AI Article Synopsis
- The paper explores how different patterns of excess mortality affect the interpretation of 2-year rodent studies used to assess cancer risks.
- It offers experimental design suggestions to improve the studies' value, including reducing doses and considering terminating entire studies instead of just certain dose groups.
- Additionally, it recommends statistical analysis changes, including a new test for determining if a dose group exceeds the maximum tolerated dose, while emphasizing the importance of consulting with regulatory agencies like the FDA before implementing any changes.
Article Abstract
This paper considers the impacts of various patterns of differential or excess mortality on the biological and statistical interpretation of 2-year rodent carcinogenicity studies. It provides suggestions on experimental design that are intended to maximize the value of such studies for carcinogenic risk assessment. Specifically, it recommends dose reduction, possibly to the level of dose cessation, when biologically feasible and considers the merits of termination of the entire study as alternatives to the commonly employed strategy of terminating particular dose groups. It then recommends statistical analysis modifications that are appropriate when these suggestions on experimental design are adopted. One of the recommended modifications is a new statistical test to determine whether a dose group exceeds the maximum tolerated dose (MTD) on the basis of mortality. While the authors provide recommendations for the most commonly occurring exigencies, they acknowledge the need for and strongly support the practice of active engagement of the appropriate regulatory agency, e.g., the FDA, prior to any action.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/01926230701748214 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
National early warning score 2 plus non-invasive capnography and perfusion index to estimate poor outcomes in emergency departments.
Am J Emerg Med
January 2025
Faculty of Medicine, Universidad de Valladolid, Valladolid, Spain; Emergency Department, Hospital Clínico Universitario, Gerencia Regional de Salud de Castilla y León, Valladolid, Spain.
Background: The study of the inclusion of new variables in already existing early warning scores is a growing field. The aim of this work was to determine how capnometry measurements, in the form of end-tidal CO2 (ETCO2) and the perfusion index (PI), could improve the National Early Warning Score (NEWS2).
Methods: A secondary, prospective, multicenter, cohort study was undertaken in adult patients with unselected acute diseases who needed continuous monitoring in the emergency department (ED), involving two tertiary hospitals in Spain from October 1, 2022, to June 30, 2023.
Dynamic treeline and cryosphere response to pronounced mid-Holocene climatic variability in the US Rocky Mountains.
Proc Natl Acad Sci U S A
January 2025
Department of Earth Sciences, Montana State University, Bozeman, MT 59717.
Climate-driven changes in high-elevation forest distribution and reductions in snow and ice cover have major implications for ecosystems and global water security. In the Greater Yellowstone Ecosystem of the Rocky Mountains (United States), recent melting of a high-elevation (3,091 m asl) ice patch exposed a mature stand of whitebark pine () trees, located ~180 m in elevation above modern treeline, that date to the mid-Holocene (c. 5,950 to 5,440 cal y BP).
View Article and Find Full Text PDFThe interaction of bacteria and harmonine in harlequin ladybird confers an interspecies competitive edge.
Proc Natl Acad Sci U S A
January 2025
Zhejiang Key Laboratory of Biology and Ecological Regulation of Crop Pathogens and Insects, Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
The harlequin ladybird, , is a predatory beetle used globally to control pests such as aphids and scale insects. Originating from East Asia, this species has become highly invasive since its introduction in the late 19th century to Europe and North America, posing a threat to local biodiversity. Intraguild predation is hypothesized to drive the success of this invasive species, but the underlying mechanisms remain unknown.
View Article and Find Full Text PDFHydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.
Proc Natl Acad Sci U S A
January 2025
Cancer Biology & Genetics Program, Sloan Kettering Institute, New York, NY 10065.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.
View Article and Find Full Text PDFUnveiling Sociocultural Barriers to Breast Cancer Awareness Among the South Asian Population: Case Study of Bangladesh and West Bengal, India.
JMIR Hum Factors
January 2025
New College of Florida, Sarasota, FL, United States.
Background: Bangladesh and West Bengal, India, are 2 densely populated South Asian neighboring regions with many socioeconomic and cultural similarities. In dealing with breast cancer (BC)-related issues, statistics show that people from these regions are having similar problems and fates. According to the Global Cancer Statistics 2020 and 2012 reports, for BC (particularly female BC), the age-standardized incidence rate is approximately 22 to 25 per 100,000 people, and the age-standardized mortality rate is approximately 11 to 13 per 100,000 for these areas.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!