BACKGROUND: The prevalence of neonatal abstinence syndrome (NAS) is on the rise in the United States, as the epidemic of opioid misuse continues1. Several infants with in utero exposure to opioids are born with NAS, and exhibit symptoms of withdrawal and dependence upon birth when the maternal source of opioid is discontinued2. Due to the novelty of the syndrome, there are several knowledge gaps in current literature that remain to be explored. LITERATURE REVIEW: The exact mechanism of development of NAS in infants remains unknown, yet the clinical symptomatology and results of a few recent studies suggest that there is an association with NAS severity and dysregulation of autonomic nervous system (ANS) functioning in these infants3. In recent years, pharmacological treatments for these infants have become standardized4. However, non-pharmacological treatments have been adopted from treatment guidelines of other high-risk infant populations and their efficacy warrants further evaluation in infants with NAS. Kangaroo care (KC) is a supportive therapy commonly applied to many high-risk infant populations because of its physiologically stabilizing effects5. The therapy has been demonstrated to be especially beneficial in the treatment of preterm infants, a population that similarly requires additional maturation of their ANS upon birth,6. Neurobehavioral theories suggest ANS functioning in infancy is a strong predictor of long-term social, behavioral, and cognitive development outcomes7,8. PROPOSED PROJECT: This prospective cohort study is designed to provide pilot data to establish if KC can be utilized to mature ANS maturation in infants with NAS. CONCLUSIONS AND SIGNIFICANCE: KC is an inexpensive, readily available, low risk intervention that could improve neurobehavioral outcomes in infants with NAS. The results of this study could reduce clinical symptoms, potentiate long-term behavior outcomes, and better define treatment practices for infants with NAS by facilitating a targeted intervention to improve outcomes.

Large scale enterprise applications are known to observe dynamic workload; provisioning correct capacity for these applications remains an important and challenging problem. Predicting high variability fluctuations in workload or the peak workload is difficult; erroneous predictions often lead to under-utilized systems or in some situations cause temporarily outage of an otherwise well provisioned web-site. Consequently, rather than provisioning server capacity to handle infrequent peak workloads, an alternate approach of dynamically provisioning capacity on-the-fly in response to workload fluctuations has become popular. Cloud platforms are particularly suited for such applications due to their ability to provision capacity when needed and charge for usage on pay-per-use basis. Cloud environments enable elastic provisioning by providing a variety of hardware configurations as well as mechanisms to add or remove server capacity. The first part of this thesis presents Kingfisher, a cost-aware system that provides a generalized provisioning framework for supporting elasticity in the cloud by (i) leveraging multiple mechanisms to reduce the time to transition to new configurations, and (ii) optimizing the selection of a virtual server configuration that minimize cost. Majority of these enterprise applications, deployed as web applications, are distributed or replicated with a multi-tier architecture. SLAs for such applications are often expressed as a high percentile of a performance metric, for e.g. 99 percentile of end to end response time is less than 1 sec. In the second part of this thesis I present a model driven technique which provisions a multi-tier application for such an SLA and is targeted for cloud platforms. Enterprises critically depend on these applications and often own large IT infrastructure to support the regular operation of these applications. However, provisioning for a peak load or for high percentile of response time could be prohibitively expensive. Thus there is a need of hybrid cloud model, where the enterprise uses its own private resources for the majority of its computing, but then "bursts" into the cloud when local resources are insufficient. I discuss a new system, namely Seagull, which performs dynamic provisioning over a hybrid cloud model by enabling cloud bursting. Finally, I describe a methodology to model the configuration patterns (i.e deployment topologies) of different control plane services of a cloud management system itself. I present a generic methodology, based on empirical profiling, which provides initial deployment configuration of a control plane service and also a mechanism which iteratively adjusts the configuration to avoid violation of control plane's Service Level Objective (SLO).

