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Effects of stimulus information and stimulus duration on amplitude and habituation of the electrodermal orienting response.

This study was designed to investigate the effects of stimulus information and stimulus duration on the skin conductance response (SCR) component of the orienting response (OR). Three levels of stimulus information were combined with two levels of stimulus duration in a 3 X 2 independent groups factorial design (N = 90). On the basis of Sokolov's (1966) theory, it was hypothesized that: (a) high information stimuli would elicit larger initial SCR'S than would stimuli of low information, (B) high-information stimuli would evoke more SCRs throughout a habituation series than would low-information stimuli, and (c) high-information stimuli would require more presentations to reach a habituation criterion than would stimuli of low information. It was also hypothesized that (d) long-duration stimuli would require fewer presentations to reach a habituation criterion and result in a faster rate of habituation than would stimuli of short duration. The stimuli consisted of black and white chequered patterns containing 12, 26 or 60 bits of information. Stimulus duration was either 0.5 or 4.5 sec, and each subject received 20 presentations at randomly ordered intervals of 20, 25, 30 and 35 sec. The results provided support for hypotheses (b), (c) and (d), but not for hypothesis (a). These results support the view that OR habituation can be conceptualized as a process of information extraction.

Adolescent↗

[Medical care research based on family doctor routine data--are interface-communicated treatment data feasible?].

AIMS OF THE STUDY: As part of an ongoing project on the utilisation of generic drugs in general practice we aimed at determining whether the transfer of prescriptions and patient characteristics from doctors' computerized medical records via the BDT (Behandlungsdatenträger) interface was feasible, and whether these data are suitable for research in pharmacoepidemiology. METHODS: All 1,395 general practitioners from 6 regions in Germany were invited to participate in the 'generics project'; 232 (17 %) agreed. The 17 software companies whose systems were used by the participating practices were asked to grant access to the BDT interface. For a prescription survey, doctors were supposed to export BDT files from two 3-month periods each in 2000 and 2001. Data were anonymised and relevant information extracted with a special programme. RESULTS: So far, BDT data are available from 79 practices. They are suitable for practice- and patient-related prescribing analyses. By filter modifications, additional information (such as diagnoses, referrals, clinical findings or accounting codes) can be obtained. The procedure was well accepted if doctors and practice staff were assisted by computer experts. Some difficulties, however, were encountered in obtaining access to the BDT-interface from the software companies. Lack of standardisation of the BDT interface required additional conditioning of the data. CONCLUSION: The BDT interface offers an opportunity to export computerised patient records without the requirement of additional documentation. If routine data are more readily available for health services research, a standardised data structure and open access must be assured e. g. by centralised certification via the Federal statutory health organisation.

Data Collection↗

Concept-based annotation of enzyme classes.

MOTIVATION: Given the explosive growth of biomedical data as well as the literature describing results and findings, it is getting increasingly difficult to keep up to date with new information. Keeping databases synchronized with current knowledge is a time-consuming and expensive task-one which can be alleviated by automatically gathering findings from the literature using linguistic approaches. We describe a method to automatically annotate enzyme classes with disease-related information extracted from the biomedical literature for inclusion in such a database. RESULTS: Enzyme names for the 3901 enzyme classes in the BRENDA database, a repository for quantitative and qualitative enzyme information, were identified in more than 100,000 abstracts retrieved from the PubMed literature database. Phrases in the abstracts were assigned to concepts from the Unified Medical Language System (UMLS) utilizing the MetaMap program, allowing for the identification of disease-related concepts by their semantic fields in the UMLS ontology. Assignments between enzyme classes and diseases were created based on their co-occurrence within a single sentence. False positives could be removed by a variety of filters including minimum number of co-occurrences, removal of sentences containing a negation and the classification of sentences based on their semantic fields by a Support Vector Machine. Verification of the assignments with a manually annotated set of 1500 sentences yielded favorable results of 92% precision at 50% recall, sufficient for inclusion in a high-quality database. AVAILABILITY: Source code is available from the author upon request. SUPPLEMENTARY INFORMATION: ftp.uni-koeln.de/institute/biochemie/pub/brenda/info/diseaseSupp.pdf.

