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Optimizing the pentetrazol infusion test for seizure threshold measurement.

Seizure thresholds in mice were determined using the pentetrazol infusion method. Concentration of infusate and rate of infusion were varied to assess the optimal parameters for seizure threshold detection. Seizure threshold elevations were produced by flurazepam and threshold decreases by FG 7142. An infusion rate of 1.1 ml min-1 was best for detecting both increases and decreases in threshold. However a concentration of 2.5 mg ml-1 gave optimal measurement of elevations in threshold whereas decreased thresholds were best detected with a concentration of 10 mg ml-1.

Animals↗

Effect of double antigen bridging immunoassay format on antigen coating concentration dependence and implications for designing immunogenicity assays for monoclonal antibodies.

The double antigen bridging immunoassay has been used extensively for detection of immunogenicity responses to therapeutic monoclonal antibodies. We have analyzed parameters affecting performance of this type of immunoassay including microtiter plate antigen coating concentration, enzyme-labeled antigen conjugate dilution and assay format (one-step versus two-step). We present results demonstrating that the format of the assay has a significant impact on the optimal parameters to maximize assay performance. A one-step assay format achieves maximal sensitivity across a broad range of coating concentrations and at a lower concentration of conjugate than that in a two-step format. In contrast, a two-step format requires very low coating concentrations and higher conjugate concentrations to achieve maximal sensitivity and suffers from significantly reduced sensitivity at higher coating concentrations. Together, these findings indicate that a one-step assay format can greatly reduce the effect of coating concentration variation on assay performance.

Antibodies, Monoclonal↗

Optimal wavelets for biomedical signal compression.

Signal compression is gaining importance in biomedical engineering due to the potential applications in telemedicine. In this work, we propose a novel scheme of signal compression based on signal-dependent wavelets. To adapt the mother wavelet to the signal for the purpose of compression, it is necessary to define (1) a family of wavelets that depend on a set of parameters and (2) a quality criterion for wavelet selection (i.e., wavelet parameter optimization). We propose the use of an unconstrained parameterization of the wavelet for wavelet optimization. A natural performance criterion for compression is the minimization of the signal distortion rate given the desired compression rate. For coding the wavelet coefficients, we adopted the embedded zerotree wavelet coding algorithm, although any coding scheme may be used with the proposed wavelet optimization. As a representative example of application, the coding/encoding scheme was applied to surface electromyographic signals recorded from ten subjects. The distortion rate strongly depended on the mother wavelet (for example, for 50% compression rate, optimal wavelet, mean+/-SD, 5.46+/-1.01%; worst wavelet 12.76+/-2.73%). Thus, optimization significantly improved performance with respect to previous approaches based on classic wavelets. The algorithm can be applied to any signal type since the optimal wavelet is selected on a signal-by-signal basis. Examples of application to ECG and EEG signals are also reported.

Algorithms↗

[Turbidimetric study of latex agglutination in 2,4-dichlorophenoxyacetic acid analysis].

By the example of 2,4-dichlorophenoxyacetic acid (2,4-D) assay by the inhibition of latex agglutination, new synthetic polymer microspheres for the conjugation with antibodies to 2,4-D and agglutinators based on ovalbumin and polyacrylamide were developed and characterized. The effect of various parameters (the concentration of reagents, the type and the degree of modification of the microsphere surface, and the nature of the carrier in the composition of the agglutinator) on the rate of agglutination and the maximal optical absorption observed during the reaction were studied by turbidimetry. The optimal parameters were found for the assay of 2,4-D by the inhibition of latex agglutination with turbidimetric registration of the results.

2,4-Dichlorophenoxyacetic Acid↗

Improving the amplitude-modulated control experiment for multislice continuous arterial spin labeling.

