FRACTURES AMONG OLDER KIDNEY TRANSPLANT RECIPIENTS: A STUDY OF THE INCIDENCE OF FRACTURES, RISK FACTORS FOR INCIDENT FRACTURES, AND SUBSEQUENT MORTALITY

BACKGROUND: Adult kidney transplant (KT) recipients are at greater risk of fractures than the general population, however, the burden of fractures has not been well studied in older KT recipients. Age plays a strong role in the risk of fractures and sequelae among older populations, in general. Therefore, the goals of this study were to identify the incidence of fractures, risk factors for fractures, and rates of subsequent outcomes in older KT recipients. We also tested whether epidemiology of fractures differs for older-old (defined in this paper as 55-64 years old) and younger-old (defined in this paper as ≥65 years old) age subgroups. METHODS: 38,382 older (≥ 55 years) adult KT recipients who had Medicare primary coverage were identified through the USRDS registry. We estimated the cumulative incidence of post-KT fractures by age, sex, race, BMI and history of diabetes, in younger-old (55-64 years) and older-old (≥65 years) KT recipients. We identified risk factors of post-KT fractures for older recipients using a Fine and Gray competing risk approach, accounting for the competing events of mortality and DCGL, and tested whether age modified the associations of sex, race, BMI and year of KT with post-KT fractures. We then tested whether post-KT fracture was a risk factor for subsequent mortality and DCGL using adjusted Cox proportional hazards models, and tested whether age, sex, race, BMI and year of KT modified the associations of post-KT fractures with morality and DCGL. RESULTS: The cumulative incidence of post­KT fractures increased with age. The risk factors of post-KT fractures included recipient (age, sex, race, BMI, history of diabetes, time on dialysis, and peak PRA), transplant (year of KT, number of HLA mismatches), and donor factors (living donor, standard deceased donor, expanded criteria donor, and donation after cardiac death). In the younger-old group, diabetes (HR=2.35, 95% CI: 2.06-2.69) and White race (White vs. African American: HR=2.28, 95% CI: 1.92-2.69) were the two strongest risk factors; in the older-old group, underweight (HR=2.06, 95% CI: 1.29-3.28) and White race (White vs. African American: HR=2.11, 95% CI: 1.74-2.56) were the two strongest risk factors. Age (younger-old vs. older-old) modified the association between diabetes and post-KT fracture (younger-old: HR=2.35, 95% CI: 2.06-2.69, older-old: HR=1.74, 95% CI: 1.53-1.97, P for interaction=0.001). Post­KT fractures were associated with a 2-fold increase in subsequent mortality (HR=2.09, 95% CI: 1.94-2.25) and a 1.9-fold increase in subsequent DCGL (HR=1.87, 95% CI: 1.75-2.00) in the older KT recipients. White race and diabetes modified the associations of post-KT fractures with mortality (White: HR=2.20, 95% CI: 2.01-2.41, non-White: HR=1.85, 95% CI: 1.62-2.11, P for interaction=0.03; diabetes: HR=1.93, 95% CI: 1.75-2.13, non-diabetes: HR=2.35, 95% CI: 2.10-2.63, P for interaction=0.008) and DCGL (White: HR=2.01, 95% CI: 1.85-2.18, non-White: HR=1.60, 95% CI: 1.43-1.78, P for interaction=0.001; diabetes: HR=1.76, 95% CI: 1.62-1.92, non-diabetes: HR=2.04, 95% CI: 1.85-2.25, P for interaction=0.03). CONCLUSION: Older-old KT recipients had a higher risk of developing post-KT fractures. Recipients, transplant, and donor factors were associated with post-KT fractures. Older KT recipients who had post-KT fractures were at increased risk of both subsequent death and graft loss. Advisor: Mara A. McAdams-DeMarco Reader: Allan B. Massi

Real-time 3D surface-shape measurement using fringe projection and system-geometry constraints

