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Indirect flow rate estimation of the NEDO PI Gyro pump for chronic BVAD experiments.

In totally implantable ventricular assist device systems, measuring flow rate of the pump is necessary to ensure proper operation of the pump in response to the recipient's condition or pump malfunction. To avoid problems associated with the use of flow probes, several methods for estimating flow rate of a rotary blood pump used as a ventricular assist device have been studied. In the present study, we have performed a chronic animal experiment with two NEDO PI gyro pumps as the biventricular assist device for 63 days to evaluate our estimation method by comparing the estimated flow rate with the measured one every 2 days. Up to 15 days after identification of the parameters, our estimations were accurate. Errors increased during postoperation days 20 to 30. Meanwhile, their correlation coefficient r was higher than 0.9 in all the acquired data, and estimated flow rate could simulate the profile of the measured one.

Animals↗

Controlled irradiative formation of penitentes.

Spike-shaped structures are produced by light-driven ablation in very different contexts. Penitentes 1-4 m high are common on Andean glaciers, where their formation changes glacier dynamics and hydrology. Laser ablation can produce cones 10-100 microm high with a variety of proposed applications in materials science. We report the first laboratory generation of centimeter-scale snow and ice penitentes. Systematically varying conditions allows identification of the parameters controlling the formation of ablation structures. We demonstrate that penitente initiation and coarsening require cold temperatures, so that ablation leads to sublimation. Once penitentes have formed, further growth of height can occur by melting. The penitentes initially appear as small structures (3 mm high) and grow by coarsening to 1-5 cm high. Our results are an important step towards understanding ablation morphologies.

Journal Article↗

Feedback error learning neural network for trans-femoral prosthesis.

Feedback-error learning (FEL) neural network was developed for control of a powered trans-femoral prosthesis. Nonlinearities and time-variations of the dynamics of the plant, in addition to redundancy and dynamic uncertainty during the double support phase of walking, makes conventional control methods very difficult to use. Rule-based control, which uses a knowledge base determined by machine learning and finite automata method is limited since it does not respond well to perturbations and environmental changes. FEL can be regarded as a hybrid control, because it combines nonparametric identification with parametric modeling and control. This paper presents simulation of a powered trans-femoral prosthesis controlled by a FEL neural network. Results suggest that FEL can be used to identify inverse dynamics of an arbitrary trans-femoral prosthesis during simple single joint movements (e.g., sinusoidal oscillations). The identified inverse dynamics then allows the tracking of an arbitrary trajectory such as a desired walking pattern within a multijoint structure. Simulation shows that the identified controller responds correctly when the leg motion is exposed to a perturbation such as a frequent change of the ground reaction force or the hip joint torque generated by the user. FEL eliminates the need for precise, tedious, and complex identification of model parameters.

Activities of Daily Living↗

Trajectory priming with dynamic fuzzy networks in nonlinear optimal control.

Fuzzy logic systems have been recognized as a robust and attractive alternative to some classical control methods. The application of classical fuzzy logic (FL) technology to dynamic system control has been constrained by the nondynamic nature of popular FL architectures. Many difficulties include large rule bases (i.e., curse of dimensionality), long training times, etc. These problems can be overcome with a dynamic fuzzy network (DFN), a network with unconstrained connectivity and dynamic fuzzy processing units called "feurons." In this study, DFN as an optimal control trajectory priming system is considered as a nonlinear optimization with dynamic equality constraints. The overall algorithm operates as an autotrainer for DFN (a self-learning structure) and generates optimal feed-forward control trajectories in a significantly smaller number of iterations. For this, DFN encapsulates and generalizes the optimal control trajectories. By the algorithm, the time-varying optimal feedback gains are also generated along the trajectory as byproducts. This structure assists the speeding up of trajectory calculations for intelligent nonlinear optimal control. For this purpose, the direct-descent-curvature algorithm is used with some modifications [called modified-descend-controller (MDC) algorithm] for the nonlinear optimal control computations. The algorithm has numerically generated robust solutions with respect to conjugate points. The minimization of an integral quadratic cost functional subject to dynamic equality constraints (which is DFN) is considered for trajectory obtained by MDC tracking applications. The adjoint theory (whose computational complexity is significantly less than direct method) has been used in the training of DFN, which is as a quasilinear dynamic system. The updating of weights (identification of DFN parameters) are based on Broyden-Fletcher-Goldfarb-Shanno (BFGS) method. Simulation results are given for controlling a difficult nonlinear second-order system using fully connected three-feuron DFN.