The use of an amplitude-modulated radiofrequency (RF) pulse for a control experiment is a proven method to control for off-resonance effects in multislice continuous arterial spin labeling (CASL) experiments. This method is also known as double adiabatic inversion. The adiabaticity factor of a single half-pulse, beta(1/2), and a new dimensionless parameter alpha, which is obtained from the labeling parameters and the flow velocity, are introduced. This makes it possible to distinguish three distinct cases: 1) With low alpha, a double inversion occurs. 2) With alpha > or = approximately 4, the efficiency with which the longitudinal magnetization is returned to the z-axis depends on the phase of the amplitude modulation at the time the spins cross the center of the labeling plane. 3) In the intermediate region, the efficiency shows undesirable fluctuations. In a Bloch equation simulation, three optimized parameter sets are determined. Near ideal performance should always be achieved by combinations of parameters for which beta(1/2) > or = approximately 2 and alpha approximately pi/beta(1/2). The efficiency increases were realized in a volunteer study, showing the practical application of the suggested optimization.

Adult↗

Comparison of 3D BOLD functional MRI with spiral acquisition at 1.5 and 4.0 T.

In order to investigate the merit of high field strength for BOLD-contrast-based functional magnetic resonance imaging (fMRI) studies, multishot gradient-echo fMRI experiments during motor cortex activation were performed on 1.5- and 4.0-T scanners with equivalent hardware, on the same volunteers. In these studies, artifactual vascular enhancement related to inflow effects was minimized, and large brain areas were covered by using a 3D scan technique. Temporal signal stability was optimized by using spiral readout gradients. The sensitivity for detection of activated regions was assessed by measuring the number of "activated voxels" and their average t score in predefined regions of interest. When comparing fMRI experiments with the same total scan time, performed on six subjects, and with acquisition parameters optimized for each field strength separately, the 4.0-T scanner proved to give superior results, with a 70% greater number of activated voxels and a 20% higher average t score for the activated voxels.

Humans↗

Optimal choice of vacuum-membrane skeletal muscle extension.

Peculiarities of skin extension under vacuum applicators (nozzles) of various design was studied in 20 volunteers aged 18-25 years. The data obtained made it possible to chose optimal parameters of elastic membranes of the vacuum cups that produce stretch sufficient for vacuum-membrane skeletal muscle extension with minimal traumatic damage to the skin. Local negative pressure varied from 10 to 70 kPa. It was found that for 4.5-cm applicator with one 1.4-2.0-cm central orifice the optimal thickness of the membrane is 0.3 cm.

Adolescent↗

Parameters of electrical stimulation of the medial preoptic area for release of gonadotrophins in male rats.

The release of LH and FSH after the application of an electrical stimulus to the anterior diencephalon of male rats has been studied. The stimulus was applied through either platinum or steel electrodes implanted stereotaxically in animals anaesthetized with urethane. The efficacy of various parameters of stimulation by means of a current consisting of balanced biphasic square waves, was tested by systematically changing the frequency, amplitude and duration of the pulses. The effect of direct current (d.c.) stimulation on hormone release was also examined. The concentrations of the hormones in blood withdrawn from the femoral vein before and at frequent intervals up to 80 min after application of the stimulus were determined by radioimmunoassay. The optimal parameters for the release of LH by square wave stimulation of the medial preoptic area were: frequency, 60 Hz; pulse amplitude, 0-50 mA; pulse duration, 1-00 ms. This stimulus was more effective when applied through steel than through platinum electrodes. Direct current stimulation (15 muA for 10 s) through steel electrodes was most effective of all. When applied through platinum electrodes to the medial preoptic and anterior hypothalamic areas, the optimal square wave stimulus produced significant increases in the concentration of LH after 5 and 10 min respectively. The concentration of plasma FSH in these animals also increased, but the increments were much less than the increments in LH. The magnitude of the respective increases of the gonadotrophins after stimulation of the two brain areas did not differ significantly. Measurement of the milk ejection response to stimulation of the hypothalamo-hypophysial tract in the lactating rat indicated that the spread of the square wave stimulus was no more than 1-5 mm from the electrode tip. The significance of these findings is discussed with respect to the importance of the medial preoptic area in the male rat, the neurones which may be involved in the regulation of gonadotrophin secretion, and the parameters of stimulation used in studying the hypothalamo-hypophysial system.

Animals↗

Intensity modulated radiation therapy using laser-accelerated protons: a Monte Carlo dosimetric study.

