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Validation of an automatic crackle (rale) counter.

Crackles are commonly used in clinical decision-making, and in certain diseases the number of crackles reflects the severity of the illness. Auditory crackle estimations are subjective; crackle counting from time amplitude plots of sound (called time-expanded waveforms) is more objective but is cumbersome. We devised a computer-based system to count crackles automatically. One hundred samples of lung sounds from 41 subjects were recorded using an electret microphone air-coupled to the chest wall. Interobserver agreement in estimating the number of crackles per breath was high (r = 0.88, p less than 0.001), and these counts were significantly correlated with counts made of spikelike deflections seen on time-expanded waveform analysis (r = 0.78, p less than 0.001). The automatic crackle counting correlated with the physician counts (r = 0.74, p less than 0.001). The average number of crackles counted per breath was greater by visual inspiration (8.8) and by automatic analysis (7.8) than it was by the physician observers (5.8). Reasons for the discrepancies include the fact that there are no absolute criteria for crackles and that rapidly occurring crackles are difficult to count by ear. Counting crackles by computer-based methods is feasible and can improve noninvasive cardiopulmonary diagnosis.

Asbestosis↗

Automatic retinal oximetry.

PURPOSE: To measure hemoglobin oxygen saturation (SO(2)) in retinal vessels and to test the reproducibility and sensitivity of an automatic spectrophotometric oximeter. METHODS: Specialized software automatically identifies the retinal blood vessels on fundus images, which are obtained with four different wavelengths of light. The software calculates optical density ratios (ODRs) for each vessel. The reproducibility was evaluated by analyzing five repeated measurements of the same vessels. A linear relationship between SO(2) and ODR was assumed and a linear model derived. After calibration, reproducibility and sensitivity were calculated in terms of SO(2). Systemic hyperoxia (n = 16) was induced in healthy volunteers by changing the O(2) concentration in inhaled air from 21% to 100%. RESULTS: The automatic software enhanced reproducibility, and the mean SD for repeated measurements was 3.7% for arterioles and 5.3% venules, in terms of percentage of SO(2) (five repeats, 10 individuals). The model derived for calibration was SO(2) = 125 - 142 . ODR. The arterial SO(2) measured 96% +/- 9% (mean +/- SD) during normoxia and 101% +/- 8% during hyperoxia (n = 16). The difference between normoxia and hyperoxia was significant (P = 0.0027, paired t-test). Corresponding numbers for venules were 55% +/- 14% and 78% +/- 15% (P < 0.0001). SO(2) is displayed as a pseudocolor map drawn on fundus images. CONCLUSIONS: The retinal oximeter is reliable, easy to use, and sensitive to changes in SO(2) when concentration of O(2) in inhaled air is changed.

Humans↗

Creation of an In vivo cytosensor using engineered mesangial cells. Automatic sensing of glomerular inflammation controls transgene activity.

Automatic control over exogenous gene expression in response to the activity of disease is a crucial hurdle for gene transfer-based therapies. Towards achieving this goal, we created a "cytosensor" that perceives local inflammatory states and subsequently regulates foreign gene expression. alpha-Smooth muscle actin is known to be expressed in glomerular mesangial cells exclusively in pathologic situations. CArG box element, the crucial regulatory sequence of the alpha-smooth muscle actin promoter, was used as a sensor for glomerular inflammation. Rat mesangial cells were stably transfected with an expression plasmid that introduces a beta-galactosidase gene under the control of CArG box elements. In vitro, the established cells expressed beta-galactosidase exclusively after stimulation with serum. To examine whether the cells are able to automatically control transgene activity in vivo, serum-stimulated or unstimulated cells were transferred into normal rat glomeruli or glomeruli subjected to anti-Thy 1 glomerulonephritis. When stimulated cells were transferred into the normal glomeruli, beta-galactosidase expression was switched off in vivo within 3 d. In contrast, when unstimulated cells were transferred into the nephritic glomeruli, transgene expression was substantially induced. These data indicate the feasibility of using the CArG box element as a molecular sensor for glomerular injury. In the context of advanced forms of gene therapy, this approach provides a novel concept for automatic regulation of local transgene expression where the transgene is required to be activated during inflammation and deactivated when the inflammation has subsided.

Actins↗

Retrieval, automaticity, vocabulary elaboration, orthography (RAVE-O): a comprehensive, fluency-based reading intervention program.

