An avoidance response was conditioned to three stimuli presented in serial order. Following conditioning, each group of subjects received a different treatment procedure. The group I procedure involved distributed CS trials, contingent, non-anxious CS terminations, and individualized treatment durations. Group 2 subjects received massed CS trials, non-contingent CS terminations, and non-individualized treatment durations. Group 3 subjects experienced distributed CS trials, contingent non-anxious CS terminations, and non-individualized treatment durations. Individual izing treatment duration (termination contingent upon operational ized measure of anxiety dissipation) was found to significantly hasten the extinction of avoidance responses. Implications for the effective practice of implosive therapy were discussed. Yoked control methods were criticized for confounding the variable of individualization of the yoked variable.

The level system is a behavioral procedure that alters the status of a participant contingent on his or her behaviors; within each level the amount of reinforcement is different. In most cases, level systems are paired with another form of treatment such as a token economy. In the current study, the effectiveness of a level system with a built in token economy was evaluated within three intensive residential group homes with 3 male participants. Each participant was diagnosed with mental retardation and behavioral issues. The level system was comprised of 5 different levels, each having different privileges and reinforcers. Each participant received token dollars for displaying replacement behaviors and the tokens were used to purchase items from a token store. A preference assessment was conducted to determine the items and their values. The results of the current study suggest that a level system with a built in token economy is an effective form of treatment in managing severe, inappropriate behaviors in individuals with mental retardation residing in a group home setting.

This dissertation, in general, is about finding stable solutions to statistical models with very large number of parameters and to analyze their asymptotic statistical properties. In particular, it is centered in the study of regularization methods based on penalized estimation. Those procedures find an estimator that is the result of an optimization problem balancing out the fitting to the data with the plausability of the estimation. The first chapter studies a smoothness regularization estimator for an infinite dimensional parameter in an exponential family model with functional predictors. We focused on the Reproducing Kernel Hilbert space approach and show that regardless the generality of the method, minimax optimal convergence rates are achieved. In order to derive the asymptotic analysis of the estimator, we developed a simultaneous diagonalization tool for two positive definite operators: the kernel operator and the operator defined by the second Frechet derivative of the expected data t functional. By using the proposed simultaneous diagonalization tool sharper bounds on the minimax rates are obtained. The second chapter studies the statistical properties of the method of regularization using Radial Basis Functions in the context of linear inverse problems. The regularization here serves two purposes, one is creating a stable solution for the inverse problem and the other is prevent the over-fitting on the nonparametric estimation of the functional target. Different degrees for the ill-posedness in the inversion of the operator A are considered: mildly and severely ill-posed. Also, we study different types for radial basis kernels classifieded by the strength of the penalization norm: Gaussian, Multiquadrics and Spline type of kernels. The third chapter deals with the problem of Individualized Treatment Rule (ITR) and analyzes the solution of it through Discriminant Analysis. In the ITR problem, the treatment assignment is done based on the particular patient's prognosis covariates in order to maximizes some reward function. Data generated from a random clinical trial is considered. Maximizing the empirical value function is an NP-hard computational problem. We consider estimating directly the decision rule by maximizing the expected value, using a surrogate function in order to make the optimization problem computationally feasible (convex programming). Necessary and sufficient conditions for Infinite Sample Consistency on the surrogate function are found for different scenarios: binary treatment selection, treatment selection with withholding and multi-treatment selection.

Emotional regulation may be an underaddressed therapeutic target in sex offender treatment. This article presents a case report of “Adam,” a Caucasian male referred to a prison-based sex offender treatment program. Adam’s social anxiety was recognized as an antecendent to his sexual offending, and treatment of such, as a critical adjunct to sex offender treatment, is discussed herein. Adam’s individualized treatment included aspects of rational emotive behavior therapy and time-limited dynamic psychotherapy. Adam showed an increased understanding of his anxiety and improvement in his social interactions, both in the context of treatment groups and with female staff, and was willing to continue follow-up care in the community. This case provides support for the individualized treatment of incarcerated offenders as opposed to exclusively utilizing manualized psychoeducational interventions.

