Statistical Contributions to Order Restricted Inference for Survival Data Analysis

This dissertation aims to study order restricted inference for survival data analysis where a hazard function is assumed to have a shape restriction with respect to continuous covariates. In the first chapter, we consider estimation of the semiparametric proportional hazards model with a completely unspecified baseline hazard function where the effect of a continuous covariate is assumed isotonic (or monotone) but otherwise unspecified. The pseudo iterative convex minorant algorithm is proposed to compute the isotonic estimator by optimizing a sequence of pseudo partial likelihood functions. A local consistency is established for a one-step update of the estimator when an initial value is in a shrinking neighborhood of the true value. Analysis of data from a recent HIV prevention study illustrates the practical utility of the methodology in estimating monotonic covariate effects that are nonlinear. In the second chapter, we consider additive hazards model with a unimodal hazard function in a continuous covariate with unknown mode. A quadratic loss function is defined, which allows efficient computations to estimate the mode and unimodal covariate effects. The methodology is applied to analyze the data from a recent randomized clinical trial of cardiovascular disease in kidney transplant patients. In the third chapter, we focus on multiple continuous covariates for a shape restricted hazard function. By assuming an additive isotonic structure of the multiple covariates under the proportional hazards model, the hazard function is defined as isotonic with respect to the partial order on the covariates. An efficient computation is proposed by combining the pseudo iterative convex minorant algorithm and the cycling algorithm. We use the proposed method to analyze the data from a recent clinical trial with cardiovascular outcome.Doctor of Philosoph

Bond Strengths of Various Resin Cements to Different Ceramics

This study evaluates the shear bond strength (SBS) of various resin cements to different ceramics. Composite resin cylinders of Z100 were fabricated and cemented to disks of feldspathic ceramic (Creation), leucite-reinforced feldspathic ceramic (Empress I), and densely sintered aluminum oxide ceramic (Procera AllCeram) using five resin cements: Panavia F (PAN), RelyX ARC (ARC), RelyX Unicem (RXU), RelyX Veneer, and Variolink II. SBS was measured after three days of water storage (baseline) and after artificial aging (180 days of water storage along with 12,000 thermal cycles). Failure mode of fractured specimens also was evaluated. Data were analyzed with Kruskal-Wallis and Mann-Whitney tests (α=0.05). RXU showed 1) the lowest baseline median SBS to feldspathic ceramic, which was not statistically different from PAN; 2) the lowest median baseline SBS to leucite-reinforced feldspathic and densely sintered aluminum-oxide ceramics. All cements performed similarly after aging, except for ARC (median 0.0 MPa) and PAN (median 16.2 MPa) in the densely sintered aluminum-oxide ceramic group. Resin cements perform differently when bonded to different ceramic substrates. While all test resin cements worked similarly in the long-term to feldspathic and leucite-reinforced feldspathic ceramics, only the MDP-containing resin cement provided durable bonds to densely sintered aluminum-oxide ceramic. © Sociedade Brasileira de Hematologia e Hemoterapia

Complementary and alternative medicine use among children with mental health issues: results from the National Health Interview Survey

Abstract Background Mental health issues in children have become a serious public health concern in the U.S. within the past few decades. Emerging evidence suggests that Complementary and Alternative Medicine (CAM) can be beneficial for various mental health issues. However, little is known about the prevalence, reasons, and associated factors of CAM use among this population in the U.S. The purpose of this study is to examine the characteristics of CAM use among U.S. children with mental health issues. Methods Utilizing the 2012 National Health Interview Survey data, we used descriptive analysis, Wald F-statistics, and multivariable survey logistic regression models to examine the prevalence, patterns, and associated factors of CAM use in children aged 4–17 (n = 10,233) adjusting for the complex sampling design. Results CAM use is more popular among children with mental health issues compared with those without (19.2% vs. 10.1%, p < 0.001). Herbal remedies (9.1%), mind-body therapies (5.5%), and chiropractic care (5.3%) were the most frequently used modalities. Primary reasons for children to use CAM are because they are helpful (69.2%), natural (55.9%), and holistic (44.7%). The majority of CAM users perceived CAM therapies are helpful. Predictors of CAM use are children who are female, whose parents had a higher educational level and socioeconomic status, and who had at least one co-morbid medical condition. Only 18.4% of CAM usage was recommended by medical doctors. Conclusions Approximately 10 million parents of children with mental health issues reported the use of CAM therapies, mainly because of their desire for a more natural and holistic healthcare approach. Given that the majority of CAM users perceived CAM therapies as helpful, future studies should investigate the unique contributions of CAM in pediatric psychiatric care. Because a low percentage of CAM use was recommended by medical doctors, educational interventions designed to equip medical professionals with CAM knowledge and experience will be conducive to improving effective patient-physician communication in clinical settings. Since CAM use is reported as more prevalent by parents’ of children with higher education and family income, effective strategies designed to reduce disparities in accessing promising CAM therapies are warranted