The most important implication of the double-deficit hypothesis (Wolf & Bowers, in this issue) concerns a new emphasis on fluency and automaticity in intervention for children with developmental reading disabilities. The RAVE-O (Retrieval, Automaticity, Vocabulary Elaboration, Orthography) program is an experimental, fluency-based approach to reading intervention that is designed to accompany a phonological analysis program. In an effort to address multiple possible sources of dysfluency in readers with disabilities, the program involves comprehensive emphases both on fluency in word attack, word identification, and comprehension and on automaticity in underlying componential processes (e.g., phonological, orthographic, semantic, and lexical retrieval skills). The goals, theoretical principles, and applied activities of the RAVE-O curriculum are described with particular stress on facilitating the development of rapid orthographic pattern recognition and on changing children's attitudes toward language.

Automation↗

Automatic discrimination of emotion from spoken Finnish.

In this paper, experiments on the automatic discrimination of basic emotions from spoken Finnish are described. For the purpose of the study, a large emotional speech corpus of Finnish was collected; 14 professional actors acted as speakers, and simulated four primary emotions when reading out a semantically neutral text. More than 40 prosodic features were derived and automatically computed from the speech samples. Two application scenarios were tested: the first scenario was speaker-independent for a small domain of speakers while the second scenario was completely speaker-independent. Human listening experiments were conducted to assess the perceptual adequacy of the emotional speech samples. Statistical classification experiments indicated that, with the optimal combination of prosodic feature vectors, automatic emotion discrimination performance close to human emotion recognition ability was achievable.

Adult↗

A comparative study of the measurement of mean arterial blood pressure using automatic oscillometers, arterial cannulation and auscultation.

Mean brachial artery pressures determined by five different non-invasive automatic oscillometric and one auscultatory preferred (oscillometric back-up) blood pressure (BP) monitors were compared with mean arterial pressures (MAP) obtained by cannulation of the radial artery of the same arm. The devices tested all performed similarly, showing a wide range of variation (+40% to -29%) compared with the directly measured MAP, and all tended to over-read at low values and under-read at high values. Trend information was generally acceptable, but occasionally was misleading. In addition, using one of the devices, systolic and diastolic blood pressure measurements were compared with those obtained by auscultation. This gives a range of differences from +22 to -25 mmHg for systolic and +20 to -12 mmHg for diastolic BP measurements. (The average fell within 1.0 mmHg of the auscultatory measurement, with a standard deviation of 10 mmHg.) Thus, the automatic oscillometric BP monitors tested were comparable in accuracy to auscultatory BP measurement, and are satisfactory for routine use in the appropriate clinical context. However, in settings where significance is to be attached to individual BP readings rather than to trends, or where a high degree of accuracy is required, automatic oscillometric machines cannot be regarded as satisfactory alternatives to arterial cannulation.

Analysis of Variance↗

Preliminary evidence for an automatic link between sex and power among men who molest children.

Understanding critical motivational processes of sexual offenders may ultimately provide important clues to more effective treatments. Implicit, automatic cognitive processes have received minimal attention; however, a lexical decision experiment revealed automatic links between the concepts of power and sex among participants who self-reported attraction to sexual aggression. The current study replicates this experiment with a group of male child molesters and forensic and analogue controls. Subliminally presented sex words elicited a facilitation effect for power words among child molesters only; that is, sex to power associations were evident, as well as a trend for the reverse. These results provide preliminary evidence for an automatic sex-power association in child molesters and may point to a crucial pathological link in the cognitive schemata of sex offenders. As well, the current study suggests that paradigms from cognitive psychology may contribute to multimodal (risk) assessment of sexual offenders.

Adult↗

preAssemble: a tool for automatic sequencer trace data processing.

BACKGROUND: Trace or chromatogram files (raw data) are produced by automatic nucleic acid sequencing equipment or sequencers. Each file contains information which can be interpreted by specialised software to reveal the sequence (base calling). This is done by the sequencer proprietary software or publicly available programs. Depending on the size of a sequencing project the number of trace files can vary from just a few to thousands of files. Sequencing quality assessment on various criteria is important at the stage preceding clustering and contig assembly. Two major publicly available packages--Phred and Staden are used by preAssemble to perform sequence quality processing. RESULTS: The preAssemble pre-assembly sequence processing pipeline has been developed for small to large scale automatic processing of DNA sequencer chromatogram (trace) data. The Staden Package Pregap4 module and base-calling program Phred are utilized in the pipeline, which produces detailed and self-explanatory output that can be displayed with a web browser. preAssemble can be used successfully with very little previous experience, however options for parameter tuning are provided for advanced users. preAssemble runs under UNIX and LINUX operating systems. It is available for downloading and will run as stand-alone software. It can also be accessed on the Norwegian Salmon Genome Project web site where preAssemble jobs can be run on the project server. CONCLUSION: preAssemble is a tool allowing to perform quality assessment of sequences generated by automatic sequencing equipment. preAssemble is flexible since both interactive jobs on the preAssemble server and the stand alone downloadable version are available. Virtually no previous experience is necessary to run a default preAssemble job, on the other hand options for parameter tuning are provided. Consequently preAssemble can be used as efficiently for just several trace files as for large scale sequence processing.

