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PubMed2006

AliBaba: PubMed as a graph.

UNLABELLED: The biomedical literature contains a wealth of information on associations between many different types of objects, such as protein-protein interactions, gene-disease associations and subcellular locations of proteins. When searching such information using conventional search engines, e.g. PubMed, users see the data only one-abstract at a time and 'hidden' in natural language text. AliBaba is an interactive tool for graphical summarization of search results. It parses the set of abstracts that fit a PubMed query and presents extracted information on biomedical objects and their relationships as a graphical network. AliBaba extracts associations between cells, diseases, drugs, proteins, species and tissues. Several filter options allow for a more focused search. Thus, researchers can grasp complex networks described in various articles at a glance. AVAILABILITY: http://alibaba.informatik.hu-berlin.de/

Abstracting and Indexing↗
PubMed2001

Efficacy of spinal manipulation for chronic headache: a systematic review.

BACKGROUND: Chronic headache is a prevalent condition with substantial socioeconomic impact. Complementary or alternative therapies are increasingly being used by patients to treat headache pain, and spinal manipulative therapy (SMT) is among the most common of these. OBJECTIVE: To assess the efficacy/effectiveness of SMT for chronic headache through a systematic review of randomized clinical trials. STUDY SELECTION: Randomized clinical trials on chronic headache (tension, migraine and cervicogenic) were included in the review if they compared SMT with other interventions or placebo. The trials had to have at least 1 patient-rated outcome measure such as pain severity, frequency, duration, improvement, use of analgesics, disability, or quality of life. Studies were identified through a comprehensive search of MEDLINE (1966-1998) and EMBASE (1974-1998). Additionally, all available data from the Cumulative Index of Nursing and Allied Health Literature, the Chiropractic Research Archives Collection, and the Manual, Alternative, and Natural Therapies Information System were used, as well as material gathered through the citation tracking, and hand searching of non-indexed chiropractic, osteopathic, and manual medicine journals. DATA EXTRACTION: Information about outcome measures, interventions and effect sizes was used to evaluate treatment efficacy. Levels of evidence were determined by a classification system incorporating study validity and statistical significance of study results. Two authors independently extracted data and performed methodological scoring of selected trials. DATA SYNTHESIS: Nine trials involving 683 patients with chronic headache were included. The methodological quality (validity) scores ranged from 21 to 87 (100-point scale). The trials were too heterogeneous in terms of patient clinical characteristic, control groups, and outcome measures to warrant statistical pooling. Based on predefined criteria, there is moderate evidence that SMT has short-term efficacy similar to amitriptyline in the prophylactic treatment of chronic tension-type headache and migraine. SMT does not appear to improve outcomes when added to soft-tissue massage for episodic tension-type headache. There is moderate evidence that SMT is more efficacious than massage for cervicogenic headache. Sensitivity analyses showed that the results and the overall study conclusions remained the same even when substantial changes in the prespecified assumptions/rules regarding the evidence determination were applied. CONCLUSIONS: SMT appears to have a better effect than massage for cervicogenic headache. It also appears that SMT has an effect comparable to commonly used first-line prophylactic prescription medications for tension-type headache and migraine headache. This conclusion rests upon a few trials of adequate methodological quality. Before any firm conclusions can be drawn, further testing should be done in rigorously designed, executed, and analyzed trials with follow-up periods of sufficient length.

Chiropractic↗
PubMed2005

Estimation of effective population sizes from data on genetic markers.

The effective population size (Ne) is an important parameter in ecology, evolutionary biology and conservation biology. It is, however, notoriously difficult to estimate, mainly because of the highly stochastic nature of the processes of inbreeding and genetic drift for which Ne is usually defined and measured, and because of the many factors (such as time and spatial scales, systematic forces) confounding such processes. Many methods have been developed in the past three decades to estimate the current, past and ancient effective population sizes using different information extracted from some genetic markers in a sample of individuals. This paper reviews the methodologies proposed for estimating Ne from genetic data using information on heterozygosity excess, linkage disequilibrium, temporal changes in allele frequency, and pattern and amount of genetic variation within and between populations. For each methodology, I describe mainly the logic and genetic model on which it is based, the data required and information used, the interpretation of the estimate obtained, some results from applications to simulated or empirical datasets and future developments that are needed.

