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PubMed2006

Context, automated decision support, and clinical practice guidelines: does the literature apply to the United States practice environment?

BACKGROUND: Context - the combined effect of factors such as physician type, clinical setting, and guideline characteristics - influences the ability of automated decision support (ADS) to improve physician compliance with clinical practice guidelines (CPGs). Our goal was to determine whether research about the utility of ADS for promoting CPG compliance is contextually applicable to United States physicians. METHODS: We extracted information about physicians, settings, and guidelines from all articles published in the last 10 years that describe original research about the use of ADS to promote CPG compliance. The extracted information was compared to the range of practice contexts seen in the United States. RESULTS: Nearly two-thirds (65.3%) of papers described studies conducted in an academic setting, but only 11% of physicians report academic affiliations (p<0.0001). Physician reimbursement structure is often not reported. Salaried physicians were explicitly included as subjects in 14% of articles, but make up 45% of US physicians (p<0.0001). There are little data about the generalizability of ADS research to emergency care settings (6% of articles), and nursing home or skilled nursing facilities (10% of articles). Finally, ADS has not been studied at all in several epidemiologically important disease categories. CONCLUSION: The literature does not adequately address some physician, setting, and guideline contexts. Before making policy or spending decisions based on the effectiveness of ADS, additional research is needed to determine whether ADS research can be generalized to under-represented contexts.

Decision Support Systems, Clinical↗
PubMed1996

Aboriginal health.

OBJECTIVE: To inform health care workers about the health status of Canada's native people. DATA SOURCES: A MEDLINE search for articles published from Jan. 1, 1989, to Nov. 31, 1995, with the use of subject headings "Eskimos" and "Indians, North American," excluding specific subject headings related to genetics and history. Case reports were excluded. Material was also identified from a review of standard references and bibliographies and from consultation with experts. STUDY SELECTION: Review and research articles containing original data concerning epidemiologic aspects of native health. Studies of Canadian populations were preferred, but population-based studies of US native peoples were included if limited Canadian information was available. DATA EXTRACTION: Information about target population, methods and conclusions was extracted from each study. RESULTS: Mortality and morbidity rates are higher in the native population than in the general Canadian population. The infant mortality rates averaged for the years 1986 to 1990 were 13.8 per 1000 live births among Indian infants, 16.3 per 1000 among Inuit infants, and only 7.3 per 1000 among all Canadian infants. Age-standardized all-cause mortality rates among residents of reserves averaged for the years 1979 to 1983 were 561.0 per 100,000 population among men and 334.6 per 100,000 among women, compared with 340.2 per 100,000 among all Canadian men and 173.4 per 100,000 among all Canadian women. Compared with the general Canadian population, specific native populations have an increased risk of death from alcoholism, homicide, suicide and pneumonia. Of the aboriginal population of Canada 15 years of age and older, 31% have been informed that they have a chronic health problem. Diabetes mellitus affects 6% of aboriginal adults, compared with 2% of all Canadian adults. Social problems identified by aboriginal people as a concern in their community include substance abuse, suicide, unemployment and family violence. Subgroups of aboriginal people are at a greater-than-normal risk of infectious diseases, injuries, respiratory diseases, nutritional problems (including obesity) and substance abuse. Initial data suggest that, compared with the general population, some subgroups of the native population have a lower incidence of heart disease and certain types of cancer. However, knowledge about contributing factors to the health status of aboriginal people is limited, since the literature generally does not assess confounding factors such as poverty. CONCLUSIONS: Canadian aboriginal people die earlier than their fellow Canadians, on average, and sustain a disproportionate share of the burden of physical disease and mental illness. However, few studies have assessed poverty as a confounding factor. Future research priorities in native health are best determined by native people themselves.

Canada↗
PubMed2004

Enhancing linkage analysis of complex disorders: an evaluation of high-density genotyping.

To explore the potential value of recently developed high-density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK multiple sclerosis linkage genome screen, using Applied Biosystems high-density microsatellite linkage mapping set, the Illumina BeadArray linkage mapping panel (version 3) and the Affymetrix GeneChip Human Mapping 10K array. We found that genotyping success, information extraction and genotyping accuracy were improved with all systems. These improvements were particularly marked with the SNP-based methods (Illumina and Affymetrix), with little difference between these. The extent of additional information extracted is considerable, indicating that reanalysis of existing multiplex families using these newer systems would substantially increase power.

