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Effects of REM sleep awakenings and related wakening paradigms on the ultradian sleep cycle and the symptoms in depression.

In 1975 Vogel and coworkers published their classical study where they compared selective rapid eye movement (REM) sleep deprivation by brief awakenings to a control intervention paradigm in depressed patients. The superior antidepressive impact of the first procedure was attributed to the REM pressure accumulating during the treatment period. The laborious procedure and the considerable effort necessary to evaluate the sleep profiles in real time have prevented similar experiments so far. Based on artificial neural networks we developed a software for the real time detection of REM sleep. In combination with an alarm system the algorithm allowed us to wake up subjects automatically and to reduce REM sleep by about 50%. The procedure was then compared to a modified nonREM intervention paradigm for a treatment period of ten consecutive nights in depressed patients (n(1)=14, n(2)=13). These simultaneously received moderate dosages of Trimipramine. We found a strong and robust but not significantly different reduction of the average Hamilton rating scores (33 and 41% of baseline levels). While the REM sleep awakenings shortened the sleep cycle duration considerably, our nonREM intervention paradigm lengthened the ultradian alternations. Both effects might be interpreted as a challenge imposed on the nonREM-REM alternating mechanism possibly responsible for the antidepressive impact. A different timing of the control interventions might have caused the discrepancy between our findings and those of Vogel and coworkers.

Adult↗

European Union System for the Evaluation of Substances (EUSES). Principles and structure.

In the European Union, Directive 92/32/EC and EC Council Regulation (EC) 793/93 require the risk assessment of new and existing substances, respectively. Principles for this risk assessment have been laid down, supported by a detailed package of Technical Guidance Documents. Against this background the European Union System for the Evaluation of Substances (EUSES) has been developed. This software can be used to carry out tiered risk assessments of increasing complexity on the basis of increasing data requirements. The exposure assessment, effects assessment and risk characterisation are carried out for environmental populations as well as for human beings, including workers, consumers and man exposed through the environment. EUSES is the result of a co-ordinated effort of EU Member States, the European Commission and the European Chemical Industry.

Animals↗

Genomic DNA sequencing methods.

Sequence analysis of cosmids from C. elegans and other organisms currently is best done using the random or "shotgun" strategy (Wilson et al., 1994). After shearing by sonication, DNA is used to prepare M13 subclone libraries which provide good coverage and high-quality sequence data. The subclones are assembled and the data edited using software tools developed especially for C. elegans genomic sequencing. These same tools facilitate much of the subsequent work to complete both strands of the sequence and resolve any remaining ambiguities. Analysis of the finished sequence is then accomplished using several additional computer tools including Genefinder and ACeDB. Taken together, these methods and tools provide a powerful means for genome analysis in the nematode.

Animals↗

Flexibility in system design and implications for aerospace systems.

The purpose of this paper is to review the concept of flexibility as discussed in various fields of investigations, to extract its characteristic features, and to explore its implications in the case of aerospace system design. In order to discuss any subject matter clearly, it is necessary to begin with a clear set of definitions. Indeed much can be gained through careful and consistent definitions of terms alone. Flexibility however is a word rich with ambiguity. While it is being increasingly used in various fields, few attempts have been made to formally define, quantify, and propose ways for achieving flexibility. This paper proposes to fill in part of this gap by synthesizing a clear and consistent definition of flexibility. It will do so by reviewing the usage of the term in various fields of inquiries, and show that it is indeed possible to clearly and unambiguously characterize flexibility, and to disentangle it from closely related concepts.

Aircraft↗

Computer assisted three-dimensional reconstruction of brain regions from serial section digitized images. Application to the organization of striato-nigral relationships in the rat.

We have developed a software which allows the three-dimensional reconstruction of brain regions from serial section digitized images. This software, which generates wire-frame three dimensional models, requires at least a 486 PC microcomputer running Microsoft Windows (3.x or 95). Mosaics of high resolution images, covering large brain areas, digitized by means of a camera fitted on a microscope equipped with a motorized stage, are handled by our software as single high resolution images. Serial sets of such images may be segmented and manually aligned. We have utilized this software to study the organization of striatal efferences within the substantia nigra pars reticulata, as well as the distribution of neuronal cell bodies within the substantia nigra pars compacta after micro-ionophoretic application of wheat germ agglutinin conjugated to horseradish peroxidase into the orofacial sensorimotor region of the striatum. The three dimensional representation of anterogradely labeled striatal efferences confirmed and determined the lamellar organization previously postulated from serial plane section micrographs. The distribution in the rat brain of retrogradely labeled nigro-striatal cell bodies, which had not yet been studied after injection of tracer into functionally identified regions of the striatum, revealed two subpopulations: a first one rather dense, located in the anterior half of the substantia nigra pars compacta, which was in close register with the striatal efferences, and a second one, much more scattered and less numerous, located in the posterior part of the structure which extended far from the substantia nigra along the medio-lateral axis. Our three dimensional reconstruction software will now be used to study the neuronal connectivity within the basal ganglia and other brain regions.

