Search for: All records

Abstract The individualized treatment rule (ITR), which recommends an optimal treatment based on individual characteristics, has drawn considerable interest from many areas such as precision medicine, personalized education, and personalized marketing. Existing ITR estimation methods mainly adopt 1 of 2 or more treatments. However, a combination of multiple treatments could be more powerful in various areas. In this paper, we propose a novel double encoder model (DEM) to estimate the ITR for combination treatments. The proposed double encoder model is a nonparametric model which not only flexibly incorporates complex treatment effects and interaction effects among treatments but also improves estimation efficiency via the parameter-sharing feature. In addition, we tailor the estimated ITR to budget constraints through a multi-choice knapsack formulation, which enhances our proposed method under restricted-resource scenarios. In theory, we provide the value reduction bound with or without budget constraints, and an improved convergence rate with respect to the number of treatments under the DEM. Our simulation studies show that the proposed method outperforms the existing ITR estimation in various settings. We also demonstrate the superior performance of the proposed method in patient-derived xenograft data that recommends optimal combination treatments to shrink the tumour size of the colorectal cancer. 

ABSTRACT Individualized modeling has become increasingly popular in recent years with its growing application in fields such as personalized medicine and mobile health studies. With rich longitudinal measurements, it is of great interest to model certain subject‐specific time‐varying covariate effects. In this paper, we propose an individualized time‐varying nonparametric model by leveraging the subgroup information from the population. The proposed method approximates the time‐varying covariate effect using nonparametric B‐splines and aggregates the estimated nonparametric coefficients that share common patterns. Moreover, the proposed method can effectively handle various missing data patterns that frequently arise in mobile health data. Specifically, our method achieves subgrouping by flexibly accommodating varying dimensions of B‐spline coefficients due to missingness. This capability sets it apart from other fusion‐type approaches for subgrouping. The subgroup information can also potentially provide meaningful insight into the characteristics of subjects and assist in recommending an effective treatment or intervention. An efficient ADMM algorithm is developed for implementation. Our numerical studies and application to mobile health data on monitoring pregnant women's deep sleep and physical activities demonstrate that the proposed method achieves better performance compared to other existing methods. 

Background:Sleep disturbances are associated with adverse perinatal outcomes. Thus, it is necessary to understand the continuous patterns of sleep during pregnancy and how moderators such as maternal age and pre-pregnancy body mass index impact sleep. Objective:This study aimed to examine the continuous changes in sleep parameters objectively (i.e. sleep stages, total sleep time, and awake time) in pregnant women and to describe the impact of maternal age and/or pre-pregnancy body mass index as moderators of these objective sleep parameters. Design:This was a longitudinal observational design. Methods:Seventeen women with a singleton pregnancy participated in this study. Mixed model repeated measures were used to describe weekly patterns, while aggregated changes describe these three pregnancy periods (10–19, 20–29, and 30–39 gestational weeks). Results:For the weekly patterns, we found significantly decreased deep (1.26 ± 0.18 min/week, p < 0.001), light (0.72 ± 0.37 min/week, p = 0.05), and total sleep time (1.56 ± 0.47 min/week, p < 0.001) as well as increased awake time (1.32 ± 0.34 min/week, p < 0.001). For the aggregated changes, we found similar patterns to weekly changes. Women (⩾30 years) had an even greater decrease in deep sleep (1.50 ± 0.22 min/week, p < 0.001) than those younger (0.84 ± 0.29 min/week, p = 0.04). Women who were both overweight/obese and ⩾30 years experienced an increase in rapid eye movement sleep (0.84 ± 0.31 min/week, p = 0.008), but those of normal weight (<30 years) did not. Conclusion:This study appears to be the first to describe continuous changes in sleep parameters during pregnancy at home. Our study provides preliminary evidence that sleep parameters could be potential non-invasive physiological markers predicting perinatal outcomes. 

Abstract Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences. 

Abstract The stepwise chemical reduction of a molecular warped nanographene (WNG) having a negatively curved π‐surface and defined C₈₀H₃₀composition with Cs metal used as the reducing and complexing agent allowed the isolation of three different reduced states with one, two, and three electrons added to itsπ‐conjugated system. This provided a unique series of nanosized carbanions with increasing negative charge for in‐depth structural analysis of consequences of controlled electron charging of non‐planar nanographenes, using X‐ray crystallographic and computational tools. The 3D molecular electrostatic potential (MEP) maps identified the negative charge localization at the central part of the WNG surface where selective coordination of Cs⁺ions is confirmed crystallographically. In‐depth theoretical investigation revealed a complex response of the WNG to the stepwise electron acquisition. The extended and contorted π‐surface of the WNG undergoes subtle swinging distortions that are accompanied by notable changes in the electronic structure and site‐dependent aromaticity of the resulting carbanions.