Investigating the Implications of a Variable RBE on Proton Dose Fractionation Across a Clinical Pencil Beam Scanned Spread-Out Bragg Peak

Purpose: To investigate the clinical implications of a variable relative biological effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in linear energy transfer (LET) in the distal regions of the spread-out Bragg peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios are still limited.

Methods and Materials: Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfraction period of 24 hours at Proton Therapy Center in Prague, Czech Republic. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a linear quadratic formalism.

Results: Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a linear quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens.

Conclusions: The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used by the modeling community for the optimization of fractionated proton therapy.

Modélisation radiobiologique pour la planification des traitements en radiothérapie à partir de données d’imagerie spécifiques aux patients

Un modèle de croissance et de réponse à la radiothérapie pour le glioblastome multiforme (GBM) basé le formalisme du modèle de prolifération-invasion (PI) et du modèle linéaire-quadratique a été développé et implémenté. La géométrie spécifique au patient est considérée en modélisant, d'une part, les voies d'invasion possibles des GBM avec l'imagerie du tenseur de diffusion (DTI) et, d'autre part, les barrières à la propagation à partir des images anatomiques disponibles. La distribution de dose réelle reçue par un patient donné est appliquée telle quelle dans les simulations, en respectant l'horaire de traitement. Les paramètres libres du modèle (taux de prolifération, coefficient de diffusion, paramètres radiobiologiques) sont choisis aléatoirement à partir de distributions de valeurs plausibles. Un total de 400 ensembles de valeurs pour les paramètres libres sont ainsi choisis pour tous les patients, et une simulation de la croissance et de la réponse au traitement est effectuée pour chaque patient et chaque ensemble de paramètres. Un critère de récidive est appliqué sur les résultats de chaque simulation pour identifier un lieu probable de récidive (SPR). La superposition de tous les SPR obtenus pour un patient donné permet de définir la probabilité d'occurrence (OP). Il est démontré qu'il existe des valeurs de OP élevées pour tous les patients, impliquant que les résultats du modèle PI ne sont pas très sensibles aux valeurs des paramètres utilisés. Il est également démontré comment le formalisme développé dans cet ouvrage pourrait permettre de définir un volume cible personnalisé pour les traitements de radiothérapie du GBM.

Wavelets and the generalization of the variogram

The experimental variogram computed in the usual way by the method of moments and the Haar wavelet transform are similar in that they filter data and yield informative summaries that may be interpreted. The variogram filters out constant values; wavelets can filter variation at several spatial scales and thereby provide a richer repertoire for analysis and demand no assumptions other than that of finite variance. This paper compares the two functions, identifying that part of the Haar wavelet transform that gives it its advantages. It goes on to show that the generalized variogram of order k=1, 2, and 3 filters linear, quadratic, and cubic polynomials from the data, respectively, which correspond with more complex wavelets in Daubechies's family. The additional filter coefficients of the latter can reveal features of the data that are not evident in its usual form. Three examples in which data recorded at regular intervals on transects are analyzed illustrate the extended form of the variogram. The apparent periodicity of gilgais in Australia seems to be accentuated as filter coefficients are added, but otherwise the analysis provides no new insight. Analysis of hyerpsectral data with a strong linear trend showed that the wavelet-based variograms filtered it out. Adding filter coefficients in the analysis of the topsoil across the Jurassic scarplands of England changed the upper bound of the variogram; it then resembled the within-class variogram computed by the method of moments. To elucidate these results, we simulated several series of data to represent a random process with values fluctuating about a mean, data with long-range linear trend, data with local trend, and data with stepped transitions. The results suggest that the wavelet variogram can filter out the effects of long-range trend, but not local trend, and of transitions from one class to another, as across boundaries.

Regularization of time-varying descriptor systems by the asvd

We study linear variable coefficient control problems in descriptor form. Based on a behaviour approach and the general theory for linear differential algebraic systems we give the theoretical analysis and describe numerically stable methods to determine the structural properties of the system.

Random regression analyses using B-splines functions to model growth from birth to adult age in Canchim cattle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Análise e desenvolvimento de controladores preditivos multivariáveis baseados em multi-modelos bilineares

This work addresses issues related to analysis and development of multivariable predictive controllers based on bilinear multi-models. Linear Generalized Predictive Control (GPC) monovariable and multivariable is shown, and highlighted its properties, key features and applications in industry. Bilinear GPC, the basis for the development of this thesis, is presented by the time-step quasilinearization approach. Some results are presented using this controller in order to show its best performance when compared to linear GPC, since the bilinear models represent better the dynamics of certain processes. Time-step quasilinearization, due to the fact that it is an approximation, causes a prediction error, which limits the performance of this controller when prediction horizon increases. Due to its prediction error, Bilinear GPC with iterative compensation is shown in order to minimize this error, seeking a better performance than the classic Bilinear GPC. Results of iterative compensation algorithm are shown. The use of multi-model is discussed in this thesis, in order to correct the deficiency of controllers based on single model, when they are applied in cases with large operation ranges. Methods of measuring the distance between models, also called metrics, are the main contribution of this thesis. Several application results in simulated distillation columns, which are close enough to actual behaviour of them, are made, and the results have shown satisfactory

Estrutura ANFIS modificada para identificação e controle de plantas com ampla faixa de operação e não linearidade acentuada