In this paper we present Monte Carlo studies of intensity modulated radiation therapy using laser-accelerated proton beams. Laser-accelerated protons coming out of a solid high-density target have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Through the introduction of a spectrometer-like particle selection system that delivers small pencil beams of protons with desired energy spectra it is feasible to use laser-accelerated protons for intensity modulated radiotherapy. The method presented in this paper is a three-dimensional modulation in which the proton energy spectrum and intensity of each individual beamlet are modulated to yield a homogeneous dose in both the longitudinal and lateral directions. As an evaluation of the efficacy of this method, it has been applied to two prostate cases using a variety of beam arrangements. We have performed a comparison study between intensity modulated photon plans and those for laser-accelerated protons. For identical beam arrangements and the same optimization parameters, proton plans exhibit superior coverage of the target and sparing of neighbouring critical structures. Dose-volume histogram analysis of the resulting dose distributions shows up to 50% reduction of dose to the critical structures. As the number of fields is decreased, the proton modality exhibits a better preservation of the optimization requirements on the target and critical structures. It is shown that for a two-beam arrangement (parallel-opposed) it is possible to achieve both superior target coverage with 5% dose inhomogeneity within the target and excellent sparing of surrounding tissue.

Algorithms↗

Asthma severity and asthma control: symptoms, pulmonary function, and inflammatory markers.

PURPOSE OF REVIEW: Asthma severity and asthma control are distinct yet related concepts. Asthma severity describes the underlying disease in the absence of therapy and is ideally defined without concurrent treatment confounding its assessment. Asthma control describes the clinical status of disease in the face of intervention. However, the individual parameters by which we define asthma severity and asthma control overlap significantly. A MEDLINE search between July 1, 2002, and June 30, 2003, was performed using keywords related to concepts of asthma severity of illness and asthma control. From these articles the author selected the articles most relevant for discussion. RECENT FINDINGS: Asthma is a complex syndrome. Although correlations exist between the various parameters used in clinical assessment, no single parameter can accurately classify all individuals. Assessment of multiple parameters including physiologic measures, symptoms, and activity limitation are necessary to categorize asthma clinical status accurately. In addition, the role biomarkers play in the assessment of disease status is an area of increasing interest. Several validated multidimensional measures for assessing asthma control are now available. Each of these measures includes the parameters of symptoms, activity limitation, and rescue medication use, yet they vary on inclusion of other important components such as physiologic measures and biomarkers. SUMMARY: Asthma is a complex syndrome. Currently available instruments demonstrate an improved understanding of the multidimensional approach required to assess asthma control accurately. However, debate continues on the optimal parameters to be included and the role biomarkers play in the clinical assessment of asthma.

Asthma↗

Cys(x)His(y)-Zn2+ interactions: possibilities and limitations of a simple pairwise force field.

In zinc proteins, the Zn2+ cation frequently binds with a tetrahedral coordination to cysteine and histidine side chains. We examine the possibilities and limitations of a classical, pairwise force field for molecular dynamics of such systems. Hartree Fock and density functional calculations are used to obtain geometries, charge distributions, and association energies of side chain analogues bound to Zn2+. Both ionized and neutral cysteines are considered. Two parameterizations are obtained, then tested and compared through molecular dynamics simulations of two small, homologous proteins in explicit solvent: Protein Kinase C and the Cysteine Rich Domain (CRD) of Raf, which have two Cys3His-Zn2+ groups each. The lack of explicit polarizability and charge transfer in the force field leads to poor accuracy for the association energies, and to parameters--including the zinc charge, that depend on the number of bound cysteines and their protonation state. Nevertheless, the structures sampled with the best parameterization are in good overall agreement with experiment, and have zinc coordination geometries compatible with related structures in the Cambridge Structural Database and the Protein Data Bank. Non-optimized parameters lead to poorer structures. This suggests that while a simple force field is not appropriate for processes involving exchange between water and amino acids in the zinc coordination sphere (e.g. protein unfolding), it can be useful for equilibrium simulations of stable Cys3His zinc fingers.

Computer Simulation↗

Deep brain stimulation in movement disorders: stereotactic coregistration of two-dimensional electrical field modeling and magnetic resonance imaging.