Chromosome Mapping↗
PubMed2004

The effect of rotational angle and experimental parameters on the diffraction patterns and micro-structural information obtained from q-space diffusion NMR: implication for diffusion in white matter fibers.

Diffusion NMR may provide, under certain experimental conditions, micro-structural information about confined compartments totally non-invasively. The influence of the rotational angle, the pulse gradient length and the diffusion time on the diffusion diffraction patterns and q-space displacement distribution profiles was evaluated for ensembles of long cylinders having a diameter of 9 and 20 microm. It was found that the diffraction patterns are sensitive to the rotational angle (alpha) and are observed only when diffusion is measured nearly perpendicular to the long axis of the cylinders i.e., when alpha= 90 degrees +/- 5 degrees under our experimental conditions. More importantly, we also found that the structural information extracted from the displacement distribution profiles and from the diffraction patterns are very similar and in good agreement with the experimental values for cylinders of 20 microm or even 9 microm, when data is acquired with parameters that satisfy the short gradient pulse (SGP) approximation (i.e., delta -->0) and the long diffusion time limit. Since these experimental conditions are hardly met in in vitro diffusion MRI of excised organs, and cannot be met in clinical MRI scanners, we evaluated the effect of the pulse gradient duration and the diffusion time on the structural information extracted from q-space diffusion MR experiments. Indeed it was found that, as expected, accurate structural information, and diffraction patterns are observed when Delta is large enough so that the spins reach the cylinders' boundaries. In addition, it was found that large delta results in extraction of a compartment size, which is smaller than the real one. The relevance of these results to q-space MRI of neuronal tissues and fiber tracking is discussed.

Diffusion Magnetic Resonance Imaging↗
PubMed2003

Mapping multiple co-sequenced T-DNA integration sites within the Arabidopsis genome.

MOTIVATION: Insertion mutagenesis, using transgenes or endogenous transposons, is a popular method for generating null mutations (knockouts) in model organisms. Insertions are mapped to specific genes by amplifying (via TAIL-PCR) and sequencing genomic regions flanking the inserted DNA. The presence of multiple TAIL-PCR templates in one sequencing reaction results in chimeric sequence of intermittently low quality. Standard processing of this sequence by applying Phred quality requirements results in loss of informative sequence, whereas not trimming low-quality sequence causes inclusion of low-complexity homopolymers from the ends of sequence runs. Accurate mapping of the flanking sequences is complicated by the presence of gene families. RESULTS: Methods for extracting informative regions from sequence traces obtained by sequencing multiple TAIL-PCR fragments in a single reaction are described. The completely sequenced Arabidopsis genome was used to identify informative TAIL-PCR sequence regions. Methods were devised to define and select high quality matches and precisely map each insert to the correct genome location. These methods were used to analyze sequence of TAIL-PCR-amplified flanking regions of the inserts from individual plants in a T-DNA-mutagenized population of Arabidopsis thaliana, and are applicable to similar situations where a reference genome can be used to extract information from poor-quality sequence.

Arabidopsis↗
PubMed2001

The use of prior information for extracting the post-edge background.

A new method for extracting the post-edge background mu0 is proposed, the method of Bayesian smoothing. A further evolution of the smoothing spline method is considered as well. Both techniques are capable to take into account prior information about the peculiarities on the mu0. In addition, since the Bayesian approach works in terms of the posterior probability density functions, it contains a natural way to determine the errors of the mu0 construction, which has always been an unresolvable problem for any other method. Even with use of the prior information, which narrows the posterior probabilities, the errors of mu0 are shown to be larger than the experimental noise.

Journal Article↗
PubMed2001

Male great tits eavesdrop on simulated male-to-male vocal interactions.

Animal communication generally occurs in the environment of a network of several potential signallers and receivers. Within a network environment, it is possible to gain relative information about conspecifics by eavesdropping on signalling interactions. We presented male great tits with the opportunity to gain such information by simulating singing interactions using two loudspeakers. Interactions were presented so that relevant information was not available in the absolute singing behaviour of either individual, only in the relative timing of their songs in the interaction as a whole. We then assayed the information extracted by focal males by subsequently introducing one of the 'interactants' (i.e. loudspeakers) into the territory of the focal male. Focal males responded with a reduced song output to males that had just 'lost' an interaction. Focal males did not respond significantly differently to 'winners' as compared with intruders recently involved in an interaction that contained no consistent information. Focal males also responded by switching song types more often when encountering males that had recently been involved in a low-intensity interaction. These results provide the clearest evidence yet that male songbirds extract information from signal interactions between conspecifics in the field.

