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A finite volume model of cardiac propagation.

This paper describes a two-dimensional cardiac propagation model based on the finite volume method (FVM). This technique, originally derived and applied within the filed of computational fluid dynamics, is well suited to the investigation of conduction in cardiac electrophysiology. Specifically, the FVM permits the consideration of propagation in a realistic structure, subject to arbitrary fiber orientations and regionally defined properties. In this application of the FVM, an arbitrarily shaped domain is decomposed into a set of constitutive quadrilaterals. Calculations are performed in a computational space, in which the quadrilaterals are all represented simply as squares. Results are related to their physical-space equivalents by means of a transformation matrix. The method is applied to a number of cases. First, large-scale propagation is considered, in which a magnetic resonance-imaged cardiac cross-section serves as the governing geometry. Next, conduction is examined in the presence of an isthmus formed by the microvasculature in a slice of papillary muscle tissue. Under ischemic conditions, the safety factor for propagation is seen to be related to orientation of the fibers within the isthmus. Finally, conduction is studied in the presence of an inexcitable obstacle and a curved fiber field. This example illustrates the dramatic influence of the complex orientation of the fibers on the resulting activation pattern. The FVM provides a means of accurately modeling the cardiac structure and can help bridge the gap between computation and experiment in cardiac electrophysiology.

Algorithms↗

Non-invasive temperature prediction of in vitro therapeutic ultrasound signals using neural networks.

In this paper, a novel black-box modelling scheme applied to non-invasive temperature prediction in a homogeneous medium subjected to therapeutic ultrasound is presented. It is assumed that the temperature in a point of the medium is non-linearly related to some spectral features and one temporal feature, extracted from the collected RF-lines. The black-box models used are radial basis functions neural networks (RBFNNs), where the best-fitted models were selected from the space of model structures using a genetic multi-objective strategy. The best-fitted predictive model presents a maximum absolute error less than 0.4 degrees C in a prediction horizon of approximately 2 h, in an unseen data sequence. This work demonstrates that this type of black-box model is well-suited for punctual and non-invasive temperature estimation, achieving, for a single point estimation, better results than the ones presented in the literature, encouraging research on multi-point non-invasive temperature estimation.

Body Temperature↗

Multigate doppler signal analysis using 3-D regularized long AR modelling.

Autoregressive (AR) modelling has already been proposed as an alternative to fast Fourier transform to process ultrasound (US) Doppler signals. Previous works introduced long AR models, set up under a regularization framework. The latter may be in 1-D (frequency) or 2-D (frequency and space or time). This study generalizes the spectrum regularization in the three dimensions frequency, space and time. The problem of the penalization function is addressed, and a new convex solution is proposed, taking into account possible nonstationarity of the Doppler signal. The parameter tuning is based on simulations using a standard Doppler signal model. The first results show that this processing improves the spectral estimation, and is well suited to flow interpretation.

Algorithms↗

[Peridural morphine in intractable cancer pains. Means and obstacles].

Long-term analgesia with epidural morphine (EM) is a new tool in the management of intractable cancer pain. Twenty-six out of 160 cancer patients referred to the Pain Division for pain assessment were selected for analgesia with long-term epidural morphine, so aiming to define its place amongst more traditional methods of treatment, such as drugs, nerve-blocks, neurosurgery or radiotherapy. All 26 patients were cases of conventional analgesic failure, with very advanced cancer states. Thirteen patients became absolutely pain free throughout the treatment period: five of them were even allowed home. Another ten patients were satisfied with EM, though some residual pain of neurogenic and visceral type persisted. In three patients, epidural morphine was judged as a complete failure. The 134 other patients could be managed with either of the other above mentioned techniques. The most important selection criterion for patients requiring epidural morphine seemed to be continuous multiple site bilateral pain of deep somatic origin. The response was variable in continuous visceral pain, while neurogenic, cutaneous and intermittent pain due to intestinal obstruction responded only exceptionally. EM was most valuable in terminal situations when systemic opiates failed to give satisfactory analgesia, or in acute transitory situations, while waiting for a response to cancer-orientated therapy. Epidural morphine considerably improved the patients' quality of life, compared with conventional methods tried beforehand. Analgesic methods in cancer are palliative procedures. In terminal or temporary situations, other more invasive methods are not suited. The EM technique is simple, adjustable to advancing pain and has few side-effects, especially when compared with neurolytic and neurosurgical procedures.

