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For missions beyond low Earth orbit to the moon or Mars, space explorers will encounter a complex radiation field composed of various ion species with a broad range of energies. Such missions pose significant radiation protection challenges that need to be solved in order to minimize exposures and associated health risks. An innovative galactic cosmic ray simulator (GCRsim) was recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The GCRsim technology is intended to represent major components of the space radiation environment in a ground analog laboratory setting where it can be used to improve understanding of biological risks and serve as a testbed for countermeasure development and validation. The current GCRsim consists of 33 energetic ion beams that collectively simulate the primary and secondary GCR field encountered by humans in space over the broad range of particle types, energies, and linear energy transfer (LET) of interest to health effects. A virtual workshop was held in December 2020 to assess the status of the NASA baseline GCRsim. Workshop attendees examined various aspects of simulator design, with a particular emphasis on beam selection strategies. Experimental results, modeling approaches, areas of consensus, and questions of concern were also discussed in detail. This report includes a summary of the GCRsim workshop and a description of the current status of the GCRsim. This information is important for future advancements and applications in space radiobiology.

• w -Values are a source of uncertainty in reference dosimetry for hadrontherapy. • MDM-Ion is a Monte Carlo code developed for swift ions transport in liquid water. • w -Values shown to be independent of both particle charge and energy. • Electronic excitation and Auger electron emission strongly affect the results. • w -Values in liquid water should be used as a benchmark for microdosimetry. To develop a particle transport code to compute w -values and stopping power of swift ions in liquid water and gases of interest for reference dosimetry in hadrontherapy. To analyze the relevance of inelastic and post-collisional processes considered. The Monte Carlo code MDM was extended to the case of swift ion impact on liquid water (MDM-Ion). Relativistic corrections in the inelastic cross sections and the post-collisional Auger emission were considered. The effects of introducing different electronic excitation cross sections were also studied. The stopping power of swift ions on liquid water, calculated with MDM-Ion, are in excellent agreement with recommended data. The w- values show a strong dependence on the electronic excitation cross sections and on the Auger electron emission. Comparisons with other Monte Carlo codes show the relevance of both the processes considered and of the cross sections employed. W and w -values for swift electron, proton, and carbon ions calculated with the MDM and MDM-Ion codes are in very close agreement with each other and with the 20.8 eV experimental value. We found that w -values in liquid water are independent of ion charge and energy, as assumed in reference dosimetry for hadrontherapy from sparse experimental results for electron and ion impact on gases. Excitation cross sections and Auger emission included in Monte Carlo codes are critical in w -values calculations. The computation of this physical parameter should be used as a benchmark for micro-dosimetry investigations, to assess the reliability of the cross sections employed. [ABSTRACT FROM AUTHOR]

• Realistic dose enhancement of gold nanoparticles for X-rays with secondary particle equilibrium. • Novel approach to estimate uncertainty of correction for lack of secondary particle equilibrium. • Set of consistency checks allowed identifying and correcting normalization problems. • Good agreement of dose enhancement ratios for extended field within uncertainty of correction. • DERs deviate from unity only within the first few 100 nm and maximum values are below 20. Results of a Monte Carlo code intercomparison exercise for simulations of the dose enhancement from a gold nanoparticle (GNP) irradiated by X-rays have been recently reported. To highlight potential differences between codes, the dose enhancement ratios (DERs) were shown for the narrow-beam geometry used in the simulations, which leads to values significantly higher than unity over distances in the order of several tens of micrometers from the GNP surface. As it has come to our attention that the figures in our paper have given rise to misinterpretation as showing 'the' DERs of GNPs under diagnostic X-ray irradiation, this article presents estimates of the DERs that would have been obtained with realistic radiation field extensions and presence of secondary particle equilibrium (SPE). These DER values are much smaller than those for a narrow-beam irradiation shown in our paper, and significant dose enhancement is only found within a few hundred nanometers around the GNP. The approach used to obtain these estimates required the development of a methodology to identify and, where possible, correct results from simulations whose implementation deviated from the initial exercise definition. Based on this methodology, literature on Monte Carlo simulated DERs has been critically assessed. [ABSTRACT FROM AUTHOR]

• EURADOS organized an inter-code intercomparison of dose enhancement of gold nanoparticles irradiated by kVp X-ray spectra. • Variations and uncertainties of dose enhancement are observed by using multiple Monte Carlo codes. • This study gives a reference range of dose enhancement in simulating gold nanoparticles irradiated by x-ray spectra. • This intercomparison improved the simulation performances by identifying differences in settings, scoring and analysis. • Further inter-code intercomparisons ensure a high quality of dose assessment for gold nanoparticle-assisted radiotherapy. [ABSTRACT FROM AUTHOR]