Algorithms↗

EVEREST: automatic identification and classification of protein domains in all protein sequences.

BACKGROUND: Proteins are comprised of one or several building blocks, known as domains. Such domains can be classified into families according to their evolutionary origin. Whereas sequencing technologies have advanced immensely in recent years, there are no matching computational methodologies for large-scale determination of protein domains and their boundaries. We provide and rigorously evaluate a novel set of domain families that is automatically generated from sequence data. Our domain family identification process, called EVEREST (EVolutionary Ensembles of REcurrent SegmenTs), begins by constructing a library of protein segments that emerge in an all vs. all pairwise sequence comparison. It then proceeds to cluster these segments into putative domain families. The selection of the best putative families is done using machine learning techniques. A statistical model is then created for each of the chosen families. This procedure is then iterated: the aforementioned statistical models are used to scan all protein sequences, to recreate a library of segments and to cluster them again. RESULTS: Processing the Swiss-Prot section of the UniProt Knoledgebase, release 7.2, EVEREST defines 20,230 domains, covering 85% of the amino acids of the Swiss-Prot database. EVEREST annotates 11,852 proteins (6% of the database) that are not annotated by Pfam A. In addition, in 43,086 proteins (20% of the database), EVEREST annotates a part of the protein that is not annotated by Pfam A. Performance tests show that EVEREST recovers 56% of Pfam A families and 63% of SCOP families with high accuracy, and suggests previously unknown domain families with at least 51% fidelity. EVEREST domains are often a combination of domains as defined by Pfam or SCOP and are frequently sub-domains of such domains. CONCLUSION: The EVEREST process and its output domain families provide an exhaustive and validated view of the protein domain world that is automatically generated from sequence data. The EVEREST library of domain families, accessible for browsing and download at 1, provides a complementary view to that provided by other existing libraries. Furthermore, since it is automatic, the EVEREST process is scalable and we will run it in the future on larger databases as well. The EVEREST source files are available for download from the EVEREST web site.

Cluster Analysis↗

Automatic extraction of candidate nomenclature terms using the doublet method.

BACKGROUND: New terminology continuously enters the biomedical literature. How can curators identify new terms that can be added to existing nomenclatures? The most direct method, and one that has served well, involves reading the current literature. The scholarly curator adds new terms as they are encountered. Present-day scholars are severely challenged by the enormous volume of biomedical literature. Curators of medical nomenclatures need computational assistance if they hope to keep their terminologies current. The purpose of this paper is to describe a method of rapidly extracting new, candidate terms from huge volumes of biomedical text. The resulting lists of terms can be quickly reviewed by curators and added to nomenclatures, if appropriate. The candidate term extractor uses a variation of the previously described doublet coding method. The algorithm, which operates on virtually any nomenclature, derives from the observation that most terms within a knowledge domain are composed entirely of word combinations found in other terms from the same knowledge domain. Terms can be expressed as sequences of overlapping word doublets that have more specific meaning than the individual words that compose the term. The algorithm parses through text, finding contiguous sequences of word doublets that are known to occur somewhere in the reference nomenclature. When a sequence of matching word doublets is encountered, it is compared with whole terms already included in the nomenclature. If the doublet sequence is not already in the nomenclature, it is extracted as a candidate new term. Candidate new terms can be reviewed by a curator to determine if they should be added to the nomenclature. An implementation of the algorithm is demonstrated, using a corpus of published abstracts obtained through the National Library of Medicine's PubMed query service and using "The developmental lineage classification and taxonomy of neoplasms" as a reference nomenclature. RESULTS: A 31+ Megabyte corpus of pathology journal abstracts was parsed using the doublet extraction method. This corpus consisted of 4,289 records, each containing an abstract title. The total number of words included in the abstract titles was 50,547. New candidate terms for the nomenclature were automatically extracted from the titles of abstracts in the corpus. Total execution time on a desktop computer with CPU speed of 2.79 GHz was 2 seconds. The resulting output consisted of 313 new candidate terms, each consisting of concatenated doublets found in the reference nomenclature. Human review of the 313 candidate terms yielded a list of 285 terms approved by a curator. A final automatic extraction of duplicate terms yielded a final list of 222 new terms (71% of the original 313 extracted candidate terms) that could be added to the reference nomenclature. CONCLUSION: The doublet method for automatically extracting candidate nomenclature terms can be used to quickly find new terms from vast amounts of text. The method can be immediately adapted for virtually any text and any nomenclature. An implementation of the algorithm, in the Perl programming language, is provided with this article.

