac transposase gene in rice. (1) Cotransfection of the two plasmids is necessary for generation of hygromycin B resistant transformants. (2) Ds excision sites are detected by Southern blot hybridization. (3) Characteristic sequence alterations are found at Ds excision sites. (4) Newly integrated Ds is detected in the rice genome. (5) Generation of 8 bp target duplications is observed at the Ds integration sites on the rice chromosomes. Our results also show that Ds can be trans-activated by the transiently expressed Ac transposase at early stages of protoplast culture and integrated stably into the rice genome, while the cotransfected Ac transposase gene is not integrated. Segregation data from such a transgenic rice plant carrying no Ac transposase gene showed that four Ds copies were stably integrated into three different chromosomes, one of which also contained the functional hph gene restored by Ds excision. The results indicate that a dispersed distribution of Ds throughout genomes not bearing the active Ac transposase gene can be achieved by simultaneous transfection with Ds and the Ac transposase gene.

Base Sequence↗

Bringing metabolic networks to life: integration of kinetic, metabolic, and proteomic data.

BACKGROUND: Translating a known metabolic network into a dynamic model requires reasonable guesses of all enzyme parameters. In Bayesian parameter estimation, model parameters are described by a posterior probability distribution, which scores the potential parameter sets, showing how well each of them agrees with the data and with the prior assumptions made. RESULTS: We compute posterior distributions of kinetic parameters within a Bayesian framework, based on integration of kinetic, thermodynamic, metabolic, and proteomic data. The structure of the metabolic system (i.e., stoichiometries and enzyme regulation) needs to be known, and the reactions are modelled by convenience kinetics with thermodynamically independent parameters. The parameter posterior is computed in two separate steps: a first posterior summarises the available data on enzyme kinetic parameters; an improved second posterior is obtained by integrating metabolic fluxes, concentrations, and enzyme concentrations for one or more steady states. The data can be heterogeneous, incomplete, and uncertain, and the posterior is approximated by a multivariate log-normal distribution. We apply the method to a model of the threonine synthesis pathway: the integration of metabolic data has little effect on the marginal posterior distributions of individual model parameters. Nevertheless, it leads to strong correlations between the parameters in the joint posterior distribution, which greatly improve the model predictions by the following Monte-Carlo simulations. CONCLUSION: We present a standardised method to translate metabolic networks into dynamic models. To determine the model parameters, evidence from various experimental data is combined and weighted using Bayesian parameter estimation. The resulting posterior parameter distribution describes a statistical ensemble of parameter sets; the parameter variances and correlations can account for missing knowledge, measurement uncertainties, or biological variability. The posterior distribution can be used to sample model instances and to obtain probabilistic statements about the model's dynamic behaviour.

Bayes Theorem↗

Clinical and biochemical aspects of depressive disorders: I. Introduction, classification, and research techniques.

The present review focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. In addition to integrating these data, problems and future directions in this research are discussed. The review is presented in three parts. This study, Part I, describes diagnostic classification schemes for depressive disorders, some epidemiological and biological correlates of the classifications, and research techniques for investigating depressive disorders. Research techniques include animal models, human biochemical techniques, and Positron Emission Tomography. In a future issue, Part II will discuss various transmitter/receptor theories of depressive disorders, e.g., noradrenergic, serotonergic, cholinergic, and dopaminergic, GABAergic, and peptidergic theories. Also in a future issue, Part III will discuss treatments for depression and some of the controversies in the field.

Depressive Disorder↗

Artificial intelligence in medicine and male infertility.

MAIN PROBLEM: fertility data is inadequately assessed by traditional statistical methods for a variety of reasons. First, the principal test of male fertility potential, the Semen Analysis (SA) is a composite of several dissimilar parameters, and the SA and other laboratory tests of fertility potential reflect physiological mechanisms that interact in complex ways. Second, patient data is often fragmented, obtained from multiple sources. Importantly, 2 patients are required for the final result. METHODS: Novel and powerful computational method, the neural network, was explored to analyze fertility data. An integrated series of programs was written in the C computer language to implement a back propagation algorithm. A model data analysis system was chosen, predicting the penetration of zona-free hamster ova by sperm (Sperm Penetration Assay (SPA)) and the distance travelled by the farthest swimming sperm (Penetrak Assay) from the SA, for these 2 assays are generally believed by the reproductive medical community to be independent of the SA. The classification accuracy of the neural network was compared to 2 standard statistical methods, linear discriminant function analysis (LDFA) and quadratic discriminant function analysis (QDFA). RESULTS: A neural network could be trained to correctly predict the Penetrak result in over 80% of assays it had not previously encountered, and another network could predict the SPA outcome in nearly 70%. The neural network was superior to LDFA and QDFA in predicting both assay outcomes (for Penetrak: LDFA = 64%, QDFA = 69%; for SPA: LDFA = 65%, QDFA = 45%).(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Intraoperative visualization of the pyramidal tract by diffusion-tensor-imaging-based fiber tracking.

