Impairment in Working Memory and Executive Function Associated with Mercury Exposure in Indigenous Populations in Upper Amazonian Peru.

The Matsigenka people living traditional lifestyles in remote areas of the Amazon rely on a fish-based diet that exposes them to methylmercury (MeHg) at levels that have been associated with decreased IQ scores. In this study, the association between Hg levels and working memory was explored using the framework of the Multicomponent Model. Working memory tasks were modified to fit the culture and language of the Matsigenka when needed and included measures for verbal storage (Word Span) visuospatial storage (Corsi Block Task) and a measure of executive functions, the Self-Ordered Pointing Task (SOPT). An innovation of the Trail Making Tests A & B (TMT A & B) was pilot tested as another potential measure of executive functions. The mean hair Hg levels of 30 participants, ages 12 to 55 years, from three different communities (Maizal, Cacaotal and Yomibato) was 7.0 ppm (sd = 2.40), well above the World Health Organization (WHO) limit for hair of 2.0 ppm and ranged from 1.8 to 14.2 ppm, with 98% of a broader sample of 152 individuals exceeding the WHO limit. Hair Hg levels showed significant associations with cognitive performance, but the degree varied in magnitude according to the type of task. Hg levels were negatively associated with executive functioning performance (SOPT errors), while Hg levels and years of education predicted visuospatial performance (Corsi Block accuracy). Education was the only predictor of Word Span accuracy. The results show that Hg exposure is negatively associated with working memory performance when there is an increased reliance on executive functioning. Based on our findings and the review of the experimental research, we suggest that the SOPT and the Corsi Block have the potential to be alternatives to general intelligence tests when studying remote groups with extensive cultural differences.

Basket Designs: Statistical Considerations for Oncology Trials.

Progress in the areas of genomics, disease pathways, and drug discovery has advanced into clinical and translational cancer research. The latest innovations in clinical trials have followed with master protocols, which are defined by inclusive eligibility criteria and devised to interrogate multiple therapies for a given tumor histology and/or multiple histologies for a given therapy under one protocol. The use of master protocols for oncology has become more common with the desire to improve the efficiency of clinical research and accelerate overall drug development. Basket trials have been devised to ascertain the extent to which a treatment strategy offers benefit to various patient subpopulations defined by a common molecular target. Conventionally conducted within the phase II setting, basket designs have become popular as drug developers seek to effectively evaluate and identify preliminary efficacy signals among clinical indications identified as promising in preclinical study. This article reviews basket trial designs in oncology settings and discusses several issues that arise with their design and analysis.