Abstracting and Indexing↗

Minimal instructions improve the performance of laypersons in the use of semiautomatic and automatic external defibrillators.

INTRODUCTION: There is evidence that use of automated external defibrillators (AEDs) by laypersons improves rates of survival from cardiac arrest, but there is no consensus on the optimal content and duration of training for this purpose. In this study we examined the use of semiautomatic or automatic AEDs by laypersons who had received no training (intuitive use) and the effects of minimal general theoretical instructions on their performance. METHODS: In a mock cardiac arrest scenario, 236 first year medical students who had not previously attended any preclinical courses were evaluated in their first study week, before and after receiving prespecified instructions (15 min) once. The primary end-point was the time to first shock for each time point; secondary end-points were correct electrode pad positioning, safety of the procedure and the subjective feelings of the students. RESULTS: The mean time to shock for both AED types was 81.2 +/- 19.2 s (range 45-178 s). Correct pad placement was observed in 85.6% and adequate safety in 94.1%. The time to shock after instruction decreased significantly to 56.8 +/- 9.9 s (range 35-95 s; P < or = 0.01), with correct electrode placement in 92.8% and adequate safety in 97%. The students were significantly quicker at both evaluations using the semiautomatic device than with the automatic AED (first evaluation: 77.5 +/- 20.5 s versus 85.2 +/- 17 s, P < or = 0.01; second evaluation: 55 +/- 10.3 s versus 59.6 +/- 9.6 s, P < or = 0.01). CONCLUSION: Untrained laypersons can use semiautomatic and automatic AEDs sufficiently quickly and without instruction. After one use and minimal instructions, improvements in practical performance were significant. All tested laypersons were able to deliver the first shock in under 1 min.

Adolescent↗

Automatic annotation of eukaryotic genes, pseudogenes and promoters.

BACKGROUND: The ENCODE gene prediction workshop (EGASP) has been organized to evaluate how well state-of-the-art automatic gene finding methods are able to reproduce the manual and experimental gene annotation of the human genome. We have used Softberry gene finding software to predict genes, pseudogenes and promoters in 44 selected ENCODE sequences representing approximately 1% (30 Mb) of the human genome. Predictions of gene finding programs were evaluated in terms of their ability to reproduce the ENCODE-HAVANA annotation. RESULTS: The Fgenesh++ gene prediction pipeline can identify 91% of coding nucleotides with a specificity of 90%. Our automatic pseudogene finder (PSF program) found 90% of the manually annotated pseudogenes and some new ones. The Fprom promoter prediction program identifies 80% of TATA promoters sequences with one false positive prediction per 2,000 base-pairs (bp) and 50% of TATA-less promoters with one false positive prediction per 650 bp. It can be used to identify transcription start sites upstream of annotated coding parts of genes found by gene prediction software. CONCLUSION: We review our software and underlying methods for identifying these three important structural and functional genome components and discuss the accuracy of predictions, recent advances and open problems in annotating genomic sequences. We have demonstrated that our methods can be effectively used for initial automatic annotation of the eukaryotic genome.

Animals↗

The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker.

Although the ensemble of voltage- and time-dependent rhythms of surface membrane ion channels, the membrane "Clock", is the immediate cause of a sinoatrial nodal cell (SANC) action potential (AP), it does not necessarily follow that this ion channel ensemble is the formal cause of spontaneous, rhythmic APs. SANC also generates intracellular oscillatory spontaneous Ca(2+) releases that ignite excitation (SCaRIE) of the surface membrane via Na(+)/Ca(2+) exchanger activation. The idea that a rhythmic intracellular Ca(2+) Clock might keep time for normal automaticity of SANC, however, has not been assimilated into mainstream pacemaker dogma. Recent experimental evidence, derived from simultaneous, confocal imaging of submembrane Ca(2+) and membrane potential of SANC, and supported by numerical modeling, indicates that normal automaticity of SANC is entrained and stabilized by the tight integration of the SR Ca(2+) Clock that generates rhythmic SCaRIE, and the surface membrane Clock that responds to SCaRIE to immediately produce APs of an adequate shape. Thus, tightly controlled, rhythmic SCaRIE does not merely fine tune SANC AP firing, but is the formal cause of the basal and reserve rhythms, insuring pacemaker stability by rhythmically integrating multiple Ca(2+)-dependent functions, and effects normal automaticity by rhythmic ignition of the surface membrane Clock.

