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On-line data acquisition system using an Apple computer: ISI and PST histograms.

A combined hardware/software system for the study of the temporal distributions of spike data is described. Through extensive use of assembly language subroutines the program is able to simultaneously acquire, analyze and display the incoming data. Production of a "Temporal Memory Map" makes possible the examination of acquired data at a wide variety of different bin widths. Interaction with the user is made extremely simple. Provisions are included for the labelling and printing of the output histograms and for the compact storage of data onto floppy disks. Maximum temporal resolution is 0.1 millisecond and maximum total acquisition width is 12.8 minutes. Hardware requirements beyond the basic computer consist of an external signal conditioning circuit and a slot-independent peripheral card containing two integrated circuits. The system has been successfully used in the analysis of neural and EMG evoked responses and should be widely useable in other applications.

Computers↗

Modeling the evolution of protein domain architectures using maximum parsimony.

Domains are basic evolutionary units of proteins and most proteins have more than one domain. Advances in domain modeling and collection are making it possible to annotate a large fraction of known protein sequences by a linear ordering of their domains, yielding their architecture. Protein domain architectures link evolutionarily related proteins and underscore their shared functions. Here, we attempt to better understand this association by identifying the evolutionary pathways by which extant architectures may have evolved. We propose a model of evolution in which architectures arise through rearrangements of inferred precursor architectures and acquisition of new domains. These pathways are ranked using a parsimony principle, whereby scenarios requiring the fewest number of independent recombination events, namely fission and fusion operations, are assumed to be more likely. Using a data set of domain architectures present in 159 proteomes that represent all three major branches of the tree of life allows us to estimate the history of over 85% of all architectures in the sequence database. We find that the distribution of rearrangement classes is robust with respect to alternative parsimony rules for inferring the presence of precursor architectures in ancestral species. Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission. Our results may be used to compute domain architecture similarities, for example, based on the number of historical recombination events separating them. Domain architecture "neighbors" identified in this way may lead to new insights about the evolution of protein function.

Cluster Analysis↗

A diagnostic test for prostate cancer from gene expression profiling data.

PURPOSE: Multiple recent studies show excellent classification accuracy using bioinformatics tools applied to expression profiling data on various tumors. However, the clinical applicability of these techniques remains unfulfilled because of difficulty in translating complex multigene mathematical algorithms into reproducible, platform independent tests. We recently developed a broadly applicable platform independent method based on simple ratios of gene expression to diagnose and predict outcome in cancer. In the current study we applied this technique to the diagnosis of prostate cancer. MATERIALS AND METHODS: We developed a ratio based predictive model using a training set of 32 samples with previously published gene profiling data. We then tested and refined the model using additional independent samples with previously published microarray data from another source (that is the test set of 34 samples). Finally, the optimal ratio based test was examined with quantitative reverse transcriptase-polymerase chain reaction for data acquisition in a third cohort of samples consisting of 10 frozen normal and 10 tumor prostate tissues. RESULTS: A 3-ratio test using 4 genes was 90% accurate (18 of 20 samples) for distinguishing normal prostate and prostate cancer samples obtained at surgery (Fisher's exact test p = 0.0007). This test did not result in any false-negative findings. CONCLUSIONS: We describe and validate a new gene ratio based test for the diagnosis of prostate cancer, which was developed from the analysis of extensive gene profiling data for the diagnosis of prostate cancer. This test can be easily adapted to the clinical arena without the need for complex computer software or hardware. We anticipate that the gene ratio based diagnosis of prostate cancer using fine needle aspirations could serve as a useful adjunct to standard histopathological techniques.

Gene Expression Profiling↗

Automatic sign language analysis: a survey and the future beyond lexical meaning.

