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Intracranial Effects of Artificial Gravity: A 3T MRI Study

INTRODUCTION Spaceflight associated neuro-ocular syndrome (SANS) is characterized by the development of optic disc edema, posterior globe flattening, choroidal/retinal folds and hyperopic refractive errors1. SANS is hypothesized to be a result of headward fluid shifts that invariably occurs in the microgravity environment. As a countermeasure, artificial gravity (AG) through centrifugation has been proposed to reduce this headward fluid shift, however there is no current proof of benefit. The goal of this study was to determine if the application of AG can prevent or reduce known changes in brain volumetry, internal carotid artery (ICA) stroke volume and cerebral spinal fluid (CSF) flow velocity that occurs during simulated chronic headward fluid shift using head down tilt bed rest (HDTBR) methodology2 as an indicator of countermeasure efficacy. METHODS Healthy volunteers were recruited for an IRB approved HDTBR study performed at the German Aerospace Center in Cologne, Germany. Strict six-degree HDTBR was used as a spaceflight analog to induce a continuous headward fluid shift. HDTBR was carried out for 60 days for all subjects. Short-arm centrifugation was utilized to generate AG equating to ~0.3g of acceleration at the level of the eye. The subjects were divided equally into three groups: NoAG (control; n=8), daily intermittent AG (6 x 5 min iAG; n=8), and daily continuous 30 min (cAG; n=8). All studies were performed on a single dedicated 3T MRI Scanner. Pulse-gated MRI phase-contrast flow imaging was used to quantify ICA stroke volume and peak-to-peak CSF flow velocity in the mid cerebral aqueduct. 3D-SPGR was acquired for volumetric segmentation of the brain and CSF spaces. MRI acquisitions were obtained at baseline (BDC), 14 days into HDTBR (HDTBR14), 52 days into HDTBR (HDTBR52) and 3-5 days after HDTBR (recovery, R+3/5).The data were analyzed by the mixed model, which included intervention and time (BDC, HDTBR 14, HDTBR 52, R+3/5) as the fixed effects and included subject as the random effect.RESULTS24 healthy subject volunteers (16 men, 8 women, mean age = 33 years ± 9 [standard deviation] and mean BMI = 24.3 kg/m2 ± 2.0) successfully completed all phases of the study. Strict six-degree HDTBR was characterized by progressive and statistically significant (p<.01) increases in mean combined brain and CSF volumes and mean aqueductal CSF peak-to-peak flow velocity, as well as statistically significant (p<.01) progressive decrease in mean ICA stroke volume from baseline to 52 days post intervention (Figs. 1-3). Compared to baseline, only combined brain and CSF volumes did not return to baseline values in the recovery period (p=NS). Neither iAG nor cAG exerted any significant effects on the measured MRI brain parameters as compared to HDTBR alone (p=NS). CONCLUSION Our results indicate that HDTBR at 6-degrees was effective in producing alterations in ICA stroke volume, aqueductal CSF flow velocity, and combined brain and CSF volumetric change that is associated with chronic headward fluid shift. Short duration, 30-min daily exposure to either iAG or cAG appears to be insufficient in preventing or reducing the effects of chronic HDTBR and thus may not be a suitable countermeasure as currently deployed. AG protocol modifications, including increased duration and magnitude of exposure, should be considered for future research.

L A Kramer↗

Empirical InfraRed Line Lists for Five SO2 Isotopologues: 32/33/34/36S16O2 and 32S18O2