Evolution, Molecular↗
PubMed2003

Bio-array images processing and genetic networks modelling.

The new tools available for gene expression studies are essentially the bio-array methods using a large variety of physical detectors (isotopes, fluorescent markers, ultrasounds...). Here we present first rapidly an image-processing method independent of the detector type, dealing with the noise and with the peaks overlapping, the peaks revealing the detector activity (isotopic in the presented example), correlated with the gene expression. After this primary step of bio-array image processing, we can extract information about causal influence (activation or inhibition) a gene can exert on other genes, leading to clusters of genes co-expression in which we extract an interaction matrix M and an associated interaction graph G explaining the genetic regulatory dynamics correlated to the studied tissue function. We give two examples of such interaction matrices and graphs (the flowering genetic regulatory network of Arabidopsis thaliana and the lytic/lysogenic operon of the phage Mu) and after some theoretical rigorous results recently obtained concerning the asymptotic states generated by the genetic networks having a given interaction matrix and reciprocally concerning the minimal (in the sense of having a minimal number of non-zero coefficients) matrices having given stationary stable states.

Arabidopsis↗
PubMed2005

Text mining and ontologies in biomedicine: making sense of raw text.

The volume of biomedical literature is increasing at such a rate that it is becoming difficult to locate, retrieve and manage the reported information without text mining, which aims to automatically distill information, extract facts, discover implicit links and generate hypotheses relevant to user needs. Ontologies, as conceptual models, provide the necessary framework for semantic representation of textual information. The principal link between text and an ontology is terminology, which maps terms to domain-specific concepts. This paper summarises different approaches in which ontologies have been used for text-mining applications in biomedicine.

Abstracting and Indexing↗
PubMed2006

Insulin pump therapy in childhood diabetes-cost implications for Primary Care Trusts.

AIMS: Primary Care Trusts (PCTs) are now responsible for the planning and delivery of health-care services throughout England and Wales. As the 25 PCTs throughout Yorkshire are representative of the national distribution in terms of population structure and socio-economic status, we aimed to address the paucity of information describing the burden of childhood diabetes in primary care and to evaluate the cost implications of insulin pump therapy on individual PCTs. METHODS: We extracted information from a population-based register in Yorkshire, including 1952 patients diagnosed under the age of 15 years from 1990 to 2003. Each patient's postcode was linked to an individual PCT. Incidence rates (per 100 000 patient years) were derived and assessed for evidence of heterogeneity across PCTs and within Strategic Health Authorities (SHAs). RESULTS: Incidence rates were lower in West Yorkshire (19.1, 95% CI 18.0-20.2) than North-east Yorkshire (20.3, 18.9-21.6), although this difference was not significant (P = 0.20). No significant evidence of heterogeneity in incidence rates was observed across PCTs (P = 0.46). Ninety per cent of all PCTs would expect four to seven newly diagnosed children per year, corresponding to a single general practitioner (GP) referring an individual for diagnosis once every 15 years on average. Assuming 1% of current patients under the age of 15 years with diabetes were to move onto insulin pump therapy, this would impose an additional cost of pound400-1300 per year for each PCT. The average cost was 15% lower for PCTs in West Yorkshire than North and East Yorkshire. CONCLUSIONS: The additional resources required to pay for insulin pump therapy for a small proportion of the diabetes population would be minimal given the potential benefits to these patients of improved control and anticipated reduction in long-term morbidity.

Adolescent↗
PubMed1992

Human HPRT mutant database: software for data entry and retrieval.

We have developed a computer database containing information on over 1,000 human hypoxanthine guanine phosphoribosyl transferase (HPRT) mutants. Both published and unpublished data are present. The database itself is maintained in a dBASE format (.DBF) and we provide a set of programs to examine and extract information from the database. A program to input information into the database is also supplied. The database and programs are available directly from us or via remote FTP (file transfer protocol) using BITNET/INTERNET. All programs require an IBM-compatible computer, the MS-DOS operating system (version 3.3 or greater), and a hard disk with about 5 megabytes of free disk space. The purpose of the database is 1) to allow investigators to contribute their HPRT mutants directly to the database in a standardized fashion, and 2) to allow access to the entire database with a set of programs that allows manipulation and extraction of data. For example, using our programs it is possible to i) order the database by base pair position, ii) examine only information regarding mutagenesis by a particular agent, iii) search for a particular author, iv) create a report which contains selected portions of the database, the report can be printed or saved as a file. The database will be updated every several months and distributed.