Research in automatic analysis of sign language has largely focused on recognizing the lexical (or citation) form of sign gestures as they appear in continuous signing, and developing algorithms that scale well to large vocabularies. However, successful recognition of lexical signs is not sufficient for a full understanding of sign language communication. Nonmanual signals and grammatical processes which result in systematic variations in sign appearance are integral aspects of this communication but have received comparatively little attention in the literature. In this survey, we examine data acquisition, feature extraction and classification methods employed for the analysis of sign language gestures. These are discussed with respect to issues such as modeling transitions between signs in continuous signing, modeling inflectional processes, signer independence, and adaptation. We further examine works that attempt to analyze nonmanual signals and discuss issues related to integrating these with (hand) sign gestures. We also discuss the overall progress toward a true test of sign recognition systems--dealing with natural signing by native signers. We suggest some future directions for this research and also point to contributions it can make to other fields of research. Web-based supplemental materials (appendicies) which contain several illustrative examples and videos of signing can be found at www.computer.org/publications/dlib.

Algorithms↗

Integrated software suite for magnetocardiographic data analysis--a proposal based on an interactive programming environment.

OBJECTIVES: This paper describes an integrated software suite (ISS) for the processing of magnetocardiographic (MCG) recordings obtained with super-conducting multi-channel systems having different characteristics. We aimed to develop a highly flexible suite including toolboxes for current MCG applications, organized consistently with an open architecture that allows function integrations and upgrades with minimal modifications; the suite was designed for the compliance not only of physicists and engineers but also of physicians, who have a different professional profile and are accustomed to retrieve information in different ways. METHODS: The MCG-ISS was designed to work with all common graphical user interface operative systems. MATLAB was chosen as the interactive programming environment (IPE), and the software was developed to achieve usability, interactivity, reliability, modularity, expansibility, interoperability, adaptability and graphics style tailoring. Three users, already experienced in MCG data analysis, have intensively tested MCG-ISS for six months. A great amount of MCG data on normal subjects and patients was used to assess software performances in terms of user compliance and confidence and total analysis time. RESULTS: The proposed suite is an all-in-one analysis tool that succeeded in speeding MCG data analysis up to about 55% with respect to standard reference routines; it consequently enhanced analysis performance and user compliance. CONCLUSIONS: Those results, together with the MCG-ISS advantage of being independent on the acquisition system, suggest that software suites like the proposed one could uphold a wider diffusion of MCG as a diagnostic tool in the clinical setting.

Diagnosis, Computer-Assisted↗

Functional plasticity after left anterior temporal lobectomy: reconstitution and compensation of verbal memory functions.

PURPOSE: This study investigated the functional plasticity of the brain to reconstitute and compensate for verbal memory functions after epilepsy surgery of left temporocortical and temporomesial structures. We hypothesized that memory outcome would be best when surgery is performed within the period of cerebral plasticity, and that the outcome should be worst when fluid intelligence starts to decrease with physiologic aging. We also raised the question of different plasticity and compensation mechanisms for temporomesial and temporocortical memory functions. METHODS: We evaluated preoperative and 1-year-postoperative memory data and other verbal functions in 104 patients with epilepsy, who underwent a standard left anterior temporal lobe resection. We used memory measures that had been previously shown to be most selective for mesial and lateral functions, respectively. Determinants of postoperative memory outcome were evaluated by multiple regression analysis. Group statistics were calculated on the basis of the periods that are usually assumed to be significant for plasticity and behavioral compensation. Individual postoperative changes in memory functions were evaluated on the basis of test-retest data obtained in a group of 100 nonsurgical patients with localization-related epilepsies (mean retest interval >12 months). RESULTS: Only changes in cortically represented learning and data acquisition were related to age, plasticity, and capacities for behavioral compensation. No patient in the youngest group (younger than 15 years), 33% of patients who had surgery between the ages of 15 and 30 years, and 61% of the patients undergoing surgery older than age 30 years had significant deterioration in verbal learning. In contrast, postoperative changes in temporomesial consolidation/retrieval processes were independent of age at the time of surgery, plasticity, and capacities for behavioral compensation. CONCLUSIONS: Our data indicate different time windows for the reconstitution and compensation of mesial and cortical aspects of memory. Whereas the reconstitution of and compensation for cortical functions appear restricted by decreasing plasticity and physiological aging, mesial functions seem to be reconstituted by contralateral mesial structures over a much longer period. Concerning drug-resistant localization-related epilepsies, our results justify early consideration of surgery, especially when cortical structures are affected.

