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PubMedDate not supplied

A guide to Mosaic and the World Wide Web for physicians.

Although the predecessor of the Internet as we know it has existed since 1969, few physicians have taken full advantage of its extensive and continuously expanding resources. This may be due in part to the perceived difficulty of navigating the sometimes circuitous routes to the data sources of interest. Newer and substantially more user-friendly interfaces have been developed recently, allowing simpler and more direct access to the full range of Internet resources. Arguably the most important of these is the National Center for Supercomputing Application's Mosaic, the link to an information domain known as the World Wide Web. This article provides an overview of the important medical resources that Mosaic offers the clinician, teacher, and researcher, together with information on how to obtain and configure the software.

Computer Communication Networks↗

PubMed2005

Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures.

Despite important progress in understanding the molecular factors underlying the development of cancer and the improvement in response rates with new drugs, long-term survival is still disappointing for most common solid tumours. This might be because very little of the modest gain for patients is the result of the new compounds discovered and marketed recently. An assessment of the regulatory agencies' performance may suggest improvements. The present analysis summarizes and evaluates the type of studies and end points used by the EMEA to approve new anticancer drugs, and discusses the application of current regulations. This report is based on the information available on the EMEA web site. We identified current regulatory requirements for anticancer drugs promulgated by the agency and retrieved them in the relevant directory; information about empirical evidence supporting the approval of drugs for solid cancers through the centralised procedure were retrieved from the European Public Assessment Report (EPAR). We surveyed documents for drug applications and later extensions from January 1995, when EMEA was set up, to December 2004. We identified 14 anticancer drugs for 27 different indications (14 new applications and 13 extensions). Overall, 48 clinical studies were used as the basis for approval; randomised comparative (clinical) trial (RCT) and Response Rate were the study design and end points most frequently adopted (respectively, 25 out of 48 and 30 out of 48). In 13 cases, the EPAR explicitly reported differences between arms in terms of survival: the range was 0-3.7 months, and the mean and median differences were 1.5 and 1.2 months. The majority of studies (13 out of 27, 48%) involved the evaluation of complete and/or partial tumour responses, with regard to the end points supporting the 27 indications. Despite the recommendations of the current EMEA guidance documents, new anticancer agents are still often approved on the basis of small single arm trials that do not allow any assessment of an 'acceptable and extensively documented toxicity profile' and of end points such as response rate, time to progression or progression-free survival which at best can be considered indicators of anticancer activity and are not 'justified surrogate markers for clinical benefit'. Anticipating an earlier than ideal point along the drug approval path and the use of not fully validated surrogate end points in nonrandomised trials looks like a dangerous shortcut that might jeopardise consumers' health, leading to unsafe and ineffective drugs being marketed and prescribed. The present Note for Guidance for new anticancer agents needs revising. Drugs must be rapidly released for patients who need them but not be at the expense of adequate knowledge about the real benefit of the drugs.

Antineoplastic Agents↗

PubMed2002

Challenges in image acquisition and distribution for clinical image service.

We have developed a centralized application for acquiring images from multiple picture archiving and communication systems (PACS) and distributing images to a clinical image web server and other repositories. Our flexible strategy addresses a number of administrative challenges associated with delivering images into clinical, research, and test environments. DICOM images flow from PACSs and modalities to a UNIX-based "distributor" application, which relays them to one or more destinations. Image volume and transmission times were collected and analyzed. Three distributors receive an average of 34 gigabytes of image data per day. Images are sent concurrently to two web-based image servers, one used clinically by physicians and one used for testing. Transmission of certain classes of studies is prioritized for key physician groups. Delivery to research systems is also supported. Acquiring images from multi-vendor PACS for distribution to a web server for clinical image viewing is a challenging task. Centralizing the acquisition and distribution process reduces both the administrative effort and the impact on clinical operations associated with maintaining dynamic clinical, testing, and research environments.

Computer Communication Networks↗

PubMed2004

Circular genome visualization and exploration using CGView.

