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PubMed2004

The Unified Medical Language System (UMLS): integrating biomedical terminology.

The Unified Medical Language System (http://umlsks.nlm.nih.gov) is a repository of biomedical vocabularies developed by the US National Library of Medicine. The UMLS integrates over 2 million names for some 900,000 concepts from more than 60 families of biomedical vocabularies, as well as 12 million relations among these concepts. Vocabularies integrated in the UMLS Metathesaurus include the NCBI taxonomy, Gene Ontology, the Medical Subject Headings (MeSH), OMIM and the Digital Anatomist Symbolic Knowledge Base. UMLS concepts are not only inter-related, but may also be linked to external resources such as GenBank. In addition to data, the UMLS includes tools for customizing the Metathesaurus (MetamorphoSys), for generating lexical variants of concept names (lvg) and for extracting UMLS concepts from text (MetaMap). The UMLS knowledge sources are updated quarterly. All vocabularies are available at no fee for research purposes within an institution, but UMLS users are required to sign a license agreement. The UMLS knowledge sources are distributed on CD-ROM and by FTP.

Animals↗
PubMed1995

The Electronic View Box: a software tool for radiation therapy treatment verification.

PURPOSE: We have developed a software tool for interactively verifying treatment plan implementation. The Electronic View Box (EVB) tool copies the paradigm of current practice but does so electronically. A portal image (online portal image or digitized port film) is displayed side by side with a prescription image (digitized simulator film or digitally reconstructed radiograph). The user can measure distances between features in prescription and portal images and "write" on the display, either to approve the image or to indicate required corrective actions. The EVB tool also provides several features not available in conventional verification practice using a light box. METHODS AND MATERIALS: The EVB tool has been written in ANSI C using the X window system. The tool makes use of the Virtual Machine Platform and Foundation Library specifications of the NCI-sponsored Radiation Therapy Planning Tools Collaborative Working Group for portability into an arbitrary treatment planning system that conforms to these specifications. The present EVB tool is based on an earlier Verification Image Review tool, but with a substantial redesign of the user interface. A graphical user interface prototyping system was used in iteratively refining the tool layout to allow rapid modifications of the interface in response to user comments. RESULTS: Features of the EVB tool include 1) hierarchical selection of digital portal images based on physician name, patient name, and field identifier; 2) side-by-side presentation of prescription and portal images at equal magnification and orientation, and with independent grayscale controls; 3) "trace" facility for outlining anatomical structures; 4) "ruler" facility for measuring distances; 5) zoomed display of corresponding regions in both images; 6) image contrast enhancement; and 7) communication of portal image evaluation results (approval, block modification, repeat image acquisition, etc.). CONCLUSION: The EVB tool facilitates the rapid comparison of prescription and portal images and permits electronic communication of corrections in port shape and positioning.

Hospital Records↗
PubMed2000

"Permanent" records: experience with data migration in radiology information system and picture archiving and communication system replacement.

In the replacement of both a radiology information system (RIS) and a picture archiving and communication system (PACS) archive, data were migrated from the prior system to the new system. We report on the process, the time and resources required, and the fidelity of data transfer. We find that for two PACS archives, both organized according to the Digital Imaging and Communications in Medicine (DICOM) information model, data may be transferred with full fidelity, but the time required for transfer is significant. Transfer from off-line backup media was found to be faster than transfer from our robotic tape library. In contrast, the RIS replacement required extensive labor to translate prior data between dissimilar information models, and some data were inevitably lost in the translation. Standards for RIS information models are needed to promote the migration of data without loss of content.

Computer Storage Devices↗
PubMed1997

Comparative genomic hybridization reveals a partial de novo trisomy 6q23-qter in an infant with congenital malformations: delineation of the phenotype.

