Fabrication, defect chemistry and microstructure of Mn-doped UO2.

Mn-doped UO2 is under consideration for use as an accident tolerant nuclear fuel. We detail the synthesis of Mn-doped UO2 prepared via a wet co-precipitation method, which was refined to improve the yield of incorporated Mn. To verify the Mn-doped UO2 defect chemistry, X-ray absorption spectroscopy at the Mn K-edge was performed, in addition to X-ray diffraction, Raman spectroscopy and high-energy resolved fluorescence detection X-ray absorption near edge spectroscopy at the U M4-edge. It was established that Mn2+ directly substitutes for U4+ in the UO2 lattice, accompanied by oxygen vacancy (Ov) charge compensation. In contrast to other divalent-element doped UO2 materials, compelling evidence for U5+ in a charge compensating role was not found. This work furthers understanding of the structure and crystal chemistry of Mn-doped UO2, which could show potential advantages as a novel efficient advanced nuclear fuel.

Cdk12 maintains the integrity of adult axons by suppressing actin remodeling.

The role of cyclin-dependent kinases (CDKs) that are ubiquitously expressed in the adult nervous system remains unclear. Cdk12 is enriched in terminally differentiated neurons where its conical role in the cell cycle progression is redundant. We find that in adult neurons Cdk12 acts a negative regulator of actin formation, mitochondrial dynamics and neuronal physiology. Cdk12 maintains the size of the axon at sites proximal to the cell body through the transcription of homeostatic enzymes in the 1-carbon by folate pathway which utilize the amino acid homocysteine. Loss of Cdk12 leads to elevated homocysteine and in turn leads to uncontrolled F-actin formation and axonal swelling. Actin remodeling further induces Drp1-dependent fission of mitochondria and the breakdown of axon-soma filtration barrier allowing soma restricted cargos to enter the axon. We demonstrate that Cdk12 is also an essential gene for long-term neuronal survival and loss of this gene causes age-dependent neurodegeneration. Hyperhomocysteinemia, actin changes, and mitochondrial fragmentation are associated with several neurodegenerative conditions such as Alzheimer's disease and we provide a candidate molecular pathway to link together such pathological events.

Solar particle event storm shelter requirements for missions beyond low Earth orbit.

Protecting spacecraft crews from energetic space radiations that pose both chronic and acute health risks is a critical issue for future missions beyond low Earth orbit (LEO). Chronic health risks are possible from both galactic cosmic ray and solar energetic particle event (SPE) exposures. However, SPE exposures also can pose significant short term risks including, if dose levels are high enough, acute radiation syndrome effects that can be mission- or life-threatening. In order to address the reduction of short term risks to spaceflight crews from SPEs, we have developed recommendations to NASA for a design-standard SPE to be used as the basis for evaluating the adequacy of proposed radiation shelters for cislunar missions beyond LEO. Four SPE protection requirements for habitats are proposed: (1) a blood-forming-organ limit of 250 mGy-equivalent for the design SPE; (2) a design reference SPE environment equivalent to the sum of the proton spectra during the October 1989 event series; (3) any necessary assembly of the protection system must be completed within 30 min of event onset; and (4) space protection systems must be designed to ensure that astronaut radiation exposures follow the ALARA (As Low As Reasonably Achievable) principle.

Knowledge, group-based medical mistrust, future expectations, and perceived disadvantages of medical genetic testing: perspectives of Black African immigrants/refugees.

BACKGROUND: Reasons for low participation of ethnic minorities in genetic studies are multifactorial and often poorly understood. Based on published literature, participation in genetic testing is low among Black African immigrants/refugees although they are purported to bear disproportionate disease burden. Thus, research involving Black African immigrant/refugee populations that examine their perspectives on participating in genetic studies is needed. OBJECTIVES: This report examines and describes the knowledge of medical genetics, group-based medical mistrust, and future expectations of genetic research and the influence of these measures on the perceived disadvantages of genetic testing among Black African immigrants/refugees. METHODS: Using a cross-sectional survey design, a nonprobability sample (n = 212) of Black African immigrants/refugees was administered a questionnaire. Participants ranged in age from 18 to 61 years (mean = 38.91, SD = 9.78). The questionnaire consisted of 5 instruments: (a) sociodemographic characteristics, (b) Knowledge of Medical Genetics scale, (c) Group-Based Medical Mistrust Scale, (d) Future Expectations/Anticipated Consequences of Genetics Research scale, and (e) Perceived Disadvantages of Genetic Testing scale. RESULTS: Participants were concerned that genetic research may result in scientists 'playing God,' interfering with the natural order of life. In multivariate analyses, the perceived disadvantages of genetic testing increased as medical mistrust and anticipated negative impacts of genetic testing increased. Increase in genetic knowledge contributed to a decrease in perceived disadvantages. CONCLUSIONS: Our findings suggest that recruitment of Black African immigrants/refugees in genetic studies should address potential low knowledge of genetics, concerns about medical mistrust, the expectations/anticipated consequences of genetic research, and the perceived disadvantages of genetic testing.

