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"Modest doubt is call'd the beacon of the wise."-William Shakespeare, Troilus and Cressida. Although the character Hector warns his fellow Trojans with this line not to engage in war against the Greeks, Shakespeare's works are replete with characters who do not incorporate modest doubt, or any consideration of uncertainty, in their risk decisions. Perhaps Shakespeare was simply a keen observer of human nature. Although risk science has developed tremendously over the last five decades (and scientific inquiry over five centuries), the human mind still frequently defaults to conviction about certain beliefs, absent sufficient scientific evidence-which has effects not just on individual lives, but on policy decisions that affect many. This perspective provides background on the Shakespearean quote in its literary and historical context. Then, as this quote is the theme of the 2023 Society for Risk Analysis Annual Meeting, we describe how "modest doubt"-incorporating the notion of uncertainty into risk analysis for individual and policy decisions-is still the "beacon of the wise" today.
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http://dx.doi.org/10.1111/risa.14139 | DOI Listing |
Fam Cancer
September 2025
School of Social Policy and Practice, University of Pennsylvania, Philadelphia, USA.
Li-Fraumeni syndrome (LFS) is an early-onset cancer syndrome caused by pathogenic germline TP53 variants. Adolescents and young adults (AYAs) with LFS may have challenges navigating new romantic partnerships given the significant effects of LFS on multiple life domains that also affect partners (e.g.
View Article and Find Full Text PDFJ Comp Eff Res
September 2025
British Heart Foundation, University of Glasgow, Glasgow, UK.
Composite endpoints amalgamate multiple clinical outcomes into a single measure, offering efficiency gains in clinical trials through increased event rates and reduced sample sizes, thus accelerating clinical development and regulatory approval. However, employing composite endpoints introduces complexities into health technology assessments (HTAs), particularly in economic modeling, due to the varying clinical significance and cost implications of the components. In this paper, we explore best modeling practice for HTAs that are based on clinical trials that employ composite endpoints.
View Article and Find Full Text PDFFront Vet Sci
August 2025
College of Food Science, Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou, China.
Introduction: Tenvermectin (TVM) is a novel avermectin-class drug that has attracted attention for its superior antiparasitic potency, low toxicity, and broad-spectrum activity. However, uncertainty about its interaction with cytochrome P450 enzymes (CYPs) has raised concerns about potential therapeutic failure, increased risk of toxicity, dangerous drug combinations, and prolonged discontinuation periods.
Method: To address these critical safety concerns, we conducted a systematic comparative study using a highly selective and quantitatively accurate substrate conversion assay to assess and compare the effects of TVM and ivermectin (IVM) on the activities of key CYPs (CYP1A1/2, 2B1, 2C6, 2D2, and 3A1/2).
Rev Cardiovasc Med
August 2025
Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, 1090 Brussels, Belgium.
Despite continued advancements in transcatheter aortic valve implantation (TAVI) techniques, the incidence of permanent pacemaker implantation (PPI) remains substantial. Established predictors of PPI include advanced age, pre-existing electrocardiographic conduction abnormalities, prosthetic valve type, implantation depth, and anatomical parameters, such as membranous septum length, which are currently under active investigation. In routine clinical practice, the management strategy often involves the temporary placement of a transvenous pacemaker lead, followed by a period of observation.
View Article and Find Full Text PDFRev Cardiovasc Med
August 2025
Center for Coronary Heart Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases of China, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, 100037 Beijing, China.
Background: Globally, acute myocardial infarction (AMI) is among the primary causes of mortality. The ideal approach for blood pressure (BP) management for patients experiencing ST-segment elevation myocardial infarction (STEMI) who receive percutaneous coronary intervention (PCI) remains a topic of ongoing debate. Current guidelines on BP management lack specific recommendations for STEMI patients undergoing PCI, resulting in substantial individual variability and uncertainties in clinical treatment strategies.
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