Tissue radiation response with maximum Tsallis entropy.

The expression of survival factors for radiation damaged cells is currently based on probabilistic assumptions and experimentally fitted for each tumor, radiation, and conditions. Here, we show how the simplest of these radiobiological models can be derived from the maximum entropy principle of the classical Boltzmann-Gibbs expression. We extend this derivation using the Tsallis entropy and a cutoff hypothesis, motivated by clinical observations. The obtained expression shows a remarkable agreement with the experimental data found in the literature.

Immune system-tumour efficiency ratio as a new oncological index for radiotherapy treatment optimization.

A dynamical system model for tumour-immune system interaction together with a method to mimic radiation therapy are proposed. A large population of virtual patients is simulated following an ideal radiation treatment. A characteristic parameter, the immune system-tumor efficiency ratio (ISTER) is introduced. ISTER dependence of treatment success and other features are studied. Radiotherapy treatment dose optimization, following ALARA (As Low As Reasonably Achievable) criterion, as well as a patient classification are drawn from the statistics results.

Assessment of cancer immunotherapy outcome in terms of the immune response time features.

A cytokine-based periodic immunotherapy treatment is included in a model of tumour growth with a delay. The effects of dose schedule are studied in the case of a weak immune system and a growing tumour. We find the existence of 'metastable' states (that may last for tens of years) induced by the treatment and also potentially adverse effects of the dosage frequency on the stabilization of the tumour. These two effects depend on the delay between the tumour growth and the immune system response, the cytokine dose burden, and other parameters considered in the model.

Support vector analysis of color-Doppler images: a new approach for estimating indices of left ventricular function.

Reliable noninvasive estimators of global left ventricular (LV) chamber function remain unavailable. We have previously demonstrated a potential relationship between color-Doppler M-mode (CDMM) images and two basic indices of LV function: peak-systolic elastance (Emax) and the time-constant of LV relaxation (tau). Thus, we hypothesized that these two indices could be estimated noninvasively by adequate postprocessing of CDMM recordings. A semiparametric regression (SR) version of support vector machine (SVM) is here proposed for building a blind model, capable of analyzing CDMM images automatically, as well as complementary clinical information. Simultaneous invasive and Doppler tracings were obtained in nine mini-pigs in a high-fidelity experimental setup. The model was developed using a test and validation leave-one-out design. Reasonably acceptable prediction accuracy was obtained for both Emax (intraclass correlation coefficient Ric, = 0.81) and tau (Ric, = 0.61). For the first time, a quantitative, noninvasive estimation of cardiovascular indices is addressed by processing Doppler-echocardiography recordings using a learning-from-samples method.

Spatio-temporal mapping of intracardiac pressure gradients. A solution to Euler's equation from digital postprocessing of color Doppler M-mode echocardiograms.

Doppler assessment of intracardiac pressure gradients using the simplified Bernoulli equation is inaccurate in the absence of a restricted orifice. The purpose of this study is to develop a new general method to map instantaneous pressure gradients inside the heart using Doppler echocardiography. Color Doppler M-mode recordings are digitally postprocessed with a software algorithm that decodes flow velocity and fits a bivariate spatio-temporal tensor-product smoothing spline. Temporal and spatial accelerations are then calculated by analytical derivation of the fitted velocity data, allowing solution of both inertial and convective terms of Euler's equation. A database of 39 transmitral inflow and transaortic outflow color Doppler M-mode recordings from 20 patients with a number of cardiac conditions was analysed, along with matched pulsed-wave spectral recordings. A close agreement was observed between the spectral and postprocessed color Doppler velocity values (error = 0.8 +/- 11.7 cm/s), validating the data decoding and fitting process. Spatio-temporal pressure-gradient maps were obtained from all studies, allowing visualisation of instantaneous pressure gradients from the atrium to the apex during left ventricular filling, and from the apex to the outflow tract during ejection. Instantaneous pressure differences between localised intracardiac sample points closely matched previously published catheterization findings, both in magnitude and waveform shape. Our method shows that intracardiac instantaneous pressure gradients can be analysed noninvasively using color Doppler M-mode echocardiography combined with image postprocessing methods.

Flow dynamics of stenotic aortic valves assessed by signal processing of Doppler spectrograms.