Animals↗

Rats and mice share common ethologically relevant parameters of exploratory behavior.

Detailed studies of rat exploratory behavior reveal that it consists of typical behavior patterns having a distinct structure. Recently we have developed interactive software that uses as input the automatically digitized time-series of the animal's location for the visualization, analysis, capturing and quantification of these patterns. We use this software here for the study of BALB/cJtau mouse behavior. The results suggest that a considerable number of rat patterns are also present in the mouse. These ethologically-relevant patterns have a significant potential as a phenotyping tool.

Algorithms↗

GenomeComp: a visualization tool for microbial genome comparison.

We have developed a software tool, GenomeComp, for summarizing, parsing and visualizing the genome sequences comparison results derived from voluminous BLAST textual output. With GenomeComp, the variation between genomes can be easily highlighted, such as repeat regions, insertions, deletions and rearrangements of genomic segments. This software provides a new visualizing tool for microbe comparative genomics.

Computational Biology↗

A CT-aided PC-based physical treatment planning of TBI: a method for dose calculation.

BACKGROUND AND PURPOSE: As for conventional radiotherapy, one of the basic requirements in Total Body Irradiation (TBI) is to know accurately the dose delivered to the entire body. Both the dosimetry and the treatment planning need to be improved. Physical, technical and dosimetrical aspects of TBI have been widely discussed in the literature. However, to our knowledge, no planning systems specifically designed for TBI are commercially available. This article describes a CT-aided PC-based planning system (TBI-Plansys) and its dose calculation algorithm, which applies scatter and inhomogeneity corrections, developed for the TBI technique currently in use at our centre (AP/PA irradiation with patient positioned on his side). MATERIAL AND METHOD: A description of the material and method followed in the dosimetrical procedure is included as it constitutes the basis of the proposed dose calculation algorithm (more than 2D). A Windows programming environment has been used to develop the software. RESULTS: TBI-Plansys uses patient CT data and indicates absolute and relative dose distributions along midline (at reference points), the transversal axis at the specification point and on transverse sections. The system also calculates the appropriate thicknesses of bolus and shielding to modify undesired dose distributions. TBI-Plansys has been checked against two other well-established systems (beam-zone method and our in vivo semiconductor probe-based system). The checks showed good accuracy with dose differences less than 1% and 3% for homogeneous and inhomogeneous tissues, respectively. CONCLUSIONS: CT calculations by TBI-Plansys allow us to detect undesired distributions which may go unnoticed by calculations at only some specific points. The system has shown clear advantages for routine clinical use as it generates more detailed and accurate information than manual calculations and diminishes the time requirements.

Algorithms↗

Individualized phantom based on CT slices and auxological data (ICTA) for dose estimations following radiotherapy for skin haemangioma in childhood.

BACKGROUND AND PURPOSE: Before 1974 about 5000 children were treated by radiotherapy at the Institut Gustave-Roussy (IGR) for a skin haemangioma. A human model whose characteristics are as close as possible to those of the patient at the time of the treatment is necessary to effectuate an accurate retrospective estimation of the radiation doses received at distant organs. METHODS: We have developed a software package which constructs an individualized phantom based on CT slices and auxological data (ICTA) for this purpose. A set of real CT slices is used to produce a 3-D representation of the human body which is then adjusted to fit the dimensions supplied by published auxological data relative to sex and age for each patient. One hundred sixty-one anatomical landmarks of epidemiological interest have been defined inside the phantom for dose estimation. RESULTS: The transverse, frontal and sagittal views of the phantom displayed permit accurate positioning of radioactive applicators. The software calculates the relevant parameters required for dose estimation based on the patient's probable anatomy.

Adult↗

Stoichiometric modeling of Clostridium acetobutylicum fermentations with non-linear constraints.

A stoichiometric model of Clostridium acetobutylicum and related strains has been previously derived. The stoichiometric matrix of the model contains a singularity which has prevented the calculation of a unique set of fluxes which describe the primary metabolic activity. To resolve the singularity, we have developed a non-linear constraint relating the acetate and butyrate uptake fluxes. Subsequently, we developed a software package utilizing a model independent heuristic global optimization approach to solve the resultant non-linear problem. We have validated the use of the non-linear constraint by correlating calculated butyrate production pathway flux profiles with measured intracellular pH profiles. Finally, we examined a controlled batch fermentation to determine that the acid formation pathways play critical roles throughout solventogenesis. The broader usefulness of reformulating the stoichiometric model as a constrained minimization problem is discussed.