Databases, Bibliographic↗
PubMed2004

Protein identification by liquid chromatography-mass spectrometry using retention time prediction.

Liquid chromatography has been coupled with mass spectrometry to improve the dynamic range and to reduce the complexity of sample introduced to the mass spectrometer at any given time. The chromatographic separation also provides information on the analytes, such as peptides in enzymatic digests of proteins; information that can be used when identifying the proteins by peptide mass fingerprinting. This paper discusses a recently introduced method based on retention time prediction to extract information from chromatographic separations and the applications of this method to protein identification in organisms with small and large genomes.

Chromatography, Liquid↗
PubMed1990

Role of spatial location in integration of pictorial information across saccades.

Identification of a fixated object in a visual display is facilitated by integrating information from a preview of that object in the periphery with information extracted on the subsequent foveal fixation (Pollatsek, Rayner, & Collins, 1984). These experiments investigated the extent to which this integration is dependent on the spatial location of the information remaining constant. Two preview objects were presented in the periphery; Ss fixated that region and named a single target object that appeared in the same spatial location in which one of the two preview objects had been presented. Of primary interest was the facilitative effect when a preview object was identical to the target object as a function of whether they were in the same spatial location. The major finding was that although there was a small effect of switching, there was still a substantial preview benefit even when the location of the identical object switched. In addition, the switching effect did not interact with the level of identity between the preview and target. There was also a preview benefit in conditions in which there were no eye movements and the preview and target objects were at least 5 degrees apart. Thus, the data indicate that the process object identification is relatively insensitive to location information and that object information and location information are coded fairly independently.

Adult↗
PubMed2005

Time series analysis of ion dynamics in glassy ionic conductors obtained by a molecular dynamics simulation.

We present several characteristics of ionic motion in glassy ionic conductors brought out by time series analysis of molecular dynamics (MD) simulation data. Time series analysis of data obtained by MD simulation can provide crucial information to describe, understand and predict the dynamics in many systems. The data have been treated by the singular spectrum analysis (SSA), which is a method to extract information from noisy short time series and thus provide insight into the unknown or partially unknown dynamics of the underlying system that generated the time series. Phase-space plot reconstructed using the principal components of SSA exhibited complex but clear structures, suggesting the deterministic nature of the dynamics.

Journal Article↗
PubMed2003

Applications of bioinformatics and computational biology to influenza surveillance and vaccine strain selection.

In recent years, collaborations often between mathematical and computational biologists and scientists in the World Health Organization (WHO) global influenza surveillance network, have resulted in a number of mathematical and computational advances including: increasing the resolution at which antigenic surveillance data can be analyzed, providing methods for genetic analysis and prediction, and an increased understanding of the determinants of repeated influenza vaccination. These advances increase the information extracted from influenza surveillance and increase the quantitative data available for the vaccine strain selection process. This mathematical and computational work is possible because of the wealth of information collected over many years by the WHO global influenza surveillance network, and further advances will be greatly facilitated by implementation of the proposed strengthening of virological and epidemiological surveillance in the WHO global agenda on influenza surveillance and control.

Computational Biology↗
PubMed1990

Anticipation in squash: differences in advance cue utilization between expert and novice players.

The time of occurrence and spatial location of the advance cues used to anticipate the direction and force of an opponent's stroke in squash were examined using a film task. This task, designed to stimulate the normal perceptual display of the defensive player, consisted of two discrete parts, each containing 160 individual stroke sequences (trials). In the first part of the film task, the display was occluded at different time intervals throughout the development of the opponent's stroke and the 16 expert and 20 novice subjects had to predict both the direction (down-wall or cross-court) and force (drive or drop shot) of the opponent's stroke. In the second part of the film task, visibility to selected advance cues was occluded by placing opaque mats on the film surface. Across all of the film task conditions experts were superior to novices in predicting the event outcome from the information available, highlighting the important contribution anticipatory skills make to expert performance in this sport. Analysis of lateral (direction) error showed that the most critical time periods for extracting information about stroke direction are the periods between 160-80 ms prior to racket-ball contact and the period of extended ball flight arising at least 80 ms after contact. Whereas both groups were attuned to this ball flight information, only the experts were capable of picking up information from the early part of the opponent's actions. This early information appeared to be provided by the opposing player's arm action. Similar time periods were found to be also important for the prediction of stroke depth, but in this case both experts and novices were similar in their cue dependence.