En inhibant la formation de caillots dans le sang, les médicaments antiplaquettaires diminuent de façon importante le risque d’événements ischémiques aigus. Cependant, une sous-population de patients souffrant de maladie coronarienne présente une inhibition inadéquate de la fonction plaquettaire malgré la prise quotidienne d’acide acétylsalicylique (AAS). Le premier volet de cette thèse démontre qu’une régénération plaquettaire accélérée pourrait expliquer en partie la variabilité dans la persistance de l’effet antiplaquettaire de l’AAS chez certains sujets souffrant de maladie coronarienne. Ces données suggèrent qu’une augmentation de la fréquence d’administration d’AAS d’une à deux fois par jour pourrait être bénéfique chez ces sujets. Des méta-analyses ont suggéré qu’une réponse plaquettaire inadéquate à l’AAS pourrait augmenter le risque d’événements ischémiques récurrents. La nature rétrospective de ces analyses ne permet pas d’établir la causalité. Dans le deuxième volet de cette thèse, les résultats d’une étude prospective visant à comparer la pertinence clinique de 6 tests de fonction plaquettaire fréquemment utilisés pour évaluer la réponse plaquettaire à l’AAS est présentée. Les résultats démontrent qu’aucun des tests de fonction plaquettaire couramment employés ne prédit la survenue d’événements ischémiques aigus chez des patients souffrant de maladie coronarienne stable. Toutefois, la cessation de la prise d’AAS est un prédicteur important d’événements thrombotiques. La cessation de médicaments antiplaquettaires a souvent été associée à la survenue d’événements thrombotiques dans les jours suivant l’interruption. À savoir si la survenue de ces événements est attribuable uniquement au retrait d’un médicament protecteur ou plutôt à une sensibilisation plaquettaire, constitue un débat d’actualité. Dans le troisième volet de cette thèse, des données sont présentées démontrant que la cessation de clopidogrel après la période recommandée par les lignes directrices actuelles provoque une sensibilisation des plaquettes nouvellement formées aux stimuli plaquettaires physiologiques. Ces résultats encouragent la recherche sur différentes modalités pour atténuer le risque thrombotique accru chez ces patients souffrant de maladie coronarienne. En conclusion, cet ouvrage présente des études visant à identifier les sous-populations de patients qui sont plus à risque de complications cardiovasculaires récurrentes. Dans ce contexte, la personnalisation de traitement est une avenue thérapeutique prometteuse, où chaque patient pourra recevoir un traitement ciblé en fonction de ses besoins et de ses contre-indications. Ce changement de paradigme d’une thérapie empirique issue d’études de grande envergure sur des données populationnelles à une thérapie ajustée aux besoins individuels représente un vaste champ de recherche, où la majorité des découvertes sont à faire. / By inhibiting the formation of blood clots, antiplatelet drugs significantly reduce the risk of acute ischemic events. However, a subpopulation of patients suffering from coronary artery disease presents with an inadequate inhibition of platelet function despite taking acetylsalicylic acid (ASA) daily. The first part of this thesis demonstrates that accelerated platelet turnover could partly explain the variability in the persistence of the antiplatelet effect of ASA in some coronary artery disease patients. These results suggest that increasing the frequency of administration of ASA from once to twice daily may be beneficial in selected patients. Meta-analyses have suggested that an inadequate platelet response to ASA may increase the risk of recurrent ischemic events. The retrospective nature of these analyses forbids the inference of causality. In the second part of this thesis, the results of a prospective study comparing the clinical relevance of 6 platelet function tests commonly used to assess platelet response to ASA are presented. The results show that none of the commonly used platelet function tests predict the occurrence of acute ischemic events in stable coronary artery disease patients. However, discontinuation of ASA is an important predictor of thrombotic events. Discontinuation of antiplatelet drugs has often been associated with thrombotic events in the days following cessation. If the occurrence of these events is due solely to the withdrawal of a protective drug or rather platelet sensitization is a topic of some debate. In the third part of this thesis, data are presented demonstrating that clopidogrel discontinuation, after the period recommended by current guidelines, leads to sensitization of newly formed platelets to physiological platelet stimuli. These results encourage research on different ways to mitigate the increased risk of thrombosis in coronary artery disease patients scheduled to discontinue clopidogrel therapy. In conclusion, this dissertation presents studies aiming to identify subpopulations of patients who are at increased risk of recurrent cardiovascular events. In this context, the personalization of treatment is a promising therapeutic avenue, where each patient can receive a targeted therapy according to his needs and contraindications. This shift in paradigm from empirical therapy based on population data retrieved from large clinical studies to therapy tailored to individual needs opens a vast field of research, where the majority of discoveries remain to be made.

