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Ultrasound-guided biopsies of abdominal organs with an automatic biopsy system. A retrospective analysis of the quality of biopsies and of hemorrhagic complications.

BACKGROUND: Ultrasound-guided biopsies of abdominal organs are not without risks for the patients; in particular, hemorrhagic complications may occur. Thus, over the last few years, automatic biopsy guns have been developed to facilitate the biopsy process. METHODS: The aim of our retrospective study was to examine the quality of specimens and the complication rate of ultrasound-guided biopsies of abdominal organs carried out in our institution using the automatic Autovac biopsy system during a period of 1.5 years. Of the total number of 321 biopsies, 290 were performed with the 1.2-mm Autovac needle, and in 31 cases the 0.95-mm needle was used. Among the 321 biopsies there were 211 of the liver parenchyma (66%), 47 of a liver tumor (14%), 38 of the pancreas (12%), 15 of the kidney parenchyma (5%), and 10 of a retroperitoneal tumor (3%). RESULTS: In 310 of the 321 biopsies it was possible to obtain sufficient diagnostically usable material for the pathologist (96.6%). In the other 11 cases the material obtained did not enable proper histologic diagnosis (3.4%). Two of these 11 biopsies were carried out with the 0.95-mm needle, and the other 9 with the 1.2-mm needle. Twenty-four hours after the biopsy each patient underwent routine ultrasound examination to exclude a possible bleeding. In eight cases an afterbleeding occurred (total hemorrhagic rate, 2.5%), four times without clinical consequences. The other four bleeding complications were more serious (1.2% of all taps), and all occurred after liver biopsies in patients with a history of liver complaints and abnormal clotting variables. There were no fatalities among our biopsies (mortality rate, 0%). CONCLUSION: The automatic Autovac biopsy system is suitable and relatively safe for obtaining sufficient histopathologic material from intra-abdominal organs.

Adolescent↗

A new method for the automatic mesh generation of bone segments from CT data.

A new procedure for the automatic generation of finite element meshes of bone segments from computed tomography (CT) data sets is described. The new method allows a direct automatic generation from the CT data and produces a very accurate unstructured hexahedral mesh. The accuracy of the method was established using the CT images of an artificial femur showing range of attenuation values comparable to those of a human femur. To establish the optimal values for the parameters controlling the mesh a sensitivity analysis was carried out using mesh-conditioning indicators. Some of the best meshes, with increasing levels of refinement, were used to analyse the stresses induced in the proximal femur by single leg stance posture. The accuracy of the meshes was evaluated using an implicit a posteriori residual-based error estimates. The number of elements with stress residuals larger than 10% of the peak stress was 7.8% using the coarsest mesh and only 1.8% with the finest mesh. The proposed method has been proved able to conjugate full automation with high-quality finite element meshes. The stress predictions obtained using these hexahedral-only meshes have been more accurate than those obtained by any other automatic mesh generation algorithm. Once properly integrated in an easy-to-use application, the described method could finally make feasible many clinical applications of finite element analysis.

Bone and Bones↗

Quantitation of megakaryocytopoiesis by computerized automatic in culture image analysis.

A computer-assisted automatic image procedure was karyocytopoiesis in culture. This analysis system was based on acetylcholinesterase staining, a specific staining for murine bone marrow megakaryocytes, and an image capturing instrument with a computer program. Two kinds of routine megakaryocyte culture methods were used, the plasma clot and the serum-free agar systems. A comparison between manual counting and the instrument was made. The image analysis software was able to distinguish between megakaryocytes (MK) at different stages of maturation. The results show that this analysis system can simultaneously detect not only the number of megakaryocytes and their colonies in each dish, but also the surface area of individual megakaryocytes. In addition, this analysis system functions automatically 24 hours a day and the results obtained are reproducible. Using this system, we have confirmed previous observations that thrombopoietin (TPO) and heparin stimulate both proliferation and maturation of megakaryocytes. In addition, we found that platelet factor 4 (PF-4) significantly reduced the number of megakaryocytes but not their cell surface area, whereas TGFbeta1 decreased both number and surface area of megakaryocytes, suggesting that PF4 and TGFbeta1 negatively regulate megakaryocytopoiesis by different mechanisms. We noticed that megakaryocytes grown under agar culture conditions regularly had an increased size in comparison with those grown in a plasma clot system, which may be an indication that the plasma clot culture media contains an inhibitor(s) of megakaryocyte maturation. Our data indicate that this image analysis system, in addition to its automatic and reproducible features, is more efficient and allows detection of more parameters than routine manual microscopic detection.

