A Monte Carlo study on the impact of indirect action on neutron relative biological effectiveness.

Recent Monte Carlo studies have linked the energy-dependent risk of neutron-induced stochastic effects to the relative biological effectiveness (RBE) of neutrons in inflicting difficult-to-repair clusters of lesions in nuclear deoxyribonucleic acid (DNA). However, an investigation on the damaging effects of indirect radiation action is missing from such studies. In this work, we extended our group's existing simulation pipeline by incorporating and validating a model for indirect action. Our updated simulation pipeline was used to study the impact of indirect action and estimate neutron RBE for inflicting clustered lesions in DNA. In our results, although indirect action significantly increased the average yield of DNA damage clusters, our neutron RBE values are lower in magnitude than previous estimates due to model limitations and the greater relative impact of indirect action in lower-linear energy transfer (LET) radiation than in higher-LET radiation.

Single-cell DNA sequencing-a potential dosimetric tool.

We hypothesised that single-cell whole-genome sequencing has the potential to detect mutational differences in the genomes of the cells that are irradiated with different doses of radiation and we set out to test our hypothesis using in silico and in vitro experiments. In this manuscript, we present our findings from a Monte Carlo single-cell irradiation simulation performed in TOPAS-nBio using a custom-built geometric nuclear deoxyribonucleic acid (DNA) model, which predicts a significant dose dependence of the number of cluster damages per cell as a function of radiation dose. We also present preliminary experimental results, obtained from single-cell whole-genome DNA sequencing analysis performed on cells irradiated with different doses of radiation, showing promising agreement with the simulation results.

A study of indirect action's impact on simulated neutron-induced DNA damage.

Objective.The risk of radiobiological stochastic effects associated with neutrons is strongly energy dependent. Recent Monte Carlo studies simulating neutron-irradiated nuclear DNA have demonstrated that this energy dependence is correlated with the relative biological effectiveness (RBE) of neutrons to inflict DNA damage clusters that contain difficult-to-repair double-strand breaks. However, these previous investigations were either limited to modeling direct radiation action or considered the effects of both direct and indirect action together without distinguishing between the two. In this study, we aimed to quantify the influence of indirect action in neutron irradiation scenarios and acquire novel estimations of the energy-dependent neutron RBE for inducing DNA damage clusters due to both direct and indirect action.Approach.We explored the role of indirect action in neutron-induced DNA damage by integrating a validated indirect action model into our existing simulation pipeline. Using this pipeline, we performed track-structure simulations of monoenergetic neutron irradiations (1 eV to 10 MeV) in a nuclear DNA model and analyzed the resulting simple and clustered DNA lesions. We repeated the irradiation simulations for 250 keV x-rays that acted as our reference radiation.Main results.Including indirect action significantly increased the occurrence of DNA lesions. We found that indirect action tends to amplify the damage due to direct action by inducing DNA lesions in the vicinity of directly-induced lesions, resulting in additional and larger damage clusters. Our neutron RBE results are qualitatively similar to but lower in magnitude than the established radiation protection factors and the results of previous similar investigations, due to the greater relative impact of indirect action in photon-induced damage than in neutron-induced damage.Significance.Although our model for neutron-induced DNA damage has some important limitations, our findings suggest that the energy-dependent risk of neutron-induced stochastic effects may not be completely modeled alone by the relative potential of neutrons to inflict clustered lesions via direct and indirect action in DNA damage.

Economic cost for implementation of the U.S. Food and Drug Administration's Code of Federal Regulations Title 21, Part 1271 in an egg donor program.

OBJECTIVE: To assess the economic cost of implementing the U.S. Food and Drug Administration's Code of Federal Regulations Title 21, Part 1271 for infectious screening of egg donors in our practice during the first year. DESIGN: Physicians and employees of our practice were surveyed to ascertain the scope of duties and the number of hours spent to implement the regulations. The economic cost to the practice and the cost of additional laboratories were calculated. SETTING: Private practice. PATIENT(S): Egg donors and recipient couples who underwent treatment in our center from May 25, 2005 (the day regulations became effective) to May 25, 2006; and physicians, administrators, and staff who were employed by the practice during this time frame. INTERVENTION(S): Using a questionnaire, structured interviews were conducted for all physicians and employees of our practice. The information regarding number of hours was provided to our chief financial officer, who calculated the cost to the practice. The cost that recipient couples paid for laboratory tests that would not otherwise be required to meet American Society for Reproductive Medicine guidelines and the cost of an external audit were also added to the overall practice costs to determine a total cost associated with the regulations in the first year. MAIN OUTCOME MEASURE(S): List of activities associated with implementation of the regulations, personnel hours involved to implement the regulations, and economic cost to the practice and to recipient couples. RESULT(S): The total number of personnel hours spent by our practice in preparation for implementation of the regulations was 623.3 hours. In the first year, 675.2 additional hours were required to implement the regulations for 40 donors who cycled during this time. The economic cost to the practice for both preparation and implementation of the regulations was $219, 838, and the cost of additional laboratory work borne by the recipient couples was $15,880. Thus, the total cost was calculated to be $235,718 at 1 year after implementation of the regulations. CONCLUSION(S): Implementation of the FDA 21 CFR, Part 1271 was associated with a very high economic cost, even if the costs incurred by the government to develop and implement the regulation are excluded.