En inhibant la formation de caillots dans le sang, les médicaments antiplaquettaires diminuent de façon importante le risque d’événements ischémiques aigus. Cependant, une sous-population de patients souffrant de maladie coronarienne présente une inhibition inadéquate de la fonction plaquettaire malgré la prise quotidienne d’acide acétylsalicylique (AAS). Le premier volet de cette thèse démontre qu’une régénération plaquettaire accélérée pourrait expliquer en partie la variabilité dans la persistance de l’effet antiplaquettaire de l’AAS chez certains sujets souffrant de maladie coronarienne. Ces données suggèrent qu’une augmentation de la fréquence d’administration d’AAS d’une à deux fois par jour pourrait être bénéfique chez ces sujets. Des méta-analyses ont suggéré qu’une réponse plaquettaire inadéquate à l’AAS pourrait augmenter le risque d’événements ischémiques récurrents. La nature rétrospective de ces analyses ne permet pas d’établir la causalité. Dans le deuxième volet de cette thèse, les résultats d’une étude prospective visant à comparer la pertinence clinique de 6 tests de fonction plaquettaire fréquemment utilisés pour évaluer la réponse plaquettaire à l’AAS est présentée. Les résultats démontrent qu’aucun des tests de fonction plaquettaire couramment employés ne prédit la survenue d’événements ischémiques aigus chez des patients souffrant de maladie coronarienne stable. Toutefois, la cessation de la prise d’AAS est un prédicteur important d’événements thrombotiques. La cessation de médicaments antiplaquettaires a souvent été associée à la survenue d’événements thrombotiques dans les jours suivant l’interruption. À savoir si la survenue de ces événements est attribuable uniquement au retrait d’un médicament protecteur ou plutôt à une sensibilisation plaquettaire, constitue un débat d’actualité. Dans le troisième volet de cette thèse, des données sont présentées démontrant que la cessation de clopidogrel après la période recommandée par les lignes directrices actuelles provoque une sensibilisation des plaquettes nouvellement formées aux stimuli plaquettaires physiologiques. Ces résultats encouragent la recherche sur différentes modalités pour atténuer le risque thrombotique accru chez ces patients souffrant de maladie coronarienne. En conclusion, cet ouvrage présente des études visant à identifier les sous-populations de patients qui sont plus à risque de complications cardiovasculaires récurrentes. Dans ce contexte, la personnalisation de traitement est une avenue thérapeutique prometteuse, où chaque patient pourra recevoir un traitement ciblé en fonction de ses besoins et de ses contre-indications. Ce changement de paradigme d’une thérapie empirique issue d’études de grande envergure sur des données populationnelles à une thérapie ajustée aux besoins individuels représente un vaste champ de recherche, où la majorité des découvertes sont à faire. / By inhibiting the formation of blood clots, antiplatelet drugs significantly reduce the risk of acute ischemic events. However, a subpopulation of patients suffering from coronary artery disease presents with an inadequate inhibition of platelet function despite taking acetylsalicylic acid (ASA) daily. The first part of this thesis demonstrates that accelerated platelet turnover could partly explain the variability in the persistence of the antiplatelet effect of ASA in some coronary artery disease patients. These results suggest that increasing the frequency of administration of ASA from once to twice daily may be beneficial in selected patients. Meta-analyses have suggested that an inadequate platelet response to ASA may increase the risk of recurrent ischemic events. The retrospective nature of these analyses forbids the inference of causality. In the second part of this thesis, the results of a prospective study comparing the clinical relevance of 6 platelet function tests commonly used to assess platelet response to ASA are presented. The results show that none of the commonly used platelet function tests predict the occurrence of acute ischemic events in stable coronary artery disease patients. However, discontinuation of ASA is an important predictor of thrombotic events. Discontinuation of antiplatelet drugs has often been associated with thrombotic events in the days following cessation. If the occurrence of these events is due solely to the withdrawal of a protective drug or rather platelet sensitization is a topic of some debate. In the third part of this thesis, data are presented demonstrating that clopidogrel discontinuation, after the period recommended by current guidelines, leads to sensitization of newly formed platelets to physiological platelet stimuli. These results encourage research on different ways to mitigate the increased risk of thrombosis in coronary artery disease patients scheduled to discontinue clopidogrel therapy. In conclusion, this dissertation presents studies aiming to identify subpopulations of patients who are at increased risk of recurrent cardiovascular events. In this context, the personalization of treatment is a promising therapeutic avenue, where each patient can receive a targeted therapy according to his needs and contraindications. This shift in paradigm from empirical therapy based on population data retrieved from large clinical studies to therapy tailored to individual needs opens a vast field of research, where the majority of discoveries remain to be made.