Adolescent↗

Detecting chlorophyll, Secchi disk depth and surface temperature in a sub-alpine lake using Landsat imagery.

Some bio-physical parameters, such as chlorophyll a concentration, Secchi disk depth and water surface temperature were mapped in the sub-alpine Lake Iseo (Italy) using Landsat Thematic Mapper (TM) data acquired on the 7 March 1997. In order to adequately investigate the water-leaving radiance, TM data were atmospherically corrected using a partially image-based method, and the atmospheric transmittance was measured in synchrony with the satellite passage. An empirical approach of relating atmospherically corrected TM spectral reflectance values to in situ measurements, collected during the satellite data acquisition, was used. The models developed were used to map the chlorophyll concentration and Secchi disk depth throughout the lake. Both models gave high determination coefficients (R2 = 0.99 for chlorophyll and R2 = 0.85 for the Secchi disk) and the spatial distribution of chlorophyll concentration and Secchi disk depth was mapped with contour intervals of 1 mg/m3 and 1 m, respectively. A scene-independent procedure was used to derive the surface temperature of the lake from the TM data with a root mean square error of 0.3 degrees C.

Atmosphere↗

Techniques for fast and accurate intrasurgical registration.

The goal of intrasurgical registration is to establish a common reference frame between presurgical and intrasurgical three-dimensional data sets that correspond to the same anatomy. This paper presents two novel techniques that have application to this problem, high-speed pose tracking and intrasurgical data selection. In the first part of this paper, we describe an approach for tracking the pose of arbitrarily shaped rigid objects at rates up to 10 Hz. Static accuracies on the order of 1 mm in translation and 1 degree in rotation have been achieved. We have demonstrated the technique on a human face using a high-speed VLSI range sensor; however, the technique is independent of the sensor used or the anatomy tracked. In the second part of this paper, we describe a general purpose approach for selecting near-optimal intrasurgical registration data. Because of the high costs of acquisition of intrasurgical data, our goal is to minimize the amount of data acquired while ensuring registration accuracy. We synthesize near-optimal intrasurgical data sets, based on an analysis of differential surface properties of presurgical data. We demonstrate, using data from a human femur, that discrete-point data sets selected using our method are superior to those selected by human experts in terms of the resulting pose-refinement accuracy.

Algorithms↗

Scopolamine inhibits cocaine-conditioned but not unconditioned stimulant effects in mice.

RATIONALE: In animal models, cocaine cues contribute to the development of conditioned responses to the psychomotor stimulating and rewarding effects of the drug. OBJECTIVES: In the present study we investigated the effect of scopolamine, known to impair learning and memory, on cocaine-induced conditioned and unconditioned responses in Swiss Webster mice. METHODS: In the first experiment, mice were treated with saline/saline, saline/cocaine (20 mg/kg), scopolamine (1.0 mg/kg)/cocaine, or scopolamine/saline for 5 days. The treatments were paired with the locomotor activity test cage twice, on days 1 and 5. This allowed to determine: (a) the induction and expression of place-dependent sensitization (PDS) to the psychomotor-stimulating effect of cocaine and (b) place-dependent hyperlocomotion (PDH; i.e., conditioning) as defined by the response to saline injection in the test cage. In the second experiment, all injections were delivered in animals' home cage in order to induce place-independent sensitization (PIS) to cocaine and to avoid the development of PDH. In the third experiment, the effect of scopolamine (1.0 mg/kg) on the acquisition of cocaine-induced conditioned place preference (CPP) was investigated. RESULTS: Data from the first experiment suggest that pretreatment with scopolamine had no specific effect on the induction and expression of cocaine-induced PIS. However, scopolamine blocked cocaine-induced PDH. Results from the second experiment confirmed that scopolamine had no effect on the induction of PIS to cocaine. Results from the third experiment showed that scopolamine completely blocked cocaine-induced CPP. CONCLUSIONS: The finding that scopolamine blocked the conditioned behaviors, PDH and CPP, that develop after exposure to cocaine supports the hypothesis that cocaine cue reactivity in the paradigms tested is associated with learning and memory.