Journal Article↗

Is automaticity of walking regained after stroke?

PURPOSE: The aim of this study was to determine whether people who have completed rehabilitation after stroke have regained a level of automaticity of walking comparable to healthy people of similar age. METHOD: Twenty stroke subjects, 20 healthy elderly controls and 20 healthy young controls were tested. To quantify the automaticity of walking, subjects were required to walk simultaneously while performing an additional task(s). Subjects walked under four counterbalanced conditions: a single walking task, a dual-cognitive task, a dual-manual task and a triple-task. Walking velocity, cadence, stride length and step length were analysed. RESULTS: Stroke subjects walked slower (p = 0.001), took shorter strides (p = 0.002) and fewer steps/min (p = 0.04) than elderly controls. Velocity declined significantly across conditions from the single to the dual-cognitive to the dual-manual and finally to the triple-task (p < 0.001). Both stroke and elderly groups showed similar deterioration in walking velocity across conditions (p = 0.99), while the deterioration in the young subjects was significantly less than for healthy elderly subjects (p = 0.04) and the stroke subjects (p = 0.02). CONCLUSION: Community dwelling stroke subjects display the same level of automaticity of walking as elderly controls, but both elderly controls and stroke subjects are less automated than young controls.

Adult↗

Mastering alternative computer access: the role of understanding, trust, and automaticity.

Many individuals use computer-based assistive devices as alternatives for the fluent, automatic skills of speech, writing, and touch-typing. This paper proposes that controlling an alternative access technique should become as automatic as touch-typing or speech. The process of acquiring a cognitive-motor skill is discussed. Prerequisites to skill acquisition and impediments to motor automaticity are outlined. Factors that promote or impede skilled control of alternative computer access systems at each stage of the design, assessment, prescription, training, and evaluation process are reviewed. Several case examples are used to illustrate relevant issues.

Cognition↗

Dual-task performance in early stage dementia: differential effects for automatized and effortful processing.

Attentional functions of individuals with early stage Alzheimer's disease (AD) and normal older adults (NC) were studied using a concurrent-task paradigm. Fourteen patients (5 men, 9 women) and 14 age- and sex-matched normal adults engaged in speeded unimanual tapping and speaking tasks during single- and dual-task trials. Speaking tasks were either relatively automatized (Speech Repetition) or relatively effortful (Speech Fluency). As single-task tapping rates were slower for the AD participants than for the NC participants, a proportional decrement score was used as an index of interference in the dual-task conditions. Interference during concurrent-task performance was greater when the cognitive task was effortful for both the NC and the AD groups. Although AD patients suffered higher levels of interference than NC participants while performing the effortful speech task, the two groups showed equivalent small changes in tapping speed while combining the automatized speaking and tapping tasks. Results suggest that a general-purpose attentional processing resource declines in the early stages of AD but dual-task performance is well-maintained when the component tasks are relatively automatized.

Activities of Daily Living↗

An automatic method for the identification and interpretation of clustered microcalcifications in mammograms.

We investigated a method for a fully automatic identification and interpretation process for clustered microcalcifications in mammograms. Mammographic films of 100 patients containing microcalcifications with known histology were digitized and preprocessed using standard techniques. Microcalcifications detected by an artificial neural network (ANN) were clustered and some cluster features served as the input of another ANN trained to differentiate between typical and atypical clusters, while others were fed into an ANN trained on typical clusters to evaluate these lesions. The measured sensitivity for the detection of grouped microcalcifications was 0.98. For the task of differentiation between typical and atypical clusters an Az value of 0.87 was computed, while for the diagnosis an Az value of 0.87 with a sensitivity of 0.97 and a specificity of 0.47 was obtained. The results show that a fully automatic computer system was developed for the identification and interpretation of clustered microcalcitications in mammograms with the ability to differentiate most benign lesions from malignant ones in an automatically selected subset of cases.

Breast Diseases↗

Automatic detection of cardiac waves on fetal magnetocardiographic signals.