Identifying App-Based Meditation Habits and the Associated Mental Health Benefits: Longitudinal Observational Study

Background: Behavioral habits are often initiated by contextual cues that occur at approximately the same time each day; so, it may be possible to identify a reflexive habit based on the temporal similarity of repeated daily behavior. Mobile health tools provide the detailed, longitudinal data necessary for constructing such an indicator of reflexive habits, which can improve our understanding of habit formation and help design more effective mobile health interventions for promoting healthier habits. Objective: This study aims to use behavioral data from a commercial mindfulness meditation mobile phone app to construct an indicator of reflexive meditation habits based on temporal similarity and estimate the association between temporal similarity and meditation app users’ perceived health benefits. Methods: App-use data from June 2019 to June 2020 were analyzed for 2771 paying subscribers of a meditation mobile phone app, of whom 86.06% (2359/2771) were female, 72.61% (2012/2771) were college educated, 86.29% (2391/2771) were White, and 60.71% (1664/2771) were employed full-time. Participants volunteered to complete a survey assessing their perceived changes in physical and mental health from using the app. Receiver operating characteristic curve analysis was used to evaluate the ability of the temporal similarity measure to predict future behavior, and variable importance statistics from random forest models were used to corroborate these findings. Logistic regression was used to estimate the association between temporal similarity and self-reported physical and mental health benefits. Results: The temporal similarity of users’ daily app use before completing the survey, as measured by the dynamic time warping (DTW) distance between app use on consecutive days, significantly predicted app use at 28 days and at 6 months after the survey, even after controlling for users’ demographic and socioeconomic characteristics, total app sessions, duration of app use, and number of days with any app use. In addition, the temporal similarity measure significantly increased in the area under the receiver operating characteristic curve (AUC) for models predicting any future app use in 28 days (AUC=0.868 with DTW and 0.850 without DTW; P\u3c.001) and for models predicting any app use in 6 months (AUC=0.821 with DTW and 0.802 without DTW; P\u3c.001). Finally, a 1% increase in the temporal similarity of users’ daily meditation practice with the app over 6 weeks before the survey was associated with increased odds of reporting mental health improvements, with an odds ratio of 2.94 (95% CI 1.832-6.369). Conclusions: The temporal similarity of the meditation app use was a significant predictor of future behavior, which suggests that this measure can identify reflexive meditation habits. In addition, temporal similarity was associated with greater perceived mental health benefits, which demonstrates that additional mental health benefits may be derived from forming reflexive meditation habits

Effects of Lip Revision Surgery on Long-Term Orosensory Function in Patients with Cleft Lip/Palate

To determine whether secondary lip revision surgery impacts sensitivity of the upper lip

Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients

Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell transplantation can be curative for patients with hematologic diseases. Reduced intensity transplants can also achieve cure, and result in less treatment related mortality but higher relapse rates. Thus, optimizing the conditioning regimens used in allogeneic transplantation remains an important goal. We conducted a Phase I/II trial to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of a continuous infusion of busulfan over 90 hours in conjunction with fludarabine followed by allogeneic related or unrelated donor transplant. Fifty-four patients with advanced hematologic malignancies were enrolled on this study. The MTD was identified as a 24 hour area under the curve (AUC) of approximately 7095 uMmin which represents a 43% increase over the standard total daily AUC dose of 4800 uMmin given by intermittent schedules. DLTs at doses over 8000 uMmin were identified as a desquamative skin rash and mucositis. No dose-related increase in hepatic, pulmonary or other organ toxicies were seen while efficacy appeared to be improved at higher dose levels. Continuous infusion busulfan with intermittent fludarabine provides an alternative treatment strategy that is generally well tolerated and permits an increase in total busulfan dose with encouraging efficacy

