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PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. CONCLUSIONS: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC.

Cu or Cu/Au (80 nm thick Cu, 50 nm thick Au) sputtered on Si were kept at 25 degrees C for a week or annealed at a temperature from 80 to 300 degrees C, then tested for THz emission under femtosecond laser irradiation (35 fs-800 nm). THz radiation was detected from samples annealed from 80 to 170 degrees C, which had a Cu2O/Cu interface as the THz source. Cu/Au/Si annealed at 80 degrees C emitted the highest THz radiation because of high laser absorption by the porous Cu2O layer formed at low temperature and the Au film reflected THz radiation and/or increased the laser absorption by the Fabry-Perot effect.

Cu or Cu/Au (80 nm thick Cu, 50 nm thick Au) sputtered on Si were kept at 25 degrees C for a week or annealed at a temperature from 80 to 300 degrees C, then tested for THz emission under femtosecond laser irradiation (35 fs-800 nm). THz radiation was detected from samples annealed from 80 to 170 degrees C, which had a Cu2O/Cu interface as the THz source. Cu/Au/Si annealed at 80 degrees C emitted the highest THz radiation because of high laser absorption by the porous Cu2O layer formed at low temperature and the Au film reflected THz radiation and/or increased the laser absorption by the Fabry-Perot effect.

Selective estrogen receptor modulators (SERMs), the earliest breast cancer (BC) hormone treatment, improve survival of hormone positive (HR+) BC patients. Aromatase inhibitors (AIs) further prolong disease free survival (DFS) for postmenopausal HR+ BC patients, but their benefits in overall survival (OS) are inconclusive. An important factor that impacts OS but not DFS is non-BC death, and cardiovascular disease (CVD) is one of the major contributors. In addition to its high prevalence in the aging population, CVD may be associated with BC cancer treatment. BC hormone treatment influences serum estrogen concentration, which is related to the occurrence of CVD; therefore, it is critical to investigate the impact of BC hormone treatment on CVD, especially in the era when prolonged hormone treatment is increasingly popular in BC care. This dissertation consists of 3 projects: 1) enhancement of an existing Bayesian Network Meta-analysis (NMA) method by allowing more reporting formats, so more studies may be included and expanding an existing consistency check of direct and indirect evidence for a NMA to include longitudinal data; 2) a Bayesian NMA exploring the effects of BC hormone drugs on changes of lipid profiles during hormone treatment; and 3) a study examining the effects of hormone treatment on dyslipidemia/coronary heart disease (CHD) throughout the whole course of BC treatment using electronic medical records. The result from the second study showed that patients on SERMs had better lipid profiles and tended to reduce the risk of dyslipidemia/CHD. The third study revealed that the beneficial effects disappeared after discontinuing SERMs. NMA demonstrated that individual AIs impact changes of lipid profiles differently. However, the third study combining AIs as a whole did not reveal the significant impact on risk of dyslipidemia/CHD, which may be caused by mixed effects of individual AIs and insufficient statistical power due to few outcome events. The public

Selective estrogen receptor modulators (SERMs), the earliest breast cancer (BC) hormone treatment, improve survival of hormone positive (HR+) BC patients. Aromatase inhibitors (AIs) further prolong disease free survival (DFS) for postmenopausal HR+ BC patients, but their benefits in overall survival (OS) are inconclusive. An important factor that impacts OS but not DFS is non-BC death, and cardiovascular disease (CVD) is one of the major contributors. In addition to its high prevalence in the aging population, CVD may be associated with BC cancer treatment. BC hormone treatment influences serum estrogen concentration, which is related to the occurrence of CVD; therefore, it is critical to investigate the impact of BC hormone treatment on CVD, especially in the era when prolonged hormone treatment is increasingly popular in BC care. This dissertation consists of 3 projects: 1) enhancement of an existing Bayesian Network Meta-analysis (NMA) method by allowing more reporting formats, so more studies may be included and expanding an existing consistency check of direct and indirect evidence for a NMA to include longitudinal data; 2) a Bayesian NMA exploring the effects of BC hormone drugs on changes of lipid profiles during hormone treatment; and 3) a study examining the effects of hormone treatment on dyslipidemia/coronary heart disease (CHD) throughout the whole course of BC treatment using electronic medical records. The result from the second study showed that patients on SERMs had better lipid profiles and tended to reduce the risk of dyslipidemia/CHD. The third study revealed that the beneficial effects disappeared after discontinuing SERMs. NMA demonstrated that individual AIs impact changes of lipid profiles differently. However, the third study combining AIs as a whole did not reveal the significant impact on risk of dyslipidemia/CHD, which may be caused by mixed effects of individual AIs and insufficient statistical power due to few outcome events. The public