Adult↗

Visualizing substructural fingerprints.

Substructural fingerprints have proven very useful for chemical library and diversity analysis, but their high dimensionality makes them poorly suited to principal components analysis and to standard nonlinear mapping methods. By using a combination of optimizable K-dissimilarity selection (OptiSim) and a modified stress function that suppresses effects of distances that fall beyond a characteristic horizon, it is possible to relax principal components analysis coordinates into more consistently meaningful projections from fingerprint space into two dimensions. The nonlinear maps so obtained are useful for characterizing combinatorial libraries, for comparing sublibraries, and for exploring the distribution of biological properties across structural space.

Combinatorial Chemistry Techniques↗

Cognitive, perceptual-speed, and psychomotor determinants of individual differences during skill acquisition.

The authors describe a series of experiments that explore 3 major ability determinants of individual differences in skill acquisition in the context of prior theory (e.g., P.L. Ackerman, 1988) and subsequent empirical and theoretical research. Experiment 1 assessed the predictability of individual differences in asymptotic skill levels on the Kanfer-Ackerman Air Traffic Controller (ATC) task. Experiment 2 provided an exploration of the construct space underlying perceptual-speed abilities. Experiment 3 concerned an evaluation of theoretical predictions for individual differences in performance over skill development in a complex air traffic control simulation task (TRACON) and the ATC task, with an extensive battery of general and perceptual-speed measures, along with a newly developed PC-based suite of psychomotor ability measures. Evidence addressing the predictability of individual differences in performance at early, intermediate, and asymptotic levels of practice is presented.

Adolescent↗

The influence of experimental design and data analysis on the determination of recovery kinetics of radiation damage between acute dose-rate treatments in vivo.

Current interest in determining the rate of recovery of damage between radiation doses in fractionated treatments has resulted in the development of several experimental designs and methods of analysis to address this. One approach is where two or more fractions are given with a varying interval. Isoeffect doses are then determined from the dose-response curves for each interval, and these are plotted on a logarithmic axis against time on a linear scale. An estimate of the rate of dose recovery can then be made if the data show monoexponential or well-defined multiexponential kinetics. However, three problems can be identified in this simple protocol. First, most repair models (e.g. Thames' IR and Curtis' LPL) assume that between two doses loge (cell survival), i.e. underlying effect, not dose itself, recovers exponentially with time. Experimental data support this assumption. Since underlying effect and dose are not linearly related, recovery measured from the change in isoeffect dose can appear substantially slower (depending on dose per fraction) than the true underlying recovery rate of damage. This artifact is avoided by converting dose increments into changes in underlying effect (with the linear-quadratic model) or by measuring underlying effect more directly in 'top-up' experiments. The use of (neutron) top-up experiments is preferred, as it enables recovery between constant X-ray doses per fraction to be studied, and makes no prior assumptions regarding either the shape of the X-ray dose-response curve or how recovery takes place, although the shape of the neutron dose-response curve must be known. Second, plotting log (unrecovered damage) against time can overestimate recovery half-times, because such plots cannot handle negative values and therefore become naturally weighted in favour of the data from the longer time intervals where the difference from complete recovery is smallest. This problem is managed by using nonlinear regression to fit the values of unrecovered damage expressed on a linear scale against interval. Third, experiments using three or more evenly spaced fractions, 'concertina'-style, permit interaction between non-adjacent fractions. If this is not taken account of, then recovery appears to be initially faster and multiexponential, even though the underlying recovery may be actually monoexponential. Thus concertina experiments are poor at resolving the precise shape of recovery-kinetics profiles and are less suited for measuring any dependence of recovery rate on dose per fraction compared with approaches using either just two fractions, or two fractions per day.