UNLABELLED: CGView (Circular Genome Viewer) is a Java application and library for generating high-quality, zoomable maps of circular genomes. It converts XML or tab-delimited input into a graphical map (PNG, JPG or Scalable Vector Graphics format), complete with sequence features, labels, legends and footnotes. In addition to the default full view map, the program can generate a series of hyperlinked maps showing expanded views. The linked maps can be explored using any Web browser, allowing rapid genome browsing and facilitating data sharing. AVAILABILITY: CGView (the standalone application, library or applet), sample input, sample maps and documentation can be obtained from http://wishart.biology.ualberta.ca/cgview/ CONTACT: david.wishart@ualberta.ca.

Chromosome Mapping↗

PubMed2000

Multimedia-based courseware in the Virtual Learning Center at the Hannover Medical School.

The commercial use of the World Wide Web causes an extensive change in information technology. Web browser are becoming the universal front-end for all kinds of client-server applications. The possibilities of telematics offer a base for multimedia applications, for instance telelearning. Learning is not limited by geography and does not cause pressure of time by the user. The development of such multimedia information and communication systems demands cooperative working teams of authors, who are able to master several areas of medical knowledge as well as the presentation of these using different multimedia facilities. A very important part of graphic design in the context of multimedia applications is the creation and interactive use of images (still, moving). The growth and the complexity of medical knowledge as well as the need for continuous, fast, and economically feasible maintenance impose requirements on the media used for medical education and training. Web-based courseware in the Virtual Learning Center at the Hannover Medical School is an innovative education resource for medical students and professionals.

Computer-Assisted Instruction↗

PubMed2005

GNARE: automated system for high-throughput genome analysis with grid computational backend.

Recent progress in genomics and experimental biology has brought exponential growth of the biological information available for computational analysis in public genomics databases. However, applying the potentially enormous scientific value of this information to the understanding of biological systems requires computing and data storage technology of an unprecedented scale. The Grid, with its aggregated and distributed computational and storage infrastructure, offers an ideal platform for high-throughput bioinformatics analysis. To leverage this we have developed the Genome Analysis Research Environment (GNARE)--a scalable computational system for the high-throughput analysis of genomes, which provides an integrated database and computational backend for data-driven bioinformatics applications. GNARE efficiently automates the major steps of genome analysis including acquisition of data from multiple genomic databases; data analysis by a diverse set of bioinformatics tools; and storage of results and annotations. High-throughput computations in GNARE are performed using distributed heterogeneous Grid computing resources such as Grid2003, TeraGrid, and the DOE Science Grid. Multi-step genome analysis workflows involving massive data processing, the use of application-specific tools and algorithms and updating of an integrated database to provide interactive web access to results are all expressed and controlled by a "virtual data" model which transparently maps computational workflows to distributed Grid resources. This paper describes how Grid technologies such as Globus, Condor, and the Gryphyn Virtual Data System were applied in the development of GNARE. It focuses on our approach to Grid resource allocation and to the use of GNARE as a computational framework for the development of bioinformatics applications.

Computational Biology↗

PubMed2006

The venomous secrets of the web droplets from the viscid spiral of the orb-weaver spider Nephila clavipes (Araneae, Tetragnatidae).

The capture web of N. clavipes presents viscous droplets, which play important roles in web mechanics and prey capture. By using scanning and transmission electron microscopy, it was demonstrated that the web droplets are constituted of different chemical environments, provided by the existence both of an aqueous and a lipid layer, which, in turn, present a suspension of tenths of vesicles containing polypeptides and/or lipids. GC/EI-MS Analysis of the contents of these vesicles led to the identification of some saturated fatty acids, such as decanoic acid, undecanoic acid, dodecanoic acid, tetradecanoic acid, octadecanoic acid, and icosanoic acid, while other components were unsaturated fatty acids, such as (Z)-tetradec-9-enoic acid, (Z)-octadec-9-enoic acid, and (Z)-icosa-11-enoic acid; and polyunsaturated fatty acids like (9Z,12Z)-octadeca-9,12-dienoic acid, (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid, and (11Z,14Z)-icosa-11,14-dienoic acid. Toxic proteins such as calcium-activated proteinase and metalloproteinase jararhagin-like precursor were also identified by using a proteomic approach, indicating the possible involvement of these enzymes in the pre-digestion of spiders' preys web-captured. Apparently, the mixture of fatty acids are relatively toxic to insects by topical application (LD50 64.3+/-7.6 ng mg(-1) honeybee), while the proteins alone present no topical effect; however, when injected into the prey-insects, these proteins presented a moderate toxicity (LD50 40.3+/-4.8 ng mg(-1) honeybee); the mixture of fatty acids and proteins is very toxic to the preys captured by the web droplets of the viscid spiral of Nephila clavipes when topically applied on them (LD50 14.3+/-1.8 ng mg(-1) honeybee).

