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PubMed2004

Gene transfer for neurologic disease: agencies, policies, and process.

Advances in molecular biology have contributed to a growing interest in gene therapy as a form of management for neurologic diseases. However, implementation requires knowledge of the regulatory policies governing this field of research, especially in view of the greater stringency imposed by the serious adverse events affecting some patients participating in gene therapy protocols. Educational resources for neurologists, or any clinicians, who hope to serve as potential principal investigators for a gene therapy protocol are not available through any single source, requiring considerable effort to discover appropriate guidance. Summarized here are the regulatory agencies and their requirements, the phases of clinical development with emphasis on a Phase I study, and specific steps leading to an Investigational New Drug application for a biologic product to be used in a gene therapy clinical trial. The links provided to all appropriate Web sites will facilitate the process for the clinician investigator.

Clinical Protocols↗

PubMed2003

Candidate's thesis: Platelet-activating factor-induced hearing loss: mediated by nitric oxide?

OBJECTIVES/HYPOTHESIS: Platelet-activating factor (PAF)in middle ear effusion is thought to induce hearing loss. The purpose of this study is to investigate the role of nitric oxide (NO) in the mechanism of PAF-induced hearing loss by studying the effects of PAF application on the round window membrane (RWM) with and without PAF-antagonist NO-blocker. STUDY DESIGN: Longitudinal study on randomized guinea pigs using PAF to induce hearing loss. METHODS Guinea pigs were divided into four groups: PBS, PAF, PAF-antagonist, and L-NAME. The PBS group received phosphate buffered saline (PBS) and the PAF groups received 10, 20, and 40 microg of PAF soaked into gelfoam and placed on the RWM. PAF-antagonist (WEB 2170) and NOS inhibitor NG-nitro-l-arginine-methylester (L-NAME) were injected intraperitoneally prior to PAF 20 microg application on the RWM. The following three tests were performed on each animal group: Hearing was tested with an auditory brainstem response (ABR) test over 24 hours. At the end of 24 hours, cochlear hair cells were examined by scanning electron microscopy (SEM) and immunohistochemistry was carried out on the cochlea to test the expression of inducible nitric oxide synthase (iNOS). RESULTS: The PAF group developed significant elevation of ABR threshold and cochlear hair cell damage in the SEM group as compared with the PBS control group. The PAF-antagonist (WEB 2170) and the L-NAME groups did not show significant elevation of ABR threshold and cochlear hair cell damage compared with the group administered PAF 20 microg, but in the PAF-antagonist group, the elevation of ABR threshold was significant compared with that of the PBS control group, whereas it was not significant compared with the PBS group in the L-NAME group. Strong expression of iNOS on cochlea was observed in the PAF group and lighter expression was seen in PBS, WEB 2170, and L-NAME groups. CONCLUSIONS: This study demonstrated that PAF placed on the RWM induced hearing loss and cochlear hair cell damage. The PAF-antagonists and L-NAME prevented the PAF-induced hearing loss and inhibited iNOS expression in the cochlea. These findings suggest that the PAF-induced hearing loss caused by cochlear hair cell damage may have been mediated by NO. PAF-antagonists and L-NAME may have future therapeutic implications in preventing sensorineural hearing loss associated with chronic otitis media. The results of this study have significant potential clinical application.

Animals↗

PubMed2006

Sources of information on postgraduate medical training programs and medical specialty career resources-2006 update.

This is the final biennial update listing directories, journal articles, Web sites, and general books that aid the librarian, house officer, or medical student in finding information on medical residency and fellowship programs. The World Wide Web provides the most complete and up-to-date source of information about postgraduate training programs and specialties. This update continues to go beyond postgraduate training resources to include selected Web sites and books on curriculum vitae writing, practice management, personal finances, the "Match," certification and licensure examination preparation, lifestyle issues, job hunting, and the DEA license application process. Print resources are included if they provide information not on the Internet, have features that are particularly useful, or cover too many relevant topics in depth to be covered in a journal article or on a Web site. The Internet is a major marketing tool for hospitals seeking to recruit the best and brightest physicians for their training programs. Even the smallest community hospital has a Web site.

Education, Medical↗

PubMed2006

Hybrid specification, storage, retrieval and runtime application of clinical guidelines.