DNA Repair↗

Asymptotically optimal blind estimation of multichannel images.

Optimal estimation of a two-dimensional (2-D) multichannel signal ideally decorrelates the data in both channel and space and weights the resulting coefficients according to their SNR. Many scenarios exist where the required second-order signal and noise statistics are not known in which the decorrelation is difficult or expensive to calculate. An asymptotically optimal estimation scheme proposed here uses a 2-D discrete wavelet transform to approximately decorrelate the signal in space and the discrete Fourier transform to decorrelate between channels. The coefficient weighting is replaced with a wavelet-domain thresholding operation to result in an efficient estimation scheme for both stationary and nonstationary signals. In contrast to optimal estimation, this new scheme does not require second-order signal statistics, making it well suited to many applications. In addition to providing vastly improved visual quality, the new estimator typically yields signal-to-noise ratio gains 12 dB or higher for hyperspectral imagery and functional magnetic resonance images.

Algorithms↗

A multimodal, multidimensional atlas of the C57BL/6J mouse brain.

Strains of mice, through breeding or the disruption of normal genetic pathways, are widely used to model human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison. We have developed a digital atlas of the adult C57BL/6J mouse brain as a comprehensive framework for storing and accessing the myriad types of information about the mouse brain. Our implementation was constructed using several different imaging techniques: magnetic resonance microscopy, blockface imaging, classical histology and immunohistochemistry. Along with raw and annotated images, it contains database management systems and a set of tools for comparing information from different techniques. The framework allows facile correlation of results from different animals, investigators or laboratories by establishing a canonical representation of the mouse brain and providing the tools for the insertion of independent data into the same space as the atlas. This tool will aid in managing the increasingly complex and voluminous amounts of information about the mammalian brain. It provides a framework that encompasses genetic information in the context of anatomical imaging and holds tremendous promise for producing new insights into the relationship between genotype and phenotype. We describe a suite of tools that enables the independent entry of other types of data, facile retrieval of information and straightforward display of images. Thus, the atlas becomes a framework for managing complex genetic and epigenetic information about the mouse brain. The atlas and associated tools may be accessed at http://www.loni.ucla.edu/MAP.

Anatomy, Artistic↗

In vivo determination of optical properties of normal and tumor tissue with white light reflectance and an empirical light transport model during endoscopy.

Determination of tissue optical properties is fundamental for application of light in either therapeutical or diagnostics procedures. In the present work we implemented a spatially resolved steady-state diffuse reflectance method where only two fibers (one source and one detector) spaced 2.5 mm apart are used for the determination of the optical properties. The method relies on the spectral characteristics of the tissue chromophores (water, dry tissue, and blood) and the assumption of a simple wavelength dependent expression for the determination of the reduced scattering coefficient. Because of the probe dimensions the method is suited for endoscopic measurements. The method was validated against more traditional models, such as the diffusion theory combined with adding doubling for in vitro measurements of bovine muscle. Mean and standard deviation of the absorption coefficient and the reduced scattering coefficient at 630 nm for normal mucosa were 0.87+/-0.22 cm(-1) and 7.8+/-2.3 cm(-1), respectively. Cancerous mucosa had values 1.87+/-1.10 cm(-1) and 8.4+/-2.3 cm(-1), respectively. These values are similar to data presented by other authors. Blood perfusion was the main variable accounting for differences in the absorption coefficient between the studied tissues.

Algorithms↗

[Possibility of conserving the heat balance of the human organism in an extremely rarefied atmosphere by vacuum evaporation of sweat from the surface of the body].

