Factor analysis for survival time prediction with informative censoring and diverse covariates

Fulfilling the promise of precision medicine requires accurately and precisely classifying disease states. For cancer, this includes prediction of survival time from a surfeit of covariates. Such data presents an opportunity for improved prediction, but also a challenge due to high dimensionality. Furthermore, disease populations can be heterogeneous. Integrative modeling is sensible, as the underlying hypothesis is that joint analysis of multiple covariates provides greater explanatory power than separate analyses. We propose an integrative latent variable model that combines factor analysis for various data types and an exponential proportional hazards (EPH) model for continuous survival time with informative censoring. The factor and EPH models are connected through low-dimensional latent variables that can be interpreted and visualized to identify subpopulations. We use this model to predict survival time. We demonstrate this model's utility in simulation and on four Cancer Genome Atlas datasets: diffuse lower-grade glioma, glioblastoma multiforme, lung adenocarcinoma, and lung squamous cell carcinoma. These datasets have small sample sizes, high-dimensional diverse covariates, and high censorship rates. We compare the predictions from our model to three alternative models. Our model outperforms in simulation and is competitive on real datasets. Furthermore, the low-dimensional visualization for diffuse lower-grade glioma displays known subpopulations.     

Accelerating Regulated Bioanalysis for Biotherapeutics: Case Examples Using a Microfluidic Ligand Binding Assay Platform

The Gyrolab? xP is a microfluidic platform for conducting ligand binding assays (LBAs) and is recognized for its utility in discovery bioanalysis. However, few reports have focused on the technology for regulated bioanalysis. This technology has the advantage of low reagent consumption, low sample volume, and automated ligand binding methods. To improve bioanalysis testing timelines and increase the speed at which biotherapeutics are delivered to patients, we evaluated the technology for its potential to deliver high-quality data at reduced testing timelines for regulated bioanalysis. Six LBA methods were validated to support bioanalysis for GLP toxicokinetic or clinical pharmacokinetic studies. Validation, sample analysis, and method transfer are described. In total, approximately 4000 samples have been tested for regulated bioanalysis to support 6 GLP toxicology studies and approximately 1000 samples to support 2 clinical studies. Gyrolab? xP had high run pass rates (≥83%) and high incurred sample reanalysis (ISR) pass rates (>94%). The maximum total error observed across all QC levels for a given assay was <30% for all six LBAs. High instrument response precision (CV ≤5%) was observed across compact discs (CDs), and methods were validated to use a single standard curve across multiple CDs within a Gyrolab? xP run. Reduced bioanalysis timelines were achieved compared to standard manual plate-based methods, and methods were successfully transferred across testing labs, paving the way for this platform for use in late-stage clinical development.     

USE OF HERBAL THERAPIES AMONG MIDLIFE MEXICAN WOMEN

The cultural traditions of Mexican women living in the United States make it likely that some women promote their health and manage their symptoms using various herbal therapies, yet we know little about this phenomenon. The purpose of this study was to describe and compare midlife Mexican women living in the U.S. who were or were not using herbal therapies with regard to the extent of their acculturation, beliefs about herbs, and factors associated with their utilization of health services. A convenience sample of 30 Mexican women between the ages of 40 and 56 years completed face-to-face interviews in either English or Spanish. Nearly half reported using herbal therapies. With the exception of positive beliefs about herbs, we found few differences between herbal users and nonusers on acculturation or access to, and satisfaction with, health services. Although acculturation did not appear to influence whether the women used herbal therapies, it did relate to the types of herbs selected. Women most commonly reported using herbs popular in traditional Mexican culture, including manzanilla (chamomile), savila (aloe vera), ajo (garlic), uña de gato (cat's claw), and yerba buena (spearmint).     

Case report and a review of the literature of two patients with gastric MALToma and pulmonary metastasis

Gastric mucosa‐associated lymphoid tissue lymphoma (or MALToma) is a relatively rare form of low‐grade B‐cell malignancy arising from the mucosal associated lymphoid tissue of the stomach. The majority of cases can be treated with Helicobacter pylori eradication with good prognosis. However, few reports have been published on the treatment of gastric MALToma with pulmonary metastasis. We report two such cases managed with systemic chemotherapy. At the time of writing, one of the cases was in static disease while the other had complete remission. In both patients, pulmonary metastases were detected upon staging thoracic computed tomography.     

Setting-Level Influences on Implementation of the Responsive Classroom Approach

We used mixed methods to examine the association between setting-level factors and observed implementation of a social and emotional learning intervention (Responsive Classroom® approach; RC). In study 1 (N?=?33 3rd grade teachers after the first year of RC implementation), we identified relevant setting-level factors and uncovered the mechanisms through which they related to implementation. In study 2 (N?=?50 4th grade teachers after the second year of RC implementation), we validated our most salient Study 1 finding across multiple informants. Findings suggested that teachers perceived setting-level factors, particularly principal buy-in to the intervention and individualized coaching, as influential to their degree of implementation. Further, we found that intervention coaches’ perspectives of principal buy-in were more related to implementation than principals’ or teachers’ perspectives. Findings extend the application of setting theory to the field of implementation science and suggest that interventionists may want to consider particular accounts of school setting factors before determining the likelihood of schools achieving high levels of implementation.