Clinical guidelines are a major tool in improving the quality of medical care. However, most guidelines are in free text, are not machine-comprehensible and are not easily accessible to clinicians at the point of care. We have designed and implemented a web-based, modular, distributed architecture, the Digital Electronic Guideline Library (DeGeL), which facilitates gradual conversion of clinical guidelines from text to a formal representation in the chosen target guideline ontology. The architecture supports guideline classification, semantic markup, context-sensitive search, browsing, run-time application and retrospective quality assessment. The DeGeL hybrid meta-ontology includes elements common to all guideline ontologies, such as semantic classification and domain knowledge; it also includes four content-representation formats: free text, semi-structured text, semi-formal representation and a formal representation. These formats support increasingly sophisticated computational tasks. Guidelines can thus be in a hybrid representation in which guidelines, and even parts of the same guideline, might exist at different formalisation levels. We have also developed and rigorously evaluated a methodology and an associated web-based tool, Uruz, for gradually structuring and semi-formalising free-text clinical guidelines. Finally, we have designed, implemented and evaluated a new approach, the hybrid runtime application model, for supporting runtime application of clinical guidelines that are not necessarily in a machine-comprehensible format; in particular, when the guideline is in a semi-formal representation and the patient's data are either in an electronic medical record or in a paper format. The tool implementing this new approach, the Spock module, is customised at this point to the Asbru guideline specification language and exploits the hybrid structure of guidelines in DeGeL. The Spock module also exploits our temporal-abstraction mediator to the patient record, IDAN, and our interactive intelligent-visualisation tool, KNAVE-II.

Decision Support Systems, Clinical↗

PubMed2005

Creating and using the urgent metadata catalogue and thesaurus.

The Urban Regeneration and the Environment Research Programme (URGENT) required a system for cataloguing its datasets and enabling its scientific community to discover what data were available to it. This community was multidisciplinary in nature and therefore needed a range of facilities for searching. Of particular importance were facilities to help those unfamiliar with specialist terminology. To meet these needs, four applications were designed and developed: a Metadata Capture Tool for describing datasets in compliance with the National Geospatial Data Framework (NGDF) standard, a Term Entry Tool for creating an ISO compliant thesaurus, a Thesaurus Builder for merging thesauri and a Search Tool. To encourage users to help in cataloguing data, the capture tools were written as stand alone applications, which users could keep and use to build their own metadatabases. The tools contained export and import facilities that allowed the URGENT Data Centre to build a central database and publish it upon the web. During the development work, it was found necessary to extend the NGDF standard as it could not adequately describe time variant or 3-D atmospheric datasets. The four applications met their design objectives. However, a number of ergonomic issues will need to be addressed if the system is to meet the needs of the much larger up coming programmes. The main challenges will be moving from the NGDF standard to the ISO standard, hence bringing the work into line with the recommendations of the INSPIRE Project, and merging the metadatabase with the scientific database, which enable metadata maintenance to be semi-automated.

Cataloging↗

PubMed2006

mGrid: a load-balanced distributed computing environment for the remote execution of the user-defined Matlab code.

BACKGROUND: Matlab, a powerful and productive language that allows for rapid prototyping, modeling and simulation, is widely used in computational biology. Modeling and simulation of large biological systems often require more computational resources then are available on a single computer. Existing distributed computing environments like the Distributed Computing Toolbox, MatlabMPI, Matlab*G and others allow for the remote (and possibly parallel) execution of Matlab commands with varying support for features like an easy-to-use application programming interface, load-balanced utilization of resources, extensibility over the wide area network, and minimal system administration skill requirements. However, all of these environments require some level of access to participating machines to manually distribute the user-defined libraries that the remote call may invoke. RESULTS: mGrid augments the usual process distribution seen in other similar distributed systems by adding facilities for user code distribution. mGrid's client-side interface is an easy-to-use native Matlab toolbox that transparently executes user-defined code on remote machines (i.e. the user is unaware that the code is executing somewhere else). Run-time variables are automatically packed and distributed with the user-defined code and automated load-balancing of remote resources enables smooth concurrent execution. mGrid is an open source environment. Apart from the programming language itself, all other components are also open source, freely available tools: light-weight PHP scripts and the Apache web server. CONCLUSION: Transparent, load-balanced distribution of user-defined Matlab toolboxes and rapid prototyping of many simple parallel applications can now be done with a single easy-to-use Matlab command. Because mGrid utilizes only Matlab, light-weight PHP scripts and the Apache web server, installation and configuration are very simple. Moreover, the web-based infrastructure of mGrid allows for it to be easily extensible over the Internet.

Computational Biology↗

PubMed2005

Anticoagulation monitoring part 2: Unfractionated heparin and low-molecular-weight heparin.

OBJECTIVE: To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in monitoring anticoagulation with unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). DATA SOURCES: Articles were identified through a MEDLINE search (1966-August 2004), device manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS: The activated partial thromboplastin time (aPTT) and activated clotting time (ACT) are common tests for monitoring anticoagulation with UFH. Multiple devices are available for POC aPTT, ACT, and heparin concentration testing. The aPTT therapeutic range for UFH will vary depending upon the reagent and instrument employed. Although recommended by the American College of Chest Physicians Seventh Conference on Antithrombotic and Thrombolytic Therapy, establishing a heparin concentration-derived therapeutic range for UFH is rarely performed. Additional research evaluating anti-factor Xa monitoring of LMWHs using POC testing is necessary. CONCLUSIONS: Multiple POC devices are available to monitor anticoagulation with UFH. For each test, there is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC anticoagulation monitoring of UFH using aPTT and, more often, ACT is common in clinical practice, particularly when evaluating anticoagulation associated with interventional cardiology procedures and cardiopulmonary bypass surgery.