Fuzzy Logic↗

The prognostic value of CD38 expression in chronic lymphocytic leukaemia patients studied prospectively at diagnosis: a single institute experience.

The purpose of this study was to assess in chronic lymphocytic leukaemia (CLL) patients the prevalence and clinical impact of CD38 expression, evaluated prospectively at disease presentation, and to verify whether this parameter changes over time. In 242 consecutive and untreated CLL patients, the percentage of CD38+ cases, according to the 7%, 20% and 30% cut-off points, was 21%, 17% and 14%, respectively. Using the 7% threshold, CD38 positivity correlated with male sex, intermediate and high-risk (Rai I-IV) disease, lower Hb and platelet levels, and higher lymphocyte count. Furthermore, patients with a CD38 expression>or=7% showed a significantly lower 3-year probability of treatment-free survival (TFS) than CD38- patients (P<0.0001). At multivariate analysis, CD38 expression remained significantly associated to TFS, together with stage, lymphocyte count and morphology. Also, in the 146 patients with stage 0 CLL a CD38 expression>or=7% identified a subgroup of patients with a significantly lower 3-year probability of TFS (P=0.0005). Furthermore, this parameter did not change in 30 of 31 (97%) re-evaluated patients. In conclusion, this study indicates that, when tested at diagnosis and on fresh material, a CD38 expression>or=7% is an important parameter for the identification of early CLL patients with more aggressive disease and that its expression remains stable over time.

ADP-ribosyl Cyclase↗

CD10 and Bcl-2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large-cell lymphoma with very good or very poor prognoses.

AIMS: Diffuse large B-cell lymphoma (DLBCL) is characterized by marked biological heterogeneity. The identification of reproducible parameters that can be combined with the International Prognostic Index (IPI) to better predict outcome could lead to the development of effective risk-adaptive strategies. METHODS AND RESULTS: Bcl-2 and CD10 expression was determined by immunohistochemistry. The impact of the positivity on survival was evaluated in combination with the IPI in 86 patients with a confirmed diagnosis of DLBCL. Patients were divided according to the IPI into low-risk (no to two factors) or high-risk (three to five factors) groups. Positivity rates were 25% for CD10 and 42% for Bcl-2. In a Cox analysis, the high-risk IPI group [hazard ratio (HR) 5.98, P < 0.0001) and Bcl-2 expression (HR 2.43, P = 0.02) were independent poor prognostic factors, and expression of CD10 (HR 0.41, P = 0.052) predicted a favourable outcome. Among patients in the low-risk IPI group, CD10 positivity was associated with an excellent 8-year overall survival (92% versus 45%, P = 0.06). In the high-risk IPI group, Bcl-2 positivity identified a subgroup with invariably fatal disease. CONCLUSIONS: The expression of CD10 in the low-risk IPI group, and the expression of Bcl-2 in the high-risk IPI group can identify two subgroups of patients who might benefit from new risk-adaptive treatment approaches.

Adult↗

Circulating levels of placental protein 5 in the mother: relation to birth weight.

A total of 914 blood samples was obtained from an unselected population of 400 women between 36 and 40 weeks gestation. Serum PP5 levels were measured by a sensitive radioimmunoassay. After ranking of PP5 levels and birth weight the value of serum PP5 in the diagnosis of intrauterine growth retardation was examined. The sensitivity, predictive value, and specificity of the test were 17.07, 16.66, and 90.25 per cent respectively; these results suggest that serum PP5 levels are less accurate than other biochemical parameters in the identification of fetal growth retardation in late pregnancy.

Birth Weight↗

Muscarinic cholinoceptor activation modulates DNA synthesis and CD40 expression in fibroblast cells.

1 The aim of the present work was to examine the role of muscarinic acetylcholine receptors (mAChR) on DNA synthesis and CD40 expression in human fibroblast cells. Neonatal human skin fibroblast cultures were stimulated with carbachol in presence or absence of specific antagonists and the following parameters were measured: identification of mAChR subtypes, DNA synthesis, inositol phosphates (InsP) production and CD40 expression. 2 Human fibroblasts express mAChR with Kd 0.47 +/- 0.11 nm and Bmax 236 +/- 22 fmol mg protein(-1). Carbachol stimulates DNA synthesis, InsP and the expression of CD40. All these effects were inhibited by atropine, mustard hydrochloride (4-DAMP) and pirenzepine but not by AF-DX 116 and tropicamide, indicating that M3 and M1 mAChR are implicated in carbachol action. The relative Ki of the antagonists obtained by competition binding assay was in parallel to the relative potency for blocking both carbachol-stimulated InsP accumulation and DNA synthesis. 3 The intracellular pathway leading to carbachol-induced biological effects involved phospholipase C and calcium/calmodulin, as U-73122 and trifluoroperazine blocked carbachol effects, respectively. Calphostin C, a protein kinase C inhibitor, had no effect, indicating that this enzyme does not participate in the system. 4 These results may contribute to a better understanding of the modulatory role of the parasympathetic muscarinic system on normal human fibroblast function.

