Search

Nuclear weapons testing in the northern Marshall Islands between 1946 and 1958 resulted in ionizing radiation (IR) exposure of the thousands of Marshallese. Furthermore, numerous islands were contaminated by radioactive fallout. Significant increases in cancer and metabolic syndrome incidences have been reported among Marshallese, and potential for further increases looms due to the latency of radiation-induced health effects. The purpose of this study was to investigate the genetic and epigenetic effects of exposure to IR that could be associated with radiation-induced disease among the Northwest Arkansas (NWA) Marshallese. We performed analysis of chromosomal aberrations and DNA methylation based on residential and exposure history of NWA Marshallese. Analysis of chromosomal aberrations demonstrated higher incidence of genetic rearrangements in women with self-reported history of radiation exposure (95% CI: 0.10, 1.22; p=.022). Further clustering of study participants based on their residential history demonstrated that participants who spent substantial amounts of time (≥6 months) in the northern atolls (thus, in the proximity of nuclear tests) before 1980 had more chromosomal aberrations than their peers who lived only in the southern atolls (95% CI: 0.08, −0.95; p=.021), and that this difference was driven by women. A relationship between the time spent in the northern atolls and increase in chromosomal aberrations was observed: 0.31 increase in chromosomal aberrations for every 10 years spent at northern atolls (95% CI: 0.06, 0.57; p=.020). Finally, significant inverse correlations between the chromosomal aberrations and the extent of DNA methylation of four LINE-1 elements L1PA2, L1PA16, L1PREC1, and L1P4B were identified. The results of this study provide first evidence of the presence of stable genetic and epigenetic rearrangements in peripheral lymphocytes of NWA Marshallese and warrant further studies to analyze the role of radiation exposure in health disparities experienced by this Pacific Island nation. [ABSTRACT FROM AUTHOR]

Reid D. Landes comments on Frommlet and Heinze's 2021 article, focusing on improving statistical analyses in replicating animal trials. Frommlet and Heinze recommend a 'Mixed-model analysis' to allow treatment effects to vary among replications, finding that power increases with more replications. They suggest using Kenward and Roger's method for computing error degrees of freedom to align Type I error rates with nominal levels and increase power in certain settings. The results are computationally reproducible, with data and software code available upon request. [Extracted from the article]

There have been some concerns about the influence of medical X rays in dose-response analysis of atomic bomb radiation on health outcomes. Among atomic bomb survivors in the Life Span Study, the association between atomic bomb radiation dose and exposures to medical X rays was investigated using questionnaire data collected by a mail survey conducted between 2007–2011, soliciting information on the history of computed tomography (CT) scans, gastrointestinal fluoroscopy, angiography and radiotherapy. Among 12,670 participants, 76% received at least one CT scan; 77%, a fluoroscopic examination; 23%, an angiographic examination; and 8%, radiotherapy. Descriptive and multivariable-adjusted analyses showed that medical X rays were administered in greater frequencies among those who were exposed to an atomic bomb radiation dose of 1.0 Gy or higher, compared to those exposed to lower doses. This is possibly explained by a greater frequency in major chronic diseases such as cancer in the ≥1.0 Gy group. The frequency of medical X rays in the groups exposed to 0.005–0.1 Gy or 0.1–1.0 Gy did not differ significantly from those exposed to ,0.005 Gy. An analysis of finer dose groups under 1 Gy likewise showed no differences in frequencies of medical X rays. Thus, no evidence of material confounding of atomic bomb effects was found. Among those exposed to atomic bomb doses,1Gy, doses were not associated with medical radiation exposures. The significant association of doses ≥1 Gy with medical radiation exposures likely produces no substantive bias in radiation effect estimates because diagnostic medical X-ray doses are much lower than the atomic bomb doses. Further information on actual medical X-ray doses and on the validity of self-reports of X-ray procedures would strengthen this conclusion. [ABSTRACT FROM AUTHOR]

The relative potency of one agent to another is commonly represented by the ratio of two quantal response parameters; for example, the LD50 of animals receiving a treatment to the LD50 of control animals, where LD50 is the dose of toxin that is lethal to 50% of animals. Though others have considered interval estimators of LD50, here, we extend Bayesian, bootstrap, likelihood ratio, Fieller's and Wald's methods to estimate intervals for relative potency in a parallel-line assay context. In addition to comparing their coverage probabilities, we also consider their power in two types of dose designs: one assigning treatment and control the same doses vs. one choosing doses for treatment and control to achieve same lethality targets. We explore these methods in realistic contexts of relative potency of radiation countermeasures. For larger experiments (e.g., ≥100 animals), the methods return similar results regardless of the interval estimation method or experiment design. For smaller experiments (e.g., < 60 animals), Wald's method stands out among the others, producing intervals that hold closely to nominal levels and providing more power than the other methods in statistically efficient designs. Using this simple statistical method within a statistically efficient design, researchers can reduce animal numbers. [ABSTRACT FROM AUTHOR]