Using the latest published, empirically refined potential energy surface (PES) Ames-1 and purely ab initio CCSD(T)/aug-cc-pVQZ dipole moment surface (DMS), we have computed Infrared line lists for five symmetric isotopologues of sulfur dioxide: 32S16O2 (626), 33S16O2 (636), 34S16O2 (646), 36S16O2 (666), and 32S18O2 (828). The line lists are based on J=0-80 rovibrational variational calculations with E’ ≤ 8000 cm-1. The 34S16O2 and 33S16O2 line lists are compared to the experiment-based models in the HIgh-resolution TRANsmission molecular absorption database (HITRAN2012, http://www.cfa.harvard.edu/hitran/) and the Cologne Database for Molecular Spectroscopy, CDMS (http://www.astro.uni-koeln.de/cdms/). The accuracy for computed 646 band origins is similar to what has been reported for the main isotopologue, i.e. 0.01 – 0.03 cm-1 for bands up to 5500 cm-1. For rovibrational transitions, the 646 line position and intensity deviation patterns are much simpler and more self-consistent than those of the main isotopologue 626. The discrepancies are mainly found for higher Ka/J transitions. 626 and 646 exhibit comparable line position and intensity agreement for lower Ka/J transitions. The line position deviations for the 636 purely rotational band are parallel to those of 626 and 646, while its line intensity deviations do not show branching patterns as we found in the 626 and 646 cases. Predictions for the other minor isotopologues are expected to exhibit similar accuracy. These line lists are accurate enough to provide alternatives for missing bands of 626 and the minor isotopologues. It may significantly facilitate the laboratory spectroscopic measurement and analysis, as well as to identify these isotopologues in various astrophysical environments.

Sulfur Dioxide↗

International Standard Measures During the AGBRESA Bed Rest Study

The Artificial Gravity Bed Rest with European Space Agency (AGBRESA) study involved 2 campaigns of 60-day bed rest at 6° head down tilt in the:envihab facility in Cologne, Germany, in 2019. The objective was to determine whether centrifugation of supine subjects mitigates physiological changes that occur due to the exposure to the spaceflight analog of 6° head down tilt. A set of international standard measures was used to evaluate bone, muscle, nutritional status, ocular changes, and psychological state and to assess cardiovascular, sensorimotor, and immune systems functions. After 60 days of bed rest, the subjects who were not exposed to centrifugation had significant decreases in mineral density at the hip and lumbar spine, decreased muscle strength of the knee and ankle, reduced maximal aerobic capacity, orthostatic intolerance, and impaired balance and locomotion, as well as significant biochemical, immunological, and psychological alterations. A daily 30-min exposure to 1 Gz supine centrifugation at the center of mass (0.3 Gz at the head, 2 Gz at the feet) mitigated mineral density loss in the femur neck and lumbar spine; and lessened the effects of bed rest on aerobic capacity, biochemistry, and immunology. However, low statistical power could contribute to the non-significant effects that are reported.

Bed rest↗

Standard measures in Analogs of Spaceflight

Standard measures are defined as research measures (physiological, performance, or otherwise) that quantify the subject’s health and performance before, during, and after a spaceflight or a spaceflight analog mission. The Standard Measures Cross-Cutting Project (SMCCP) collects and analyzes standard measures that support assessment and quantification of health risks and efficacy of countermeasures and technologies required to prevent or mitigate adverse outcomes from exposure to the spaceflight environment. SMCCP uses the following spaceflight analogs: - Human Exploration Research Analog (HERA) in Houston, TX: 4-person isolation/confinement; nominal mission duration of 45 days; run by the Human Research Program (HRP). SMCCP uses weekly questionnaires to gather data on the crewmembers’ emotional and mental state and collects blood samples biweekly to measure crewmembers’ serum cortisol levels at the start, middle, and end of the mission. - Institute for Biomedical Problems (IBMP) Ground-Based Experimental Complex, called NEK, in Moscow, Russia: 6-person isolation/confinement; duration of 8 months; run by IBMP. Standard measures data collected during NEK are the same as for HERA above. - :envihab in Cologne, Germany: 12-person bed rest facility; closed environment; 30 to 60-day campaigns; run by the German Aerospace Center (DLR). For bedrest studies, SMCCP uses the international standard measures as documented in the International Academy of Astronautics publication titled Guidelines for Standardization of Bed Rest Studies in the Spaceflight Context (June 2014). These international standard measures evaluate potential changes in bone, muscle, cardiovascular, and visual systems, as well as changes in psychology and nutrition. The international standard measures complement those collected during studies by individual investigators and allow comparison of responses across different bed rest and countermeasures durations. In this presentation, we will review available SMCCP data collected during the recent isolation studies in HERA (C6) and NEK (SIRIUS-21), and during the SANS (SM1, SM2) bed rest studies in :envihab. These standard measures datasets are made available to concurrent investigators in the given mission or campaign via data sharing agreements and/or data sharing plans and to other investigators that have been granted retrospective access to the data (researchers with IRB approved protocols, risk custodians) to advance understanding of physiological and behavioral risks associated with these spaceflight analogs.

