Extrapolating Dosein Vitroto Dosein Vivoof a Neurotoxic Pyrethroid Pesticide Using Empirical Approaches and a PBPK Model

2012 ◽  
pp. 229-241
Author(s):  
Michael F. Hughes ◽  
Melissa P. L. Chan ◽  
James M. Starr ◽  
Timothy J. Shafer ◽  
Edward J. Scollon ◽  
...  
Keyword(s):  
Pbpk Model ◽  
Pyrethroid Pesticide ◽  
Empirical Approaches

The Science of Wisdom in a Polarized World: Knowns and Unknowns

2020 ◽  
Author(s):  
Igor Grossmann ◽  
Nic M. Weststrate ◽  
Monika Ardelt ◽  
Justin Peter Brienza ◽  
Mengxi Dong ◽  
...  
Keyword(s):  
Individual Differences ◽  
Problem Solving ◽  
Best Practices ◽  
Cognitive Sciences ◽  
Methodological Challenges ◽  
The Common ◽  
Empirical Approaches ◽  
And Training ◽  
Contextual Differences

Interest in wisdom in the cognitive sciences, psychology, and education has been paralleled by conceptual confusions about its nature and assessment. To clarify these issues and promote consensus in the field, wisdom researchers met in Toronto in July of 2019, resolving disputes through discussion. Guided by a survey of scientists who study wisdom-related constructs, we established a common wisdom model, observing that empirical approaches to wisdom converge on the morally-grounded application of metacognition to reasoning and problem-solving. After outlining the function of relevant metacognitive and moral processes, we critically evaluate existing empirical approaches to measurement and offer recommendations for best practices. In the subsequent sections, we use the common wisdom model to selectively review evidence about the role of individual differences for development and manifestation of wisdom, approaches to wisdom development and training, as well as cultural, subcultural, and social-contextual differences. We conclude by discussing wisdom’s conceptual overlap with a host of other constructs and outline unresolved conceptual and methodological challenges.

scholarly journals Beaten ballots: political participation dynamics amidst police interventions

2021 ◽  
pp. 1-18
Author(s):  
Toni Rodon ◽  
Marc Guinjoan
Keyword(s):  
Political Participation ◽  
Negative Impact ◽  
Spatial Dynamics ◽  
Spillover Effects ◽  
Political Mobilization ◽  
Starting Point ◽  
Positive Spillover ◽  
Police Crackdown ◽  
Surrounding Areas ◽  
Empirical Approaches

Abstract What is the effect of violence on political mobilization? Taking the repression-mobilization nexus debate as a starting point, we study the effects of police interventions on political participation, focusing on the Spanish police crackdown on Catalonia's independence referendum on 1 October 2017. We analyze the effect of police actions on turnout using detailed aggregate data, as well as a survey conducted a few days after the referendum. The two empirical approaches show that police interventions had both deterrent and inverse spatial spillover effects. Although police raids had a local negative impact on turnout, they induced positive spillover effects in the surrounding areas. Our findings also indicate heterogeneity in the spatial dynamics, with police actions encouraging people to go to vote in nearby areas, but also mobilizing residents in neighboring areas to participate, especially those individuals with fewer incentives to turn out to vote.

scholarly journals Development of Physiologically Based Pharmacokinetic Model for Orally Administered Fexuprazan in Humans

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 813
Author(s):  
Yoo-Seong Jeong ◽  
Min-Soo Kim ◽  
Nora Lee ◽  
Areum Lee ◽  
Yoon-Jee Chae ◽  
...  
Keyword(s):  
Gastric Acid ◽  
Pbpk Model ◽  
Pbpk Modeling ◽  
Drug Candidate ◽  
Metabolite Formation ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

Fexuprazan is a new drug candidate in the potassium-competitive acid blocker (P-CAB) family. As proton pump inhibitors (PPIs), P-CABs inhibit gastric acid secretion and can be used to treat gastric acid-related disorders such as gastroesophageal reflux disease (GERD). Physiologically based pharmacokinetic (PBPK) models predict drug interactions as pharmacokinetic profiles in biological matrices can be mechanistically simulated. Here, we propose an optimized and validated PBPK model for fexuprazan by integrating in vitro, in vivo, and in silico data. The extent of fexuprazan tissue distribution in humans was predicted using tissue-to-plasma partition coefficients in rats and the allometric relationships of fexuprazan distribution volumes (VSS) among preclinical species. Urinary fexuprazan excretion was minimal (0.29–2.02%), and this drug was eliminated primarily by the liver and metabolite formation. The fraction absorbed (Fa) of 0.761, estimated from the PBPK modeling, was consistent with the physicochemical properties of fexuprazan, including its in vitro solubility and permeability. The predicted oral bioavailability of fexuprazan (38.4–38.6%) was within the range of the preclinical datasets. The Cmax, AUClast, and time-concentration profiles predicted by the PBPK model established by the learning set were accurately predicted for the validation sets.

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