Atropine↗

Tilt testing: is it necessary in all patients with suspected vaso-vagal syncope?

BACKGROUND: Head-up tilt testing (HUTT) is a well-established diagnostic tool in patients with suspected vaso-vagal syncope (VVS). However, it is time-consuming and requires special equipment. Thus, identification of simple parameters which could predict the outcome of HUTT could simplify diagnostic steps by obviating the need for HUTT. AIM: To assess which symptoms associated with spontaneous syncope or other details from medical history can predict HUTT results. METHODS: The study group consisted of 202 unselected patients (69 males, mean age 43 +/- 20 years) who were admitted to our syncope unit for HUTT due to suspected VVS. They filled in a detailed questionnaire including 34 standard questions concerning medical history as well as circumstances and symptoms associated with syncopal episodes. Patients were tilted to 70 degrees for 45 minutes or the test was stopped earlier if syncope occurred. A stepwise multiple logistic regression was performed in order to assess which parameters independently predicted the results of HUTT. A point-score was developed by assigning +/-1, +/-2, or +/-3 points to each of the factors based on the relative magnitude of the estimated regression coefficient. The points were then summed and a diagnostic threshold chosen using plots of sensitivity and specificity curves. RESULTS: Syncope was induced by HUTT in 67 (33%) patients. In the whole study group, a point-score identified patients with positive HUTT with a sensitivity of 87.9%, and specificity of 36.3%. When the analysis was confined to the subgroup with >4 syncopal episodes in the past, the sensitivity of a point-score was 94.4%, and specificity--60%, and in the subgroup with >2 syncopal episodes occurring within 1 month preceding HUTT, sensitivity values reached 88.2% at the specificity level of 90.9%. CONCLUSIONS: In patients with frequent syncopal episodes, especially clustered shortly before performing HUTT, in whom symptoms are very suggestive of VVS, a simple point-score system based on medical history accurately predicts HUTT results. Thus, HUTT may not be necessary for establishing diagnosis in this group of patients.

Adult↗

Limited utility of interictal apparent diffusion coefficient in the evaluation of hippocampal sclerosis.

OBJECTIVE: Quantitative measurement of diffusion has been studied as an independent parameter for the identification and characterization of abnormal hippocampi and temporal lobes in epileptic patients. MATERIAL AND METHODS: In order to study the diagnostic value of magnetic resonance diffusion weighted imaging (DWI) and the apparent diffusion coefficient (ADC) from the temporal region, interictal DWI and ADC values were prospectively obtained from both hippocampal areas and temporal lobes bilaterally and compared between 19 normal volunteers and 20 medial temporal lobe epilepsy (MTLE) patients. RESULTS: In all patients, visual assessment of DWI failed to lateralize the lesion. However, the overall correct lateralization rate of interictal ADC was 100% (20/20) if the side with the higher ADC value was considered to be abnormal. Comparison of the MTLE lesion side values with those of the normal volunteers revealed that the ADC values measured from the hippocampal areas and temporal lobes of the MTLE patients were significantly higher than those from the normal volunteers on the lesion side (P < 0.05) and also on the contralateral side although not statistically significant. The absolute differences between the ADC values of the higher and lower side, in both the hippocampus and the temporal lobe, were not significant among the normal volunteers and the MTLE patients. CONCLUSION: Although the correct lateralization rate of interictal ADC in the MTLE patients was 100%, the application of elevated ADC value as a diagnostic criteria for MTLE was disappointing because such elevation in ADC values was not limited only to the ipsilateral temporal region but also in the contralateral side in MTLE.

Adult↗

Optimizing culture conditions for the production of animal cells in microcarrier culture.