Amino Acid Sequence↗

PubMed2005

KAT: a flexible XML-based knowledge authoring environment.

As part of an enterprise effort to develop new clinical information systems at Intermountain Health Care, the authors have built a knowledge authoring tool that facilitates the development and refinement of medical knowledge content. At present, users of the application can compose order sets and an assortment of other structured clinical knowledge documents based on XML schemas. The flexible nature of the application allows the immediate authoring of new types of documents once an appropriate XML schema and accompanying Web form have been developed and stored in a shared repository. The need for a knowledge acquisition tool stems largely from the desire for medical practitioners to be able to write their own content for use within clinical applications. We hypothesize that medical knowledge content for clinical use can be successfully created and maintained through XML-based document frameworks containing structured and coded knowledge.

Artificial Intelligence↗

PubMed2000

An evaluation of patient access to their electronic medical records via the World Wide Web.

This paper describes initial experience with the Web-based Patient Clinical Information System (PatCIS). The system was designed to serve as a framework for the integration of applications that help patients access their electronic medical record, add data to their record, review on-line health information, and apply their own clinical data (automatically) to guideline programs that offer health advice. The architecture supports security functions and records user activities, relieving application developers from concerns about safe information practices and the evaluation process. PatCIS is being used to study the social and cognitive impact of allowing patients to have access to their health records via the Web. To date, PatCIS has grown to include 15 clinical functions and 4 dynamic links to literature (called infobuttons). Eleven patients have been enrolled since April, 1999; five have been active users. Experience shows that the PatCIS architecture supports application integration while providing adequate security and evaluation functions. Initial caution with the patient enrollment process has limited recruitment and, consequently, usage. However, experience thus far suggests that PatCIS has good usability and utility. No adverse events, including undesirable impact on doctor-patient interactions, have been reported. There do not appear to be any technical impediments to scaling up the enrollment to continue to observe patient usage.

Computer Security↗

PubMed2005

[Digital teaching archive. Concept, implementation, and experiences in a university setting].

Film-based teaching files require a substantial investment in human, logistic, and financial resources. The combination of computer and network technology facilitates the workflow integration of distributing radiologic teaching cases within an institution (intranet) or via the World Wide Web (Internet). A digital teaching file (DTF) should include the following basic functions: image import from different sources and of different formats, editing of imported images, uniform case classification, quality control (peer review), a controlled access of different user groups (in-house and external), and an efficient retrieval strategy. The portable network graphics image format (PNG) is especially suitable for DTFs because of several features: pixel support, 2D-interlacing, gamma correction, and lossless compression. The American College of Radiology (ACR) "Index for Radiological Diagnoses" is hierarchically organized and thus an ideal classification system for a DTF. Computer-based training (CBT) in radiology is described in numerous publications, from supplementing traditional learning methods to certified education via the Internet. Attractiveness of a CBT application can be increased by integration of graphical and interactive elements but makes workflow integration of daily case input more difficult. Our DTF was built with established Internet instruments and integrated into a heterogeneous PACS/RIS environment. It facilitates a quick transfer (DICOM_Send) of selected images at the time of interpretation to the DTF and access to the DTF application at any time anywhere within the university hospital intranet employing a standard web browser. A DTF is a small but important building block in an institutional strategy of knowledge management.

Computer-Assisted Instruction↗

PubMedDate not supplied

A Web terminology server using UMLS for the description of medical procedures.

The Model for Assistance in the Orientation of a User within Coding Systems (MAOUSSC) project has been designed to provide a representation for medical and surgical procedures that allows several applications to be developed from several viewpoints. It is based on a conceptual model, a controlled set of terms, and Web server development. The design includes the UMLS knowledge sources associated with additional knowledge about medico-surgical procedures. The model was implemented using a relational database. The authors developed a complete interface for the Web presentation, with the intermediary layer being written in PERL. The server has been used for the representation of medico-surgical procedures that occur in the discharge summaries of the national survey of hospital activities that is performed by the French Health Statistics Agency in order to produce inpatient profiles. The authors describe the current status of the MAOUSSC server and discuss their interest in using such a server to assist in the coordination of terminology tasks and in the sharing of controlled terminologies.