Animals↗

Sensitivity analysis of respiratory parameter uncertainties: impact of criterion function form and constraints.

A sensitivity analysis based on weighted least-squares regression is presented to evaluate alternative methods for fitting lumped-parameter models to respiratory impedance data. The goal is to maintain parameter accuracy simultaneously with practical experiment design. The analysis focuses on predicting parameter uncertainties using a linearized approximation for joint confidence regions. Applications are with four-element parallel and viscoelastic models for 0.125- to 4-Hz data and a six-element model with separate tissue and airway properties for input and transfer impedance data from 2-64 Hz. The criterion function form was evaluated by comparing parameter uncertainties when data are fit as magnitude and phase, dynamic resistance and compliance, or real and imaginary parts of input impedance. The proper choice of weighting can make all three criterion variables comparable. For the six-element model, parameter uncertainties were predicted when both input impedance and transfer impedance are acquired and fit simultaneously. A fit to both data sets from 4 to 64 Hz could reduce parameter estimate uncertainties considerably from those achievable by fitting either alone. For the four-element models, use of an independent, but noisy, measure of static compliance was assessed as a constraint on model parameters. This may allow acceptable parameter uncertainties for a minimum frequency of 0.275-0.375 Hz rather than 0.125 Hz. This reduces data acquisition requirements from a 16- to a 5.33- to 8-s breath holding period. These results are approximations, and the impact of using the linearized approximation for the confidence regions is discussed.

Airway Resistance↗

Growth without growth hormone receptor: estradiol is a major growth hormone-independent regulator of hepatic IGF-I synthesis.

UNLABELLED: The role of estrogens in the regulation of pubertal growth independently of GH and its receptor was studied in male mice with disrupted GHRKO. E(2) rescued skeletal growth rates in GHRKO associated with an increase in hepatic and serum IGF-I. These data show that E(2) rescues pubertal growth during GH resistance through a novel mechanism of GHR-independent stimulation of hepatic IGF-I production. INTRODUCTION: Growth hormone (GH) and estrogen play a pivotal role in pubertal growth and bone mineral acquisition. Estrogens can affect GH secretion and thereby provide a GH-dependent mechanism for their effects on skeletal growth. It is presently unclear if or to what extent estrogens are able to regulate pubertal growth and bone mineral accrual independently of GH and its receptor. MATERIALS AND METHODS: Estradiol (E(2); 0.03 mug/day by subcutaneous silastic implants) was administered to orchidectomized (ORX) male mice with disrupted GHR (GHRKO) and corresponding WTs during late puberty (6-10 weeks). Longitudinal and radial bone growth, IGF-I in serum and its expression in liver, muscle, and bone, and liver gene expression were studied by histomorphometry, RIA, RT-PCR, microarrays, and Western blotting, respectively. RESULTS: E(2) stimulated not only longitudinal (femur length and growth plate thickness) and radial growth (cortical thickness and periosteal perimeter), but also rescued longitudinal and periosteal growth rates in ORX GHRKO, whereas no significant changes occurred in WT. E(2) thereby upregulated serum IGF-I and liver IGF-I synthesis (+21% and +52%, respectively) in ORX GHRKO, whereas IGF-I synthesis in femur or muscle was unaffected. Study of the underlying mechanism of the stimulation of hepatic IGF-I expression showed that E(2) restored downregulated receptor signaling systems, such as the estrogen receptor alpha and the prolactin receptor. E(2) thereby recovered the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway as evidenced by a significantly increased activation of the transcription factor STAT5 in ORX GHRKO. CONCLUSIONS: Our data show a stimulation of skeletal growth through upregulation of hepatic IGF-I by a hormone other than GH. E(2) rescues pubertal skeletal growth during GH resistance through a novel mechanism of GHR-independent stimulation of IGF-I synthesis in the liver.

