Proteome-wide association study using cis and trans variants and applied to blood cell and lipid-related traits in the Women's Health Initiative study.

In most Proteome-Wide Association Studies (PWAS), variants near the protein-coding gene (±1 Mb), also known as cis single nucleotide polymorphisms (SNPs), are used to predict protein levels, which are then tested for association with phenotypes. However, proteins can be regulated through variants outside of the cis region. An intermediate GWAS step to identify protein quantitative trait loci (pQTL) allows for the inclusion of trans SNPs outside the cis region in protein-level prediction models. Here, we assess the prediction of 540 proteins in 1002 individuals from the Women's Health Initiative (WHI), split equally into a GWAS set, an elastic net training set, and a testing set. We compared the testing r2 between measured and predicted protein levels using this proposed approach, to the testing r2 using only cis SNPs. The two methods usually resulted in similar testing r2, but some proteins showed a significant increase in testing r2 with our method. For example, for cartilage acidic protein 1, the testing r2 increased from 0.101 to 0.351. We also demonstrate reproducible findings for predicted protein association with lipid and blood cell traits in WHI participants without proteomics data and in UK Biobank utilizing our PWAS weights.

G-formula for observational studies under stratified interference, with application to bed net use on malaria.

Assessing population-level effects of vaccines and other infectious disease prevention measures is important to the field of public health. In infectious disease studies, one person's treatment may affect another individual's outcome, that is, there may be interference between units. For example, the use of bed nets to prevent malaria by one individual may have an indirect effect on other individuals living in close proximity. In some settings, individuals may form groups or clusters where interference only occurs within groups, that is, there is partial interference. Inverse probability weighted estimators have previously been developed for observational studies with partial interference. Unfortunately, these estimators are not well suited for studies with large clusters. Therefore, in this paper, the parametric g-formula is extended to allow for partial interference. G-formula estimators are proposed for overall effects, effects when treated, and effects when untreated. The proposed estimators can accommodate large clusters and do not suffer from the g-null paradox that may occur in the absence of interference. The large sample properties of the proposed estimators are derived assuming no unmeasured confounders and that the partial interference takes a particular form (referred to as 'weak stratified interference'). Simulation studies are presented demonstrating the finite-sample performance of the proposed estimators. The Demographic and Health Survey from the Democratic Republic of the Congo is then analyzed using the proposed g-formula estimators to assess the effects of bed net use on malaria.

Reservoir-Style Polymeric Drug Delivery Systems: Empirical and Predictive Models for Implant Design.

Controlled drug delivery systems can provide sustained release profiles, favorable pharmacokinetics, and improved patient adherence. Here, a reservoir-style implant comprising a biodegradable polymer, poly(ε-caprolactone) (PCL), was developed to deliver drugs subcutaneously. This work addresses a key challenge when designing these implantable drug delivery systems, namely the accurate prediction of drug release profiles when using different formulations or form factors of the implant. The ability to model and predict the release behavior of drugs from an implant based on their physicochemical properties enables rational design and optimization without extensive and laborious in vitro testing. By leveraging experimental observations, we propose a mathematical model that predicts the empirical parameters describing the drug diffusion and partitioning processes based on the physicochemical properties of the drug. We demonstrate that the model enables an adequate fit predicting empirical parameters close to experimental values for various drugs. The model was further used to predict the release performance of new drug formulations from the implant, which aligned with experimental results for implants exhibiting zero-order release kinetics. Thus, the proposed empirical models provide useful tools to inform the implant design to achieve a target release profile.

Observability Decomposition-Based Decentralized Kalman Filter and Its Application to Resilient State Estimation under Sensor Attacks.

This paper considers a discrete-time linear time invariant system in the presence of Gaussian disturbances/noises and sparse sensor attacks. First, we propose an optimal decentralized multi-sensor information fusion Kalman filter based on the observability decomposition when there is no sensor attack. The proposed decentralized Kalman filter deploys a bank of local observers who utilize their own single sensor information and generate the state estimate for the observable subspace. In the absence of an attack, the state estimate achieves the minimum variance, and the computational process does not suffer from the divergent error covariance matrix. Second, the decentralized Kalman filter method is applied in the presence of sparse sensor attacks as well as Gaussian disturbances/noises. Based on the redundant observability, an attack detection scheme by the χ2 test and a resilient state estimation algorithm by the maximum likelihood decision rule among multiple hypotheses, are presented. The secure state estimation algorithm finally produces a state estimate that is most likely to have minimum variance with an unbiased mean. Simulation results on a motor controlled multiple torsion system are provided to validate the effectiveness of the proposed algorithm.

A Novel Path Planning Algorithm for Truck Platooning Using V2V Communication.

In truck platooning, the leading vehicle is driven manually, and the following vehicles run by autonomous driving, with the short inter-vehicle distance between trucks. To successfully perform platooning in various situations, each truck must maintain dynamic stability, and furthermore, the whole system must maintain string stability. Due to the short front-view range, however, the following vehicles' path planning capabilities become significantly impaired. In addition, in platooning with articulated cargo trucks, the off-tracking phenomenon occurring on a curved road makes it hard for the following vehicle to track the trajectory of the preceding truck. In addition, without knowledge of the global coordinate system, it is difficult to correlate the local coordinate systems that each truck relies on for sensing environment and dynamic signals. In this paper, in order to solve these problems, a path planning algorithm for platooning of articulated cargo trucks has been developed. Using the Kalman filter, V2V (Vehicle-to-Vehicle) communication, and a novel update-and-conversion method, each following vehicle can accurately compute the trajectory of the leading vehicle's front part for using it as a target path. The path planning algorithm of this paper was validated by simulations on severe driving scenarios and by tests on an actual road. The results demonstrated that the algorithm could provide lateral string stability and robustness for truck platooning.