We report the use of comparative genomic hybridization (CGH) to define the origin of a small extra segment (unidentifiable by classical cytogenetics) present in a de novo add(13)q34 chromosome that we found in the karyotype of a newly born boy with congenital heart defects, brain anomalies and dysmorphic signs. Initial investigation with fluorescence in situ hybridization (FISH) and a chromosome-13-specific library revealed that the excess material was not derived from chromosome 13. To uncover the origin of the unknown chromosome material, CGH was carried out on DNA isolated from blood lymphocytes of the patient. By using a conventional fluorescence microscope with no digital imaging devices, a single distinct region with gain of fluorescent intensity was observed on distal chromosome 6q. Confirmation of this finding by FISH with a chromosome-6-specific paint and a subtelomeric yeast artificial chromosome clone from 6q26-q27, in combination with the band morphology of the small extra chromosomal segment, allowed us to diagnose the additional material as being derived from chromosome 6q23-qter. FISH with a telomere 13q probe detected a terminal deletion of 13q34-qter on the derivative chromosome 13, indicating that the der(13) was a result of a translocation event. Genotyping of the hypervariable apolipoprotein (a) gene, which lies within 6q26-q27, showed that the additional chromosome 6 material was inherited from the mother. The karyotype of the proposita is therefore: 46,XY,-13,+der(13)t(6;13)(q23;q34) de novo (mat). Our results confirm the usefulness of CGH as an attractive alternative method for the characterization of constitutional small genetic imbalances and contribute to the delineation of the trisomy 6q23-qter phenotype.

Abnormalities, Multiple↗
PubMed2001

The portable UNIX programming system (PUPS) and CANTOR: a computational environment for dynamical representation and analysis of complex neurobiological data.

Many problems in analytical biology, such as the classification of organisms, the modelling of macromolecules, or the structural analysis of metabolic or neural networks, involve complex relational data. Here, we describe a software environment, the portable UNIX programming system (PUPS), which has been developed to allow efficient computational representation and analysis of such data. The system can also be used as a general development tool for database and classification applications. As the complexity of analytical biology problems may lead to computation times of several days or weeks even on powerful computer hardware, the PUPS environment gives support for persistent computations by providing mechanisms for dynamic interaction and homeostatic protection of processes. Biological objects and their interrelations are also represented in a homeostatic way in PUPS. Object relationships are maintained and updated by the objects themselves, thus providing a flexible, scalable and current data representation. Based on the PUPS environment, we have developed an optimization package, CANTOR, which can be applied to a wide range of relational data and which has been employed in different analyses of neuroanatomical connectivity. The CANTOR package makes use of the PUPS system features by modifying candidate arrangements of objects within the system's database. This restructuring is carried out via optimization algorithms that are based on user-defined cost functions, thus providing flexible and powerful tools for the structural analysis of the database content. The use of stochastic optimization also enables the CANTOR system to deal effectively with incomplete and inconsistent data. Prototypical forms of PUPS and CANTOR have been coded and used successfully in the analysis of anatomical and functional mammalian brain connectivity, involving complex and inconsistent experimental data. In addition, PUPS has been used for solving multivariate engineering optimization problems and to implement the digital identification system (DAISY), a system for the automated classification of biological objects. PUPS is implemented in ANSI-C under the POSIX.1 standard and is to a great extent architecture- and operating-system independent. The software is supported by systems libraries that allow multi-threading (the concurrent processing of several database operations), as well as the distribution of the dynamic data objects and library operations over clusters of computers. These attributes make the system easily scalable, and in principle allow the representation and analysis of arbitrarily large sets of relational data. PUPS and CANTOR are freely distributed (http://www.pups.org.uk) as open-source software under the GNU license agreement.

Algorithms↗
PubMed1999

The applications of FISH in tumor pathology.

The current FISH technology was greatly improved during the past 10 years. A large number of cosmids and yeast (YACs), bacterial (BACs), phage P1 derived (PACs) artificial chromosomes have been rapidly mapped and are useful as probes. In parallel, methods were established to specifically "paint" entire chromosomes or chromosome segments. Using these chromosome libraries as probes, complex rearrangements and marker chromosomes can be identified irrespective of their banding pattern. Ripetitive DNA probes specific for each chromosome centromere (alpha satellite sequences), are also available and may be used to identify specific aneuploidies. The use of sensitive digital imaging systems on the basis of "colour" rather than morphology increased the improvement of new FISH techniques. In particular, colour karyotyping results in the differential colour display of all human chromosomes. Another recent development of FISH technology is comparative genome hybridization (CGH), a genome-scanning technique that allows to identify and map chromosomal and subchromosomal gains and losses. FISH techniques may be used to investigate chromosome abnormalities not only on metaphasic chromosomes but also on interphasic nuclei. Any given tissue or cell source, such as sections of frozen tumors, imprinted cells, cultured cells, paraffin-embedded sections may be hybridized. The interphasic FISH may be extremely informative in tumor pathology even if the results are dependent on a good technical quality and adequate controls.