J-score: a robust measure of clustering accuracy

Background Clustering analysis discovers hidden structures in a data set by partitioning them into disjoint clusters. Robust accuracy measures that evaluate the goodness of clustering results are critical for algorithm development and model diagnosis. Common problems of clustering accuracy measures include overlooking unmatched clusters, biases towards excessive clusters, unstable baselines, and difficulties of interpretation. In this study, we presented a novel accuracy measure, J-score, to address these issues. Methods Given a data set with known class labels, J-score quantifies how well the hypothetical clusters produced by clustering analysis recover the true classes. It starts with bidirectional set matching to identify the correspondence between true classes and hypothetical clusters based on Jaccard index. It then computes two weighted sums of Jaccard indices measuring the reconciliation from classes to clusters and vice versa. The final J-score is the harmonic mean of the two weighted sums. Results Through simulation studies and analyses of real data sets, we evaluated the performance of J-score and compared with existing measures. Our results show that J-score is effective in distinguishing partition structures that differ only by unmatched clusters, rewarding correct inference of class numbers, addressing biases towards excessive clusters, and having a relatively stable baseline. The simplicity of its calculation makes the interpretation straightforward. It is a valuable tool complementary to other accuracy measures. We released an R/jScore package implementing the algorithm

Complementary and alternative medicine use among children with mental health issues: results from the National Health Interview Survey

Abstract Background Mental health issues in children have become a serious public health concern in the U.S. within the past few decades. Emerging evidence suggests that Complementary and Alternative Medicine (CAM) can be beneficial for various mental health issues. However, little is known about the prevalence, reasons, and associated factors of CAM use among this population in the U.S. The purpose of this study is to examine the characteristics of CAM use among U.S. children with mental health issues. Methods Utilizing the 2012 National Health Interview Survey data, we used descriptive analysis, Wald F-statistics, and multivariable survey logistic regression models to examine the prevalence, patterns, and associated factors of CAM use in children aged 4–17 (n = 10,233) adjusting for the complex sampling design. Results CAM use is more popular among children with mental health issues compared with those without (19.2% vs. 10.1%, p < 0.001). Herbal remedies (9.1%), mind-body therapies (5.5%), and chiropractic care (5.3%) were the most frequently used modalities. Primary reasons for children to use CAM are because they are helpful (69.2%), natural (55.9%), and holistic (44.7%). The majority of CAM users perceived CAM therapies are helpful. Predictors of CAM use are children who are female, whose parents had a higher educational level and socioeconomic status, and who had at least one co-morbid medical condition. Only 18.4% of CAM usage was recommended by medical doctors. Conclusions Approximately 10 million parents of children with mental health issues reported the use of CAM therapies, mainly because of their desire for a more natural and holistic healthcare approach. Given that the majority of CAM users perceived CAM therapies as helpful, future studies should investigate the unique contributions of CAM in pediatric psychiatric care. Because a low percentage of CAM use was recommended by medical doctors, educational interventions designed to equip medical professionals with CAM knowledge and experience will be conducive to improving effective patient-physician communication in clinical settings. Since CAM use is reported as more prevalent by parents’ of children with higher education and family income, effective strategies designed to reduce disparities in accessing promising CAM therapies are warranted

Oxidized LDL is stable in human serum under extended thawed-state conditions ranging from −20 °C to room temperature

Introduction: Oxidized LDL (oxLDL) is formed by the spontaneous reaction between aldehyde byproducts of lipid peroxidation and lysine residues of apolipoprotein B within LDL. Clinically, oxLDL is used as a marker of coronary artery disease and predictor of metabolic syndrome risk. Despite its popularity as a clinical marker, no systematic studies of oxLDL stability, in which serum or plasma has been pre-analytically exposed to an array of different time and temperature conditions, have been carried out. Objective: To systematically evaluate the stability of oxLDL in human serum samples exposed to thawed conditions (> −30 °C) for varying periods of time while monitoring a second protein/small molecule redox system as a positive control for non-enzymatic biomolecular activity. Methods: OxLDL was measured in serum samples, from 24 different humans, that had been pre-exposed to three different time courses at 23 °C, 4 °C and −20 °C using ELISA kits from Mercodia that employ the 4E6 mouse monoclonal antibody. A liquid chromatography/mass spectrometry-based marker of serum exposure to thawed conditions known as ΔS-Cys-Albumin was employed as a positive control. Results: OxLDL was stable in serum exposed to 23 °C for up to 48 h, 4 °C for 21 days, or −20 °C for 65 days. ΔS-Cys-Albumin changed dramatically during these time courses (p < 0.001). Conclusions: OxLDL is remarkably stable ex vivo in human serum samples exposed to thawed conditions