Fetal magnetocardiography (fMCG) provides fetal cardiac traces useful for the prenatal monitoring of fetal heart function. In this paper, we describe an analytical model (ACWD) for the automatic detection of cardiac waves boundaries that works on fetal signals reconstructed from fMCG by means of independent component analysis. ACWD was validated for 45 healthy and 4 arrhythmic fetuses ranging from 22 to 37 weeks; ACWD outcomes were compared with the estimates of three independent investigators. Descriptive statistics were used to assess correspondence between the outcomes of the automatic and manual approaches. The parametric two-tailed Pearson correlation test (alpha=0.01) was employed to quantify, by means of the coefficients of determination, the amount of common variation between the sequences of intervals quantified automatically and manually. ACWD performances on short and long rhythm strips were investigated. ACWD demonstrated to be a robust tool providing dependable estimates of cardiac intervals and their variability during the third gestational trimester also in case of fetal arrhythmias. SNR and stability of fetal traces were the factors limiting ACWD performances. ACWD computation time, which was approximately 1:600 with respect to the manual procedure, was comparable with the time required for fCTI estimation on averaged beats.

Algorithms↗

Automatic detection, segmentation and assessment of snoring from ambient acoustic data.

Snoring is a prevalent condition with a variety of negative social effects and associated health problems. Treatments, both surgical and therapeutic, have been developed, but the objective non-invasive monitoring of their success remains problematic. We present a method which allows the automatic monitoring of snoring characteristics, such as intensity and frequency, from audio data captured via a freestanding microphone. This represents a simple and portable diagnostic alternative to polysomnography. Our system is based on methods that have proved effective in the field of speech recognition. Hidden Markov models (HMMs) were employed as basic elements with which to model different types of sound by means of spectrally based features. This allows periods of snoring to be identified, while rejecting silence, breathing and other sounds. Training and test data were gathered from six subjects, and annotated appropriately. The system was tested by requiring it to automatically classify snoring sounds in new audio recordings and then comparing the result with manually obtained annotations. We found that our system was able to correctly identify snores with 82-89% accuracy, despite the small size of the training set. We could further demonstrate how this segmentation can be used to measure the snoring intensity, snoring frequency and snoring index. We conclude that a system based on hidden Markov models and spectrally based features is effective in the automatic detection and monitoring of snoring from audio data.

Acoustics↗

Automatic scanning of interphase FISH for prenatal diagnosis in uncultured amniocytes.

Fluorescence in situ hybridization (FISH) of uncultured amniocytes using chromosome-specific DNA probes offers the opportunity for rapid aneuploidy screening. Between 80 and 95% of all chromosomal disorders expected in the second trimester of pregnancy can be discovered within 24 hr if DNA probes specific for chromosomes 21, 18, 13, X, and Y are used. Rapid results are crucial for clinical decision-making and are helpful in decreasing the anxiety level in most patients. One of the major factors that have been preventing the rapid FISH test from being broadly incorporated into the clinical setting is the limited staff in the cytogenetics laboratories. The present study demonstrates the use of an automated scanning system (Duet, BioView Ltd. Rehovot, Israel) for analyzing FISH in uncultured amniocytes. Fifty-six amniotic fluid samples were evaluated in parallel by karyotyping, manual FISH analysis, and automatic FISH scanning. Automatic scanning provided accurate results compared to both manual FISH scoring and karyotype analysis. The correlation between automatic and manual FISH scanning was found to be very high (r = 0.9, p < 0.0001). The availability of automation for aneuploidy screening in amniotic fluid samples will enable offering this test to a broader patient population while providing fast and reliable results.

Amnion↗

BIOESTIM: software for automatic design of estimators in bioprocess engineering.

This paper describes BIOESTIM, a software package devoted to on-line estimation in bioprocess engineering. BIOESTIM enables bioengineers automatically to design state and parameter estimators from a minimal knowledge of the process kinetics. Such estimators allow development of software sensors capable of coping with the lack of reliable instrumentation suited to real-time monitoring. The estimator building procedure through BIOESTIM starts up from a dynamical material balance model of the bioprocess. This model, supplied by the user, is next completed by other information with no requirement for numerical values: the user has only to specify available measurements, coupled reactions and the known yield coefficients. On the base of this knowledge, BIOESTIM proceeds to symbolic algebraic manipulations on the model in order to study estimation possibilities and check identifiability of yield coefficients. When the design of an estimator is possible, the corresponding equations are automatically generated. Moreover, these estimators are stored in a user-specified file which is automatically interfaced with a specialized simulation software including data treatment and numerical integration packages. Thus, the user can simulate the estimator performances under various operational conditions using available experimental measurements. A typical example dealing with microbial growth and biosynthesis reactions is given in order to illustrate the main functional capabilities of BIOESTIM. BIOESTIM has been designed and written in a modular fashion. The module dealing with estimators design makes use of symbolic computation; it is written in Mathematica and runs on every computer on which this language is available.

