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Abstract Objective:The progression of long-term diabetes complications has led to a decreased quality of life. Our objective was to evaluate the adverse outcomes associated with diabetes based on a patient’s clinical profile by utilizing a multistate modeling approach. Methods:This was a retrospective study of diabetes patients seen in primary care practices from 2013 to 2017. We implemented a five-state model to examine the progression of patients transitioning from one complication to having multiple complications. Our model incorporated high dimensional covariates from multisource data to investigate the possible effects of different types of factors that are associated with the progression of diabetes. Results:The cohort consisted of 10,596 patients diagnosed with diabetes and no previous complications associated with the disease. Most of the patients in our study were female, White, and had type 2 diabetes. During our study period, 5928 did not develop complications, 3323 developed microvascular complications, 1313 developed macrovascular complications, and 1129 developed both micro- and macrovascular complications. From our model, we determined that patients had a 0.1334 [0.1284, .1386] rate of developing a microvascular complication compared to 0.0508 [0.0479, .0540] rate of developing a macrovascular complication. The area deprivation index score we incorporated as a proxy for socioeconomic information indicated that patients who reside in more disadvantaged areas have a higher rate of developing a complication compared to those who reside in least disadvantaged areas. Conclusions:Our work demonstrates how a multistate modeling framework is a comprehensive approach to analyzing the progression of long-term complications associated with diabetes. 

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. There was significant upregulation of inflammatory genes in microglia 24 h after hypoxia. Single-cell RNA sequencing (scRNAseq) revealed two microglia subclusters of interest following HIE. Pseudobulk analysis revealed increased microglia motility gene expression and upregulation of epigenetic machinery and neurodevelopmental genes in macrophages following HIE. No sex differences were found in any measures. These results support a two-hit noninvasive model pairing MIA and hypoxia as a model for HIE in humans. This model results in a milder phenotype compared to established HIE models; however, HIE is a clinically heterogeneous injury resulting in a variety of outcomes in humans. The pathways identified in our model of HIE may reveal novel targets for therapy for neonates with HIE. 

In recent years, the US has experienced an opioid epidemic with an unprecedented number of drugs overdose deaths. Research finds such overdose deaths are linked to neighborhood-level traits, thus providing opportunity to identify effective interventions. Typically, techniques such as Ordinary Least Squares (OLS) or Maximum Likelihood Estimation (MLE) are used to document neighborhood-level factors significant in explaining such adverse outcomes. These techniques are, however, less equipped to ascertain non-linear relationships between confounding factors. Hence, in this study we apply machine learning based techniques to identify opioid risks of neighborhoods in Delaware and explore the correlation of these factors using Shapley Additive explanations (SHAP). We discovered that the factors related to neighborhoods’ environment, followed by education and then crime, were highly correlated with higher opioid risk.We also explored the change in these correlations over the years to understand the changing dynamics of the epidemic. Furthermore, we discovered that, as the epidemic has shifted from legal (i.e., prescription opioids) to illegal (e.g., heroin and fentanyl) drugs in recent years, the correlation of environment, crime and health related variables with the opioid risk has increased significantly while the correlation of economic and socio-demographic variables has decreased. The correlation of education related factors has been higher from the start and has increased slightly in recent years suggesting a need for increased awareness about the opioid epidemic. 

Abstract We propose an efficient estimator for the coefficients in censored quantile regression using the envelope model. The envelope model uses dimension reduction techniques to identify material and immaterial components in the data, and forms the estimator based only on the material component, thus reducing the variability of estimation. We will demonstrate the guaranteed asymptotic efficiency gain of our proposed envelope estimator over the traditional estimator for censored quantile regression. Our analysis begins with the local weighing approach that traditionally relies on semiparametric ‐estimation involving the conditional Kaplan–Meier estimator. We will instead invoke the independent identically distributed (i.i.d.) representation of the Kaplan–Meier estimator, which eliminates this infinite‐dimensional nuisance and transforms our objective function in ‐estimation into a ‐process indexed by only an Euclidean parameter. The modified ‐estimation problem becomes entirely parametric and hence more amenable to analysis. We will also reconsider the i.i.d. representation of the conditional Kaplan–Meier estimator. 

Abstract Advancement in next-generation sequencing, transcriptomics, proteomics and other high-throughput technologies has enabled simultaneous measurement of multiple types of genomic data for cancer samples. These data together may reveal new biological insights as compared to analyzing one single genome type data. This study proposes a novel use of supervised dimension reduction method, called sliced inverse regression, to multi-omics data analysis to improve prediction over a single data type analysis. The study further proposes an integrative sliced inverse regression method (integrative SIR) for simultaneous analysis of multiple omics data types of cancer samples, including MiRNA, MRNA and proteomics, to achieve integrative dimension reduction and to further improve prediction performance. Numerical results show that integrative analysis of multi-omics data is beneficial as compared to single data source analysis, and more importantly, that supervised dimension reduction methods possess advantages in integrative data analysis in terms of classification and prediction as compared to unsupervised dimension reduction methods.