Acetates↗

[Three-dimensional 3D modeling: First applications in radioanatomy and interventional radiology under CT guidance].

PURPOSE: To model vertebrae in 3D to improve radioanatomic knowledge of the spine with the vascular and nerve environment and simulate CT-guided interventions. METHOD AND MATERIALS: Vertebra acquisitions were made with multidetector CT. We developed segmentation software and specific viewer software using the Delphi programming environment. RESULTS: This segmentation software makes it possible to model 3D high-resolution segments of vertebrae and their environment from multidetector CT acquisitions. Then the specific viewer software provides multiplanar reconstructions of the CT volume and the possibility to select different 3D objects of interest. DISCUSSION: This software package improves radiologists' radioanatomic knowledge through a new 3D anatomy presentation. Furthermore, the possibility of inserting virtual 3D objects in the volume can simulate CT-guided intervention. CONCLUSION: The first volumetric radioanatomic software has been born. Furthermore, it simulates CT-guided intervention and consequently has the potential to facilitate learning interventions using CT guidance.

Algorithms↗

Early diagnosis of coxarthrosis (in-shoe plantar pressure measurements).

INTRODUCTION:: Plantar pressure measurement during walking adds dynamic functional data to evaluation of gait disorders of teenagers with coxarthrosis. The duration of the complete gait cycle, its phases (stance and swing phase for right and left feet, double support) and phases of roll-over process are found useful in many clinical applications. METHODS:: In-shoe measurements were completed with Pedar system (99 element capacitive insoles from Novel, Munich, Germany) for 38 teenagers from military school (controls) and 29 teenagers with coxarthrosis. The data from 3 - 5 trials for each subject were collected. The distance was about 10 m, no requirements to the speed and step length were established. Special software was developed. RESULTS:: Time parameters for the complete gait cycle, its phases, phases of roll-over-process were calculated both for the controls and the teenagers with coxarthrosis It was found that stance phase and heel contact phase are decreased for the teenagers with coxarthrosis. DISCUSSION:: Decrease of stance phase, insufficient loading of the heel and decrease of heel contact time are a result of attempts to compensate the painfulness in the hip joint during walking. CONCLUSION:: Time parameters of the complete gait cycle and its phases may be useful in early diagnosis of coxarthrosis and evaluation of efficiency of the treatment.

Journal Article↗

Comparative analysis of the anxiety-related behaviors in four inbred mice.

An anxiety-related behavior is an emotional response of an organism, which is quantitatively measured by several behavioral paradigms. We employed two most frequently used behavioral tests, the open field and light-dark exploration, to comparatively analyze the anxiety-like behaviors in four inbred mice. For an accurate recording of movement, motion analysis software was developed that acquires a real-time video input to generate a behavioral path. Effects of the strains on the test results were evaluated by ANOVA with the Newman-Keuls post hoc comparison. Eight different behavioral indices, four from each tests, were grouped into two classes; the results of duration, center crossing, transition, rearing, and ambulation indicate strain differences of FVB/N>C57BL/6J>/=BALB/cA>/=CBA/N (I), while stretched-attend posture, peeping, and defecation show the tendency of FVB/N=C57BL/6J<CBA/N</=BALB/cA (II). The peeping is a novel type of behavior observed in this work. Although there is a variation among behavioral indices in their discrimination between inbred lines, the behaviors are highly correlated one another such that each class I or class II behaviors are clustered on two orthogonal factor planes as a result of the principal component analysis. The polarization of each inbred line toward these two behavioral biases may reflect genetic backgrounds of these strains.

Journal Article↗

Determination of the dissociation constants of the cephalosporins cefepime and cefpirome using UV spectrometry and pH potentiometry.

UV spectrometry and pH potentiometry were used for the determination and direct characterization of the dissociation constants of cefepime (Cef) and cefpirome. The absorbance/pH profiles at two analytical wavelengths and different conditions were assessed and found to conform to those of diprotic acids. The titration curves indicated a triprotic acid profile with two overlapping dissociation constants. The comparison of the results of both techniques permitted the direct attribution of the three dissociation constants to the carboxylic group at position 4 of the Delta-3 cephem nucleus, the aminothiazole group and the amide group at position 7 of the Delta-3 cephem nucleus. Stability studies of Cef in alkaline solutions were also performed in order to evaluate the accuracy of the measurements carried out for the determination of the third pK(a) value. The experimental pK(a) values were compared to the corresponding predicted values derived by PALLAS/PKALC and Advanced Chemical Development (ACD) software packages.