Algorithms↗

Using radiology records to improve epidemiological information in paediatric fractures: a feasibility study.

OBJECTIVES: To assess the feasibility of using routine computerised radiology records for community injury surveillance data using fractures in the child population as an example. DESIGN: Radiology and in-patient computerised files were accessed to extract information concerning type of fracture, age, sex, and home address. Diagnostic coding of radiological report was carried out using the ICD-9 classification. Children were assigned to local authority wards using home postcodes derived from home addresses. Ward fracture rates were calculated using 1991 census data. The association between ward fracture rates and deprivation was explored using Townsend scores. SETTING: North Tyneside General Hospital. SUBJECTS: Children age 10-14 y receiving care as in-patients or out-patients for long-bone fractures. RESULTS: Between April 1991 and March 1996 a total of 497 long-bone fractures were identified. Fractures in boys exceeded those in girls by a ratio of 2:1. The most common fracture identified was of the radius and ulna. There was no evidence of an ecological association between long-bone fracture rates in children aged 10-14 y and social deprivation. CONCLUSIONS: Computerised radiological records may be used to improve epidemiological information concerning fractures. However, at present, considerable time and effort is required to access the information, to identify and to classify, long-bone fractures. Such data could be used to assist in the audit of clinical care and long-term outcomes, and to inform effective local planning and evaluation of injury prevention initiatives.

Adolescent↗

Wnt pathway curation using automated natural language processing: combining statistical methods with partial and full parse for knowledge extraction.

MOTIVATION: Wnt signaling is a very active area of research with highly relevant publications appearing at a rate of more than one per day. Building and maintaining databases describing signal transduction networks is a time-consuming and demanding task that requires careful literature analysis and extensive domain-specific knowledge. For instance, more than 50 factors involved in Wnt signal transduction have been identified as of late 2003. In this work we describe a natural language processing (NLP) system that is able to identify references to biological interaction networks in free text and automatically assembles a protein association and interaction map. RESULTS: A 'gold standard' set of names and assertions was derived by manual scanning of the Wnt genes website (http://www.stanford.edu/~rnusse/wntwindow.html) including 53 interactions involved in Wnt signaling. This system was used to analyze a corpus of peer-reviewed articles related to Wnt signaling including 3369 Pubmed and 1230 full text papers. Names for key Wnt-pathway associated proteins and biological entities are identified using a chi-squared analysis of noun phrases over-represented in the Wnt literature as compared to the general signal transduction literature. Interestingly, we identified several instances where generic terms were used on the website when more specific terms occur in the literature, and one typographic error on the Wnt canonical pathway. Using the named entity list and performing an exhaustive assertion extraction of the corpus, 34 of the 53 interactions in the 'gold standard' Wnt signaling set were successfully identified (64% recall). In addition, the automated extraction found several interactions involving key Wnt-related molecules which were missing or different from those in the canonical diagram, and these were confirmed by manual review of the text. These results suggest that a combination of NLP techniques for information extraction can form a useful first-pass tool for assisting human annotation and maintenance of signal pathway databases. AVAILABILITY: The pipeline software components are freely available on request to the authors. CONTACT: dstates@umich.edu SUPPLEMENTARY INFORMATION: http://stateslab.bioinformatics.med.umich.edu/software.html.

Animals↗

Histogram-based scoring schemes for protein NMR resonance assignment.