Computer Communication Networks↗

PubMed2026

Beyond da Vinci: a systematic review of next-generation multiport robotic platforms in pediatric surgery.

As robotic surgery expands beyond the da Vinci platform, the relevance of new-generation systems to pediatric patients remains uncertain. This review examined the technical characteristics, applications, and perioperative outcomes of alternative multiport robotic platforms in children. PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library were searched through 28 February 2026 in accordance with PRISMA 2020. Owing to clinical heterogeneity, findings were synthesized narratively, with Wilson 95% confidence intervals for key binary outcomes. Six studies reported 166 patients across 27 procedure types. Senhance accounted for 164 patients, while Hugo RAS and Hinotori were each represented by one patient. Ages ranged from 15 days to 17 years and weights from 3.8 to more than 100 kg. Senhance was the only platform used with 3-mm robotic instruments. Conversion or planned escalation occurred in 19 patients (11.4%; 95% CI, 7.5-17.2%). Four intraoperative complications were reported (2.4%; 95% CI, 0.9-6.0%). Across all reports, 20 patients experienced postoperative complications (12.0%; 95% CI, 7.9-17.9%). In the largest cohort, seven patients required reintervention (4.6%; 95% CI, 2.2-9.2%) and seven were readmitted (4.6%; 95% CI, 2.2-9.2%). No deaths or comparative pediatric studies were reported. Published experience remains sparse and is almost entirely limited to Senhance. Current evidence describes early clinical use without establishing comparative safety, effectiveness, or platform superiority. Prospective multicenter studies with standardized reporting are needed.

Humans↗

PubMed2004

Improved and automated prediction of effective siRNA.

Short interfering RNAs are used in functional genomics studies to knockdown a single gene in a reversible manner. The results of siRNA experiments are highly dependent on the choice of siRNA sequence. In order to evaluate siRNA design rules, we collected a database of 398 siRNAs of known efficacy from 92 genes. We used this database to evaluate previously proposed rules from smaller datasets, and to find a new set of rules that are optimal for the entire database. We also trained a regression tree with full cross-validation. It was however difficult to obtain the same precision as methods previously tested on small datasets from one or two genes. We show that those methods are overfitting as they work poorly on independent validation datasets from multiple genes. Our new design rules can predict siRNAs with efficacy >/= 50% in 91% of cases, and with efficacy >/=90% in 52% of cases, which is more than a twofold improvement over random selection. Software for designing siRNAs is available online via a web server at or as a standalone version for high-throughput applications.

Algorithms↗

PubMed2003

Fatty acid trophic markers in the pelagic marine environment.

Fatty acids have been used as qualitative markers to trace or confirm predator-prey relationships in the marine environment for more than thirty years. More recently, they have also been used to identify key processes impacting the dynamics of some of the world's major ecosystems. The fatty acid trophic marker (FATM) concept is based on the observation that marine primary producers lay down certain fatty acid patterns that may be transferred conservatively to, and hence can be recognized in, primary consumers. To identify these fatty acid patterns the literature was surveyed and a partial least squares (PLS) regression analysis of the data was performed, validating the specificity of particular microalgal FATM. Microalgal group specific FATM have been traced in various primary consumers, particularly in herbivorous calanoid copepods, which accumulate large lipid reserves, and which dominate the zooplankton biomass in high latitude ecosystems. At higher trophic levels these markers of herbivory are obscured as the degree of carnivory increases, and as the fatty acids originate from a variety of dietary sources. Such differences are highlighted in a PLS regression analysis of fatty acid and fatty alcohol compositional data (the components of wax esters accumulated by many marine organisms) of key Arctic and Antarctic herbivorous, omnivorous and carnivorous copepod species. The analysis emphasizes how calanoid copepods separate from other copepods not only by their content of microalgal group specific FATM, but also by their large content of long-chain monounsaturated fatty acids and alcohols. These monounsaturates have been used to trace and resolve food web relationships in, for example, hyperiid amphipods, euphausiids and fish, which may consume large numbers of calanoid copepods. Results like these are extremely valuable for enabling the discrimination of specific prey species utilized by higher trophic level omnivores and carnivores without the employment of invasive techniques, and thereby for identifying the sources of energetic reserves. A conceptual model of the spatial and temporal dominance of group-specific primary producers, and hence the basic fatty acid patterns available to higher trophic levels is presented. The model is based on stratification, which acts on phytoplankton group dominance through the availability of light and nutrients. It predicts the seasonal and ecosystem specific contribution of diatom and flagellate/microbial loop FATM to food webs as a function of water column stability. Future prospects for the application of FATM in resolving dynamic ecosystem processes are assessed.