Optical three-dimensional (3D) surface-shape measurement has diverse applications in engineering, computer vision and medical science. Fringe projection profilometry (FPP), uses a camera-projector system to permit high-accuracy full-field 3D surface-shape measurement by projecting fringe patterns onto an object surface, capturing images of the deformed patterns, and computing the 3D surface geometry. A wrapped phase map can be computed from the camera images by phase analysis techniques. Phase-unwrapping can solve the phase ambiguity of the wrapped phase map and permit determination of camera-projector correspondences. The object surface geometry can then be reconstructed by stereovision techniques after system calibration. For real-time 3D measurement, geometry-constraint based methods may be a preferred technique over other phase-unwrapping methods, since geometry-constraint methods can handle surface discontinuities, which are problematic for spatial phase unwrapping, and they do not require additional patterns, which are needed in temporal phase unwrapping. However, the fringe patterns used in geometry-constraint based methods are usually designed with a low frequency in order to maximize the reliability of correspondence determination. Although using high-frequency fringe patterns have proven to be effective in increasing the measurement accuracy by suppressing the phase error, high-frequency fringe patterns may reduce the reliability and thus are not commonly used. To address the limitations of current geometry-constraint based methods, a new fringe projection method for surface-shape measurement was developed using modulation of background and amplitude intensities of the fringe patterns to permit identification of the fringe order, and thus unwrap the phase, for high-frequency fringe patterns. Another method was developed with background modulation only, using four high-frequency phase-shifted fringe patterns. The pattern frequency is determined using a new fringe-wavelength geometry-constraint model that allows only two point candidates in the measurement volume. The correct corresponding point is selected with high reliability using a binary pattern computed from the background intensity. Equations of geometry-constraint parameters permit parameter calculation prior to measurement, thus reducing computational cost during measurement. In a further development, a new real-time 3D measurement method was devised using new background-modulated modified Fourier transform profilometry (FTP) fringe patterns and geometry constraints. The new method reduced the number of fringe patterns required for 3D surface reconstruction to two. A short camera-projector baseline allows reliable corresponding-point selection, even with high-frequency fringe patterns, and a new calibration approach reduces error induced by the short baseline. Experiments demonstrated the ability of the methods to perform real-time 3D measurement for a surface with geometric discontinuity, and for spatially isolated objects. Although multi-image FPP techniques can achieve higher accuracy than single-image methods, they suffer from motion artifacts when measuring dynamic object surfaces that are either moving or deforming. To reduce the motion-induced measurement error for multi-image FPP techniques, a new method was developed to first estimate the motion-induced phase shift errors by computing the differences between phase maps over a multiple measurement sequence. Then, a phase map with reduced motion-induced error is computed using the estimated phase shift errors. This motion-induced error compensation is computed pixel-wise for non-homogeneous surface motion. Experiments demonstrated the ability of the method to reduce motion-induced error in real-time, for real-time shape measurement of surfaces with high depth variation, and moving and deforming surfaces