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Utvecklingen av datorer och deras förmåga ökar klyftan mellan datorer och skapar en stormångfald av hårdvarutillgänglighet. Kapaciteten som datorer besitter varierar kraftigt ochdärmed även förmågan att hantera komplexa applikationer. Moderna applikationer erbju-der inställningar som användare kan anpassa för datorn, något som kräver att användarenhar tillräcklig kunskap för att förstå inställningarnas e ekt. Att välja ut de optimala in-ställningarna för datorn är en process som är både svår och tidskrävande. Detta arbetegranskar hur ett dynamiskt adaptivt system automatiskt kan anpassa inställningarna förapplikationen medan den kör, utan manuell extern inverkan. Systemet mäter kontinuerligtapplikationen och individuella teknikers prestanda. Baserat på mätresultat anpassar detadaptiva systemet applikationens inställningar. Genom att abstrahera funktionaliteten attjustera applikationen kan datorns kapacitet utnyttjas, utan varken användarens kunskapeller påverkan. Arbetet undersöker hur olika tekniker kan in uera applikationens prestandaoch genomför tester av ett dynamiskt anpassande systems förmåga att skräddarsy appli-kationen för exekveringsmiljön. / The development of computers and their ability increases the gap between computers andcreate a wide variety of hardware availability. The capacity that computers possess varyconsiderably and thus the ability to handle complex applications. Modern applicationsprovides settings that users can customize for the computer, which requires the user tohave su cient knowledge to understand the attitude of the e ect. To select the optimalsettings for your PC is a process that is both di cult and time consuming. This thesisexamines how a dynamically adaptive system can automatically adjust the settings for theapplication while it is running, without manual external impact. The system continuouslymonitors the application and individual technologies performance. Based on measurementsthe adaptive system can customize applications settings. By abstracting the functionalityto adjust the application the computer's capacity is utlizied, without neither the user'sknowledge or in uence. The thesis examines how various technologies can in uence ap-plication performance and conducts tests of a dynamically adaptive system's ability tocustomize the application for execution environment.

The purpose of this investigation was to examine the potential differences in autonomic nervous system adaptations, as assessed by heart rate variability techniques, between a group of stabilized CHF patients randomized to either a training group (aerobic+resistance) or a control group (usual care). In a single-blind, randomized controlled trial of 3-months of supervised exercise training and a further 3-months of home-based exercise, 28 stabilized CHF patients (NYHA 1-111) were randomized to either a training (AERWT) (n=16;11M,5F; age, 64.9±2.3; LVEF, 29.4±1.7%) or usual care (UC) (n=12; 10M,2F; age, 58.0±2.8; LVEF, 24.4±2.0%) group. Upon completion of the supervised exercise program, the AERWT group increased peak oxygen uptake (V02) (13.2±0.5 to 15.5±0.84 ml/kg/min, p<0.05), and single-arm curl scores (16.2±2.8 to 19.2±3.3 kg, p<0.05) significantly compared to the UC group, without any deleterious effect upon clinical status or left-ventricular function (LVEF: 31.3±1.7 to 33.2±1.9%, p=0.99). Physical training reduced expired ventilation and carbon dioxide based on successive workloads during symptom-limited incremental cycle ergometry in the AERWT group; however, this was found to be non-significant, in addition to changes in resting heart rate, anaerobic threshold, maximal exercise duration, maximal power output, and double product following training. Supine, resting power spectral indices remained unchanged from baseline to 6-months in both groups, as did the recovery of power spectral indices during supine rest following a symptom-limited incremental cycle ergometry test. A qualitative comparison of the power spectral changes from supine to standing revealed no significant differences between groups with respect to improvements in the baroreceptor response to orthostatic stress. Time domain parameters, derived from 24-hour ambulatory bolter monitoring, were also obtained at baseline, 3-months, and 6-months. The indices believed to be largely representative of vagal modulation, SDNN-Index, r-MSSD, and pNN50, tended to increase in the AERWT group with increased participation in the training program; however, the results did not