Animals↗
PubMed2004

Ab initio quantum dynamics with very weak van der Waals interactions: Structure and stability of small Li2(1Sigmag+)-(He)n clusters.

The potential energy surface (PES) for the interaction between Li2(1Sigmag+) and 4He has been computed using an accurate, post-Hartree-Fock quantum calculation for its ground electronic state. The orientational anisotropy of the forces and the interplay between repulsive and attractive effects within the PES are analyzed to extract information on the possible existence of bound states in the triatomic system. The structures of a few of the Li2(He)n small clusters are examined by comparing a classical approach with a full quantum one to generate bound configurations and to extract information on the possible spatial arrangements of the smaller clusters via à vis the location of the Li2 dopant. Some significant consequences on the Li2 behavior in larger clusters and droplets are drawn from the above findings.

Journal Article↗
PubMed2001

Microarray data analysis: a practical approach for selecting differentially expressed genes.

BACKGROUND: The biomedical community is rapidly developing new methods of data analysis for microarray experiments, with the goal of establishing new standards to objectively process the massive datasets produced from functional genomic experiments. Each microarray experiment measures thousands of genes simultaneously producing an unprecedented amount of biological information across increasingly numerous experiments; however, in general, only a very small percentage of the genes present on any given array are identified as differentially regulated. The challenge then is to process this information objectively and efficiently in order to obtain knowledge of the biological system under study and by which to compare information gained across multiple experiments. In this context, systematic and objective mathematical approaches, which are simple to apply across a large number of experimental designs, become fundamental to correctly handle the mass of data and to understand the true complexity of the biological systems under study. RESULTS: The present report develops a method of extracting differentially expressed genes across any number of experimental samples by first evaluating the maximum fold change (FC) across all experimental parameters and across the entire range of absolute expression levels. The model developed works by first evaluating the FC across the entire range of absolute expression levels in any number of experimental conditions. The selection of those genes within the top X% of highest FCs observed within absolute expression bins was evaluated both with and without the use of replicates. Lastly, the FC model was validated by both real time polymerase chain reaction (RT-PCR) and variance data. Semi-quantitative RT-PCR analysis demonstrated 73% concordance with the microarray data from Mu11K Affymetrix GeneChips. Furthermore, 94.1% of those genes selected by the 5% FC model were found to lie above measurement variability using a SDwithin confidence level of 99.9%. CONCLUSION: As evidenced by the high rate of validation, the FC model has the potential to minimize the number of required replicates in expensive microarray experiments by extracting information on gene expression patterns (e.g. characterizing biological and/or measurement variance) within an experiment. The simplicity of the overall process allows the analyst to easily select model limits which best describe the data. The genes selected by this process can be compared between experiments and are shown to objectively extract information which is biologically & statistically significant.

Animals↗
PubMed1996

Hemispheric asymmetry for visual information processing.

The left and right hemispheres of humans do not handle all aspects of visual information processing with equal ability. This is illustrated by a review of research concerning the processing of global versus local stimulus properties, low versus high spatial frequencies, and coordinate versus categorical spatial relationships. In general, the right hemisphere is dominant for processing global aspects of visual stimuli that are carried by low spatial frequencies, for the processing of coordinate spatial relationships and, perhaps, for extracting information from the magnocellular visual pathway. In something of a complementary manner, the left hemisphere is dominant for processing local aspects of visual stimuli that are carried by high spatial frequencies and, perhaps, for processing categorical spatial relationships and for extracting information from parvocellular visual pathway. Consideration is given to developmental mechanisms that may underlie the emergence of hemispheric asymmetry for these interrelated aspects of visual information processing.

Brain↗
PubMed2005

Extraction of transcript diversity from scientific literature.