Cell Nucleus↗
PubMed1998

Fast-painting of human metaphase spreads using a chromosome-specific, repeat-depleted DNA library probe.

For chromosome painting, in situ suppression of repetitive DNA sequences has been well established. Such standard protocols usually require large amounts of Cot-I DNA. Recently, it has become possible to deplete repetitive DNA sequences from library probes by magnetic purification and PCR-assisted affinity chromatography. These "repeat-depleted library probes" appear to be extremely useful for Fast-FISH, a technique that omits denaturing chemical agents such as formamide in the hybridization buffer, resulting in a substantial acceleration and simplification of the complete protocol. Shown here is the application of Fast-FISH to a repeat-depleted, directly fluorochrome-labeled library probe of the q-arm of chromosome 15 (Fast-Painting) for human lymphocyte metaphase spreads. Following painting without Cot-I DNA and without formamide, visual inspection revealed sufficient chromosome painting after a few hours of hybridization. The fluorescence signals of the labeling sites were analyzed after hybridization times of 1 and 2 h (in one case, 4 h) using digital fluorescence microscopy. The painting efficiency expressed in values of relative fluorescence signal ratios was quantitatively evaluated by image analysis using line-scan procedures and area-morphometry of mean luminance. Two preparation protocols (ethanol dehydration without and with RNase A treatment followed by pepsin digestion for four different exposure times) were compared. These results indicated that RNase A treatment and pepsin digestion are steps that can be omitted.

Adult↗
PubMed1989

A reference shape library for computer aided socket design in above-knee prostheses.

A Reference Library of socket shapes for an Above-Knee Computer Aided Socket Design (CASD) System has been created. This library forms part of a more general CASD System (Dean & Saunders, 1985; Novicov & Foort, 1982). It consists of a matrix of reference shapes representing above-knee socket characteristics and is based upon skeletal structure, residuum length and tissue mass. A set of 27 biomechanical reference shapes in the form of male plaster casts were produced by a combination of CNC milling and traditional artisan techniques. Each reference shape was digitized to obtain its cylindrical coordinates. Cross-sectional areas and tissue distributions within each shape and between the shapes were analyzed, modified and then stored numerically within the computer for further implementation of the CASD System for the above-knee amputees. The creation and the analysis of the reference shape data is described.

Artificial Limbs↗
PubMed2005

Parallel synthesis of 5-cyano-6-aryl-2-thiouracil derivatives as inhibitors for hepatitis C viral NS5B RNA-dependent RNA polymerase.

From random screening of our compound libraries, we identified a hit compound with an IC50 of 27 microM against hepatitis C viral NS5B RNA-dependent RNA polymerase. By using a parallel synthetic strategy, a series of its derivatives were synthesized. From their anti-HCV activity screening, compounds with single digital 3.8 micromolar activity were obtained.

Antiviral Agents↗
PubMed2006

Characterization and quantification of mRNA transcripts in ejaculated spermatozoa of fertile men by serial analysis of gene expression.

BACKGROUND: Accumulated evidence proves that mature spermatozoa contain a complex yet specific array of mRNA, which could provide information on the past events of spermatogenesis. OBJECTIVE: To quantitatively microdissect these mRNA transcripts by a digital approach. METHODS: Serial analysis of gene expression (SAGE) was used to study the mRNA transcripts from ejaculate of a fertile individual and of a pool of 10 fertile men. Online DAVID software suite was also utilized to cluster the UniGene data. RESULTS: A SAGE library from the individual produced 20,237 raw tags representing 2459 unique tags and that from pooled 10 men generated 21,052 raw tags representing 2712 unique tags. When the unique tags occurring > or = 4 times were analysed, 564 overlapping tags were produced by 638 unique tags from the individual and 682 from the pooled library. Fifty-four of these overlapped tags were considered to be novel genes. Online analysis of the overlapping tags revealed 25 functional gene groups, with the dominant one comprising 96 nuclear protein genes involving transcription and transcription regulation and also a group with 84 ribosomal subunit genes involving protein synthesis. CONCLUSION: A SAGE analysis of ejaculate from fertile men has revealed a large number of transcripts, which occur in steady frequencies and probably have important roles in spermatogenesis and fertilization.