Animals↗

The cognitive deficits responsible for developmental dyslexia: review of evidence for a selective visual attentional disorder.

There is strong converging evidence suggesting that developmental dyslexia stems from a phonological processing deficit. However, this hypothesis has been challenged by the widely admitted heterogeneity of the dyslexic population, and by several reports of dyslexic individuals with no apparent phonological deficit. In this paper, we discuss the hypothesis that a phonological deficit may not be the only core deficit in developmental dyslexia and critically examine several alternative proposals. To establish that a given cognitive deficit is causally related to dyslexia, at least two conditions need to be fulfilled. First, the hypothesized deficit needs to be associated with developmental dyslexia independently of additional phonological deficits. Second, the hypothesized deficit must predict reading ability, on both empirical and theoretical grounds. While most current hypotheses fail to fulfil these criteria, we argue that the visual attentional deficit hypothesis does. Recent studies providing evidence for the independence of phonological and visual attentional deficits in developmental dyslexia are reviewed together with empirical data showing that phonological and visual attentional processing skills contribute independently to reading performance. A theoretical model of reading is outlined in support of a causal link between a visual attentional disorder and a failure in reading acquisition.

Attention↗

Evolutionary studies on an alpha-amylase gene segment in bats and other mammals.

Comparative studies of salivary glands showed that they maybe related to the adaptive radiation of bats, especially in the family Phylostomidae. In this study we have been searching for a likely relationship between different feeding habits found in bats and possible adaptive changes in a coding segment of the alpha-amylase enzyme. We have also tested some hypothesis about the phylogenetic relationship of bats and other mammals. A 663 bp segment of the alpha-amylase gene, corresponding to the exon 4 and part of the intron c, was sequenced in nine bat species. The exon 4 was also sequenced in further ten mammalian species. The phylogenetic trees generated with different methods produced the same results. When the intron c and the exon 4 were independently analyzed, they showed distinct topologies involving the bat species Sturnira lilium, different from the traditional bat phylogeny. Phylogenetic analysis of bats, primates and rodents supports the Euarchontoglires-Laurasiatheria hypothesis about the relationship among these groups. Selection tests showed that the alpha-amylase exon 4 is under strong purifying selection, probably caused by functional constraints. The conflicting bat phylogenies could not be explained by evolutionary convergence due to adaptive forces, and the different topologies may be likely due to the retention of plesiomorphic characters or the independent acquisition by evolutionary parallelism.

Amino Acid Sequence↗

Implementation of a dynamic platform-independent DICOM-server.

Hospital-wide image and patient data transfer within heterogeneous hard- and software infrastructures can be facilitated by using standardized communication protocols and data formats such as digital imaging and communications in medicine (DICOM). Each DICOM application entity (AE) usually provides a static and fixed set of services according to its functionality. However, certain security concepts, changing demands of medical users, or restricted hardware capabilities may be more easily addressed by applications that dynamically provide variable subsets of DICOM services. In a new approach, an object-oriented DICOM server framework was developed that served as a basis for assembling various DICOM applications. These applications may be set up dynamically to offer variable subsets of services at runtime, similar to "plug-ins". The framework was designed and implemented in Java in order to provide low-cost platform-independent solutions. As an example, a DICOM server was implemented and tested in a clinical application providing access to MR and CT images through a Java/DICOM viewer. Data retrieval was optimized by storing parts of the image acquisition and patient data into a relational database.

Computer Systems↗

Carriage of methicillin-resistant Staphylococcus aureus, ceftazidime-resistant Gram-negative bacilli, and vancomycin-resistant enterococci before and after intensive care unit admission.