In NMR protein structure determination, after the resonance peaks have been identified and chemical shifts from peaks across multiple spectra have been grouped into spin systems, associating these spin systems to their host residues is the key toward the success of structural information extraction and thus the key to the success of the structure calculation. To achieve accurate enough structure calculation, a near complete and accurate assignment is a prerequisite. There are two pieces of information that can be used into the assignment, one of which is the adjacency information among the spin systems and the other is the signature information of the spin systems. The signature information reflects the fact that, generally speaking, for one type of amino acid residing in a specific local structural environment, the chemical shifts for the atoms inside the amino acid fall into some very narrow distinct ranges. In most of the existing work, normal distributions are assumed with means and standard deviations statistically collected from the available data. In this paper, we followed a simple yet effective histogram-based way to estimate for every spin system the probability that its host is a certain type of amino acid residing in a certain type of secondary structure. We used two combinations of chemical shifts to demonstrate the effectiveness of this type of histogram-based scoring schemes.

Algorithms↗

Bayesian analysis for the meiosis I non-disjunction fraction in numerical chromosomal anomalies.

The main causes of numerical chromosomal anomalies, including trisomies, arise from an error in the chromosomal segregation during the meiotic process, named a non-disjunction. One of the most used techniques to analyze chromosomal anomalies nowadays is the polymerase chain reaction (PCR), which counts the number of peaks or alleles in a polymorphic microsatellite locus. It was shown in previous works that the number of peaks has a multinomial distribution whose probabilities depend on the non-disjunction fraction F. In this work, we propose a Bayesian approach for estimating the meiosis I non-disjunction fraction F. in the absence of the parental information. Since samples of trisomic patients are, in general, small, the Bayesian approach can be a good alternative for solving this problem. We consider the sampling/importance resampling technique and the Simpson rule to extract information from the posterior distribution of F. Bayes and maximum likelihood estimators are compared through a Monte Carlo simulation, focusing on the influence of different sample sizes and prior specifications in the estimates. We apply the proposed method to estimate F. for patients with trisomy of chromosome 21 providing a sensitivity analysis for the method. The results obtained show that Bayes estimators are better in almost all situations.

Algorithms↗

Effects of lesion conspicuity on visual search in mammogram reading.

RATIONALE AND OBJECTIVES: The goal of mammography screening is to detect breast cancer at early stages, but because of the complexity of the breast parenchyma and the variability of signs of the disease, many cancers go unreported when initially visible on the mammogram. We compared the visual search strategy used by experienced mammographers in a case set where they examined both the mammogram in which a malignant mass was discovered at screening mammography and the most recent prior mammogram. MATERIALS AND METHODS: Four experienced mammographers participated in this experiment. They read a case set of 20 two-view mammograms, of which 15 contained a malignant mass and 5 were lesion-free, in two trials. For each of the cancer cases, two versions were shown to the observers: the one in which the cancer was reported in the clinical practice, called the "current" mammograms, and the most recent prior. Each trial had a balanced mix of current and prior mammograms. In addition, the same set of lesion-free cases was shown to the observers in both trials. The eye movements of the observers were tracked, and visual search parameters such as time to hit the location of the malignant mass, dwell, and mean pupil size in the location of the cancer were collected. Statistical analyses were used to determine whether there were differences between the current and prior mammograms. RESULTS: A total of 66% of the malignant masses in the current mammograms and 57% in the priors attracted some amount of visual attention. From these, 71% yielded a report on the current mammograms, but only 40% on the priors. In the cases where the observer saw the malignant mass, they did so within 2 seconds of image display, regardless of whether the mammogram was current or prior. CONCLUSION: Most unreported malignant masses attracted some amount of visual attention, but it was in the processing of the information extracted in the location of the lesion that most errors occurred. In our experiment, approximately 70% of the total time used by the observers for visual scan of the cases was spent gathering information to corroborate the hypothesis already formed by the radiologist.

Breast Neoplasms↗

Insights into recombination from population genetic variation.