Lead zirconate titanate (PZT) thin films have received much attention due to their excellent ferroelectric, pyroelectric and piezoelectric properties, making them excellent candidates for next generation high-precision micro/nano electromechanical systems, integrated circuit resonators and actuators. In these applications, the functional property is determined by ferroelectric and ferroelastic domain wall movement (i.e., electromechanical response). It has been shown that electromechanical response enhancement can be achieved by fabricating multilayered heterostructures. Moreover, new polar phases can arise from interfacial effects in these multilayers. In this dissertation, tetragonal (T) PbZr0.30Ti0.70O3 / rhombohedral (R) PbZr0.55Ti0.45O3 / La0.67Sr0.33MnO3 (LSMO) heterostructures were grown by pulsed laser deposition. A (001) oriented SrTiO3 (STO) substrate was used to achieve high quality epitaxial growth. The T and R films were both ~100 nm thick and the LSMO layer (bottom electrode) was ~20 nm thick. Ferroelastic herringbone c/a1/c/a2 domains were found in the T layer. In contrast, reducing the T layer thickness to ~20 nm, a-axis oriented domains were observed. Additionally, local regions (~50 nm wide) were observed exhibiting fine c/a non-equilibrium domains. Cross-sectional transmission electron microscopy revealed crystallographic relationships between the domains and domain walls. Systematic piezoresponse force microscopy studies revealed complex interactions between the electrical and mechanical fields. These bilayered samples exhibited enhanced electromechanical properties due to the presence of extremely mobile ferroelastic domains in the T layer, where the local symmetry within the domain walls differed from the bulk. These domains were formed by elastic interactions between T and R layers. Atomic-resolution imaging was used to further investigate how domains interacted near, or at, the interfaces. The location of interface between adjacent layers was

The focus of this thesis was to apply advanced statistical methods to the American Heart Association Get With The Guidelines-Resuscitation (AHA GWTG-R) registry, a registry data set derived from a prospective multi-sites observational study, the American Heart Association’s National Registry of Cardiopulmonary Resuscitation (NRCPR). The data comprise comprehensive information related to the cardiopulmonary resuscitation (CPR) process, patients’ outcome, and characteristics of both the patients and the hospitals. The purpose of the registry data is to provide information that can be used to improve the outcomes of sudden cardiac arrest (SCA) patients and updates protocol of CPR. This thesis has two purposes. The first one is to investigate the relationship between the patients’ disease and survival for SCA patients receiving different durations of chest compression. The second one is to establish a model for predicting the probability of survival according to the duration of CPR. In the clinical setting, a categorized variable may provide more meaningful inferences. To explore this option, a Generalized additive model (GAM) was used to identify cutoff points for the categorization of chest compression duration. This categorized variable was then used for the development of prediction models for survival and the Net reclassification index (NRI) was used to select the appropriate predictors for this model. Logistic regression, generalized estimating equations (GEE), and a generalized linear mixed model (GLMM) were performed to obtain the estimates of parameters. Thereafter, the probability of survival was estimated based on the results of the regression model. Comprehensive registry data have been established for many healthcare problems, which include many observations and variables. A systematic process to analyze registry data is necessary. This thesis used multiple statistical techniques to create meaningful variables, select appropriate predictors, fit regression

The focus of this thesis was to apply advanced statistical methods to the American Heart Association Get With The Guidelines-Resuscitation (AHA GWTG-R) registry, a registry data set derived from a prospective multi-sites observational study, the American Heart Association’s National Registry of Cardiopulmonary Resuscitation (NRCPR). The data comprise comprehensive information related to the cardiopulmonary resuscitation (CPR) process, patients’ outcome, and characteristics of both the patients and the hospitals. The purpose of the registry data is to provide information that can be used to improve the outcomes of sudden cardiac arrest (SCA) patients and updates protocol of CPR. This thesis has two purposes. The first one is to investigate the relationship between the patients’ disease and survival for SCA patients receiving different durations of chest compression. The second one is to establish a model for predicting the probability of survival according to the duration of CPR. In the clinical setting, a categorized variable may provide more meaningful inferences. To explore this option, a Generalized additive model (GAM) was used to identify cutoff points for the categorization of chest compression duration. This categorized variable was then used for the development of prediction models for survival and the Net reclassification index (NRI) was used to select the appropriate predictors for this model. Logistic regression, generalized estimating equations (GEE), and a generalized linear mixed model (GLMM) were performed to obtain the estimates of parameters. Thereafter, the probability of survival was estimated based on the results of the regression model. Comprehensive registry data have been established for many healthcare problems, which include many observations and variables. A systematic process to analyze registry data is necessary. This thesis used multiple statistical techniques to create meaningful variables, select appropriate predictors, fit regression

Structure formation in an ionic liquid adlayer: First molecularly resolved scanning tunneling microscopy images of an ionic liquid adlayer ([Py1,4]+ [FAP]− (see image)), evaporated on a Au(111) surface, resolve a molecular pattern at 210 K with a distinct short range order, indicating a 2D solid, while at room temperature, the mobility of the adlayer is too high to resolve molecular features, as expected for a 2D liquid.