OBJECTIVE: To measure patients' risk for acquiring antibiotic-resistant microorganisms associated with intensive care unit admission. DESIGN: Prospective, observational study. SETTING: Ten public hospitals including one university medical center. PATIENTS: Consecutive patients admitted to ten intensive care units. INTERVENTIONS: Serial patient surveillance cultures were screened for vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus (MRSA), ceftazidime-resistant Gram-negative bacilli (CR-GNB), Acute Physiology and Chronic Health Evaluation II score, and antibiotic and medical device exposures. MEASUREMENTS AND MAIN RESULTS: A total of 1,697 patient admissions in ten intensive care units were enrolled. The overall carriage rate of antibiotic-resistant bacteria at intensive care unit entry was 12.1% for MRSA, 14% for CR-GNB and 4.7% for both. At discharge from the intensive care unit, new carriage of MRSA, CR-GNB, and both was found in 11.1%, 14.2%, and 2.4% of the patients, respectively. The acquisition rates in the individual units correlated highly and positively with proportion of patients with carriage at intensive care unit entry for both MRSA (n = 10, Pearson's r =.89, p < 0.001) and CR-GNB (n = 10, Pearson's r =.92, p < 0.001). By logistic regression, severity of illness (odds ratio, 1.4), length of stay (odds ratio, 1.7), use of penicillins (odds ratio, 1.9), and number of antibiotics (odds ratio, 1.2) and medical devices (odds ratio, 1.2) were independently associated with intensive care unit acquisition of MRSA. In comparison, variables independently associated with intensive care unit acquisition of CR-GNB were Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.5), number of antibiotics (odds ratio, 1.1), and artificial airway (odds ratio, 1.5). CONCLUSIONS: These data suggest that hospitalization in the intensive care unit introduces significant risk to patients in terms of transmission of MRSA and/or CR-GNB. This risk seems to be influenced strongly by the proportion of patients with colonization at intensive care unit admission and is associated with severity of illness, length of stay, and exposures to antibiotics and medical devices.

Aged↗

Prototype of a JAVA/DICOM image server with integrated findings and data security.

The transfer of medical data within heterogeneous hard- and software infrastructures requires platform-independent standardized protocols and data formats such as DICOM. To avoid costly vendor-specific solutions a DICOM server was implemented in JAVA thereby enabling the data access via internet browser technology. The most important patient and image acquisition information were extracted from the DICOM images and stored into a relational database. For an integrated view patient information such as radiological findings were transferred from the Radiological Information System (RIS) into the data base. Image data were accessed either by a fast preview tool or using a DICOM viewer. Since DICOM does not include inherent data security mechanisms, a second tool allowed the DICOM-conform encryption of DCIOM data for a secure long term storage on CD-R or across unsecure networks.

Computer Security↗

[Fast and ultra-fast MRI of the brain].

Fast spin-echo sequences, which are based on the RARE sequence, accelerate MRI significantly. The basic principle of fast- or turbo-spin-echo sequences (FSE, TSE), as well as of the gradient-and-spin-echo sequences (GRASE, TGSE), is the sampling of multiple independently phase-encoded echos after each excitation. The basic principles of these sequences and the potentials and limitations of their clinical application are discussed. Their main advantage is a significant reduction of the time for data acquisition, which allows either a reduction of imaging time or high-resolution images even with T2-weighting. The fast sequences provide all possibilities of contrast variation and of preparation pulses such as fat saturation or water suppression. Despite some restrictions, of which reduced susceptibility is clinically relevant, they can replace conventional spin-echo sequences in brain imaging.

Brain↗

Methods for diagnosis and treatment of stimulus-correlated motion in generic brain activation studies using fMRI.

Movement-related effects in realigned fMRI timeseries can be corrected by regression on linear functions of estimated positional displacements of an individual subject's head during image acquisition. However, this entails biased (under)estimation of the experimental effect whenever subject motion is not independent of the experimental input function. Methods for diagnosing such stimulus-correlated motion (SCM) are illustrated by application to fMRI data acquired from 5 schizophrenics and 5 normal controls during periodic performance of a verbal fluency task. The schizophrenic group data were more severely affected by SCM than the control group data. Analysis of covariance (ANCOVA) was used, with a voxelwise measure of SCM as a covariate, to estimate between-group differences in power of periodic signal change while controlling for variability in SCM across groups. Failure to control for SCM in this way substantially exaggerated the number of voxels, apparently demonstrating a between-group difference in task response.

Adult↗