Standard Measures↗

Intracranial Effects of Intermittent Lower Body Negative Pressure with Head Down Tilt Bed Rest: Comparison to Upright Posture

INTRODUCTION Spaceflight-associated neuro-ocular syndrome (SANS) affects a majority of astronauts during long-duration spaceflight. SANS is hypothesized to result from an unrelenting headward fluid shift that occurs in the microgravity environment. Altered intracranial structure and physiology documented in spaceflight and head-down tilt (HDT) experiments(1, 2) are also theorized to be related to chronic headward fluid shift and thereby can provide an independent quantitative assessment related to this mechanism. As a potential countermeasure, lower body negative pressure (LBNP) applied in the supine posture has shown efficacy in reducing headward fluid shift(3). However, it remains unknown if intermittent LBNP simulating daily upright posture fluid redistribution can mitigate SANS and intracranial changes associated with long-duration spaceflight. The goal of this study was to quantify the effects of daily application of LBNP or daily exposure to the upright posture on intracranial structure and physiology during long-term HDT in order to evaluate the potential efficacy of LBNP as a countermeasure to SANS. METHODS 22 healthy volunteers (11 men; 11 women; mean age = 35 years (SD=9.2)(age range = 24 to 52 years); mean BMI = 24.0 kg/m2 (SD=2.8)) completed an MRI study performed at the German Aerospace Facility in Cologne, Germany. Strict six-degree head-down tilt (HDT) bedrest was used as a spaceflight analog to induce a continuous headward fluid shift for 30 days. The subjects were divided equally into two groups of interventions: 1) LBNP for 3-hour sessions twice daily and 2) seated position for 3-hour sessions twice daily. Interventions were divided into morning and afternoon sessions for both groups. The LBNP intervention was maintained at 25 mmHg  2 mmHg. Pulse-gated MRI phase-contrast flow imaging was used to quantify cerebral artery stroke volume (CASV) and peak-to-peak cerebral spinal fluid (CSF) velocity (CSFVp-p) within the cerebral aqueduct. A 3D T1-MPRAGE sequence was used to quantify volumetric changes of the brain and intracranial CSF spaces using MRI Cloud software. MRI acquisitions were obtained at baseline (BDC, supine posture), 15 days into HDT (HDT15), 29 days into HDT (HDT29), and 12 days after recovery (R12, supine posture). The data were analyzed by a mixed model, which included intervention, time (four nominal levels BDC, HDT15, HDT29, R12), and intervention-time interaction as the fixed effects and included subject as a random effect. RESULTS Compared to BDC there was no statistically significant difference in CASV and CSFVp-p during HDT except for CASV at HDT29 (seated group) where there was a 1.7 mL (12%) decrease (P<0.01). Compared to BDC there was a statistically significant increase in intracranial volume (ICV; ICV = white matter + gray matter + CSF) for both interventions at HDT15 (Δ13 mL, 0.9 % (LBNP group); Δ15 mL, 1.0%, (seated group)) and HDT29 (Δ19 mL, 1.2%, (LBNP group); Δ23 mL, 1.5%) (seated group)) (All Ps<.001). Compared to baseline, lateral ventricular volume increased at HDT15 (Δ0.9 mL, 5.5%) and HDT29 (Δ1.8 mL, 10%)) for LBNP only (P=.001 for each). During HDT, white matter volume remained stable compared to baseline for both interventions. There were no significant intervention effects in the overall response to HDT (All Ps >.2). CONCLUSION LBNP had a similar response to the seated posture during 29 days of HDT. Although there was an increase in ICV and lateral ventricular volume with HDT there was no change in intracranial physiological parameters with LBNP suggesting an overall diminished response to the long-term effects of HDT. The lack of any significant increase in white matter volume during HDT with LBNP suggests maintenance of cerebral interstitial fluid transport. Final conclusions are pending the data collection for the control group (no intervention) which will be completed in 2023.