Anticoagulants↗

PubMed1997

[Multi-media presentation of radiologic image data with the Internet].

AIM: Recent developments of the Internet (World Wide Web) allow the integration of audio, video, digital film sequences, and three-dimensional data. The applicability of these innovations for medical documentation is demonstrated. METHODS: Our existing software for medical image processing and 3D reconstruction was extended to provide images, film sequences, and complex 3D models in an Internet-compatible data format. RESULTS: The multimedia results of the image processing were integrated into Internet documents. Specialized programs are no longer necessary for visualization. The Internet software allows for user-friendly handling and interactive presentation of the 2D and 3D data. CONCLUSIONS: The Internet offers public-domain software for display of images, audio/video, and 3D data. Thus, the tools of the Internet represent an ideal basis for local hospital information systems, computer-aided medical education, and teleconferencing.

Computer Communication Networks↗

PubMed2000

[Radiological information searching on the Internet: data banks, search machines and intelligent agents].

UNLABELLED: The Internet plays an important role in a growing number of medical applications. Finding relevant information is not always easy as the amount of available information on the Web is rising quickly. Even the best search engines can only collect links to a fraction of all existing Web pages. In addition, many of these indexed documents have been changed or deleted. The vast majority of information on the Web is not searchable with conventional methods. New search strategies, technologies and standards are combined in intelligent search agents (ISA) and robots, which can retrieve desired information in a specific approach. CONCLUSION: The article describes differences between ISAs and conventional search engines and how communication between agents improves their ability to find information. Examples of existing ISAs are given and the possible influences on the current and future work in radiology is discussed.

Databases, Factual↗

PubMedDate not supplied

IAEA Nuclear Data Section: provision of atomic and nuclear databases for user applications.

The Nuclear Data Section (NDS) of the International Atomic Energy Agency (IAEA) provides a wide range of atomic and nuclear data services to scientists worldwide, with particular emphasis placed on the needs of developing countries. Highly focused Co-ordinated Research Projects and multinational data networks are sponsored under the auspices of the IAEA for the development and assembly of databases through the organised participation of specialists from Member States. More than 100 data libraries are readily available cost-free through the Internet, CD-ROM and other media. These databases are used in a wide range of applications, including fission- and fusion-energy, non-energy applications and basic research studies. Further information concerning the various services can be found through the web address of the IAEA Nuclear Data Section: and a mirror site at IPEN, Brazil that is maintained by NDS staff:.

Databases, Factual↗

PubMed2004

The successful management of congenital laryngeal web with endoscopic lysis and topical mitomycin-C.

Laryngeal web is a rare congenital anomaly. The primary goals of management for congenital laryngeal web are to provide a patent airway and to achieve a good voice quality. However, vocal cords have a tendency for fibrosis and granulation tissue formation after surgical interventions. Traditionally, the treatment of choice for laryngeal web is laryngofissure and placement of a stent or keel. This report presents the successful management of a congenital laryngeal web in a 10-month-old boy with endoscopic lysis and topical mitomycin-C application.

Airway Obstruction↗

PubMed1999

Improving interorganizational data interchange for drug development.

This paper presents a reengineered process that uses a markup language to do interorganizational data interchange between the participants in the US drug development process. The two major goals of this paper are to present (1) a detailed enough description of the reengineered version of this process that a practitioner will be able to use it and (2) a case-study of the reengineering of an interorganizational data interchange system that is applicable to other areas in health care. The detailed description is augmented with a companion web-site that shows all programs in a working prototype. The case-study uses an IDEF0 model to show the structure of benefits from markup standards for interorganizational data interchange.

Computer Communication Networks↗

PubMed2002

The virtual blood film.