Cefepime↗

Computer-assisted decision analysis in orthopedics: resurfacing the patella in total knee arthroplasty as an example.

The purpose of the present study was to illustrate the use of computer-assisted decision analysis in making decisions in the field of orthopaedic surgery, using the choice between resurfacing and not resurfacing the patella in total knee arthroplasty as an example. We used a decision analysis technique based on probability theory and on Bayesian logic, with the help of an especially developed computer software. The process involves building a decision tree, searching for probabilities and utilities in the literature, folding back the tree to compute the baseline result, and running sensitivity analyses. Our literature search provided 26 useful articles, only 3 of which were randomized controlled trials. In the baseline analysis, both options were rated similarly, with resurfacing the patella faring slightly better. Sensitivity analyses revealed that not resurfacing becomes the procedure of choice if the probability of postoperative anterior knee pain with an unresurfaced patella falls below 14%, or if the probability of having pain with a resurfaced patella rises above 8% or if the utility of patellar implant failure falls below 80% of the utility of a perfect health state. Computer-assisted decision analysis is a promising, evidence-based tool to assist clinical decision making in orthopaedic surgery. However, its validity is limited by the poor quality of data found in the orthopaedic literature, especially the scarcity of randomized controlled trials.

Arthroplasty, Replacement, Knee↗

eLoom and Flatland: specification, simulation and visualization engines for the study of arbitrary hierarchical neural architectures.

eLoom is an open source graph simulation software tool, developed at the University of New Mexico (UNM), that enables users to specify and simulate neural network models. Its specification language and libraries enables users to construct and simulate arbitrary, potentially hierarchical network structures on serial and parallel processing systems. In addition, eLoom is integrated with UNM's Flatland, an open source virtual environments development tool to provide real-time visualizations of the network structure and activity. Visualization is a useful method for understanding both learning and computation in artificial neural networks. Through 3D animated pictorially representations of the state and flow of information in the network, a better understanding of network functionality is achieved. ART-1, LAPART-II, MLP, and SOM neural networks are presented to illustrate eLoom and Flatland's capabilities.

Computer Simulation↗

Acoustic quantification indexes of left ventricular size and function: effects of signal averaging.

BACKGROUND: The aim of this study was to evaluate the clinical utility of using signal-averaged acoustic quantification (SAAQ) waveforms for improved assessment of left ventricular (LV) size and function. METHODS AND RESULTS: Four separate protocols were performed in 47 subjects. SAAQ waveforms were used to assess alterations in LV function induced by dobutamine (15 microg/kg per minute) and esmolol (200 microg/kg per minute) in eight normal subjects. Subsequently, we analyzed SAAQ waveforms obtained in 12 patients with LV dysfunction secondary to dilated cardiomyopathy and 12 age-matched normal subjects. Finally, we developed computer software for monitoring of LV function on the basis of continuous acquisition and repeated analysis of SAAQ waveforms. We compared the interbeat variability in indexes of LV function obtained from raw AQ and SAAQ during 10 minutes of steady-state monitoring in eight patients undergoing transesophageal echocardiography. The feasibility of long-term monitoring in the intensive care setting was then studied in seven patients undergoing abdominal surgery. Our analysis tracked variations in LV function induced by dobutamine and esmolol. Significant differences in all measured indexes were found between normal subjects and patients with dilated cadiomyopathy. Signal averaging during steady-state monitoring significantly reduced the interbeat variability of all indexes (21% to 42%). In the operating room, the SAAQ monitoring system tracked hemodynamic changes in close agreement with invasive measurements. CONCLUSIONS: SAAQ allows fast and easy quantification of LV function and can track hemodynamic trends in the operating room setting.

Adrenergic beta-Agonists↗

Accurate computation of coincidence summing corrections in low level gamma-ray spectrometry

The GESPECOR (Germanium Spectrometry Correction factors) software, previously developed for computing the self-attenuation and coincidence summing corrections, was applied to the computation of the coincidence summing correction factors for a well-type and two coaxial HPGe detectors. Cylindrical samples as well as Marinelli beaker samples were considered. The computed values are in good agreement with carefully measured values. A detailed study of the uncertainties assigned to the results was carried out. The analysis shows that the procedures used in GESPECOR are reliable and provide results with a well defined accuracy.

Journal Article↗