Larry A Kramer↗

Orbital-Radar v1.0.0: a tool to transform suborbital radar observations to synthetic EarthCARE cloud radar data

The Earth Cloud, Aerosol and Radiation Explorer (EarthCARE) satellite developed by the European Space Agency (ESA) and the Japan Aerospace Exploration Agency (JAXA) launched in May 2024 carries a novel 94 GHz cloud profiling radar (CPR) with Doppler capability. This work describes the open-source instrument simulator Orbital-Radar, which transforms high-resolution radar data from field observations or forward simulations of numerical models to CPR primary measurements and uncertainties. The transformation accounts for sampling geometry and surface effects. We demonstrate Orbital-Radar's ability to provide realistic CPR views of typical cloud and precipitation scenes. The presented case studies show small-scale convection, marine stratus clouds, and Arctic mixed-phase cloud cases. These results provide valuable insights into the capabilities and challenges of the EarthCARE CPR mission and its advantages over the CloudSat CPR. Finally, Orbital-Radar allows for evaluating kilometre-scale numerical weather prediction models with EarthCARE CPR observations. So, Orbital-Radar can generate calibration and validation (Cal/Val) data sets already pre-launch. Nevertheless, an evaluation of synthetic CPR output data to accurate EarthCARE CPR data is missing.

54 ENVIRONMENTAL SCIENCES↗

Confronting Large‐Eddy Simulations With Stereo Camera Data by Means of Reconstructed Hemispheric Cloud Size Distributions

High-resolution hemispheric camera images at a meteorological site in western Germany are used to analyze the multi-dimensional spatial characteristics of continental cumulus cloud fields, and to evaluate Large-Eddy Simulations on this aspect. Traditional non-hemispheric cloud-detecting instruments provide additional reference data. The main model-observation comparison focuses on cloud size distributions (CSDs), employing two methods: (a) directly using three-dimensional model fields, direct CSDs, and (b) using rendered hemispheric images of the model fields as produced by a camera simulator based on path-tracing. In the latter method, both the real and rendered images are used to three-dimensionally reconstruct the cloud fields, yielding hemispheric CSDs. Advantages of hemispheric comparisons over more classic approaches include (a) fair comparisons between model and data, and (b) full use of the enhanced resolutions and hemispheric spatial coverage of the camera imagery. Basic evaluation of the simulations demonstrates good agreement on thermodynamic structure and its diurnal cycle. Cloud heights and cloud cover are intercompared between the model, camera data and other instrumentation, providing insight into their structural differences. A consistent alignment is found between the hemispheric CSDs from both the model and the cameras. Power law fits reveal structurally lower exponents in hemispheric CSDs compared to non-hemispheric CSDs, which particularly caution against directly comparing hemispheric CSDs to non-hemispheric distributions. This result is robust for sample size and fitting method. These findings inform future use of hemispheric camera systems for studying cumulus cloud field morphology and model evaluation.

54 ENVIRONMENTAL SCIENCES↗

Synthesis and Characterization of Homo- and Heteroleptic Neptunium(IV) Heteroarylalkenolate Complexes

Heteroleptic An IV (An = U, Np) chlorido-ketoenaminate complexes of the type [AnCl 2 (TFB-tBuA) 2 (THF)] (An-1 type: U-1, Np-1; TFB-tBuA = 4-(tertbutylamino)- 1,1,1-trifluorobut-3-en-2-one) and the homoleptic Np IV heteroarylalkenolate complexes [Np(PyTFP) 4 ] (Np-2, PyTFP = 1-(pyridin-2-yl)-3,3,3-trifluoroprop- 1-en-2-ol) and [Np(DMOTFP) 4 ] (Np-3, DMOTFP = 1-(4,5-dimethyloxazol- 2-yl)-3,3,3-trifluoroprop-1-en-2-ol) were synthesized and characterized (SC-XRD, NMR, Vis-NIR, MS). While their solid-state structures compare well to those of their uranium analogues, the behavior in solution showed significant differences. The binding motif of the DMOTFP ligand in complex Np-3 can change to form two different complex isomers, as seen by paramagnetic chemical shifts in NMR experiments. Furthermore, the flexibility and the influence of the steric effects at the N-side of the ligands are discussed and compared with its uranium counterpart.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