obtain statistical significance (p=0.07). In addition, there were no significant changes in mean 24-hour heart rate or NN-interval, SDNN, or SDANN in the AERWT group (p=0.21). The present investigation revealed some evidence to suggest that exercise training in selected populations of CHF patients results in favourable changes in vagal modulation and baroreceptor sensitivity; however, unlike Coats et al. (1992), the present investigation failed to note any significant alterations in HRV frequency domain indices as a result of exercise training despite identical improvements in peak V02. The lack of significant findings in both the frequency and time domain HRV data could indicate that the autonomic dysfunction is so widespread and rampant in CHF that we cannot induce alterations through training as would be demonstrated in normal, healthy controls. In effect, these findings reinforce the hypothesis that in CHF the heart is the 'slave' of the periphery, and that due to the progressive lack of neural control of both the heart and circulation, in addition to an impairment in pump function, that the only effective means of improving physiological variables is through changes at the peripheral level. / Thesis / Master of Science (MS)

Obesity is associated with sympathetic neural activation and elevated blood pressure(1,2). However, it is unclear whether modest elevations in body weight are sufficient to induce increases sympathetic activity (3). Furthermore, there is a large amount of individual variability in the blood pressure response to weight change (4). The reason(s) for this inter-individual variability are still uncertain, but body fat distribution and cardiorespiratory fitness may play a role (5,6). To address these and other issues regarding the relation between adiposity, sympathetic neural activity and blood pressure, we first examined the effects of modest, diet-induced weight gain on muscle sympathetic nervous system activity (MSNA) in healthy, lean, normotensive individuals. We hypothesized that modest weight gain would increase MSNA in these individuals, and that this neural activation would be accompanied by increases in blood pressure. Concordant with this hypothesis, MSNA and resting blood pressure were significantly elevated following weight gain. The increase in MSNA was correlated with the magnitude of body weight and fat gain, but was not obviously related to increases in visceral fat. We next examined the ability of cardiorespiratory fitness (CRF) to modulate the weight gain-induced increase in blood pressure in the same cohort of young, nonobese and normotensive individuals. We hypothesized that the increase in blood pressure would be attenuated in individuals with higher- compared with lower CRF (HCRF and LCRF, respectively). Indeed, we found that HCRF experienced significantly smaller increases in resting and ambulatory blood pressure compared to LCRF. In the pooled sample, baseline fitness was inversely related to the changes in resting systolic and diastolic pressure, and this relation was not diminished after statistically controlling for changes in abdominal visceral fat. The results of the present investigation suggest that even modest weight gain increases sympathetic activity and blood pressure, which, if left untreated, may contribute to the development of hypertension and other cardiovascular disorders. Maintenance of higher levels of CRF during periods of weight gain may reduce cardiovascular disease risk by mitigating the increases in blood pressure. Collectively, these findings may have important implications for understanding the link between obesity and hypertension. References 1. Davy KP. The global epidemic of obesity: are we becoming more sympathetic? Curr Hypertens Rep. 2004;6:241-6. 2. Grassi G, Seravalle G, Cattaneo BM, et al. Sympathetic activation in obese normotensive subjects. Hypertension. 1995;25:560-3. 3. Huggett RJ, Scott EM, Gilbey SG, Bannister J, Mackintosh AF, Mary DA. Disparity of autonomic control in type 2 diabetes mellitus. Diabetologia. 2005;48:172-9. 4. Masuo K, Mikami H, Ogihara T, Tuck ML. Weight gain-induced blood pressure elevation. Hypertension. 2000;35:1135-40. 5. Hayashi T, Boyko EJ, Leonetti DL, et al. Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans. Ann Intern Med. 2004;140:992-1000. 6. Barlow CE, LaMonte MJ, Fitzgerald SJ, Kampert JB, Perrin JL, Blair SN. Cardiorespiratory fitness is an independent predictor of hypertension incidence among initially normotensive healthy women. Am J Epidemiol. 2006;163:142-50. / Ph. D.