OBJECT: Adjusting electrical parameters used in deep brain stimulation (DBS) for dystonia remains time consuming and is currently based on clinical observation alone. The goal of this study was to visualize electrical parameters around the electrode, to correlate these parameters with the anatomy of the globus pallidus internus (GPI), and to study the relationship between the volume of stimulated tissue and the electrical parameter settings. METHODS: The authors developed a computer-assisted methodological model for visualizing electrical parameters (the isopotential and the isoelectric field magnitude), with reference to the stereotactic target, for different stimulation settings (monopolar and bipolar) applied during DBS. Electrical field values were correlated with the anatomy of the GPI, which was determined by performing stereotactic magnetic resonance imaging in one reference patient. By using this method it is possible to compare potential and electrical field distributions for different stimulation modes. In monopolar and bipolar stimulation, the shape and distribution of the potential and electrical field are different and depend on the stimulation voltage. Distributions visualized for patient-specific parameters can be subsequently correlated with anatomical information. The application of this method to one patient demonstrated that the 0.2-V/ mm isofield line fits best with the lateral GPI borders at the level of the stimulated contacts. CONCLUSIONS: The electrical field is a crucial parameter because it is assumed to be responsible for triggering action potentials. Electrical field visualization allows the calculation of the stimulated volume for a given isoline. Its application to an entire series of patients may help determine a threshold for obtaining a therapeutic effect, which is currently unknown, and consequently may aid in optimizing parameter settings in individual patients.

Adolescent↗

Source localization using a current-density minimization approach.

Determining the location of cortical activity from electroencephalographic (EEG) data is important clinically. In this paper, a method is presented which uses the powerful optimization method of simulated annealing in conjunction with a finite-element-based model of the search domain for single-time slice solution of the EEG-inverse problem. The algorithm highlights a new objective function based on the current-density boundary integral associated with the finite-element formulation as the basis for parameter optimization. In two-dimensional experiments in a shallow tank containing saline, single dipoles are located within 2 mm. Simulations studying the algorithms response to structured noise are also presented. The new objective function is shown to take advantage of the natural framework associated with finite-elements and the results suggest that the approach is capable of resolving dipole locations in simulations and experiments.

Brain Mapping↗

Influence of non-bonded parameters on the quality of NMR structures: a new force field for NMR structure calculation.

The effects of different non-bonded parameters of force fields for NMR structure calculation on the quality of the resulting NMR solution structures were investigated using Interleukin 4 as a model system. NMR structure ensembles were calculated with an ab initio protocol using torsion angle dynamics. The calculations were repeated with five different non-bonded energy functions and parameters. The resulting ensembles were compared with the available X-ray structures, and their quality was assessed with common structure validation programs. In addition, the impact of torsion angle restraints and dihedral energy terms for the sidechains and the backbone was studied. The further improvement of the quality by refinement in explicit solvent was demonstrated. The optimal parameters, including those necessary for water refinement, are available in the new version of the PARALLHDG force field.

Interleukin-4↗

Development of a high efficiency personal/environmental radon dosimeter using polycarbonate detectors.

Passive radon dosimeters, based on alpha particle etched track detectors, are widely used for the assessment of radon exposure. These methods are often applied in radon dosimetry for long periods of time. In this research work, we have developed a highly efficient method of personal/environmental radon dosimetry that is based upon the detection of alpha particles from radon daughters, (218)Po and (214)Po, using a polycarbonate detector (PC). The radon daughters are collected on the filter surface by passing a fixed flow of air through it and the PC detector, placed at a specified distance from the filter, is simultaneously exposed to alpha particles. After exposure, the latent tracks on the detector are made to appear by means of an electrochemical etching process; these are proportional to the radon dose. The air flow rate and the detector-filter distance are the major factors that can affect the performance of the dosimeter. The results obtained in our experimental investigations have shown that a distance of 1.5 cm between the detector and the filter, an absorber layer of Al with a thickness of 12 microm and an air flow rate of 4 l min(-1) offer the best design parameters for a high efficiency radon dosimeter. Then, the designed dosimeter was calibrated against different values of radon exposures and the obtained sensitivity was found to be 2.1 (tracks cm(-2)) (kBq h m(-3))(-1). The most important advantages of this method are that it is reliable, fast and convenient when used for radon dose assessment. In this paper, the optimized parameters of the dosimeter structure and its calibration procedure are presented and discussed.