On-Chip Tuning of Superconductivity in Fullerides via Current-Driven Rb + Intercalation

An in-operando electro-intercalation method for the on-chip synthesis of alkali-metal-intercalated materials and their Raman spectroscopic and transport characterization in ultrahigh vacuum (UHV) is developed. We apply this method to synthesize fulleride superconductors via Rb + intercalation into a C 60 film. During the intercalation, we monitor the stoichiometry via UHV-Raman spectroscopy and probe superconductivity via transport measurements. An increase of the superconducting transition temperature from 7.0 K to 14.5 K is observed when the stoichiometry is tuned from Rb 2.7 C 60 to Rb 3 C 60 . In our experiment, an ionic Rb+ flux into the host material is induced by an applied electronic current via a Butler–Volmer-type mechanism. Electro-intercalation captivates through improved stoichiometric precision, the ability to smoothly vary stoichiometry via duration of current application, and the absence of a lower limit of the volume of the host material. It represents a powerful concept for the on-chip synthesis of intercalated materials, battery research, and beyond.

Raman↗

Flower‐Type Organized Trade‐Wind Cumulus: A Multi‐Day Lagrangian Large Eddy Simulation Intercomparison Study

Shallow cumulus cloud fields in subtropical marine trade wind environments, particularly over the tropical Atlantic Ocean, show distinct organizational patterns. Among these, Flower‐type clouds are characterized by expansive stratiform cloud patches surrounded by regions of scattered convection. The objectives of this study were (a) to construct a case study of a time period during the EUREC 4 A/ATOMIC field campaign when Flower‐type organization was observed, (b) to evaluate the fidelity of a multi‐model ensemble of large eddy simulations of that case, and (c) to analyze the interaction between cloud and precipitation processes and mesoscale organization in the simulations. The simulations follow a quasi‐Lagrangian trajectory, allowing mesoscale features to develop over time in a domain that follows the boundary‐layer airmass. The results show a broad agreement in simulated thermodynamic properties across different LES codes, with Flower‐type cloud patches appearing within hours of each other. The consensus among models is consistent with observations made during the EUREC 4 A/ATOMIC field campaign on the specific day of interest. The cloud structure reveals three distinct peaks in the joint probability densities of cloud base and cloud top height, with the dominant peak at any given time influenced by the stage of cloud organization. The simulated cloud system evolution reveals consistent occurrence of maxima in liquid water path and rain rate before Flower reaches its maximum length scale. Targeted sensitivity tests reveal a weak relationship between Cloud Droplet Number concentration and the extent/degree/type of organization.

EUREC4A↗

Flat-band driven Kondo breakdown and reentrant effects in heavy-fermion moiré superlattices

Moiré superlattices (MSLs) in van der Waals heterostructures have demonstrated their incredible power in driving emergent electronic phenomena, some of which are reminiscent of those usually only observed in bulk strongly correlated quantum materials. With the recent discovery of van der Waals 𝑓-electron materials, the design of novel MSLs of intrinsic strong correlation is now within the reach. Here we study the novel electron phases of two-dimensional heavy-fermion MSL with increasingly diluted 𝑓-electron local moments. By applying dynamical mean-field theory with numerical renormalization group as an impurity solver, we demonstrate the appearance of a different energy scale and a reentrant Kondo breakdown in connection with the emergence of a flat band in the system. We further compare our numerical findings with predictions derived from the Lieb-Mattis theorem and show the necessity of this energy scale to consistently reconcile the predictions with the conventional single-impurity limit for exceedingly large unit cells.