Algorithms↗

A novel method for automatic functional annotation of proteins.

MOTIVATION: To cope with the increasing amount of sequence data, reliable automatic annotation tools are required. The TrEMBL database contains together with SWISS-PROT nearly all publicly available protein sequences, but in contrast to SWISS-PROT only limited functional annotation. To improve this situation, we had to develop a method of automatic annotation that produces highly reliable functional prediction using the language and the syntax of SWISS-PROT. RESULTS: An algorithm was developed and successfully used for the automatic annotation of a testset of unknown proteins. The predicted information included description, function, catalytic activity, cofactors, pathway, subcellular location, quaternary structure, similarity to other protein, active sites, and keywords. The algorithm showed a low coverage (10%), but a high specificity and reliability. AVAILABILITY: The results can be obtained by anonymous ftp from ftp.ebi.ac.uk/pub/databases/sp_tr_nrdb. The source code is available on request from the authors.

Algorithms↗

Automatic rule generation for protein annotation with the C4.5 data mining algorithm applied on SWISS-PROT.

MOTIVATION: The gap between the amount of newly submitted protein data and reliable functional annotation in public databases is growing. Traditional manual annotation by literature curation and sequence analysis tools without the use of automated annotation systems is not able to keep up with the ever increasing quantity of data that is submitted. Automated supplements to manually curated databases such as TrEMBL or GenPept cover raw data but provide only limited annotation. To improve this situation automatic tools are needed that support manual annotation, automatically increase the amount of reliable information and help to detect inconsistencies in manually generated annotations. RESULTS: A standard data mining algorithm was successfully applied to gain knowledge about the Keyword annotation in SWISS-PROT. 11 306 rules were generated, which are provided in a database and can be applied to yet unannotated protein sequences and viewed using a web browser. They rely on the taxonomy of the organism, in which the protein was found and on signature matches of its sequence. The statistical evaluation of the generated rules by cross-validation suggests that by applying them on arbitrary proteins 33% of their keyword annotation can be generated with an error rate of 1.5%. The coverage rate of the keyword annotation can be increased to 60% by tolerating a higher error rate of 5%. AVAILABILITY: The results of the automatic data mining process can be browsed on http://golgi.ebi.ac.uk:8080/Spearmint/ Source code is available upon request. CONTACT: kretsch@ebi.ac.uk.

Algorithms↗

An automatic block and spot indexing with k-nearest neighbors graph for microarray image analysis.

MOTIVATION: In this paper, we propose a fully automatic block and spot indexing algorithm for microarray image analysis. A microarray is a device which enables a parallel experiment of ten to hundreds of thousands of test genes in order to measure gene expression. Due to this huge size of experimental data, automated image analysis is gaining importance in microarray image processing systems. Currently, most of the automated microarray image processing systems require manual block indexing and, in some cases, spot indexing. If the microarray image is large and contains a lot of noise, it is very troublesome work. In this paper, we show it is possible to locate the addresses of blocks and spots by applying the Nearest Neighbors Graph Model. Also, we propose an analytic model for the feasibility of block addressing. Our analytic model is validated by a large body of experimental results. RESULTS: We demonstrate the features of automatic block detection, automatic spot addressing, and correction of the distortion and skewedness of each microarray image.

Algorithms↗

Automatic analysis of DNA microarray images using mathematical morphology.

MOTIVATION: DNA microarrays are an experimental technology which consists in arrays of thousands of discrete DNA sequences that are printed on glass microscope slides. Image analysis is an important aspect of microarray experiments. The aim of this step is to reduce an image of spots into a table with a measure of the intensity for each spot. Efficient, accurate and automatic analysis of DNA spot images is essential in order to use this technology in laboratory routines. RESULTS: We present an automatic non-supervised set of algorithms for a fast and accurate spot data extraction from DNA microarrays using morphological operators which are robust to both intensity variation and artefacts. The approach can be summarised as follows. Initially, a gridding algorithm yields the automatic segmentation of the microarray image into spot quadrants which are later individually analysed. Then the analysis of the spot quadrant images is achieved in five steps. First, a pre-quantification, the spot size distribution law is calculated. Second, the background noise extraction is performed using a morphological filtering by area. Third, an orthogonal grid provides the first approach to the spot locus. Fourth, the spot segmentation or spot boundaries definition is carried out using the watershed transformation. And fifth, the outline of detected spots allows the signal quantification or spot intensities extraction; in this respect, a noise model has been investigated. The performance of the algorithm has been compared with two packages: ScanAlyze and Genepix, showing its robustness and precision.

