Changwu Wu's doctoral dissertation with the date of the award decision on the title page. Changwu Wu defended his dissertation on March 21, 2023 and was awarded the Dr.rer.med by the University of Leipzig School of Medicine on March 28, 2023. The dissertation is entitled 'RNA-sequencing-based risk stratification and individualized immunotherapy strategies for soft tissue sarcoma'.

This thesis focuses on obtaining better estimates of remaining life for on-condition (OC) parts in aircraft engines. Aircraft engine components are commonly classified into three categories, life-limited parts (LLP), OC-parts and consumables. Engine maintenance typi-cally accounts for 10% to 20% of aircraft-related operating cost. Current methods to esti-mate remaining life for OC parts have been found insufficient and this thesis aims to devel-op a method that obtains better life estimates of OC part. Improved life estimates are es-sential to facilitate more reliable maintenance plans and lower maintenance costs. In the thesis, OC parts that need a better life estimates are identified and suitable prognosis methodologies for estimating the remaining life are presented. Three papers are appended to the thesis. The first paper lays out the main principles of air-craft engine maintenance and identifies the potential for improving maintenance planning by improving the remaining life estimation for the OC parts. The paper concludes that re-search is needed to find better estimates so that the right amount of maintenance is per-formed at each maintenance occasion. The second paper describes the aircraft and its engine from a system of system perspective. The aim of the paper is to show that no system is stronger than its weakest part and that there is a potential to increase the availability and readiness of the complete system, the aircraft engine, by introducing better life estimates for OC parts. Furthermore, a review of all engine parts, no matter if they are life-limited or on-condition, which needs to be incor-porated in a replacement model for maintenance optimization, is given. The paper con-cludes that the reliability of the complete aircraft engine would be increased if better life estimates are presented also for the OC parts. The third paper includes an evolved analysis of the subject and the analysis moves deeper in to a subsystem/module of the engine, the low pressure turbine. The specific subsys-tem/module is further analyzed to show the potential of increased reliability for the subsys-tem/module and the complete system, the aircraft engine, if better life estimates for the OC parts are obtained. Methods on how to estimate remaining life is discussed in this paper. It is stated that life estimates can be based on visual inspections, available testing methods (e.g. non destructive testing ) or new techniques that may be need to be developed based on remaining useful life estimations. To estimate the remaining life for the OC parts well es-tablished prognostic techniques such as physic-based, data-driven, symbolic, hybrid, or context awareness approaches that combine contextual/situation information awareness will be considered.

Background: Type 2 diabetes mellitus is one of the leading chronic diseases affecting Americans. There is a lack of literature discussing the link between diet and prognosis of those already diagnosed with DM. Objective: To provide insight into which diet is better for the outlook of diabetes mellitus by examining the associations between the low-carbohydrate diet (LCD) score and three diabetes-related health indicators: blood hemoglobin (HbA1c), triglycerides, and retinopathy. Methods: A total of 3,313 U.S. adults with DM were selected from the National Health and Nutrition Examination Survey 2005-2016. Presence of retinopathy was ascertained through self-reporting. Dietary intake was measured with 24- hour dietary recalls, and LCD scores were calculated from the proportion of energy of three macronutrients. Scores ranged from 0-30, with a higher score indicating lower carbohydrate intake. Results: There was no significant difference in HbA1c levels between the highest and the lowest quintile of LCD score (mean = 7.42% [95% CI: 7.23, 7.61] vs. 7.32% [95% CI: 7.13, 7.51]). There was no significant association between blood triglyceride levels and LCD score, comparing quintile 1 to quintile 5 (mean= 168.64 mg/dl; 95% CI = [150.14, 187.14] vs. mean= 162.44 mg/dl; 95% CI = [143.76, 181.11]). In multivariable logistic regression analysis, the odds ratio of having retinopathy comparing the highest to the lowest quintile was 1.01 (95% CI: 0.59, 1.72). Conclusion: Proportion of carbohydrate in diet was not associated with DM prognosis factors. Future studies should focus on carbohydrate quality as well as quantity.