36 MATERIALS SCIENCE↗

Almost strong zero modes at finite temperature

Interacting fermionic chains exhibit extended regions of topological degeneracy of their ground states as a result of the presence of Majorana or parafermionic zero modes localized at the edges. In the opposite limit of infinite temperature, the corresponding nonintegrable spin chains, obtained via generalized Jordan-Wigner mapping, are known to host so-called almost strong zero modes, which are long-lived with respect to any bulk excitations. Here we study the fairly unexplored territory that bridges these two extreme cases of zero and infinite temperature. We blend two established techniques for states, the Lanczos series expansion and a tensor network ansatz, uplifting them to the level of operator algebra. This allows us to efficiently simulate large system sizes for arbitrarily long timescales and to extract the temperature-dependent decay rates. We observe that for the Kitaev-Hubbard model, the decay rate of the edge mode depends exponentially on the inverse temperature 𝛽, and on an effective energy scale Δ eff that is greater than the thermodynamic gap of the system Δ.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Triaxiality of neutron-rich ruthenium nuclei studied by lifetime measurements

The breaking of axial symmetry in nuclei enables otherwise precluded behaviours, making it an interesting phenomenon to study. Experimental fingerprints such as very low-lying $2^+_2$ states suggest pronounced triaxial deformation for the neutron-rich ruthenium isotopes. Nevertheless, theoretical calculations differ in the description of the triaxial deformation and its evolution with neutron number, making experimental data crucial to understanding it. We investigated the evolution of the degree of triaxiality and $γ$ rigidity in neutron-rich ruthenium isotopes by measuring lifetimes of excited states in 108-112 Ru with the recoil distance Doppler-shift method. The experiment was carried out at the Grand Accélérateur National d’Ions Lourds using the Advanced Gamma Tracking Array coupled to the Variable Mode Spectrometer. We obtained B(E2) values for 29 transitions in the studied nuclei and compared them with fully microscopic symmetry conserving configuration mixing calculations, and phenomenological generalized triaxial rotor and triaxial particle-rotor models. The models generally reproduce the measured transition strengths, and show an increase in triaxiality with neutron number, reaching near maximum triaxiality in 112 Ru. The results are consistent with a transition from soft to rigid motion as the neutron number increases.

Heines, Johannes Sorby [Univ. of Oslo (Norway); No↗

The NASA ACTIVATE Mission

The NASA Aerosol Cloud Meteorology Interactions over the Western Atlantic Experiment (ACTIVATE) conducted 162 joint flights with two aircraft over the northwest Atlantic to study aerosol–cloud interactions (ACIs), which represent the largest uncertainty in estimating total anthropogenic radiative forcing. The combination of a high-flying King Air and low-flying HU-25 Falcon, equipped with remote sensing and in situ instruments, characterized trace gases, aerosol particles, clouds, and meteorological variables with data collected nearly simultaneously below, within, and above marine boundary layer (MBL) clouds. Flights spanning warm and cold seasons across 3 years (2020–22) provided a broad range of conditions associated with aerosol particles, cloud properties (including particle size and phase), and meteorology, ideally suited for robust ACI calculations and assessing how well models simulate a wide range of MBL clouds from stratiform to cumulus. ACTIVATE data suggest that drivers of cloud droplet number concentration N d , including aerosol particles and MBL dynamics, vary between winter and summer months with a stronger potential to convert aerosol particles into cloud droplets in winter. Models of varying complexity not only highlight some skills in simulating winter and summer cloud types but also identify challenges that still need to be addressed such as treatment of turbulence, wet scavenging, and mesoscale organization. Remote sensing advances range from new retrieval methods for N d , cloud phase classification, vertically resolved aerosol and cloud condensation nuclei number concentration, and ocean surface wind speed. This work describes these scientific and technological advances along with efforts in outreach and open data science.

aerosol indirect effect↗

Misclassification of primary liver cancer in the Life Span Study of atomic bomb survivors