Algorithms↗

Automatic discovery and classification of bioinformatics Web sources.

MOTIVATION: The World Wide Web provides an incredible resource to genomics researchers in the form of query access to distributed data sources--e.g. BLAST sequence homology search interfaces. The number of these autonomous sources and their rate of change outpaces the speed at which they can be manually classified, meaning that the available data is not being utilized to its full potential. Manually maintaining a wrapper library will not scale to accommodate the growth of genomics data sources on the Web, challenging us to produce an automated system that can find, classify and wrap new sources without constant human intervention. Previous research has not addressed the problem of automatically locating, classifying and integrating classes of bioinformatics data sources. RESULTS: This paper presents an overview of a system for finding classes of bioinformatics data sources and integrating them behind a unified interface. We describe our approach for automatic classification of new Web sources into relevance categories that eliminates the human effort required to maintain a current repository of sources. Our approach is based on a meta-data description of classes of interesting sources that describes the important features of an entire class of services without tying that description to any particular Web source. We examine the features of this format in the context of BLAST sources to show how it relates to Web sources that are being described. We then show how a description can be used to determine if an arbitrary Web source is an instance of the described service. To validate the effectiveness of this approach, we have constructed a prototype that correctly classifies approximately two-thirds of the BLAST sources we tested. We conclude with a discussion of these results, the factors that affect correct automatic classification and areas for future study.

Algorithms↗

Fundamentals of massive automatic pairwise alignments of protein sequences: theoretical significance of Z-value statistics.

MOTIVATION: Different automatic methods of sequence alignments are routinely used as a starting point for homology searches and function inference. Confidence in an alignment probability is one of the major fundamentals of massive automatic genome-scale pairwise comparisons, for clustering of putative orthologs and paralogs, sequenced genome annotation or multiple-genomic tree constructions. Extreme value distribution based on the Karlin-Altschul model, usually advised for large-scale comparisons are not always valid, particularly in the case of comparisons of non-biased with nucleotide-biased genomes (such that of Plasmodium falciparum). Z-values estimates based on Monte Carlo technics, can be calculated experimentally for any alignment output, whatever the method used. Empirically, a Z-value higher than approximately 8 is supposed reasonable to assess that an alignment score is significant, but this arbitrary figure was never theoretically justified. RESULTS: In this paper, we used the Bienaymé-Chebyshev inequality to demonstrate a theorem of the upper limit of an alignment score probability (or P-value). This theorem implies that a computed Z-value is a statistical test, a single-linkage clustering criterion and that 1/Z-value(2) is an upper limit to the probability of an alignment score whatever the actual probability law is. Therefore, this study provides the missing theoretical link between a Z-value cut-off used for an automatic clustering of putative orthologs and/or paralogs, and the corresponding statistical risk in such genome-scale comparisons (using non-biased or biased genomes).

Algorithms↗

Effect of automatic record keeping on vigilance and record keeping time.

We have evaluated the effect of an automatic anaesthesia record keeper (AARK) on record keeping time and vigilance. With informed patient consent and institutional approval, we videotaped the attending anaesthetist and his/her immediate surroundings during 66 surgical procedures. Thirty-seven cases were charted manually and the remaining 29 were charted with a commercially available AARK. In order to evaluate vigilance, a physician examiner entered the operating room unannounced once during 33 of the manually charted cases and during 22 of the automatically charted cases and asked the anaesthetist to turn away from the monitors and recall the current value of eight patient physiological variables. The examiner recorded the recalled values and also the actual current monitor values of these variables. The videotapes were reviewed and the anaesthetist's intraoperative time was categorized into 15 predefined activities, including intraoperative anaesthesia record keeping time. We compared recalled and actual variable values to determine if the recalled values were within clinically relevant error limits. There was no statistical difference between the mean percentage case time spent recording manually (14.11 (SD 3.98)%) and automatically (12.39 (3.92)%). Moreover, use of the AARK did not significantly affect vigilance. Despite major advances in monitoring technology over the past 14 years, record keeping still occupies 10-15% of the anaesthetist's intraoperative time. It appears that in using an AARK, the anaesthetist reallocates intraoperative record keeping time from manual charting to dealing with problems in the anaesthetist machine interface caused by inadequate design.

Anesthesiology↗