Transcript diversity generated by alternative splicing and associated mechanisms contributes heavily to the functional complexity of biological systems. The numerous examples of the mechanisms and functional implications of these events are scattered throughout the scientific literature. Thus, it is crucial to have a tool that can automatically extract the relevant facts and collect them in a knowledge base that can aid the interpretation of data from high-throughput methods. We have developed and applied a composite text-mining method for extracting information on transcript diversity from the entire MEDLINE database in order to create a database of genes with alternative transcripts. It contains information on tissue specificity, number of isoforms, causative mechanisms, functional implications, and experimental methods used for detection. We have mined this resource to identify 959 instances of tissue-specific splicing. Our results in combination with those from EST-based methods suggest that alternative splicing is the preferred mechanism for generating transcript diversity in the nervous system. We provide new annotations for 1,860 genes with the potential for generating transcript diversity. We assign the MeSH term "alternative splicing" to 1,536 additional abstracts in the MEDLINE database and suggest new MeSH terms for other events. We have successfully extracted information about transcript diversity and semiautomatically generated a database, LSAT, that can provide a quantitative understanding of the mechanisms behind tissue-specific gene expression. LSAT (Literature Support for Alternative Transcripts) is publicly available at http://www.bork.embl.de/LSAT/.

Journal Article↗
PubMed1984

Compton scatter axial tomography with x-rays: SCAT-CAT.

A method of extracting information from the backscattered field produced in parallel beam x-ray computed tomography (CT) is presented. A calculational model to predict the backscattered field based on Compton scattering is described, and the model is verified by measurements of simple phantoms. The phantoms tested--cylinders of polymethylmethacrylate (PMM) with air gaps and aluminium rods placed internally--are irradiated on a scanning assembly, built to simulate a first generation CT scanner with a transmission and a scatter detector (the SCAT-CAT). Data from the transmission detector are reconstructed by traditional CT methods to provide a transmission image; it is the data from the backscatter detector which are analysed in this study. After verification of the model for the scattered field calculations, a method of extracting information from the scattered field is developed, based on ratios of scatter signals from non-uniform to uniform phantoms. This method is demonstrated for predicted data of a simulated phantom and for measured data of the same and two additional phantoms. The method is very sensitive to air gaps in the phantoms because of the relative electron density of air with respect to PMM; it is not as sensitive to aluminium rods for the same reason. Various methods of applying the scattered field information to produce an image representing a simulated phantom are considered, and a preferred method is chosen to reconstruct scattered field data into an image for the three phantoms studied.

Humans↗
PubMed1985

Kinetic analysis of channel gating. Application to the cholinergic receptor channel and the chloride channel from Torpedo californica.

Identification of the minimum number of ways in which open and closed states communicate is a crucial step in defining the gating kinetics of multistate channels. We used certain correlation functions to extract information about the pathways connecting the open and closed states of the cation channel of the purified nicotinic acetylcholine receptor and of the chloride channel of Torpedo californica electroplax membranes. Single channel currents were recorded from planar lipid bilayers containing the membrane channel proteins under investigation. The correlation functions are conveniently computed from single channel current records and yield information on E, the minimum number of entry/exit states into the open or closed aggregates. E gives a lower limit on the numbers of transition pathways between open and closed states. For the acetylcholine receptor, the autocorrelation analysis shows that there are at least two entry/exit states through which the open and closed aggregates communicate. The chloride channel fluctuates between three conductance substates, here indentified as C, M, and H for closed, intermediate, and high conductance, respectively. Correlation analysis shows that E is greater than or equal to 2 for the M aggregate, indicating that there are at least two distinct entry/exit states in the M aggregate. In contrast, there is no evidence for the existence of more than one entry/exit state in the C or H aggregates. Thus, these correlation functions provide a simple and general strategy to extract information on channel gating kinetics.

Animals↗
PubMed2005

A prognostic score for prediction of cardiac mortality risk after adenosine stress myocardial perfusion scintigraphy.