Cytodex 1 microcarriers have been used for the successful culture of more than 80 different types of animal cells--including primary cells, normal diploid cell strains and established or transformed cell lines. culture volumes have ranged from a few milliliters for diagnostic studies to over several hundred liters for vaccine production. Experience with this wide variety of cell types and culture volumes has enabled the identification of several parameters critical for obtaining maximum cell yields from microcarrier cultures. The most vital stage for the successful microcarrier culture of many cell types was the initial stage of the culture cycle. To achieve high cell yields, it was necessary to use culture procedures which maximized plating efficiency and final cell yield could be further increased by ensuring that the inoculation cell density exceeded a critical viable cell/microcarrier ratio. Modifications of the standard microcarrier culture procedures included reducing initial culture volume, reducing the initial stirring speed and/or supplementing the medium during the early stages of the culture cycle. Control of pH, nutrient supply, and gas tension were all critical throughout the culture cycle. Results with low-serum and serum-free media indicate that the requirement for fetal calf serum in the microcarrier culture of Vero and MRC-5 cells can be reduced or even eliminated. Large scale microcarrier culture equipment should take into account the modified culture procedures which are often required to achieve the full potential of this culture method. The design of a new flexible culture system suitable for pilot and production scale cultures is presented. This system accomodates a wide variety of culture and production procedures and through a recirculation system permits: (a) "in-line" monitoring and control of culture parameters; (b) provides an efficient gas exchange capacity which obviates the need for fermenter headspace and sparging; and (c) allows for maximal utilization of medium components and rapid harvesting of medium or cell products.

Animals↗

Tissue engineering: functional assessment and clinical outcome.

The issues that should be considered as part of the design and evaluation of tissue engineering constructs with respect to their targeted clinical application are reviewed. This paper provides a general framework for the process of bringing tissue-engineering constructs from the laboratory bench to the patient's bedside, rather than presenting a detailed review of the engineering or biologic principles or mechanisms that are necessary for successful tissue engineering. Many of the principles are animated by using examples from current studies being developed in my laboratory or those of my collaborators. In all likelihood, multiple solutions or approaches will be found that lead to successful tissue-engineering constructs. The focus here is on the identification of critical parameters to be considered rather than specific design solutions. The review is therefore organized to reflect feasible sequences of activities formulated to take tissue engineering from concept to clinical reality.

Animals↗

An automated procedure for the extraction of metabolic network information from time series data.

Novel high-throughput measurement techniques in vivo are beginning to produce dense high-quality time series which can be used to investigate the structure and regulation of biochemical networks. We propose an automated information extraction procedure which takes advantage of the unique S-system structure and supports model building from time traces, curve fitting, model selection, and structure identification based on parameter estimation. The procedure comprises of three modules: model Generation, parameter estimation or model Fitting, and model Selection (GFS algorithm). The GFS algorithm has been implemented in MATLAB and returns a list of candidate S-systems which adequately explain the data and guides the search to the most plausible model for the time series under study. By combining two strategies (namely decoupling and limiting connectivity) with methods of data smoothing, the proposed algorithm is scalable up to realistic situations of moderate size. We illustrate the proposed methodology with a didactic example.

Algorithms↗

Detection of lipid in abdominal tissues with opposed-phase gradient-echo images at 1.5 T: techniques and diagnostic importance.

T1-weighted gradient-echo magnetic resonance images can be acquired with an echo time such that water and lipid spins are in phase or opposed phase. Observation of relative loss of signal intensity on opposed-phase images compared with that on in-phase images allows qualitative assessment of relatively small amounts of lipid in tissues. Conversely, frequency-selective fat saturation techniques are useful primarily for identifying predominantly fatty masses such as angiomyolipomas. Both in-phase and opposed-phase images should be acquired with similar parameters because unequivocal identification of lipid requires comparison with in-phase images to control for T1 and T2* effects. Opposed-phase imaging has been used to differentiate adrenal adenomas, which contain lipid, from adrenal metastases, which do not. The technique can be expanded to examine a spectrum of intraabdominal tumors and conditions that are characterized by intracellular lipid. These include hepatic steatosis, hepatocellular neoplasms, myelolipoma, adrenocortical carcinoma, angiomyolipoma, and renal cell carcinoma. In liver masses, the presence of lipid is largely restricted to primary hepatocellular tumors. Renal and adrenal masses may contain focal fat (angiomyolipomas and myelolipomas, respectively) or diffuse lipid (clear cell renal carcinomas and adenomas, respectively).

Abdomen↗

Vena cavography with CO(2) versus with iodinated contrast material for inferior vena cava filter placement: a prospective evaluation.