Adult↗
PubMed1989

Microprocessor-controlled vector scan display system for generation of real-time visual stimuli.

The paper describes a low-cost, versatile, widely applicable digital display system in which a high-resolution, high-intensity display unit is driven by a real-time vector scan controller. The actual online display control of this device is preceded by an offline software stimulus-frame editor, designed to create and support a library of stimulus patterns (standard frames without any timing information and without any referencing to a special display co-ordinate system). The display times can be set individually for each single frame (containing at maximum 1023 pixels) with relative ease. Display frequency is set to 1 kHz. Writing time per pixel is less than 1 microsecond. A graphic display system like the one presented in this paper can be applied to generate a variety of real-time optical stimuli, such as intensity modulation of single spots or distinct display areas, abrupt displacements of a certain pattern, continuous movement or onset and offset of steady motion of a pattern.

Animals↗
PubMed2005

Building research administration applications for the academic health center: a case study.

The academic health center information environment is saturated with information of varying quality and overwhelming quantity. The most significant challenge is transforming data and information into knowledge. The University of Cincinnati Medical Center's (UCMC) focus is to develop an information architecture comprising data structures, Web services, and user interfaces that enable individuals to manage the information overload so that they can create new knowledge. UCMC has accomplished much of what is reported in this article with the help of a four-year Integrated Advanced Information Management Systems (IAIMS) operation grant awarded by the National Library of Medicine in 2003. In the UCMC vision for knowledge management, individuals have reliable, secure access to information that is filtered, organized, and highly relevant for specific tasks and personal needs. Current applications and tool sets will evolve to become the next generation knowledge management applications or smart digital services. When smart digital services are implemented, silo applications will disappear. A major focus of UCMC's IAIMS grant is research administration. Testing and building out existing and new research administration applications and digital services is underway. The authors review UCMC's progress and results in developing a software architecture, tools, and services for research administration. Included are sections on the evolution to full integration, the impact of the work at UCMC to date, lessons learned during this research and development process, and future plans and needs.

Academic Medical Centers↗
PubMed2006

Digital tools for collecting data from cervigrams for research and training in colposcopy.

Colposcopy is a critical part of gynecologic practice but has documented deficiencies, including lack of correlation between the colposcopic appearance and the severity of underlying neoplasia, limited reproducibility, and difficulty in the optimal placement of colposcopically directed biopsies. In a collaborative effort to improve colposcopy, we are analyzing digitized cervigram images from National Cancer Institute-funded studies. Specifically, the National Cancer Institute has collected close to 100,000 cervigrams, digitized to create a database of images of the uterine cervix for research, training, and education. In addition to the cervigram images, this database contains clinical, cytologic, and molecular information at multiple examinations of 15,000 women, with password and ID labeling strategies to protect patient privacy. The National Library of Medicine has designed two web-accessible software tools. The Boundary Marking Tool allows experts on colposcopy to perform an evaluation of the pictures and to mark boundary regions of normal and abnormal regions of the uterine cervix; these evaluations are collected and saved in the database. The Multimedia Database Tool enables retrieval of test and image biomedical data according to specific queries, for example, all women with cervical intraepithelial neoplasia 3 whose cytologic results are atypical squamous cells of undetermined significance. The resource soon will be available as an open resource, via a teaching tool coordinated by a database manager, which will permit a variety of applications for teaching and research. In this article, we describe the perceived need for the resource and its components.

Biomedical Research↗
PubMed1991

Expression of the homeobox Hox-4 genes and the specification of position in chick wing development.

The chicken Hox-4 homeogenes, like those of the mouse, are coordinately expressed in partially overlapping domains during wing development. Local application of retinoic acid, a putative endogenous morphogen, induces de novo transcription of Hox-4 genes. The mirror-image patterns of Hox-4 gene expression, which are obtained in this way, correlate with the subsequent development of mirror-image patterns of digits. Hox-4 genes probably encode positional information.