Functional neuronavigation allows intraoperative visualization of cortical eloquent brain areas. Major white matter tracts, such as the pyramidal tract, can be delineated by diffusion-tensor-imaging based fiber tracking. These tractography data were integrated into 3-D datasets applied for neuronavigation by rigid registration of the diffusion images with standard anatomical image data so that their course could be superimposed onto the surgical field during resection of gliomas. Intraoperative high-field magnetic resonance imaging was used to compensate for the effects of brain shift, which amounted up to 8 mm. Despite image distortion of echo planar images, which was identified by non-linear registration techniques, navigation was reliable. In none of the 19 patients new postoperative neurological deficits were encountered. Intraoperative visualization of major white matter tracts allows save resection of gliomas near eloquent brain areas. A possible shifting of the pyramidal tract has to be taken into account after major tumor parts are resected.

Adult↗

Cost-effectivenes of paclitaxel plus cisplatin in advanced non-small-cell lung cancer.

The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized trial comparing: paclitaxel 135 mg m(-2) by 24-h intravenous (i.v.) infusion + cisplatin; paclitaxel 250 mg m(-2) by 24-h i.v. infusion + cisplatin + granulocyte colony-stimulating factor (G-CSF); and standard etoposide/cisplatin in patients with stage IIIb or IV NSCLC. We also modelled the regimens with paclitaxel 135 mg m(-2) + cisplatin administered as an outpatient by 3-h infusion, as clinical data suggest that this is equivalent to 24-h infusion. We collected costing data from the Ottawa Regional Cancer Centre and applied it to the resources consumed in the randomized trial. We integrated these data into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated with each regimen. The POHEM model assigned diagnostic work-up, treatment, disease progression and survival characteristics to each individual in these cohorts and tabulated the costs associated with each. We did sensitivity analyses around the costs of chemotherapy and its administration, and the survival differences between the two regimens. All costs are in 1997 Canadian dollars ($1.00 Canadian approximately Pound 0.39 sterling). The perspective is that of the Canadian health care system. In the trial, the two paclitaxel-containing arms had almost identical survival curves with a median survival of 9.7 months compared with 7.4 months for etoposide/cisplatin. As administered in the trial, paclitaxel/cisplatin cost $76,370 per life-year gained (LYG) and paclitaxel/cisplatin/G-CSF $138,578 per LYG relative to etoposide/cisplatin. However, when modelled as an outpatient 3-h infusion, paclitaxel/cisplatin was moderately cost-effective at $30,619 per LYG. When compared with historical controls treated with best supportive care, this regimen of paclitaxel/cisplatin cost $4539 per LYG. Assuming a 3-h paclitaxel infusion yields the same survival advantage as the 24-h infusion did in the randomized trial, paclitaxel/cisplatin is a cost-effective improvement over standard etoposide/cisplatin for patients with advanced non-small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Imaging databases and neuroscience.

Brain atlases are equivalent to neuroimage databases provided an appropriate coordinate system to enable multisubject comparisons, along with comprehensive descriptions of the data, are included. Warping tools, visualization, and statistical analyses that accommodate the various neuroimaging modalities can be used to integrate diverse data and form comprehensive maps describing a particular subpopulation's brain structure and function. By linking task performance and genetic information to brain morphology, complex interrelations between genotype, phenotype, and behavior can be established. Several examples of these multimodal, multisubject atlases, including those that are dynamic, are presented.

Animals↗

[HeiDATAProViT--a universal software tool for evaluating biomedical data].

Evaluation of large sets of biomedical data can be divided into three universal stages: 1. archiving of clinical data together with data obtained from measurements, 2. processing of numerical data using signal processing algorithms and 3. visualizing the results. In this paper a software is presented which tightly integrates a data base under MS Access and the possibilities for data processing and visualization offered by Matlab. This software tool provides an interface between a data base containing large sets of biomedical data and an extensible pool of evaluation and visualization procedures. It can serve both as an instrument for data processing in clinical routine and an important component for evaluation of measurement data in any medical research project.

Algorithms↗

Creating notifications tailored for individual workers by using a database: a conceptual framework and its application.

Although prevention strategies to assure good mental health in the workplace have become important, worker notification in studies using psychometric tests has rarely been discussed. Until now it has been difficult to prepare a large number of notifications that are tailored well for individual workers. We have developed a system to create notifications that explain the results for individual workers in plain language using a relational database (RDB). First, scores for each test were divided into categories and the workers' data was classified. Then, explanations were written for each category. RDB software read component files into a database file, integrated all data, and printed out notifications. After the system was developed, we realized its high potential for use in occupational health care, as well as in many other fields. We also report an example of its application.

Databases, Factual↗

Text management in a healthcare information system.

Virtually there. Natural language or textual data in the patient record plays a critical role in medicine. Read about the innovative system LDS Hospital has implemented to integrate textual data into the computerized patient record.