Patterns of genetic variation in natural populations are shaped by, and hence carry valuable information about, the underlying recombination process. In the past five years, the increasing availability of large-scale population genetic data on dense sets of markers, coupled with advances in statistical methods for extracting information from these data, have led to several important advances in our understanding of the recombination process in humans. These advances include the identification of large numbers of 'hotspots', where recombination appears to take place considerably more frequently than in the surrounding sequence, and the identification of DNA sequence motifs that are associated with the locations of these hotspots.

Animals↗

Combining gene expression profiles and protein-protein interaction data to infer gene functions.

The ever-increasing flow of gene expression profiles and protein-protein interactions has catalyzed many computational approaches for inference of gene functions. Despite all the efforts, there is still room for improvement, for the information enriched in each biological data source has not been exploited to its fullness. A composite method is proposed for classifying unannotated genes based on expression data and protein-protein interaction (PPI) data, which extracts information from both data sources in novel ways. With the noise nature of expression data taken into consideration, importance is attached to the consensus expression patterns of gene classes instead of the actual expression profiles of individual genes, thus characterizing the composite method with enhanced robustness against microarray data variation. With regard to the PPI network, the traditional clear-cut binary attitude towards inter- and intra-functional interactions is abandoned, whereas a more objective perspective into the PPI network structure is formed through incorporating the varied function-function interaction probabilities into the algorithm. The composite method was implemented in two numerical experiments, where its improvement over single-data-source based methods was observed and the superiority of the novel data handling operations was discussed.

Algorithms↗

Assessment of groundwater quality by means of self-organizing maps: application in a semiarid area.

The Kohonen neural network was applied to hydrochemical data from the Detritic Aquifer of the Lower Andarax, situated in a semiarid zone in the southeast of Spain. An activation map was obtained for each of the sampling points, in which the spatial distribution of the activated neurons indicated different water qualities. To extract the information contained in the activation maps, they were divided into nine quadrats. Cartesian coordinates were assigned to each quadrant ( x, y), and for each sampling point, three derived variables were selected, which were assigned the values x and y of the corresponding quadrat. A classification was defined based on this simple matrix system which allows an easy and rapid means of evaluating the water quality. This assessment highlights the various processes that affect groundwater quality. The method generates output that is easier to interpret than from traditional statistical methods. The information is extracted from the activation maps without significant loss of information. The method is proposed for assessing water quality in hydrogeochemically complex areas, where large numbers of observations are made.

Desert Climate↗

Mitochondrial involvement in Atuna racemosa induced toxicity.

Our group has developed a system to extract information regarding potential novel pharmaceuticals from historic herbal texts. We have shown that one of the plants identified through this technique has the purported antibacterial properties suggested by the text. Here, the toxicity of this antibacterial extract was examined. Using a Jurkat cell model, a therapeutic window between the minimal inhibitory concentration for Gram-positive bacteria and the dose-dependent toxicity of the Atuna racemosa extract was established. Using cells with a mutated caspase 8, it was shown that the toxicity does not involve caspase 8. However, by transmission electron microscopy and a potentiometric dye, the toxicity was shown to involve the mitochondria. This toxicity also resulted in DNA cleavage and activation of caspase 3. This work suggests that the extract, originally reported as an antimicrobial therapeutic in a 400-year-old Dutch herbal text, may maintain a therapeutic window as an antibiotic. Furthermore, this work shows toxicity would occur in a mitochondrial dependent fashion.

Anti-Bacterial Agents↗

Identification of intonation contours by normally hearing and profoundly hearing-impaired listeners.

Fundamental frequency (F0) information extracted from low-pass-filtered speech and aurally presented as frequency-modulated sinusoids can greatly improve speechreading performance [Grant et al., J. Acoust. Soc. Am. 77, 671-677 (1985)]. To use this source of information, listeners must be able to detect the presence or absence of F0 (i.e., voicing), discriminate changes in frequency, and make judgments about the linguistic meaning of perceived variations in F0. In the present study, normally hearing and hearing-impaired subjects were required to locate the stressed peak of an intonation contour according to the extent of frequency transition at the primary peak. The results showed that listeners with profound hearing impairments required frequency transitions that were 1.5-6 times greater than those required by normally hearing subjects. These results were consistent with the subjects' identification performance for intonation and stress patterns in natural speech, and suggest that natural variations in F0 may be too small for some impaired listeners to perceive and follow accurately.