In this work a modification on ANFIS (Adaptive Network Based Fuzzy Inference System) structure is proposed to find a systematic method for nonlinear plants, with large operational range, identification and control, using linear local systems: models and controllers. This method is based on multiple model approach. This way, linear local models are obtained and then those models are combined by the proposed neurofuzzy structure. A metric that allows a satisfactory combination of those models is obtained after the structure training. It results on plant s global identification. A controller is projected for each local model. The global control is obtained by mixing local controllers signals. This is done by the modified ANFIS. The modification on ANFIS architecture allows the two neurofuzzy structures knowledge sharing. So the same metric obtained to combine models can be used to combine controllers. Two cases study are used to validate the new ANFIS structure. The knowledge sharing is evaluated in the second case study. It shows that just one modified ANFIS structure is necessary to combine linear models to identify, a nonlinear plant, and combine linear controllers to control this plant. The proposed method allows the usage of any identification and control techniques for local models and local controllers obtaining. It also reduces the complexity of ANFIS usage for identification and control. This work has prioritized simpler techniques for the identification and control systems to simplify the use of the method

Random regression analyses using B-spline functions to model growth of Nellore cattle

The objective of this study was to estimate (co)variance components using random regression on B-spline functions to weight records obtained from birth to adulthood. A total of 82 064 weight records of 8145 females obtained from the data bank of the Nellore Breeding Program (PMGRN/Nellore Brazil) which started in 1987, were used. The models included direct additive and maternal genetic effects and animal and maternal permanent environmental effects as random. Contemporary group and dam age at calving (linear and quadratic effect) were included as fixed effects, and orthogonal Legendre polynomials of age (cubic regression) were considered as random covariate. The random effects were modeled using B-spline functions considering linear, quadratic and cubic polynomials for each individual segment. Residual variances were grouped in five age classes. Direct additive genetic and animal permanent environmental effects were modeled using up to seven knots (six segments). A single segment with two knots at the end points of the curve was used for the estimation of maternal genetic and maternal permanent environmental effects. A total of 15 models were studied, with the number of parameters ranging from 17 to 81. The models that used B-splines were compared with multi-trait analyses with nine weight traits and to a random regression model that used orthogonal Legendre polynomials. A model fitting quadratic B-splines, with four knots or three segments for direct additive genetic effect and animal permanent environmental effect and two knots for maternal additive genetic effect and maternal permanent environmental effect, was the most appropriate and parsimonious model to describe the covariance structure of the data. Selection for higher weight, such as at young ages, should be performed taking into account an increase in mature cow weight. Particularly, this is important in most of Nellore beef cattle production systems, where the cow herd is maintained on range conditions. There is limited modification of the growth curve of Nellore cattle with respect to the aim of selecting them for rapid growth at young ages while maintaining constant adult weight.

Genetic parameter estimates for live weight and daily live weight gain obtained for Nellore bulls in a test station using different models

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

VCO Banda Larga Integrado para Receptor a Cinco Portas

This work presents an wideband ring VCO for cognitive radio five-port based receivers. A three-stage differential topology using transmission gate was adopted in order to maintain wide and linear tuning range and a low phase-noise. Monte-Carlo analysis were performed for phase-shift response of individual stages, which is an important figure of merit in five-port works. It was observed a fairly linear correlation between control voltage and oscillation frequency in the range between 200 MHz and 1800 MHz. The VCO was preliminarily designed for IBM 130nm CMOS technology

Regulador automático de tensão robusto utilizando técnicas de controle adaptativo

The stability of synchronous generators connected to power grid has been the object of study and research for years. The interest in this matter is justified by the fact that much of the electricity produced worldwide is obtained with the use of synchronous generators. In this respect, studies have been proposed using conventional and unconventional control techniques such as fuzzy logic, neural networks, and adaptive controllers to increase the stabilitymargin of the systemduring sudden failures and transient disturbances. Thismaster thesis presents a robust unconventional control strategy for maintaining the stability of power systems and regulation of output voltage of synchronous generators connected to the grid. The proposed control strategy comprises the integration of a sliding surface with a linear controller. This control structure is designed to prevent the power system losing synchronism after a sudden failure and regulation of the terminal voltage of the generator after the fault. The feasibility of the proposed control strategy was experimentally tested in a salient pole synchronous generator of 5 kVA in a laboratory structure

Controle por modos deslizantes com compensação difusa aplicado a sistemas com descontinuidade

The development of non-linear controllers gained space in the theoretical ambit and of practical applications on the moment that the arising of digital computers enabled the implementation of these methodologies. In comparison with the linear controllers more utilized, the non -linear controllers present the advantage of not requiring the linearity of the system to determine the parameters of control, which permits a more efficient control especially when the system presents a high level of non-linearity. Another additional advantage is the reduction of costs, since to obtain the efficient control through linear controllers it is necessary the utilization of sensors and more refined actuators than when it is utilized a non-linear controller. Among the non-linear theories of control, the method of control by gliding ways is detached for being a method that presents more robustness, before uncertainties. It is already confirmed that the adoption of compensation on the region of residual error permits to improve better the performance of these controllers. So, in this work it is described the development of a non-linear controller that looks for an association of strategy of control by gliding ways, with the fuzzy compensation technique. Through the implementation of some strategies of fuzzy compensation, it was searched the one which provided the biggest efficiency before a system with high level of nonlinearities and uncertainties. The electrohydraulic actuator was utilized as an example of research, and the results appoint to two configurations of compensation that permit a bigger reduction of the residual error

Discrete approximations for strict convex continuous time problems and duality

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Anaerobic threshold estimation by statistical modelling.

Anaerobic threshold (AT) is usually estimated as a change point problem by visual analysis of the cardiorespiratory response to incremental dynamic exercise. In this study, two phase linear (TPL) models of the linear-linear and linear-quadratic type were used for the estimation of AT. The correlation coefficient between the classical and statistical approaches was 0.88, and 0.89 after outlier exclusion. The TPL models provide a simple method for estimating AT that can be easily implemented using a digital computer for the automatic pattern recognition of AT.