PURPOSE: To determine whether carbon dioxide (CO(2)) vena cavography can safely guide the placement of inferior vena cava (IVC) filters. MATERIALS AND METHODS: One hundred nineteen patients were prospectively enrolled in this study. CO(2 )cavograms were obtained and evaluated for IVC diameter, location of renal veins, and presence of thrombus and venous anomalies. If CO(2 )cavography was judged to be adequate, an IVC filter was deployed. After filter placement, cavography was performed with iodinated contrast material; these images were compared with the CO(2) cavograms. RESULTS: Two patients experienced mild side effects related to venous CO(2) injection. Comparison of cavograms obtained with CO(2) and iodinated contrast-enhanced material showed the caval size to be within 3 mm in all 119 patients. In 116 patients (97.5%), CO(2) cavography was judged to be adequate, and in 115 patients, filters were placed. In three (2.5%) patients, it was necessary to perform iodinated contrast-enhanced cavography before filter deployment. All six cases of venous anomaly and 11 (78.6%) of 14 cases of thrombosis were clearly identified with CO(2) cavography. One filter was maldeployed owing to misinterpretation of the CO(2) cavogram. CONCLUSION: CO(2) cavography is well tolerated, safe, and adequate for identification of the parameters necessary for filter deployment. It is especially valuable in patients with a history of reaction to iodinated contrast material or renal insufficiency.

Adolescent↗

Gram-negative bacterial endotoxin- induced infertility: a birds eye view.

Alleviation of infertility on the one hand and development of improved methods of contraception on the other are global concerns to woman's health. The molecular signals that regulate implantation are of clinical relevance since understanding the nature of these signals may lead to strategies to correct implantation failure and to develop novel contraceptive approaches. The other pressing concern is the poor pregnancy rate resulting from in vitro fertilization (IVF). The pregnancy rate in IVF programs remains about 20-30% in spite of the high rate of successful fertilization. This has led to the proposition that additional uterine factors, critical for the implantation process, must be limiting. Identification of such parameters could help in determining the appropriate physiological state of the uterus for embryo transfer. Several factors are known to have a direct or indirect impact on the ability of the uterus to develop to a functionally receptive state. This would disrupt the normal coordination between embryonic and uterine development even though all molecular players may seem otherwise normal.

Endotoxins↗

Evaluation of human panelists in assessing coronary atherosclerosis.

The Cholesterol Lowering Atherosclerosis Study, a randomized, angiographic clinical trial, has demonstrated the beneficial effect of niacin/colestipol therapy on coronary and femoral atherosclerosis. The primary outcome was a panel-determined consensus score evaluating global coronary changes determined angiographically at 2 years. This article presents an evaluation of interreader agreement in independently assessing the status of native coronary arteries and overall coronary condition. Parameters include 1) identification of the presence of lesions and lesion changes; 2) estimation of lesion severity (percent stenosis) and amount of change in lesion severity; and 3) global assessment of change in coronary status. Readers independently agreed on 1) presence of lesions (82%) and change in lesions (51%); 2) percent stenosis +/- 10% (76%) and change in stenosis +/- 10% (81%); and 3) global assessment of change in coronary status within one step (96%). Results of these analyses may be useful in effectively designing angiographic trials that use a panel of human evaluators as well as computerized methods for angiographic interpretation.

Adult↗

The Sicilian gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology.

The Queen's Gambit is an opening move in chess that provides a variety of aggressive options to the player electing it. This report represents a similar gambit (the Sicilian Gambit) on the part of a group of basic and clinical investigators who met in Taormina, Sicily to consider the classification of antiarrhythmic drugs. Paramount to their considerations were 1) dissatisfaction with the options offered by existing classification systems for inspiring and directing research, development, and therapy, 2) the disarray in the field of antiarrhythmic drug development and testing in this post-Cardiac Arrhythmia Suppression Trial (CAST) era, and 3) the desire to provide an operational framework for consideration of antiarrhythmic drugs that will both encourage advancement and have the plasticity to grow as a result of the advances that occur. The multifaceted approach suggested is, like the title of the article, a gambit. It is an opening rather than a compendium and is intended to challenge thought and investigation rather than to resolve issues. The article incorporates first, a discussion of the shortcomings of the present system for drug classification; second, a review of the molecular targets on which drugs act (including channels and receptors); third, a consideration of the mechanisms responsible for arrhythmias, including the identification of "vulnerable parameter" that might be most accessible to drug effect; and finally, clinical considerations with respect to antiarrhythmic drugs. Information relating to the various levels of information is correlated across categories (i.e., clinical arrhythmias, cellular mechanisms, and molecular targets), and a "spread sheet" approach to antiarrhythmic action is presented that considers each drug as a unit, with similarities to and dissimilarities from other drugs being highlighted. A complete reference list for this work would require as many pages as the text itself. For this reason, referencing is selective and incomplete. It is designed, in fact, to provide sufficient background information to give the interested reader a starting frame of reference rather than to recognize the complete body of literature that is the basis for this article.

Animals↗