Auditory Threshold↗

Fermentation diagnosis by multivariate statistical analysis.

During the course of fermentation, online measuring procedures able to estimate the performance of the current operation are highly desired. Unfortunately, the poor mechanistic understanding of most biologic systems hampers attempts at direct online evaluation of the bioprocess, which is further complicated by the lack of appropriate online sensors and the long lag time associated with offline assays. Quite often available data lack sufficient detail to be directly used, and after a cursory evaluation are stored away. However, these historic databases of process measurements may still retain some useful information. A multivariate statistical procedure has been applied for analyzing the measurement profiles acquired during the monitoring of several fed-batch fermentations for the production of erythromycin. Multivariate principal component analysis has been used to extract information from the multivariate historic database by projecting the process variables onto a low-dimensional space defined by the principal components. Thus, each fermentation is identified by a temporal profile in the principal component plane. The projections represent monitoring charts, consistent with the concept of statistical process control, which are useful for tracking the progress of each fermentation batch and identifying anomalous behaviors (process diagnosis and fault detection).

Biotechnology↗

The reliability of the functional independence measure: a quantitative review.

OBJECTIVE: The reliability of the Functional Independence Measure (FIMSM) for adults was examined using procedures of meta-analysis. DATA SOURCES: Eleven published studies reporting estimates of reliability for the FIM were located using computer searches of Index Medicus, Psychological Abstracts, the Functional Assessment Information Service, and citation tracking. STUDY SELECTION: Studies were identified and coded based on type of reliability (interrater, test-retest, or equivalence), method of data analysis, size of sample, and training or experience of raters. DATA EXTRACTION: Information from the articles was coded by two independent raters. Interrater reliability for coding all elements included in the analysis ranged from .89 to 1.00. DATA SYNTHESIS: The 11 investigations included a total of 1,568 patients and produced 221 reliability coefficients. The majority of the reliability values (81%) were from interrater reliability studies, and the intraclass correlation coefficient (ICC) was the most commonly used statistical procedure to compute reliability. The reported reliability values were converted to a common correlation metric and aggregated across the 11 studies. The results revealed a median interrater reliability for the total FIM of .95 and median test-retest and equivalence reliability values of .95 and .92, respectively. The median reliability values for the six FIM subscales ranged from .95 for Self-Care to .78 for Social Cognition. For the individual FIM items, median reliability values varied from .90 for Toilet Transfer to .61 for Comprehension. Median and mean reliability coefficients for FIM motor items were generally higher than for items in the cognitive or communication subscales. CONCLUSIONS: Based on the 11 studies examined in this review the FIM demonstrated acceptable reliability across a wide variety of settings, raters, and patients.

Activities of Daily Living↗

How outbreaks can contribute to prevention of nosocomial infection: analysis of 1,022 outbreaks.

OBJECTIVE: To describe the epidemiology of nosocomial outbreaks published in the scientific literature. DESIGN: Descriptive information was obtained from a sample of 1,022 published nosocomial outbreaks from 1966 to 2002. METHODS: Published nosocomial outbreaks of the most important nosocomial pathogens were included in the database. A structured questionnaire was devised to extract information in a systematic manner on nosocomial outbreaks published in the literature. The following items were used: the reference, type of study (case reports or studies applying epidemiologic or fingerprinting methods), type of microorganism, setting, patients and personnel involved, type of infection, source of infection, mode of transmission, risk factors identified, and preventive measures applied. RESULTS: Bloodstream infection was the most frequently identified type of infection (37.0%), followed by gastrointestinal infection (28.5%) and pneumonia (22.9%). In 37% of the outbreaks, the authors were not able to identify the sources. The most frequent sources were patients (25.7%), followed by medical equipment or devices (11.9%), the environment (11.6%), and the staff (10.9%). The mode of transmission remained unclear in 28.3% of the outbreaks. Transmission was by contact in 45.3%, by invasive technique in 16.1%, and through the air in 15.0%. The percentage of outbreaks investigated by case-control studies or cohort studies over the years was small (21% and 9%, respectively, for the whole time period). CONCLUSION: Outbreak reports in the literature are a valuable resource and should be used for educational purposes as well as for preparing outbreak investigations.