As a result of 64 experiments carried out on 24 test subjects, it has been shown that extreme overwarming due to moderate and heavy thermal loads can be prevented with the aid of heat release through sweat evaporation from the surface of the body under the action of a rarefied atmosphere (termed vacuum sweat evaporation). The test subjects wearing altitude suits remained in a thermal altitude chamber at 40 and 55 degrees C for 8 to 3 hours at rest and doing light work at altitudes of 7 to 25 km without marked signs of overwarming. The entire heat release occurred only through vacuum sweat evaporation from the surface of the body that was under the altitude suit during a gradual decrease of the chamber pressure to 20 mm Hg (equivalent to an altitude of 25 km). The findings give support to the hypothesis that heart release via vacuum sweat evaporation from the surface of the body can be used as a method of controlling thermal homeostasis during high altitude and space flights.

Altitude↗

Long-term intrathecal catheterization in the rat.

We report an intrathecal (i.t.) catheter system that permits repeated administration of volumes of 10 microl or more in the awake rat over many months. A small skin incision is made and a 32 ga polyurethane catheter is inserted in the sacral subarachnoid space using a modified 22 ga needle. The other end of the catheter is tunneled subcutaneously to the flank and exteriorized through a titanium port. The device is well tolerated, does not cause sensory or motor deficits, and does not interfere with behavioral testing. Rats equipped with this device can be housed with other rats. Over the 9 month observation period the function of the catheter was verified by repeated injection of 15 microl of 2% lidocaine that caused temporary paraplegia. Out of 12 implanted rats, the number of fully functional catheters was 10 at 3 months, seven at 6 months, and six at 9 months. At 3 months, i.t. injection of anti-dopamine-beta-hydroxylase antibodies conjugated to saporin (DBH-SAP, 5 microg/10 microl) resulted in noradrenergic denervation of the spinal cord in all rats (n=10). We propose that intrathecal catheterization is well suited for long term behavioral and pharmacological studies.

Animals↗

Second-degree twinning and dynamic disorder in the crystal structure of deca-dodecasil 3R.

The structure of deca-dodecasil 3R (DD-3R), Si120O240, a very well suited material for the synthesis of inorganic/organic composites structured on a nanometer level, has been investigated in detail. So far, a highly complicated twinning has hampered its structure description at a desirable level of accuracy. This twinning has now been resolved and a new structure determination is presented. Structure refinement in the R\bar 3 space group revealed a large, unusually shaped atomic displacement ellipsoid for oxygen-bridging units (tetrahedra), bridging Si-O bonds shorter than expected and the linear Si-O-Si' bond angle dictated by special positions at a threefold axis. A structure model based on a statistically disordered bridging O atom improved the accuracy of the Si-O bonds of interest, but provided unacceptable O-O contacts. To solve this dilemma, ab initio NVT molecular dynamics calculations were performed to study the possible configurations. Wavelet analysis of the time variations of selected Si-O distances pointed to a synchronous shift of the whole building units (tetrahedra). Low-frequency features of the calculated phonon density of states agree well with the published INS (inelastic neutron scattering) spectra of several silica polymorphs, indicating that the nature of the disorder in DD-3R is dynamic rather than static.

Journal Article↗

Crystallization and preliminary X-ray analysis of porcine muscle prolyl oligopeptidase.

Prolyl oligopeptidase from pig muscle has been crystallized in complex with an inhibitor, using PEG 8000 and calcium acetate as precipitants. The crystals are orthorombic and the space group is P212121 with cell dimensions a = 111.8, b = 101.8, c = 72.4 A. The asymmetric unit contains a single chain of prolyl oligopeptidase, corresponding to a specific volume of 2.55 A3 Da-1 and a solvent content of 52%. The observed diffraction pattern extends to 2.3 A resolution and the native crystals are well suited for structural analysis by X-ray diffraction methods.

Animals↗

A combined CT and angiography suite with a pivoting table.

In a suite with fully interactive computed tomography (CT) and C-arm fluoroscopy units, emergency and elective interventional procedures were performed successfully in 41 patients (overall time range, 40-180 minutes [mean, 80 minutes]). The table can be manually pivoted from the fixed CT position to the free-floating angiography position, in an overall working space of about 40 m(2), with room for anesthesiology and monitoring equipment and personnel.