Primary liver cancer is difficult to diagnose accurately at death, due to metastases from nearby organs and to concomitant diseases, such as chronic hepatitis and cirrhosis. Trends in diagnostic accuracy could affect radiation risk estimates for incident liver cancer by altering background rates or by impacting risk modification by sex and age. We quantified the potential impact of death‐certificate inaccuracies on radiation risk estimates for liver cancer in the Life Span Study of atomic bomb survivors. True‐positive and false‐negative rates were obtained from a previous study that compared death‐certificate causes of death with those based on pathological review, from 1958 to 1987. We assumed various scenarios for misclassification rates after 1987. We obtained estimated true positives and estimated false negatives by stratified sampling from binomial distributions with probabilities given by the true‐positive and false‐negative rates, respectively. Poisson regression methods were applied to highly stratified person‐year tables of corrected case counts and accrued person years. During the study period (1958–2009), there were 1,885 cases of liver cancer, which included 383 death‐certificate‐only (DCO) cases; 1,283 cases with chronic liver disease as the underlying cause of death; and 150 DCO cases of pancreatic cancer among 105,444 study participants. Across the range of scenarios considered, radiation risk estimates based on corrected case counts were attenuated, on average, by 13–30%. Our results indicated that radiation risk estimates for liver cancer were potentially sensitive to death‐certificate inaccuracies. Additional data are needed to inform misclassification rates in recent years.

French, Benjamin↗

Chromosome aberrations among atomic-bomb survivors exposed in utero: updated analysis accounting for revised radiation doses and smoking

A previous study of peripheral blood lymphocyte translocations around age 40 among atomic-bomb survivors exposed in utero revealed no overall association with radiation dose—despite a clear association between translocations and dose among their mothers—but the data suggested an increase at doses below 100 mGy with a definite peak. That analysis of the in utero-exposed survivors did not adjust for their subsequent smoking behavior, an established cause of chromosomal aberrations, or their subsequent exposures to medical irradiation, a potential mediator. In addition, atomic-bomb survivor radiation dose estimates have subsequently been updated and refined. We therefore re-estimated the dose response using the latest DS02R1 dose estimates and adjusting for smoking as well as for city and proximal–distal location at the time of exposure to the atomic bomb. Sex of the survivor, mother’s age around the time of conception, and approximate trimester of gestation at the time of exposure were also considered as explanatory variables and modifiers. Precision of the estimated dose response was slightly lower due to greater variability near zero in the updated dose estimates, but there was little change in evidence of a low-dose increase and still no suggestion of an overall increase across the entire dose range. Adjustment for smoking behavior led to a decline in background number of translocations (the dose–response intercept), but smoking did not interact with dose overall (across the entire dose range). Adjustment for medical irradiation did not alter the association between dose and translocation frequency. Sex, mother’s age, and trimester were not associated with number of translocations, nor did they interact with dose overall. Interactions with dose in the low-dose range could not be evaluated because of numerical instability.

59 BASIC BIOLOGICAL SCIENCES↗

Radiation effects on atherosclerosis in atomic bomb survivors: a cross-sectional study using structural equation modeling

Past reports indicated that total-body irradiation at low to moderate doses could be responsible for cardiovascular disease risks, but the mechanism remains unclear. The purpose of this study was to investigate the association between radiation exposure and atherosclerosis, an underlying pathology of cardiovascular diseases, in the Japanese atomic bomb survivors. We performed a cross-sectional study measuring 14 clinical-physiological atherosclerosis indicators during clinical exams from 2010 to 2014 in 3274 participants of the Adult Health Study cohort. Multivariable analyses were performed by using a structural equation model with latent factors representing underlying atherosclerotic pathologies: (1) arterial stiffness, (2) calcification, and (3) plaque as measured with indicators chosen a priori on the basis of clinical-physiological knowledge. Radiation was linearly associated with calcification (standardized coefficient per Gy 0.15, 95 % confidence interval: CI [0.070, 0.23]) and plaque (0.11, 95 % CI [0.029, 0.20]), small associations that were comparable to about 2 years of aging per Gy of radiation exposure, but not with arterial stiffness (0.036, 95 % CI [-0.025, 0.095]). The model fitted better and had narrower confidence intervals than separate ordinary regression models explaining individual indicators independently. The associations were less evident when the dose range was restricted to a maximum of 2 or 1 Gy. By combining individual clinical-physiological indicators that are correlated because of common, underlying atherosclerotic pathologies, we found a small, but significant association of radiation with atherosclerosis.

59 BASIC BIOLOGICAL SCIENCES↗