Adolescent↗

New understanding from epidemiology--the next 25 years.

The epidemiology of radiation carcinogenesis is likely to be dominated during the next 25 y by the gradual maturation of major studies of populations exposed to substantial levels of radiation dose. During this period, for example, most of the new information on cancer risk among survivors of the 1945 atomic bombings of Hiroshima and Nagasaki will pertain to persons exposed at ages under 30. From the A-bomb survivor data and from a number of medically and occupationally irradiated populations now under study, it will be possible to construct a fairly complete picture of the temporal distribution of excess cancer risk over the remaining life span following exposure, a major source of uncertainty and controversy in current risk estimates. Provided that the necessary efforts are made, it should be possible to greatly increase our understanding of which organs and tissues are vulnerable to radiation carcinogenesis, variation by age at exposure and sex, and (what is most difficult at the present time) the influence of other risk factors and possible modifying factors on the magnitude of risk associated with radiation exposure. For some sites it may be possible, as it is now for breast cancer, to rule out certain broad classes of simple dose-response models. While the data gathered during the next 25 y will be nearly the last from some very important series, their information content should be extremely high. Thus, there is every reason to improve the resources, e.g., by improving dosimetry, enlarging samples, tapping new sources of case ascertainment, and gathering information on factors other than radiation dose. Modeling in epidemiological investigations depends heavily on work in experimental radiobiology. Thus far, the exchange has been largely in one direction, since epidemiological study design is mostly a matter of extracting information from "experiments" that have already taken place. With more epidemiological information, it seems reasonable to hope that detailed hypotheses, with direct relevance to areas of epidemiological uncertainty, may be generated suitable for experimental investigation. It seems likely that findings from large studies of populations exposed to relatively low levels of radiation, for which the signal-to-noise ratio is low, and for which random error and subtle sources of bias may have more than usual influence on reported results, will continue to generate controversy.(ABSTRACT TRUNCATED AT 400 WORDS)

Accidents↗

Representation of behaviourally relevant information by blowfly motion-sensitive visual interneurons requires precise compensatory head movements.

Flying blowflies shift their gaze by saccadic turns of body and head, keeping their gaze basically fixed between saccades. For the head, this results in almost pure translational optic flow between saccades, enabling visual interneurons in the fly motion pathway to extract information about translation of the animal and thereby about the spatial layout of the environment. There are noticeable differences between head and body movements during flight. Head saccades are faster and shorter than body saccades, and the head orientation is more stable between saccades than the body orientation. Here, we analyse the functional importance of these differences by probing visual interneurons of the blowfly motion pathway with optic flow based on either head movements or body movements, as recorded accurately with a magnetic search coil technique. We find that the precise head-body coordination is essential for the visual system to separate the translational from the rotational optic flow. If the head were tightly coupled to the body, the resulting optic flow would not contain the behaviourally important information on translation. Since it is difficult to resolve head orientation in many experimental paradigms, even when employing state-of-the-art digital video techniques, we introduce a 'headifying algorithm', which transforms the time-dependent body orientation in free flight into an estimate of head orientation. We show that application of this algorithm leads to an estimated head orientation between saccades that is sufficiently stable to enable recovering information on translation. The algorithm may therefore be of practical use when head orientation is needed but cannot be measured.

Algorithms↗