The computer and the digital camera offer unprecedented possibilities for improving hematology education, research, and patient service. Peripheral blood smear images of exceptional quality can be acquired rapidly and conveniently from the peripheral blood smear with a modern, high-resolution digital camera and a quality microscope. Digital cameras use CCD or CMOS image sensors to measure light energy and additional circuitry to convert the measured information into a digital signal. Because digital cameras do not use photographic film, images are immediately available for incorporation into web sites or digital publications, printing, transfer to other individuals by e-mail, or other applications. Several excellent consumer digital still cameras are now available for less than $1000 that capture high-quality images comprised of more than three megapixels. These images are essentially indistinguishable from conventional film images when viewed on a quality color monitor or printed on a quality color or black and white printer at sizes up to 8 x 10 in. Several recent dedicated digital photomicroscopy cameras provide an ultrahigh quality image output of more than 12 megapixels and have low noise circuit designs permitting the direct capture of darkfield and fluorescence images. There are many applications of digital images of peripheral blood smears. Because hematology is a visual science, the inclusion of quality digital images into lectures, teaching handouts, and electronic documents is essential. A few institutions have gone beyond the basic application of digital images to develop large electronic hematology atlases; animated, audio-enhanced learning experiences; multidisciplinary Internet conferences; and other innovative applications. Digital images of single microscopic fields (single-frame images) are the most widely used in hematology education at this time, but single images of many adjacent microscopic fields can be stitched together to prepare zoomable panoramas that encompass a large part of a microscope slide and closely stimulate observation through a real microscope. With further advances in computer speed and Internet streaming technology, the virtual microscope could easily replace the real microscope in pathology education. Interactive, immersive computer experiences may completely revolutionize hematology education and make the conventional lecture and laboratory format obsolete later in this decade. Patient care is enhanced by the transmission of digital images to other individuals for consultation and education, and by the inclusion of these images in patient care documents. In research laboratories, digital cameras are widely used to document experimental results and obtain experimental data.

Blood Cell Count↗

PubMed2003

Going provincial: preceptoring and mentoring revisited in the health sciences. Part I.

This article describes the Preceptor & Mentor Initiative for Health Sciences in BC, a provincial strategy to facilitate preceptoring and mentoring. A web site was developed with a comprehensive preceptor/mentor framework and resources, based on best practices and applicable to all health sciences. Informal feedback indicates this Initiative is effective in supporting health sciences preceptoring and mentoring in BC. A formal evaluation will be conducted by March 2003 and reported in a future FORUM article.

Benchmarking↗

PubMedDate not supplied

CoNTub: an algorithm for connecting two arbitrary carbon nanotubes.

We have developed the first computer program for determining the coordinates of heterojunctions between two arbitrary carbon nanotubes. This software implements the topological algebra based on the concept of strip, a continuous subset of carbon rings containing all the topological defects (nonhexagonal carbon rings). The user easily generates any heterojunction by merely introducing the indices (i,j) and length of the two nanotubes to be connected. The resulting structure is immediately visualized and can be exported in the protein-data-bank (PDB) format. Two classes of heterojunctions are distinguished depending on whether a cone between the connected nanotubes is required. This method is applicable to all kinds of two nanotube heterojunctions, including Dunlap's knees and others related. In addition, this program also generates single- and multiwalled carbon nanotubes (SWNT and MWNT). This application has been implemented as a Java applet, and it is freely available at the following web address: http://www.ugr.es/local/gmdm/java/contub/contub.html

Journal Article↗

PubMed2006

PEDANT genome database: 10 years online.

The PEDANT genome database provides exhaustive annotation of 468 genomes by a broad set of bioinformatics algorithms. We describe recent developments of the PEDANT Web server. The all-new Graphical User Interface (GUI) implemented in Javatrade mark allows for more efficient navigation of the genome data, extended search capabilities, user customization and export facilities. The DNA and Protein viewers have been made highly dynamic and customizable. We also provide Web Services to access the entire body of PEDANT data programmatically. Finally, we report on the application of association rule mining for automatic detection of potential annotation errors. PEDANT is freely accessible to academic users at http://pedant.gsf.de.

Computer Graphics↗

PubMedDate not supplied

Application of continuous time random walk theory to tracer test measurements in fractured and heterogeneous porous media.

We examine a set of analytical solutions based on the continuous time random walk (CTRW) approach, which can be evaluated numerically and used to analyze breakthrough data from tracer tests. Practical application of these solutions, with discussion of the physical meaning of the relevant model parameters, is emphasized. The CTRW theory accounts for the often observed non-Fickian (or scale-dependent) dispersion behavior that cannot be properly quantified by using the advection-dispersion equation. The solutions given here, valid for a wide range of dispersive behaviors of conservative tracers, and useful for both characterization and prediction, have been integrated into a library of external functions for use with the GRACE graphical display and analysis package. Example applications of these solutions are presented. The library and graphics software are freely accessible from a Web site.

Chemical Phenomena↗

PubMed2001

Connecting to success: practice management on the Net.

Profound changes in the way dental practices manage data, patient records, and communication are beginning to unfold. Sooner than most of us can imagine, secured patient medical and dental records will reside on the Internet. Additionally, communication between health care providers and patients will become virtually 100% electronic. As the Application Service Provider (ASP) dental models mature, practices will transition from paper to "paperless" to "web-based" management and clinical systems. This article examines and explains these future frontiers.

Appointments and Schedules↗