Many research questions in public health and medicine concern sustained interventions in populations defined by substantive priorities. Existing methods to answer such questions typically require a measured covariate set sufficient to control confounding, which can be questionable in observational studies. Differences-in-differences rely instead on the parallel trends assumption, allowing for some types of time-invariant unmeasured confounding. However, most existing difference-in-differences implementations are limited to point treatments in restricted subpopulations. We derive identification results for population effects of sustained treatments under parallel trends assumptions. In particular, in settings where all individuals begin follow-up with exposure status consistent with the treatment plan of interest but may deviate at later times, a version of Robins' g-formula identifies the intervention-specific mean under stable unit treatment value assumption, positivity, and parallel trends. We develop consistent asymptotically normal estimators based on inverse-probability weighting, outcome regression, and a double robust estimator based on targeted maximum likelihood. Simulation studies confirm theoretical results and support the use of the proposed estimators at realistic sample sizes. As an example, the methods are used to estimate the effect of a hypothetical federal stay-at-home order on all-cause mortality during the COVID-19 pandemic in spring 2020 in the United States.
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http://dx.doi.org/10.1111/biom.13862 | DOI Listing |
Cell Biol Toxicol
January 2025
Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain.
The underlying mechanisms explaining the differential course of SARS-CoV-2 infection and the potential clinical consequences after COVID-19 resolution have not been fully elucidated. As a dysregulated mitochondrial activity could impair the immune response, we explored long-lasting changes in mitochondrial functionality, circulating cytokine levels, and metabolomic profiles of infected individuals after symptoms resolution, to evaluate whether a complete recovery could be achieved. Results of this pilot study evidenced that different parameters of aerobic respiration in lymphocytes of individuals recuperated from a severe course lagged behind those shown upon mild COVID-19 recovery, in basal conditions and after simulated reinfection, and they also showed altered glycolytic capacity.
View Article and Find Full Text PDFPurpose: In glioblastoma, the therapeutically intractable and resistant phenotypes can be derived from glioma stem cells, which often have different underlying mechanisms from non-stem glioma cells. Aberrant signaling across the EGFR-PTEN-AKT-mTOR pathways have been shown as common drivers of glioblastoma. Revealing the inter and intra-cellular heterogeneity within glioma stem cell populations in relations to signaling patterns through these pathways may be key to precision diagnostic and therapeutic targeting of these cells.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, United States.
Macrocyclization or stapling is an important strategy for increasing the conformational stability and target-binding affinity of peptides and proteins, especially in therapeutic contexts. Atomistic simulations of such stapled peptides and proteins could help rationalize existing experimental data and provide predictive tools for the design of new stapled peptides and proteins. Standard approaches exist for incorporating nonstandard amino acids and functional groups into the force fields required for MD simulations and have been used in the context of stapling for more than a decade.
View Article and Find Full Text PDFCancer Causes Control
January 2025
Epidemiology Department, College of Public Health, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Purpose: To examine incidence trends and patterns for early- and late-onset liver cancer.
Methods: Liver and intrahepatic bile duct (IBD) cancers diagnosed between 2000 and 2019 were acquired from 22 SEER registries. Variables included early-onset (20-49) vs.
Alzheimers Dement
December 2024
Herbert and Jackeline Krieger Klein Alzheimer's Research Center, Rutgers Biomedical and Health Sciences, Newark, NJ, USA.
Background: Increasing prevalence of Alzheimer's Disease (AD) and limited pharmacological intervention benefits to decelerate early neurodegeneration have prompted exploration of non-pharmacological options. Recent studies indicate that combining cognitive-motor training enhances outcomes.
Methods: In a single-blind, parallel-group, randomized controlled trial of middle-aged adults with a parental history of AD, the experimental group (N = 22) underwent training with newly developed "real-world" intensive, progressive, virtual reality (VR) tasks, while walking on a treadmill.
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