The use of subclinical vascular markers of atherosclerosis in youth

The foundations for cardiovascular disease (CVD) in adults are laid in childhood and accelerated by the presence of comorbid conditions. Early detection of manifestations of cardiovascular pathology is an important clinical objective to identify those at risk for subsequent cardiovascular morbidity and events, and to initiate behavioral and medical interventions to reduce risk. Children were once considered to be at low risk, but with the growing health concerns related to lifestyle, cardiovascular screening may be needed earlier. Several noninvasive procedures are available to assess the cumulative effect of these exposures. These include carotid ultrasound, flow-mediated dilation, pulse wave velocity and measures left ventricular mass. This dissertation analyzes the comorbid conditions that increase cardiovascular risk in youth, namely obesity and low physical fitness, using carotid intima-media thickness to objectively detect early manifestations of cardiovascular pathology. Until recently researchers have not used surrogate markers of subclinical atherosclerosis to examine the role of a single bout of exercise. Utilizing the acute exercise model can be advantageous as it allows for an efficient manipulation of exercise variables and permits greater experimental control of confounding variables. It is possible that the effects of a bout of exercise can predict the effects of chronic exercise. We analyze the physiological factors pertinent to arterial stiffness using arterial distensibility and pulse wave velocity in the context of acute exercise in children and adults. In some instances, those who amend their trajectory by not maintaining risk factors into adulthood experience reductions in subclinical markers to levels associated with never having had the risk factor. Though avoidance of risk factors in youth is ideal, there is still a window for intervention where long-lasting cardiovascular effects might be avoided. In this dissertation we present preliminary findings linking modifiable youth risk factors to subclinical markers of CVD in adulthood.As bases da doença cardiovascular (DCV) em adultos são estabelecidas na infância e aceleradas pela presença de comorbidades. A deteção precoce de manifestações da patologia cardiovascular é um objetivo clínico importante na identificação daqueles com risco de subsequente morbidade e eventos cardiovasculares, e no estabelecimento de intervenções comportamentais e médicas para reduzir o risco. As crianças já foram considerados de baixo risco, mas com as crescentes preocupações de saúde associadas ao estilo de vida, o rastreio cardiovascular é cada vez mais precoce. Vários procedimentos não invasivos estão disponíveis para avaliar o efeito cumulativo dessas exposições. Estes incluem ultrassom da artéria carótida, a dilatação fluxo-mediada, velocidade de onda de pulso e medidas da massa ventricular esquerda. Esta dissertação analisa comorbidades conhecidas que aumentam o risco cardiovascular em crianças e adolescentes, como a obesidade, pressão arterial elevada e baixa aptidão física, usando a espessura da parede intima-media da carótida para detetar objetivamente as manifestações precoces de patologia cardiovascular. Até recentemente, estes marcadores subclínicos de aterosclerose foram pouco utilizados para examinar os efeitos de uma única sessão de exercício físico. No entanto, a utilização do modelo de exercício agudo pode ser vantajoso, pois permite uma manipulação eficiente das variáveis do exercício e permite maior controle experimental de variáveis de enviezamento. É possível que os efeitos de uma sessão de exercício possam prever os efeitos do exercício crónico. Nesta dissertação analisamos os fatores fisiológicos associados à rigidez arterial usando a distensibilidade arterial e velocidade da onda de pulso no contexto de exercício agudo em crianças e adultos. Em alguns casos, aqueles que melhoram o seu perfil de risco de risco para as DCV até à idade adulta experienciam reduções em marcadores subclínicos de aterosclerose para níveis saudáveis. Embora a prevenção de fatores de risco na juventude seja o ideal, existe ainda uma janela para a intervenção em que os efeitos cardiovasculares de longa duração pode ser evitada. Nesta dissertação apresentamos resultados preliminares que ligam fatores de risco modificáveis na juventude com marcadores subclínicos de DCV na idade adulta

Integrated Geomechanical Characterization of Anisotropic Gas Shales: Field Appraisal, Laboratory Testing, Viscoelastic Modelling,and Hydraulic Fracture Simulation

This research provides a multiscale geomechanical characterization workflow for ultra-tight and anisotropic Goldwyer gas shales by integrating field appraisal, laboratory deformation and ultrasonic testing, viscoelastic modelling, and hydraulic fracture simulation. The outcome of this work addresses few of the practical challenges in unconventional reservoirs including but not limited to (i) microstructure & compositional control on rock mechanical properties, (ii) robust estimation of elastic anisotropy, (iii) viscous stress relaxation to predict the least principal stress Shmin at depth from creep, (iv) influence of specific surface area on creep, and (v) impact of stress layering on hydraulic fracturing design

Novel therapies for hypertension and associated cardiovascular risk

University of Minnesota Ph.D. dissertation. August 2018. Major: Biomedical Engineering. Advisor: Alena Talkachova. 1 computer file (PDF); xvii, 134 pages.This thesis is comprised of two parts. The first part investigates a novel therapy, vagus nerve stimulation, for hypertension and hypertension-induced heart disease. Hypertension impacts over 1 billion people worldwide, and clinical management is challenging. Left uncontrolled, high blood pressure can significantly increase the risk of cardiovascular events. The majority of hypertensive patients are treated with anti-hypertensive drugs to control blood pressure, but many limitations exist including resistant hypertension, inability to tolerate therapy, and non-compliance with the medication regime. For these patients, an alternative approach is needed to control blood pressure. Recently, the imbalance in the autonomic nervous system, evident in hypertension, has been the target of novel device-based therapies such as vagus nerve stimulation. The main goal of this research is to evaluate the efficacy of vagus nerve stimulation to treat hypertension and hypertension-induced heart disease. This thesis investigates the impact of vagus nerve stimulation on disease progression, survival, and cardiovascular remodeling in Dahl salt-sensitive hypertensive rats. Overall, the results of this work provide evidence for the beneficial therapeutic effects of vagus nerve stimulation in hypertension and motivate future studies to optimize therapy parameters and further understand therapeutic mechanisms. The second part of this thesis focuses on atrial fibrillation and the evaluation of new mapping techniques for improving rotor localization for ablation procedures. Currently, success rates for ablation procedures for non-paroxysmal atrial fibrillation are low and require repeat procedures or a lifetime of pharmacological agents to reduce the risk of stroke. Improved signal processing techniques for mapping electrical activity in the atrium can help further our understanding of the generation and maintenance of atrial fibrillation and ultimately improve ablation procedure success rates and terminate the arrhythmia. The main goal of this work was to validate new signal processing techniques – multiscale frequency, kurtosis, Shannon entropy, and multiscale entropy – to identify regions of abnormal electrical activity. The results of this work demonstrate improved accuracy of these novel techniques in mapping rotors in cardiac arrhythmias and motivates further studies evaluating more complex arrhythmias and human intracardiac electrograms