Authorship↗

Pulmonary artery pressure monitoring: when, how, and what else to use.

The integration of data from a pulmonary artery catheter when used as part of a goal-directed plan of care may benefit certain groups of critically ill patients. Integral to the successful use of the pulmonary artery catheter is to accurately obtain and interpret invasive pressure monitoring data. This article addresses commonly asked clinical questions and considerations for decision making under complex care conditions, such as obtaining hemodynamic measurements when the patient is prone or has marked respiratory pressure variations or increased intraabdominal pressure. Recommendations to optimize the invasive pressure monitoring system are presented. Finally, functional hemodynamic indices, which are more sensitive and specific indices than static indices (pulmonary artery and right artrial pressure) of the ability to respond to a fluid bolus, will be introduced.

Algorithms↗

AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data.

AntiJen is a database system focused on the integration of kinetic, thermodynamic, functional, and cellular data within the context of immunology and vaccinology. Compared to its progenitor JenPep, the interface has been completely rewritten and redesigned and now offers a wider variety of search methods, including a nucleotide and a peptide BLAST search. In terms of data archived, AntiJen has a richer and more complete breadth, depth, and scope, and this has seen the database increase to over 31,000 entries. AntiJen provides the most complete and up-to-date dataset of its kind. While AntiJen v2.0 retains a focus on both T cell and B cell epitopes, its greatest novelty is the archiving of continuous quantitative data on a variety of immunological molecular interactions. This includes thermodynamic and kinetic measures of peptide binding to TAP and the Major Histocompatibility Complex (MHC), peptide-MHC complexes binding to T cell receptors, antibodies binding to protein antigens and general immunological protein-protein interactions. The database also contains quantitative specificity data from position-specific peptide libraries and biophysical data, in the form of diffusion co-efficients and cell surface copy numbers, on MHCs and other immunological molecules. The uses of AntiJen include the design of vaccines and diagnostics, such as tetramers, and other laboratory reagents, as well as helping parameterize the bioinformatic or mathematical in silico modeling of the immune system. The database is accessible from the URL: http://www.jenner.ac.uk/antijen.

Journal Article↗

Approaches and informatics tools to assist in the integration of similar clinical research questionnaires.

OBJECTIVE: The integration of similar clinical research questionnaires is a complex process that can benefit from informatics approaches and tools that provide a systematic structure for performing mapping and integration. This systematic approach is necessary to address complex issues in integration such as data heterogeneity, differing levels of granularity of questions and responses, and other issues involving semantic differences. Informatics tools and approaches have been successfully applied to various standard clinical vocabulary integration processes but not for questionnaire integration or mapping. METHODS: A systematic approach to questionnaire integration was developed in the context of a collaboration of researchers using Trial/DB, a database designed to support clinical research. This approach was applied to the integration of questionnaires involving breast cancer risk factors from each of three research sites. RESULTS: From 375 questions on the three original questionnaires, we identified 65 concepts that were measured by two or three of the sites. An algorithm was developed and used to formalize the process of mapping questions and answers across the questionnaires. The approach was applied to previously collected data and prospective data in disparate data-base systems to import and merge the data from these three sites into Trial/DB. CONCLUSION: Informatics tools that support a systematic approach to mapping questionnaires can be used throughout the research process from questionnaire integration and creation, legacy data integration to data library maintenance and curation.

Biomedical Research↗

Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance.

That endogenous retrovirus (ERV) is present within the placenta of humans and other mammals has been known for the past 25 years, but the significance of this observation is still not fully understood. Much molecular biological data have emerged in recent years to support the earlier electron microscopic data on the presence of placental ERV. The evidence for ERV in animal and human placental tissue is presented, then integrated with data on the presence of ERV in a range of other tissues, in particular teratocarcinoma cells. Placental invasiveness and maternal immunosuppression are then discussed in relation to metalloproteinase secretion, the immunosuppressive potential of retroviruses, and placental growth factors, while the evidence for a functional link between placental protooncogenes and trophoblast malignancy is reviewed. Finally, placental development, structure, and life span are discussed within an evolutionary context. The hypothesis that one or more ancient trophoblastic ERVs could have played a role in the evolution and divergence of all placental mammals is evaluated.

Animals↗

Is the use of QOL data really any different than other medical testing?

QOL data and routine clinical data such as laboratory data, whether used in clinical practice or research, can be viewed by clinicians in the same way. Both provide important patient-related information using instruments which are reliable and valid. Both require that the clinician or researcher understand how to utilize and interpret the data and gain comfort with doing so through experience. It is through this repeated usage of QOL data that clinicians will, hopefully, come to accept QOL data as a routine and invaluable part of their practice and view it just as they view other clinical data. Whether it is a clinician looking at QOL data or laboratory data for the first time, or a clinical researcher including QOL data in a clinical trial for the first time, training, repetitive use, and experience is necessary to feel comfortable with integrating the data to recommend an appropriate clinical action or to capture the meaningful effect.

Clinical Laboratory Techniques↗