• EURADOS organized an inter-code intercomparison of dose enhancement of gold nanoparticles irradiated by kVp X-ray spectra. • Variations and uncertainties of dose enhancement are observed by using multiple Monte Carlo codes. • This study gives a reference range of dose enhancement in simulating gold nanoparticles irradiated by X-ray spectra. • This intercomparison improved the simulation performances by identifying differences in settings, scoring and analysis. • Further inter-code intercomparisons ensure a high quality of dose assessment for gold nanoparticle-assisted radiotherapy. Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models. [ABSTRACT FROM AUTHOR]

Objective : To investigate the relationship of clinical response of Juvenile Idiopathic Arthritis (JIA) to etanercept (ETN) with ETN levels, and the presence of anti-drug antibodies to ETN (ADAb). Methods : Prospective study of JIA patients under 18 years old. Clinical and pharmacological data were collected at two visits. JIA clinical inactivity and activity were assessed according to the Wallace criteria and to the Juvenile Arthritis Disease Activity Score (JADAS). ETN and ADAb serum levels assessments were determined using ELISA-based assays. Results : 126 patients were enrolled. The median duration of ETN treatment at inclusion was 569 days (range 53–2340). ADAb were undetectable (<10 ng/ml) in 171/218 (78%) samples and were > 25 ng/mL in 2/218 samples. No significant relationship between ETN concentration and the clinical inactivity status and JIA activity was found using either univariate logistic regression or multiple logistic regression analysis, adjusted on one individual descriptors, time since diagnosis, time of sampling, use of corticosteroids or methotrexate and classification of JIA. No correlation was found between the remission status and the detection of ADAb. Conclusion: This study did not demonstrate any correlation between JIA activity and circulating ETN levels in a large population of patients with JIA previously treated with ETN for at least 1.5 months. As described for adults, our study confirms that ETN is marginally immunogenic in pediatric patients. These results do not support the clinical usefulness of a monitoring of ADAb or ETN concentrations for the management of this group of JIA patients if they fail to achieve clinical inactive disease. [ABSTRACT FROM AUTHOR]

It is evident that immediate skin-to-skin care after birth has the potential to improve breastfeeding outcomes and maternal satisfaction after a caesarean section; hence partners and infants should be present on the postoperative ward. Objective To investigate the intensive care nurses’ experiences of having the infant and partner present on the postoperative ward after emergency caesarean sections. Design Interviews with semi-structured interviews were conducted and analysed using qualitative content analysis. Setting The interviews were conducted at a hospital in Stockholm, Sweden; where close to 10,000 births occur each year. After a caesarean section the mother is treated on a postoperative ward for at least two hours. Eight intensive care nurses participated in the study. Result The analysis yields the theme ‘ The challenges of caring for infants on a postoperative unit ’ covering the following categories; collision between the intensive care nurse and midwife, responsibility versus knowledge and organisational issues. The study concluded that improved routines and increased continuity between involved clinics could improve care. There is also a need for education for staff involved in caesarean section regarding the benefits of early skin-to-skin care between the mother and her infant. [ABSTRACT FROM AUTHOR]

The use of radioisotopes in nuclear medicine is essential for diagnosing and treating cancer. The optimization of their production is a key factor in maximizing the production yield and minimizing the associated costs. An efficient approach to this problem is the use of Monte Carlo simulations prior to experimentation. By predicting isotopes yields, one can study the isotope of interest expected activity for different energy ranges. One can also study the target contamination with other radioisotopes, especially undesired radioisotopes of the wanted chemical element which are difficult to separate from the irradiated target and might result in increasing the dose when delivering the radiopharmaceutical product to the patient. The aim of this work is to build and validate a Monte Carlo simulation platform using the GEANT4 toolkit to model the solid target system of the South Australian Health and Medical Research Institute (SAHMRI) GE Healthcare PETtrace cyclotron. It includes a GEANT4 Graphical User Interface (GUI) where the user can modify simulation parameters such as the energy, shape and current of the proton beam, the target geometry and material, the foil geometry and material and the time of irradiation. The paper describes the simulation and presents a comparison of simulated and experimental/theoretical yields for various nuclear reactions on an enriched nickel 64 target using the GEANT4 physics model QGSP_BIC_AllHP, a model recently developed to evaluate with high precision the interaction of protons with energies below 200 MeV available in Geant4 version 10.1. The simulation yield of the 64 Ni(p,n) 64 Cu reaction was found to be 7.67 ± 0.074 mCi · μ A −1 for a target energy range of 9–12 MeV. Szelecsenyi et al. (1993) gives a theoretical yield of 6.71 mCi · μ A −1 and an experimental yield of 6.38 mCi · μ A −1 . The 64 Ni(p,n) 64 Cu cross section obtained with the simulation was also verified against the yield predicted from the nuclear database TENDL and compared to experimental yield obtained from literature. [ABSTRACT FROM AUTHOR]