Amino Acid Sequence↗
PubMed1975

Computer aided nystagmus analysis.

The electronystagmogram (ENG) is analyzed with the assistance of a PDP-8 minicomputer for calculating the instantaneous slope, average slope, lead frequency, lag frequency and cycle frequency of both the fast and slow wave components of the ENG. The ENG data is first digitized and displayed on a storage scope in order to permit the operator to select an epoch of data. The results are then displayed on the scope, and the mean and variance of the important parameters are outputted on the teletype. The programs include a system for storing a large library of records.

Computers↗
PubMed2004

POCOman: new system for quantifying posterior capsule opacification.

PURPOSE: To describe a new method of measuring posterior capsule opacification (PCO) and intraocular lens (IOL) rotation and report the validation of the method. SETTING: Ophthalmology Department, St. Thomas' Hospital, and Medical Imaging, Department of Physics, King's College, London, United Kingdom. METHOD: A new interactive software program, POCOman, was developed for the semiobjective assessment of PCO. Digital images of the posterior capsule, which can be acquired by any technique, are analyzed by the observer to determine the percentage area of PCO and assign a severity score. The system was validated by comparing it to clinical slitlamp evaluation of PCO and automated POCO system analysis using a library of 100 images taken from archives. The software also measures sequential IOL rotation for the evaluation of toric IOLs. RESULTS: An image could be analyzed in approximately 2 minutes. The results of the POCOman system correlated well with the results of the automated POCO system and clinical evaluation. CONCLUSIONS: The POCOman is an effective, user-friendly system for quantifying PCO. It can be obtained for free and has advantages over other methods.

Cataract↗
PubMed2005

Information-seeking behavior of nursing students and clinical nurses: implications for health sciences librarians.

OBJECTIVES: This research was conducted to provide new insights on clinical nurses' and nursing students' current use of health resources and libraries and deterrents to their retrieval of electronic clinical information, exploring implications from these findings for health sciences librarians. METHODS: Questionnaires, interviews, and observations were used to collect data from twenty-five nursing students and twenty-five clinical nurses. RESULTS: Nursing students and clinical nurses were most likely to rely on colleagues and books for medical information, while other resources they frequently cited included personal digital assistants, electronic journals and books, and drug representatives. Significantly more nursing students than clinical nurses used online databases, including CINAHL and PubMed, to locate health information, and nursing students were more likely than clinical nurses to report performing a database search at least one to five times a week. CONCLUSIONS AND RECOMMENDATIONS: Nursing students made more use of all available resources and were better trained than clinical nurses, but both groups lacked database-searching skills. Participants were eager for more patient care information, more database training, and better computer skills; therefore, health sciences librarians have the opportunity to meet the nurses' information needs and improve nurses' clinical information-seeking behavior.

Adult↗
PubMed2001

Proteomic analysis of rare molecular species of translated polypeptides from a mouse fetal thymus cDNA library.

Proteomic patterns from an ordered cDNA library of mouse fetal thymus origin of an overall complexity of 1536 clones are described. Patterns have been analyzed at 96, 12, or 8 clones in a mixture, or as individual clones. Clones yield in some instances a single spot, in other cases a complex cluster or family of spots is formed. The determination of the clonal address (a six-digit number, indicating the interception of three pooling dimensions) by inspection of pools of 8, 12 or 16 clones is a reliable approach; nevertheless a complete proof consists in retrieving the clone and then submitting to transcription, translation and proteomic analysis. The spot clusters are meaningful clone identifiers; cluster components (families of polypeptides) are characteristic of individual clones and are independent of clones coexisting (and being co-expressed) in a given pool. A 'cluster' originates from a single cloned message and might be due to post-translational modification (offered by the reticuleocyte machinery) or as a result of programmed degradation. Thirteen clones or families of clonal products are shown, and the heterogeneity of the 'appearance' of clones is documented. In about half, the assignment of a clonal polypeptide product to a storage well position has failed; this might be due to a variety of considerations elaborated herein. The arguments are presented, that analysis of abundant proteins of a cell (activated lymphocyte) comprises 'classical proteomics', but for the analysis of the rare molecular species of proteins, Poissonian approaches of replicable material have to be used.

Animals↗