Animals↗

PubMed1998

Reduced space hidden Markov model training.

MOTIVATION: Complete forward-backward (Baum-Welch) hidden Markov model training cannot take advantage of the linear space, divide-and-conquer sequence alignment algorithms because of the examination of all possible paths rather than the single best path. RESULTS: This paper discusses the implementation and performance of checkpoint-based reduced space sequence alignment in the SAM hidden Markov modeling package. Implementation of the checkpoint algorithm reduced memory usage from O(mn) to O (m square root n) with only a 10% slowdown for small m and n, and vast speed-up for the larger values, such as m = n = 2000, that cause excessive paging on a 96 Mbyte workstation. The results are applicable to other types of dynamic programming. AVAILABILITY: A World-Wide Web server, as well as information on obtaining the Sequence Alignment and Modeling (SAM) software suite, can be found at http://www.cse.ucsc. edu/research/compbio/sam.html. CONTACT: rph@cse.ucsc.edu

Algorithms↗

PubMed2005

InterProScan: protein domains identifier.

InterProScan [E. M. Zdobnov and R. Apweiler (2001) Bioinformatics, 17, 847-848] is a tool that combines different protein signature recognition methods from the InterPro [N. J. Mulder, R. Apweiler, T. K. Attwood, A. Bairoch, A. Bateman, D. Binns, P. Bradley, P. Bork, P. Bucher, L. Cerutti et al. (2005) Nucleic Acids Res., 33, D201-D205] consortium member databases into one resource. At the time of writing there are 10 distinct publicly available databases in the application. Protein as well as DNA sequences can be analysed. A web-based version is accessible for academic and commercial organizations from the EBI (http://www.ebi.ac.uk/InterProScan/). In addition, a standalone Perl version and a SOAP Web Service [J. Snell, D. Tidwell and P. Kulchenko (2001) Programming Web Services with SOAP, 1st edn. O'Reilly Publishers, Sebastopol, CA, http://www.w3.org/TR/soap/] are also available to the users. Various output formats are supported and include text tables, XML documents, as well as various graphs to help interpret the results.

Databases, Protein↗

PubMed2000

InternetQuestion and Answer (iQ&A): a Web-based survey technology.

This paper presents InternetQuestion and Answer, a Web-based survey development and implementation technology, which has been designed for constructing on-line surveys for educational, medical, or administrative purposes. The system, called iQ&A, is a three-tiered database-backed Web system that has been developed to support a wide range of applications. Surveys are considered as general data collection instruments and include a wide field of application. iQ&A facilitates rapid survey construction and administration which is ideally suited for biomedical research as well as other research and educational activities. Full report management capabilities provide the survey publisher on-line access to current information on survey responses. Current implementations of this technology in the areas of biomedical applications of clinical trials, longitudinal research, and other research-related systems are presented. Further refinement of the current system should lead to a powerful general survey technology for broad-based applications.

Data Collection↗

PubMed2005

Stable isotope labeling with amino acids in cell culture (SILAC) for studying dynamics of protein abundance and posttranslational modifications.

Stable isotope labeling with amino acids in cell culture (SILAC) is a simple and straightforward approach for in vivo incorporation of a tag into proteins for relative quantitation by mass spectrometry. SILAC is a simple, yet powerful, method for investigating the dynamics of protein abundance and posttranslational modifications. Here, we provide detailed instructions for using this method to study protein complexes, protein-protein interactions, and the dynamics of protein abundance and posttranslational modifications. We expect that SILAC will become a routine technique because of its applicability to most areas of cell biology. We have also developed a Web site (http://www.silac.org) to provide researchers with updated information about this method and related resources.

Amino Acids↗