Cell-Selective Proteomic Profiling in Complex Biological Systems

Cells within biological systems are constantly adjusting their protein synthesis in response to various environmental changes. To study the rapid cellular regulations in complex biological systems, global proteomic profiling provides important information on system-level regulations, yet physiological properties characteristic of individual cellular subpopulations could be hidden under the characterization. Instead, cell-selective proteomic profiling allows researchers to reveal the heterogeneities in biological systems with phenotypically and even genetically distinct subpopulations under different microenvironments. Chapter 1 describes the development of bioorthogonal noncanonical amino acid tagging (BONCAT) for proteomic profiling with resolution in both space and time: its initial role is protein labeling with temporal resolution via pulse-addition of noncanonical amino acid, which could be recognized by endogenous aminoacyl tRNA-synthetase (aaRS), into systems of interest; later on, mutant aaRSs are identified through mutant synthetase library screening, which allows for efficient incorporation of various types of noncanonical amino acids that could hardly be activated by endogenous machineries. The identification and exploitation of mutant aaRSs allow sensitive cellular selectivity during protein labeling. With unprecedented spatiotemporal resolution of BONCAT, and the advancement in high-resolution mass spectrometry and computational algorithms, BONCAT is a powerful technique for selective proteomic profiling to study physiological regulations in a wide range of complex biological systems. Chapter 2 describes the application of the BONCAT method in cell-selective proteomic profiling in Pseudomonas aeruginosa biofilms. In this work, we targeted an iron-starved subpopulation in biofilms and compared its proteomic profile with that of the entire system. Key gene and pathway regulations in the subpopulation are found through the analysis of the proteomic data, which suggest that iron-starved cells shift their priority towards housing keeping pathways, adapt an energy- and resources-saving mode to cope with their harsh local environmental conditions, and get prepared to disperse for better survival. Analysis of poorly studied proteins highly upregulated in the subpopulation led to the discovery of a previously uncharacterized protein (PA14_52000) that is potentially related to iron acquisition. The transposon insertion mutant PA14_52000::tn showed significantly enhanced pyoverdine production in rich medium and reduced biofilm formation. Chapter 3 describes the study of physiological regulations in Bacillus subtilis K-state subpopulation via BONCAT. A subset of B. subtilis cells, typically 10% - 20% of the entire population, enter K-state in a stochastic manner. With the low level of K-state entry rate and high randomness, we challenged BONCAT to specifically capture gene and pathway regulations in K-state cells and compared the proteomic profiling with that of the entire population. Regardless of the difficulties of selective protein labeling inherent in the system, our results indicate that BONCAT has high specificity and resolution in proteomic profiling for minor subpopulations and proteins with low overall absolute abundance. We found multiple pathways and genes characteristic of K-state regulated differentially from the entire population, either significantly up- or down-regulated. Proteins that are uncharacterized or previously known for functions irrelevant of K-state are highly abundant in the subpopulation, providing new insight toward their alternative functions critical for K-state cells and future investigation directions of K-state study.</p

Privatisation policy with different oligopolistic competition in the public utilities market

This study constructs an oligopoly model in public utilities sector to explore the optimal privatisation policy and the factors affecting equilibrium outcomes and explores the optimal proportion of state-owned shares. We also offer empirical evidence of China’s public utilities from 1985 to 2019 to prove the applicability of model results. The results show that, depending on product differentiation, cost variance, technical level, nationalisation, partial or full privatisation can be optimal. Improving capital efficiency increases social welfare in Model PP, but not in Model PS. Product differentiation improves social welfare at the expense of profits in SS model. In Model PM, technical improvements boost private enterprise profits but induce a decrement in social welfare. A high proportion of state-owned shares fail to improve social welfare in Model SM. In a word, the value range of parameters and competition modes in public utilities sector affect market players’ welfare distribution, which identifies with the empirical analysis of China’s public utilities development

Does regional value chain participation affect global value chain positions? Evidence from China

Does participation in the ASEAN-China regional value chain (RVC) affect China’s manufacturing enterprises’ global value chain (GVC) positions in the context of the establishment of the ASEAN-China Free Trade Area (ACFTA)? In this paper, we discuss the theoretical mechanisms and impacts of RVC participation on GVC positions and use an input-output model to decompose the gross exports of China by different sources and destinations. The model measures China’s manufacturing industries’ total, upstream and downstream participation within the ASEAN-China regional value chain. Using panel data from the OECD for 2005 to 2015, the empirical results show that (1) the participation of China’s manufacturing industries in the RVC is conducive to improvement in their GVC positions, (2) moving to more upstream can indeed promote the GVC positions of enterprises, and (3) in contrast to labour-intensive and capitalintensive manufacturing, knowledge-intensive manufacturing in upstream activities of the RVC contributes the most to GVC positions. It is suggested that China should develop knowledge-oriented industries and move to more upstream of the ASEAN-China RVC to raise manufacturing industries’ positions in the GVC