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Gastrointestinal Bile Salt Concentrations in Healthy Adults Under Fasted and Fed Conditions: A Systematic Review and Meta-Analysis for Mechanistic Physiologically-Based Pharmacokinetic (PBPK) Modelling.
AAPS J
January 2025
Certara UK Limited, Level 2, Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK.
Bile salts are biosurfactants released into the intestinal lumen which play an important role in the solubilisation of fats and certain drugs. Their concentrations vary along the gastrointestinal tract (GIT). This is significant for implementation in physiologically based pharmacokinetic (PBPK) modelling to mechanistically capture drug absorption.
View Article and Find Full Text PDFThe development of diffusion models, such as Glide, DALLE 2, Imagen, and Stable Diffusion, marks a significant advancement in generative AI for image synthesis. In this paper, we introduce a novel framework for synthesizing intrinsic connectivity networks (ICNs) by utilizing the nonlinear capabilities of denoising diffusion probabilistic models (DDPMs). This approach builds upon and extends traditional linear methods, such as independent component analysis (ICA), which are commonly used in neuroimaging studies.
View Article and Find Full Text PDFSafety and Efficacy of Selexipag for Pediatric Pulmonary Arterial Hypertension in Japanese Patients - An Open-Label Phase 2 Study.
Circ J
January 2025
Department of Echo-imaging Center, Aizawa Hospital.
Background: Selexipag, an oral prostacyclin (PGI) receptor agonist, is approved for adult patients with pulmonary arterial hypertension (PAH). This study evaluated the efficacy and safety of selexipag for Japanese pediatric patients with PAH.
Methods And Results: The study enrolled 6 patients who received selexipag twice daily at an individualized dose based on body weight; maintenance doses were determined for each patient by 12 weeks after starting administration.
Partitioning for Enhanced Statistical Power and Noise Reduction: Comparing One-Way and Repeated Measures Analysis of Variance (ANOVA).
Cureus
December 2024
Biostatistics, The Oxford Center, Brighton, USA.
Using simulated data with duplicate observational data points, this research aims to highlight the notable efficiency of repeated measures analysis of variance (ANOVA) compared to one-way ANOVA as a more powerful statistical model. One of the principal advantages of repeated measures ANOVA is its design, in which each subject acts as their own control. This methodology allows for the statistical mitigation of individual differences among subjects, thereby reducing extraneous variability (noise) that can obscure the effects of the experimental conditions under investigation.
View Article and Find Full Text PDFCharacterization of lamotrigine disposition changes during and after pregnancy in women with epilepsy.
Pharmacotherapy
January 2025
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Background: Lamotrigine clearance can change drastically in pregnant women with epilepsy (PWWE) making it difficult to assess the need for dosing adjustments. Our objective was to characterize lamotrigine pharmacokinetics in PWWE during pregnancy and postpartum along with a control group of nonpregnant women with epilepsy (NPWWE).
Methods: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study was a prospective, observational, 20 site, cohort study conducted in the United States (December 2012 and February 2016).
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