The main challenge of radiotherapy is to focus the irradiation dose in cancer cells while preserving the healthy cells surrounding the tumor. Among the different strategies, the use of radiosensitizers aims to amplify the destructive effects of dose in the tumor [1] . Nanoparticles of heavy metals such as gold, are particularly promising radiosensitizers. If their radiosensitizer effect has been studied for about two decades, the origin of this phenomenon is yet quite unknown and barely quantified. Literature suggests that irradiation would generate a physical effect called Auger cascades. This effect would lead to a local increase secondary electrons around the nanoparticle, thus amplifying the critical cell damages of direct sensible molecules such as DNA, or through a boost of free radicals. These effects are produced at nanometric scales and at very short time ( 10 - 15 to 10 - 12 seconds) but have consequences on the patient scale. Because these physical and chemical effects are not directly observable, the simulation tool is therefore mandatory to better understand the initial mechanisms. Our goal is to first develop a simulation that enables us to calculate the spatial dose and free radicals distribution around the nanoparticles, and to quantify the induced boost [2,3] . To achieve this first step, we developed a low energy Monte Carlo code which can, on nanometric scales, track secondary electrons down to thermalization energy both in water and gold. Solid physics models have been implemented for gold (surface/bulk plasmons), and the code accounts for macroscopic potential differences between two media. Secondly, we want to inject the results in the model NanOx [4] , originally developed at IPNL to calculate the biological dose in hadrontherapy. These two allow us to assess the quality of our models, and the relevance of the scenarii offered in literature. The final aim is to guide the development of the nanoparticles and, if possible, to help to planify clinical treatment of nanoparticle-based radiotherapy. We show a dependance of the nanodosimetry in a specific range around nanoparticles according to the energy (20–90 keV) of photons and the nanoparticle size, and the impact in the free radical production compared to pure water. [ABSTRACT FROM AUTHOR]

Objective: Various gonadotropins are used for ovarian stimulation (OS). This study investigated the cost-effectiveness of different gonadotropins based on real-world data from the French National Health Database (SNDS) over a 7-year follow-up of assisted reproductive technology (ART) treatments., Design: Cost-effectiveness analysis of different gonadotropins based on real-world data from the SNDS was conducted., Participants: Women from SNDS undergoing OS leading to oocyte pick-up registered between January 31, 2013, and December 31, 2018 (N = 245,534 stimulations), and receiving either recombinant human follicle stimulating hormone (r-hFSH alfa originator; 110,439), its biosimilars (12,287), or urinaries (mainly highly purified human menopausal gonadotropin [HP-hMG; 65,654] and marginally highly purified urinary-human follicle stimulating hormone [7,821]) were included (follow-up: December 31, 2019)., Settings and Methods: Clinical inputs for this model, including live birth (LB) and cumulative LB (CLB) were calculated from data as published in [Best Pract Res Clin Obstet Gynaecol. 2023;88:102308]. A decision-tree model was developed comprising pregnancy and live birth rate (LBR) states for a complete ART cycle, including one fresh and ≤4 frozen/thawed embryo transfers and related costs. Cost inputs included those of drugs, ART procedure, pregnancy and delivery, and adverse events. Cost per LB and CLB and incremental cost-effectiveness ratio (ICER) were assessed. Robustness of results was determined by comprehensive sensitivity analyses., Results: Overall, r-hFSH alfa originator was found to be associated with a lower cost per LB and per CLB (cost per LB: EUR 26,010; CLB: EUR 22,278) versus its biosimilars (cost per LB: EUR 28,037; CLB: EUR 23,807) and versus urinaries (cost per LB: EUR 26,636; CLB: EUR 23,335). Calculated ICERs with r-hFSH alfa for LB were EUR 5,538 and EUR 14,090, whereas for CLB were EUR 1,945 and EUR 13,742 versus biosimilars and urinaries, respectively. Cost-effectiveness acceptability curve showed that in a majority of iterations, r-hFSH alfa originator had a probability of being cost-effective at a hypothetical threshold of EUR 20,000/LB. Sensitivity analyses showed that the most important variable impacting the outcome in fresh transfers was the probability of birth for biosimilars and the probability of pregnancy for urinaries, while for cumulative transfers, it was the probability of pregnancy for biosimilars and the probability of birth for urinaries., Limitations: As the clinical data were obtained from a non-interventional study and not a randomized controlled trial, the results may still be susceptible to residual confounding or other biases., Conclusions: r-hFSH alfa originator is cost-effective compared to its biosimilars and to urinaries (mainly HP-hMG) and is associated with a lower cost per LB compared to these gonadotropins, where the main driver is the higher LB efficacy rate achieved with it., (© 2024 The Author(s). Published by S. Karger AG, Basel.)