Adolescent↗
PubMed2006

Surgical Infection Society guideline: prophylactic antibiotic use in open fractures: an evidence-based guideline.

BACKGROUND: Prolonged courses of broad-spectrum antibiotics are often cited as the standard of care for prevention of infective complications of open fractures. The origins of these recommendations are obscure, however, and multi-drug-resistant systemic infections attributable to antibiotic overuse are common life-threatening problems in current intensive care unit practice. OBJECTIVE: To review systematically the effects of prophylactic antibiotic administration on the incidence of infections complicating open fractures. DATA SOURCES: Computerized bibliographic search of published research and citation review of relevant articles. STUDY SELECTION: All published clinical trials claiming to evaluate, or cited elsewhere as being authoritative regarding, the role of antibiotics in open fracture management were identified and then evaluated according to published guidelines for evidence-based medicine. Only small studies (<20 patients), practice surveys, pharmacokinetic studies, and reviews or duplicative publications presenting primary data already considered were excluded from analysis. DATA EXTRACTION: Information on demographics, study dates, fracture grade, antibiotic type, duration and route of administration, surgical interventions, infection-related outcomes, and the methodologic quality of the studies was extracted by the authors. The primary results were submitted to the Therapeutic Agents Committee of the Surgical Infection Society for review prior to creation of the final consensus document. DATA SYNTHESIS: Current antibiotic management of open fractures is based on a small number of studies that generally are more than 30 years old and do not reflect current management priorities in trauma and critical care. With a few noteworthy exceptions, these primary studies suffer from a variety of methodologic problems, including co-mingling of prospective and retrospective data sets, absence of or inappropriate statistical analysis, lack of blinding, or failure of randomization. CONCLUSIONS: The data support the conclusion that a short course of first-generation cephalosporins, begun as soon as possible after injury, significantly lowers the risk of infection when used in combination with prompt, modern orthopedic fracture wound management. There is insufficient evidence to support other common management practices, such as prolonged courses or repeated short courses of antibiotics, the use of antibiotic coverage extending to gram-negative bacilli or clostridial species, or the use of local antibiotic therapies such as beads. Large, randomized, blinded trials are needed to prove or disprove the value of these traditional approaches. Such trials should be performed in patients with high-grade fractures who (1) are well-stratified according to the degree of local injury and (2) undergo standardized fracture and wound management. Trials also must be powered to study the effects of extended antibiotic coverage on nosocomial infections. Antibiotic regimens confirmed to improve local fracture outcomes in such studies could then be used rationally, balancing the risks of local fracture-related infections and of multi-drug-resistant systemic infections to achieve optimal global outcomes.

Antibiotic Prophylaxis↗
PubMed2002

The role of quantitative structure--activity relationships (QSAR) in biomolecular discovery.

Empirical methods for building predictive models of the relationships between molecular structure and useful properties are becoming increasingly important. This has arisen because drug discovery and development have become more complex. A large amount of biological target information is becoming available through molecular biology. Automation of chemical synthesis and pharmacological screening has also provided a vast amount of experimental data. Tools for designing libraries and extracting information from molecular databases and high-throughput screening experiments robustly and quickly enable leads to be discovered more effectively. As drug leads progress down the development pipeline, the ability to predict physicochemical, pharmacokinetic and toxicological properties of these leads is becoming increasingly important in reducing the number of expensive, late development failures. Quantitative structure-activity relationship (QSAR) methods have much to offer in these areas. However, QSAR analysis has many traps for unwary practitioners. This review introduces the concepts behind QSAR, points out problems that may be encountered, suggests ways of avoiding the pitfalls and introduces several exciting, new QSAR methods discovered during the last decade.

Models, Molecular↗
PubMed2000

One thousand health-related quality-of-life estimates.