Angiography↗

Estimation of individually adapted control parameters for an artificial beta cell.

For optimum long-term glycemic regulation using a miniaturized artificial beta cell it is indispensible to estimate control parameters suited to the individual requirements of each diabetic patient. To solve this problem, a strategy has been developed which is based on engineering optimum-control theory with a model involving glucose and insulin interactions. The model considers physiologically relevant unit processes like endogenous glucose production, insulin-independent glucose uptake from its apparent distribution space, insulin-dependent glucose utilization, glucose-dependent insulin supply, and insulin catabolism. The assumed model structure is validated by results obtained in experimentally diabetic dogs using partition analysis. The individual parameter values of the model are obtained by a digital computer procedure based on a simple test which involves a bolus injection of glucose + insulin when a constant basal insulin dose is being administered in the diabetic in whom normoglycemia was re-established before the test. The method presented is recommended for future use in all cases where an optimized insulin regimen is to be worked out.

Animals↗

Laparoscopic partial nephrectomy: comparison of transperitoneal and retroperitoneal approaches.

PURPOSE: Laparoscopic partial nephrectomy has become an effective alternative for small renal tumors. Previous reports include transperitoneal and retroperitoneal approaches but to our knowledge the indications for when to apply the techniques have not been defined. We report our experience with comparing the 2 techniques. MATERIALS AND METHODS: A retrospective review of 51 laparoscopic partial nephrectomies was performed. Patients were analyzed based on the surgical approach, operative parameters and postoperative recovery. The 2 approaches used similar operative techniques to control parenchymal bleeding and collecting system entry. RESULTS: There were 32 retroperitoneal and 19 transperitoneal partial nephrectomies. Mean operative time (3.5 vs 5.4 hours, p = 0.000001) and blood loss (192 vs 403 cc, p = 0.002) was significantly less for the retroperitoneal approach. Renal vessel clamping was performed in 81% of retroperitoneal and 63% of transperitoneal operations. Warm ischemia time was not significantly different between the groups. Patients undergoing the retroperitoneal approach had a statistically significant decrease in time to tolerating a regular diet (1.2 vs 1.7 days, p = 0.02), catheter removal (1.4 vs 2.5 days, p = 0.004) and discharge home (2.3 vs 3.6 days, p = 0.0008). CONCLUSIONS: Based on tumor location as the selection criteria the retroperitoneal approach was associated with shorter operative time, less blood loss, more rapid return of bowel function and shorter hospitalization compared with those in patients selected for the transperitoneal technique. Based on our experience we believe that the decision on the approach should be based on the tumor location on the kidney surface. For polar or posterolateral masses the retroperitoneal approach is preferred. The transperitoneal approach is best suited to anterior and medial lesions.

Blood Loss, Surgical↗

Subjective reality, objective reality, modes of relatedness, and therapeutic action.

This paper describes a dialectic believed to be at the heart of therapeutic interaction within a relational model. The dialectic consists of the interrelationship of two modes: the dyadic and the triadic. In the dyadic mode, the analyst responds with aspects of his or her self that singularly reflect the patient's subjectivity. This mode of attunement is uniquely suited to bringing the patient's experience into a place where it can then be seen and known. In the triadic mode, realities are recognized that are important to, but still outside of, the subjectivity of the patient. The analyst invites the patient to see him- or herself not only from inside his or her own space, but also from a point outside, through the perspective of others. The analyst is charged with asymmetric but not exclusive responsibility for negotiating and sustaining a fluid and flexible relationship between these modes. Optimally, this occurs through spontaneous and authentic engagement informed by intuition, empathy, and clinical judgment. However, when this dialectic loses its robust and kinetic quality (as frequently occurs in approaches ranging from the classical to the postmodern), an impermeable dyad is formed by extruding potentially triangulating aspects of reality (and subjectivity). This can result in curiosity and the openness of uncertainty being replaced by closed-mindedness and proclamation.

Abreaction↗