Dose-Response Relationship, Radiation↗

Comprehensive model of transport and metabolism of adenosine and S-adenosylhomocysteine in the guinea pig heart.

Regulation of blood flow and mitochondrial respiration in the heart would be clarified by improved knowledge of interstitial concentrations and cellular production rates of adenosine; however, these variables cannot be measured directly. To interpret indexes that are available, a comprehensive mathematical model was developed, based on a large body of experimental data. The model describes most of the important pathways of capillary-tissue transport and cellular metabolism of adenosine in the guinea pig heart. It includes capillary flow, solute transport between tissue regions, nonlinear enzyme kinetics for adenosine kinase and adenosine deaminase, and reversible biunireactant kinetics for S-adenosylhomocysteine hydrolase in cardiomyocytes and endothelial cells, intracellular production of adenosine via AMP hydrolysis and transmethylation, and extracellular production of adenosine. A single set of parameter values for the model was obtained in the first stage of the analysis by taking certain values directly from published sources, other values were subject to specific constraints, and other values were determined by parameter optimization. The effects of flow and endothelial metabolism on the relation between interstitial and venous adenosine concentrations were determined. The relation between myocardial adenosine production rate and S-adenosylhomocysteine accumulation in the presence of excess homocysteine was estimated. In the second stage of the analysis, the model was used to investigate the mechanism of myocardial adenosine production, without changing the parameter values. Cellular adenosine production rates were estimated by fitting measurements of venous adenosine release obtained during altered energetic conditions in experiments by different investigators. The original results showed a dissociation between measurements of cytosolic AMP concentrations and venous adenosine release. It is concluded that 1) it is essential to account for the effect of flow on interstitial and venous adenosine concentrations, since decreased flow may produce effects outwardly resembling inhibition of the enzyme 5'-nucleotidase, 2) adenosine concentrations in epicardial transudate are not in equilibrium with interstitial fluid, and 3) the rate of cellular adenosine production increases monotonically with free cytosolic concentrations of AMP during a variety of alterations in energy balance of the guinea pig heart.

Adenosine↗

Fitting piecewise linear regression functions to biological responses.

An iterative approach was achieved for fitting piecewise linear functions to nonrectilinear responses of biological variables. This algorithm is used to estimate the parameters of the two (or more) regression functions and the separation point(s) (thresholds, sensitivities) by statistical approximation. Although it is often unknown whether the response of a biological variable is adequately described by one rectilinear regression function or by piecewise linear regression function(s) with separation point(s), an F test is proposed to determine whether one regression line is the optimal fitted function. A FORTRAN-77 program has been developed for estimating the optimal parameters and the coordinates of the separation point(s). A few sets of data illustrating this kind of problem in the analysis of thermoregulation, osmoregulation, and the neuronal responses are discussed.

Algorithms↗

Treatment of venous malformations with an intense pulsed light source (IPLS) technology: A retrospective study.

BACKGROUND AND OBJECTIVE: The intense pulsed light source (IPLS) technology provides an innovative concept in the treatment of vascular lesions. We investigated the effectiveness of IPLS in the treatment of venous malformations. STUDY DESIGN/MATERIALS AND METHODS: A retrospective study of 11 patients with venous malformations (VMA) treated with IPLS was initiated. Clinical VMA characteristics recorded were size and location. Data collected included treatment parameters (filters, pulse duration, fluence, and pulse sequencing), % clearance, and side effects (e.g., swelling, blisters, crusting, pain, altered pigmentation, and scarring). RESULTS: Good and very good (70-100%) clearance was achieved in 8 malformations smaller than 100 cm(2). Especially small lesions needed only 2-3 treatments. Three VMA larger than 100 cm(2) could be cleared well in an average of 18 sessions. The most frequently used parameters were the 590 nm filter in long pulse mode, triple pulses, and fluences at an average of 80.4 J/cm(2). Side effects included prolonged erythema in 23.6, swelling in 17.9%, crusting in 4.7%. Bleeding, hypo-, hyperpigmentation, and scarring were rare (0.9% respectively). CONCLUSION: IPLS presents an effective method for treating VMA, especially small malformations, with a justifiable rate of side effects when optimal parameters are chosen.

Adolescent↗