Animals↗

Disruption of automatic speech following a right basal ganglia lesion.

Following a right basal ganglia lesion, a right-handed man, age 75, was unable to recite familiar verses. Serial automatic speech, singing, recitation of rhymes, and swearing were impaired, and only idioms and social greetings were preserved. Speech no longer contained overused phrases and he could comprehend automatic speech. In contrast, propositional speech was preserved in both French and Hebrew. Right basal ganglia lesions may impair production but not comprehension of automatic speech.

Aged↗

Antiarrhythmic anesthetic action. II. The effect of methoxyflurane on ventricular automaticity.

During the course of surgical anesthesia, the majority of patients experience some arrhythmias, virtually all of which can be attributed to changes in cardiac pacemaker automaticity and/or alterations in cardiac conduction velocity. Therefore, a better understanding of these mechansims is of importance to anesthesiologists. Cardiac automaticity in the intact heart of dogs under methoxyflurane anesthesia was assessed by measuring changes in ventricular escape time (VET) and ventricular escape rate (VER). A slight shortening of VET was noted, while there was virtually no change from control in VER. Unexpectedly, however, a nonsinus supraventricular escape focus became prominent in many animals at a low anesthetic dose and in all animals at a higher anesthetic concentration. This effect was shown to be preventable by pretreatment with reserpine or a beta-blocking agent. It is concluded that methoxyflurane increases the automaticity of parts of the atrial conducting system, other than the sinus, either by a direct effect or by increasing the sensitivity to prevailing background adrenergic levels.

Anesthesia, Inhalation↗

Developmental changes of Ni(2+) sensitivity and automaticity in Nkx2.5-positive cardiac precursor cells from murine embryonic stem cell.

BACKGROUND: It is controversial which subtypes of T type Ca(2+) channels are implicated in automaticity of cardiac cells during the embryonic period. METHOD AND RESULTS: The effect of Ni(2+) on the automaticity of Nkx2.5-positive cardiac precursor cells sorted from embryonic stem cells during their differentiation was examined using patch clamp techniques. Although 40 micromol/L Ni(2+), which is enough to block Ni(2+)sensitive T type-Ca(2+) channels, decreased the spontaneous beating rate in all cells in the early and intermediate stage, Ni(2+) did not show any effects on the automaticity of 50% of the cells in the late stage. CONCLUSION: These results indicate that Ni(2+)-sensitive T-type Ca(2+) channels expressed in the Nkx2.5-positive cardiac precursor cells are developmentally regulated.

Animals↗

Comparison of manual and computer-assisted automatic measurements of wall thickness of the left ventricle in two-dimensional echocardiography.

To investigate the clinical applicability of automatic analysis of wall thickness in two-dimensional echocardiography, computer-assisted and conventional manual methods were compared in 26 cases. An echo threshold was automatically set in short-axis echo images through a discriminatory variance analysis of the signal-to-noise ratio. A fixed standard was determined inside the left ventricle using the circle window method, which we developed previously. Two abrupt echo reflections were selected as candidate points for the borders, and an outward search was conducted in all directions from a fixed standard to separately delineate the endocardial and epicardial interfaces. Interpolation using a spline function was applied to these points to complete the border lines. Differentiation was also used to eliminate the anterior and posterior papillary muscles. Significant correlations of r = 0.98 were found between the computer and manual assessments of the epicardial and endocardial intraluminal ventricular areas (p < 0.01). A correlation of r = 0.87 was also obtained for myocardial wall thickness as determined by the 2 methods (p < 0.01). Variability of the reproducibility using the computer method was 0.22% for the epicardial area and 0.64% for the endocardial area. These results confirm that computer-aided automatic measurement of wall thickness is clinically applicable to two-dimensional echocardiography.

Adult↗

Further investigations on potassium-induced automaticity of isolated human renal artery.

Experiments were designed to investigate generation of automaticity of isolated human renal arteries induced by administration of potassium in vitro. Helical strips of human renal arteries showed marked oscillations in the potassium-induced contractions which persisted for 2 hr. Indomethacin and aspirin dose-dependently inhibited these oscillations. Tranylcypromine and mepacrine also had an inhibitory action on the oscillations of the strips induced by potassium. In the strips which reached a steady state 2 hr after administration of potassium, phospholipase A2 and bradykinin produced marked oscillations. Our results indicate that human renal arteries can generate automaticity in the contractions induced by potassium, and that such automaticity may be related to the biosynthesis of prostaglandins.

Adult↗