OBJECTIVES: We sought to derive and validate a score to estimate risk after adenosine stress. BACKGROUND: Maximizing the prognostic information extracted from adenosine stress myocardial perfusion scintigraphy, a commonly performed test, is often challenging for referring physicians. METHODS: A split-set validation of a score predicting cardiovascular mortality was performed in 5,873 consecutive patients studied by adenosine stress, dual-isotope single-photon emission computed tomography (SPECT; follow-up 94% complete, mean 2.2 +/- 1.1 years). RESULTS: On follow-up, 387 cardiac deaths occurred (6.6%). The Cox proportional hazards model most predictive of cardiac death included age, % myocardium ischemic, % myocardium fixed, early revascularization, dyspnea, diabetes mellitus, rest and peak stress heart rates, abnormal rest electrocardiogram (ECG), and an interaction between % myocardium ischemic and early revascularization (chi-square = 376). The final prognostic score was calculated as follows: (age [decades] x 5.19) + (% myocardium ischemic [per 10%] x 4.66) + (% myocardium fixed [per 10%] x 4.81) + (diabetes mellitus x 3.88) + (if patient treated with early revascularization, 4.51) + (if dyspnea was a presenting symptom, 5.47) + (resting heart rate [per 10 beats] x 2.88) - (peak heart rate [per 10 beats] x 1.42) + (ECG score x 1.95) - (if patient treated with early revascularization, % myocardium ischemic [per 10%] x 4.47). Scores of <49, 49 to 57, and >57 identified low, intermediate, and high risk (0.9%, 3.3%, and 9.5% cardiac death/year, respectively). Score results further risk stratified patients with respect to cardiac death in all categories of SPECT abnormality. CONCLUSIONS: We derived and validated a score incorporating data available after adenosine stress perfusion SPECT. This score maximizes the prognostic information extracted from this test and may enhance the application of this test as part of an overall strategy.

Adenosine↗
PubMed2005

Extraction of regulatory gene/protein networks from Medline.

MOTIVATION: We have previously developed a rule-based approach for extracting information on the regulation of gene expression in yeast. The biomedical literature, however, contains information on several other equally important regulatory mechanisms, in particular phosphorylation, which we now expanded for our rule-based system also to extract. RESULTS: This paper presents new results for extraction of relational information from biomedical text. We have improved our system, STRING-IE, to capture both new types of linguistic constructs as well as new types of biological information [i.e. (de-)phosphorylation]. The precision remains stable with a slight increase in recall. From almost one million PubMed abstracts related to four model organisms, we manage to extract regulatory networks and binary phosphorylations comprising 3,319 relation chunks. The accuracy is 83-90% and 86-95% for gene expression and (de-)phosphorylation relations, respectively. To achieve this, we made use of an organism-specific resource of gene/protein names considerably larger than those used in most other biology related information extraction approaches. These names were included in the lexicon when retraining the part-of-speech (POS) tagger on the GENIA corpus. For the domain in question, an accuracy of 96.4% was attained on POS tags. It should be noted that the rules were developed for yeast and successfully applied to both abstracts and full-text articles related to other organisms with comparable accuracy. AVAILABILITY: The revised GENIA corpus, the POS tagger, the extraction rules and the full sets of extracted relations are available from http://www.bork.embl.de/Docu/STRING-IE

Abstracting and Indexing↗
PubMed2006

Extracting quantitative information from tissue--an industrial perspective.

The focus of this article is to provide an overview of the current technologies for the pharmaceutical and biotech industry. Disease processes express themselves in the functional and structural disturbance of cellular systems. Cells and their metabolites constitute the building blocks of tissues and entire organisms. Studying the spatial and temporal phenotype of disease processes in tissues at the cellular level reveals a multitude of information about the progress and status of a disease. Detailed exploration of tissues by slide-based cytometry is an important source of information about disease processes. Technological and analytical advances allow us to shed a new light on tissues and to come to a better understanding of the complexity of disease processes. Dealing with complex multidimensional datasets from tissue samples requires an advanced approach to image processing and data management. The increase in computing power and the continuing research into imaging algorithms allow us to improve the exploration of the data content of tissues.

Animals↗
PubMed2006

GARBAN II: an integrative framework for extracting biological information from proteomic and genomic data.

Genomic and proteomic analyses generate a massive amount of data that requires specific bioinformatic tools for its management and interpretation. GARBAN II, developed from the previous GARBAN platform, provides an integrated framework to simultaneously analyse and compare multiple datasets from DNA microarrays and proteomic studies. The general architecture, gene classification and comparison, and graphical representation have been redesigned to ensure a user-friendly feature and to improve the capabilities and efficiency of this system. Additionally, GARBAN II has been extended with new applications to display networks of coexpressed genes and to integrate access to BioRag and MotifScanner so as to facilitate the holistic analysis of users' data.

Animals↗