The competition between intermolecular interactions and lateral variations in the molecule-substrate interactions has been studied by scanning tunneling microscopy (STM), comparing the phase formation of (sub)monolayers of the organic molecule 2,4′-BTP on buckled graphene/Ru(0001) and Ag(111) oriented thin films on Ru(0001). On the Ag films, the molecules form a densely packed 2D structure, while on graphene/Ru(0001), only the areas between the maxima are populated. The findings are rationalized by a high corrugation in the adsorption potential for 2,4′-BTP molecules on graphene/Ru(0001). These findings are supported by temperature programmed desorption (TPD) experiments and theoretical results.

The competition between intermolecular interactions and lateral variations in the molecule-substrate interactions has been studied by scanning tunneling microscopy (STM), comparing the phase formation of (sub)monolayers of the organic molecule 2,4′-BTP on buckled graphene/Ru(0001) and Ag(111) oriented thin films on Ru(0001). On the Ag films, the molecules form a densely packed 2D structure, while on graphene/Ru(0001), only the areas between the maxima are populated. The findings are rationalized by a high corrugation in the adsorption potential for 2,4′-BTP molecules on graphene/Ru(0001). These findings are supported by temperature programmed desorption (TPD) experiments and theoretical results.

Structure formation in an ionic liquid adlayer: First molecularly resolved scanning tunneling microscopy images of an ionic liquid adlayer ([Py1,4]+ [FAP]− (see image)), evaporated on a Au(111) surface, resolve a molecular pattern at 210 K with a distinct short range order, indicating a 2D solid, while at room temperature, the mobility of the adlayer is too high to resolve molecular features, as expected for a 2D liquid.

The advantages of adopting a new software system for Supply Chain Management (SCM) enable the organization to enhance work efficiency as well as customer satisfaction in the supply chain network. These advantages make enterprises update their SCM system through project as a method of realize their strategic change. This research explores how the project manager leads the project team, a temporarily formed unit with multi-functional members, by looking into three focus concepts of the practice perspective: Practitioner, Praxis, and Practices. The empirical study utilized two projects in the electronics firms as the case study. It was decided that a qualitative approach was the most appropriate method to gather the data based on the practice perspective. The findings of this thesis support this primacy of communication. To successfully execute the short duration project for system change, intra-organizational communication has an important part to play in the success of change initiatives. Analysis revealed that the project managers’ soft skills are more important than their knowledge of using project-specific tools or techniques in managing short-duration projects. In the empirical study, the requirements of all project practitioners were not met due to tight schedule and limited resource. However, the project objectives were still achieved on time. Some key success factors were identified, such as top management commitment to the project, correct prioritization of different stakeholders’ power, and involvement of employees as early as possible within the change process. The study concludes that the three focus concepts of the practice perspective interplay during the project process and they contribute to the general framework in the short duration project for realizing strategic change, which can be a reference for industry participants in managing similar projects.

The advantages of adopting a new software system for Supply Chain Management (SCM) enable the organization to enhance work efficiency as well as customer satisfaction in the supply chain network. These advantages make enterprises update their SCM system through project as a method of realize their strategic change. This research explores how the project manager leads the project team, a temporarily formed unit with multi-functional members, by looking into three focus concepts of the practice perspective: Practitioner, Praxis, and Practices. The empirical study utilized two projects in the electronics firms as the case study. It was decided that a qualitative approach was the most appropriate method to gather the data based on the practice perspective. The findings of this thesis support this primacy of communication. To successfully execute the short duration project for system change, intra-organizational communication has an important part to play in the success of change initiatives. Analysis revealed that the project managers’ soft skills are more important than their knowledge of using project-specific tools or techniques in managing short-duration projects. In the empirical study, the requirements of all project practitioners were not met due to tight schedule and limited resource. However, the project objectives were still achieved on time. Some key success factors were identified, such as top management commitment to the project, correct prioritization of different stakeholders’ power, and involvement of employees as early as possible within the change process. The study concludes that the three focus concepts of the practice perspective interplay during the project process and they contribute to the general framework in the short duration project for realizing strategic change, which can be a reference for industry participants in managing similar projects.