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<p><strong>Background:</strong> Heart failure (HF) constitutes an important growing medical and economic problem with high prevalence and mortality. Prognosis assessment remains a challenge because of the dynamic nature of HF and the existence of some unexplained variation in outcomes. Our objective was to refine the process of prognostic assessment in current HF patients.</p> <p><strong>Methods:</strong> We conducted a systematic review to identify existing risk prediction models in ambulatory HF patients, a meta-analysis to identify mortality predictors in HF patients treated with an implantable cardioverter defibrillator (ICD), a retrospective cohort study to validate a new model, the HF Meta-Score, derived from the results of the meta-analysis and a cross-sectional and prospective cohort study to evaluate whether circulating progenitor cells (CPCs) are associated with functional capacity and mortality in ambulatory HF patients.</p> <p><strong>Results:</strong> We identified 20 risk prediction models in ambulatory HF patients; only five were externally validated showing limited discrimination and calibration. The two most validated models were derived from HF cohorts from the 1990s and reported limited performance in ICD patients. In a meta-analysis, we identified that age, baseline renal function, history of heart failure, chronic obstructive pulmonary disease, diabetes, peripheral vascular disease, left ventricular ejection fraction, NYHA class, atrial fibrillation, wide QRS and the occurrence of appropriate or inappropriate ICD shocks were independent mortality predictors. Some of these predictors were omitted in previously identified models. From the results of the meta-analysis, we developed the HF Meta-Score that showed better performance that an existing model. We observed that CPCs were independently associated with functional capacity and outcomes in ambulatory HF patients.</p> <p><strong>Conclusions:</strong> These results open many pathways to further refine the prognostic assessment in ambulatory HF patients. The HF Meta-Score is a promising score. The clinical utility of the HF Meta-Score and of the incorporation of new predictive factors, such as CPCs, needs to be tested.</p> / Doctor of Philosophy (PhD)

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The understanding of how structural components endure loads, in particular variable loads, is that these components gradually, over some period of time depending on the nature of the loading and the material, develop a microcrack. After some additional time and loading, the microcrack grows to a size that might be detected. Beyond that point, the microcrack propagates in a manner that can be reliably predicted by computer analysis codes. Consequently, one can define different stages for the life of a structural component. These are: 1) the period prior to the formation of a microcrack, 2) the period of microcrack growth, and finally 3) the period of crack growth. To date, structural health monitoring approaches that seek to detect cracks offer no insight into the extent of deterioration occurring in the initial stage that is a precursor to the formation of the microcrack or its growth. However, an approach that would facilitate monitoring the extent of the deterioration that takes place during this stage promises to improve life prediction capabilities of structural components. The challenge, thus, is to develop quantitative assessment of damage accumulation from the earliest stages of the fatigue process and to provide a structure's signature that is dependent of the damage stage. One such signature is the structure's response to forced excitation. The realization of such a goal would help in advancing structural health monitoring procedures using interrogative system identification techniques and determine sensitivities of physical parameters to damage. Additionally, vibration-based spectral quantities are related to physical properties of the structure under test. In this thesis, nonlinear response to parametric excitation is exploited for nonlinear system identification of metallic and composite beam-mass systems before damage initiation through intermediate states of damage progression to failure. Parametric identification procedure combines linear and higher order spectral analysis of vibration measurements and perturbation techniques for the derivation of the approximate solution of the system nonlinear governing differential equation. The possibility of using optical Fiber Bragg Grating sensors technology for damage localization is also assessed. Spectral moments and quantities obtained from fiber optic strain measurements are evaluated near and away from cracks to assess the relation between these moments and cracks. Variations in parameters representing natural frequency, damping and effective nonlinearities for different levels of progressive damage in a beam-mass system have been determined. Their percentage variations have been quantified to establish their sensitivities to damage initiation. The results show that damping and effective nonlinearity parameters are more sensitive to damage conditions than the natural frequency of the first mode. Crack localization is assessed by means of optical fiber technology for a composite beam-mass system. The results show that noise levels in fiber optic signals are high in comparison to strain gage signals. Of particular interest, however, is the observation that the nonlinear response is more pronounced near the cracks than away from them. / Ph. D.