Clinical assessment of aortic stenosis (AS) is sometimes challenging, because all hemodynamic indexes of severity are modified by flow rate. However, the mechanisms underlying flow dependence remain controversial. Analysis of instantaneous flow dynamics has provided crucial information in a number of cardiovascular disorders and may add new insight into this phenomenon. This study was designed to analyze in vivo the effects of flow interventions on instantaneous valvular dynamics of stenotic valves. For this purpose, a custom algorithm for signal processing of Doppler spectrograms was developed and validated against a control population. Digital Doppler recordings at the aortic valve and left ventricular outflow tract were obtained in 15 patients with AS, at baseline and during low-dose dobutamine infusion; 10 normal subjects were studied as controls. Spectrograms were processed by signal averaging, time alignment, modal-velocity enhancement, envelope tracing, and numerical interpolation. Instantaneous relative aortic valve area (rAVA) was obtained by the continuity equation and plotted against normalized ejection time. Curves were classified as either type A (rapid, early-systolic opening) or type B (slow, end-systolic opening). Curves from controls closely matched prior knowledge of normal valve dynamics, but curves from patients were clearly different: all controls except 2 (80%) had type A, whereas all patients except 3 (80%) had a type B pattern (p = 0.03). Dobutamine infusion in patients increased and slightly anticipated peak rAVA by accelerating valve opening. Despite similar values of area and pressure difference, type B dynamics were associated with lower blood pressure (p = 0.01) and worse long-term outcome (>3 years) than type A flow dynamics (p = 0.02). Signal processing of Doppler spectrograms allows a comprehensive assessment of aortic flow dynamics. Differences in timing of valve aperture and in maximal leaflet excursion account for flow-mediated changes in valve area, suggesting complementary effects of inertia and elasticity on the kinetics of stenotic aortic valves. Flow-dynamic analysis provides novel clinical information regarding physiology of AS unavailable to conventional indexes.

Bethe lattice representation for sandpiles.

Avalanches in sandpiles are represented by a process of percolation in a Bethe lattice with a feedback mechanism. The results indicate that the frequency spectrum and probability distribution of avalanches provide a better resemblance to the experimental results than other models using cellular automata simulations. Apparent discrepancies between experiments performed by different authors are reconciled. Critical behavior is expressed here by the critical properties of percolation phenomena.

Tubular vacuum-powered blood-pumping device with active valves.

We propose a new vacuum-driven blood pump having a tubular shape with active valves. This design avoids any possible problems caused by membrane breakage, thereby minimizing the risk of gas embolic events and stagnation regions. By using active valves, it is possible to ensure better flow control and minimize pressure gradients inside and outside the pump. The low cost of the pump's disposable parts enables it to be used for such applications as a ventricular assist device, a pulsatile pump device in extracorporeal circulation, a pump in hemodialysis and apheresis circuits, and a pump in extracorporeal membrane oxygenator systems.

Hydrodynamic response of a VAD with a compliant cannula: results of in vitro tests.

We report on comparative in vitro tests of two ventricular assist devices (VAD) one with a rigid input cannula and the other with a collapsible (compliant) inlet cannula. We show how this compliant cannula yields significant improvements in the hydrodynamic performance of the system.

Development and clinical assay of the BCM ventricular assist device.

The development of a ventricular assist device is depicted. The seven subprograms that make up the project are described briefly. Results obtained during the clinical assay showed that the new design of the input cannula working as a false auricle provides better efficiency, as well as a certain level of autoregulation for the device.

Improvement of the hydrodynamic response of a ventricular assist device: a false auricle solution.

We propose a new design of the auricular cannula in ventricular assist devices (VADs), consisting of a collapsible large cannula with a capacity approximately equal to the ejection volume of the VAD. The device works as a false auricle and filters the negative pressure that occurs during diastole. We show that the use of this type of cannula improves the hydrodynamic efficiency and the stability of the working conditions. Moreover, during chronic implantation in sheep, hemolysis stays well below pathological levels. These improvements result in much better controllability of the whole VAD.

First clinical implantation of the BCM 3.5 ventricular assist device (VAD).

We report on the first human implantation of the BCM 3.5 ventricular assist device in a 46-year-old man suffering from terminal stage cardiomyopathy. The circulatory support was used as a bridge to heart transplantation. The patient was in cardiogenic shock and was on assisted circulation for 18 days after which he underwent cardiac transplantation. While receiving support from the ventricular assist device, the patient's condition improved remarkably and 50 days after transplantation he was discharged from hospital. We give a detailed description of the surgical technique, with special emphasis on the procedures for air extraction. We describe the evolution of the hemodynamic status before and after implantation. Final inspection of the device and cannulae after removal showed no thrombi and only small fibrin deposits in the membrane-wall junction.

Blood biochemistry values of sheep (Ovis aries ligeriensis).

1. Analysis of biochemical parameters were carried out on material pooled from 30 female sheep (Ovis aries ligeriensis). 2. The values determined were for the common metabolites and enzymes utilized for specific studies in general metabolism (urea, glucose, cholesterol, lipids, bilirubin, uric acid, creatinine, alkaline phosphatase, GOT, GPT, LDH, LAP, CGT, CK and amylase). 3. Results of these studies were compared with values from normal human adults. 4. The differences obtained in human and sheep ranges can be explained by the different physiology of the two species. 5. This study gives values for the sheep as an experimental animal in biomedical research.