OBJECTIVE: Analysts performing cost-effectiveness analyses often do not have the resources to gather original quality-of-life (QOL) weights. Furthermore, variability in QOL for the same health state hampers the comparability of cost-effectiveness analyses. For these reasons, opinion leaders such as the Panel on Cost-Effectiveness in Health and Medicine have called for a national repository of QOL weights. Some authors have responded to the call by performing large primary studies of QOL. We take a different approach, amassing existing data with the hope that it will be combined responsibly in meta-analytic fashion. Toward the goal of developing a national repository of QOL weights to aid cost-effectiveness analysts, 1,000 health-related QOL estimates were gathered from publicly available source documents. METHODS: To identify documents, we searched databases and reviewed the bibliographies of articles, books, and government reports. From each document, we extracted information on the health state, QOL weight, assessment method, respondents, and upper and lower bounds of the QOL scale. Detailed guidelines were followed to ensure consistency in data extraction. RESULTS: We identified 154 documents yielding 1,000 original QOL weights. There was considerable variation in the weights assessed by different authors for the same health state. Methods also varied: 51% of authors used direct elicitation (standard gamble, time tradeoff, or rating scale), 32% estimated QOL based on their own expertise or that of others, and 17% used health status instruments. CONCLUSIONS: This comprehensive review of QOL data should lead to more consistent use of QOL weights and thus more comparable cost-effectiveness analyses.

Attitude to Health↗
PubMed2004

Neural networks as robust tools in drug lead discovery and development.

Empirical methods for building predictive models of the relationships between molecular structure and useful properties are becoming increasingly important. This has arisen because drug discovery and development have become more complex. A large amount of biological target information is becoming available though molecular biology. Automation of chemical synthesis and pharmacological screening has also provided a vast amount of experimental data. Tools for designing libraries and extracting information from molecular databases and high-throughput screening (HTS) experiments robustly and quickly enable leads to be discovered more effectively. As drug leads progress down the development pipeline, the ability to predict physicochemical, pharmacokinetic, and toxicological properties of these leads is becoming increasingly important in reducing the number of expensive, late-development failures. Neural network methods have much to offer in these areas. This review introduces the concepts behind neural networks applied to quantitative structure-activity relationships (QSARs), points out problems that may be encountered, suggests ways of avoiding the pitfalls, and introduces several exciting new neural network methods discovered during the last decade.

Animals↗
PubMed2006

Status of text-mining techniques applied to biomedical text.

Scientific progress is increasingly based on knowledge and information. Knowledge is now recognized as the driver of productivity and economic growth, leading to a new focus on the role of information in the decision-making process. Most scientific knowledge is registered in publications and other unstructured representations that make it difficult to use and to integrate the information with other sources (e.g. biological databases). Making a computer understand human language has proven to be a complex achievement, but there are techniques capable of detecting, distinguishing and extracting a limited number of different classes of facts. In the biomedical field, extracting information has specific problems: complex and ever-changing nomenclature (especially genes and proteins) and the limited representation of domain knowledge.

Abstracting and Indexing↗
PubMed2004

iProLINK: an integrated protein resource for literature mining.

The exponential growth of large-scale molecular sequence data and of the PubMed scientific literature has prompted active research in biological literature mining and information extraction to facilitate genome/proteome annotation and improve the quality of biological databases. Motivated by the promise of text mining methodologies, but at the same time, the lack of adequate curated data for training and benchmarking, the Protein Information Resource (PIR) has developed a resource for protein literature mining--iProLINK (integrated Protein Literature INformation and Knowledge). As PIR focuses its effort on the curation of the UniProt protein sequence database, the goal of iProLINK is to provide curated data sources that can be utilized for text mining research in the areas of bibliography mapping, annotation extraction, protein named entity recognition, and protein ontology development. The data sources for bibliography mapping and annotation extraction include mapped citations (PubMed ID to protein entry and feature line mapping) and annotation-tagged literature corpora. The latter includes several hundred abstracts and full-text articles tagged with experimentally validated post-translational modifications (PTMs) annotated in the PIR protein sequence database. The data sources for entity recognition and ontology development include a protein name dictionary, word token dictionaries, protein name-tagged literature corpora along with tagging guidelines, as well as a protein ontology based on PIRSF protein family names. iProLINK is freely accessible at http://pir.georgetown.edu/iprolink, with hypertext links for all downloadable files.

Computational Biology↗