Health-related quality of life of HIV-infected intravenous drug users.

To investigate health-related quality of life in HIV-infected intravenous drug users registered but not engaged in HIV outpatient care (missing ≥2 outpatient appointments over 1 year or non-attendance for ≥6 months) we conducted a cross-sectional study to examine health-related quality of life of HIV-infected intravenous drug users registered for care at an inner city HIV unit. EQ-5D, SF-36, SF-6D, mood disorder, clinical and substance misuse data were collected. Mean scores and preference derived utility scores were calculated. Statistical relationships between health-related quality of life and other variables were explored using univariate and multivariate analysis. Fifty-five patients were recruited, 64% were males. The mean anxiety value was 11.44 (anxious) and mean depression score was 9.3 (borderline depressed). The mean EQ-5D utility was 0.45 (95% CI 0.35, 0.55) and mean SF-6D utility was 0.52 (95% CI 0.48, 0.55). There was no statistical relationship between HIV indices, substance misuse and EQ-5D and SF-6D utility. Anxiety and depression were significantly correlated with EQ-5D and SF-6D utility values on univariate and multivariate analysis. Health-related quality of life was reduced in this HIV-infected intravenous drug user population. Whilst hepatitis C co-infection and substance misuse did not affect health-related quality of life, anxiety and depression had a significant impact on it.

Chronic cocaine exposure during pregnancy increases postpartum neuroendocrine stress responses.

The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, Sprague-Dawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 1-20). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured before and after testing throughout the test day, whereas plasma and brain oxytocin concentrations were measured post-testing only. The results obtained indicated increased CORT response after the OFT in CC-treated dams (P ≤ 0.05). CC-treated dams also exhibited altered FST behaviour (P ≤ 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (P ≤ 0.05). Peripheral oxytocin and CORT increased after the FST, regardless of treatment condition (P ≤ 0.05). Changes in stress-responsiveness, both behaviourally and hormonally, may underlie some deficits in maternal behaviour; thus, a clearer understanding of the effect of CC on the stress response system may potentially lead to treatment interventions that could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations.

Charged particle equilibrium effects on the electron absorbed fraction in the extrathoracic airways.

Estimates of the dose to the extrathoracic airway (nasal vestibule) from inhaled beta-emitting radionuclides, obtained using the respiratory tract model presented in Publication 66 of the International Commission on Radiological Protection, frequently predict that the basal cells in this region are the most highly irradiated tissues of the body. The dose to the basal cells is averaged over a layer of tissue 10 microm thick located at a depth of 40 microm into the airway assuming that charged particle equilibrium exists. Since the target (basal cell layer) is very small and thin (10 cm(2) area and 10 microm thickness), charged particle equilibrium does not exist. In this work the effect on the absorbed fraction of the lack of charged particle equilibrium is investigated.

Shielding for a cyclotron used for medical isotope production in China.

Monte Carlo and discrete ordinate calculations have been performed to determine the doses at several locations in a positron emission tomography (PET) facility in China, where the radiation source is a cyclotron that is used for the production of the isotopes necessary for PET scans. The energy-dependent neutron source term is obtained by calculations using the ALICE code, and is interpolated for input to Monte Carlo and discrete ordinate calculations. The building that houses the cyclotron has a labyrinth of walls to minimise dose to operators and to other occupants of the building. Unbiased Monte Carlo calculations did not converge after more than one week of CPU time, whereas direction biasing alone resulted in convergence in several days. A study of several biasing techniques indicated that about a factor of 3 in computational efficiency is obtained using evaluated biasing methods. The use of adjoint fluxes for biasing Monte Carlo calculations can improve computational efficiencies by one or two orders of magnitude for some problems.

Premorbid adjustment in first episode schizophrenia and schizoaffective disorders: a comparison of social and academic domains.

OBJECTIVE: Recent evidence suggests that premorbid adjustment in schizophrenia and related disorders can be separated into social and academic domains. In this paper, we examine the correlates of and prognostic significance of social and academic premorbid adjustment in a sample of 113 patients. METHOD: Premorbid adjustment, symptoms and cognitive functioning were assessed at presentation for treatment and symptoms were re-assessed after a year of treatment. RESULTS: Females and those with a diagnosis of schizoaffective disorder were found to have better premorbid adjustment in the academic domain, but not in the social domain. Neurocognitive functioning was more consistently related to academic than social adjustment. Better social and academic premorbid adjustment was correlated with lower negative symptoms after 1 year of treatment, but neither was a significant predictor of positive symptoms. CONCLUSION: Social and academic premorbid adjustments show different relations to gender, specific diagnosis and neurocognitive functioning in schizophrenia and related disorders.

Multiple solar particle event dose time profile predictions using Bayesian inference.

The prediction of solar particle event occurrence and the resulting effects on humans and electronics continues to be a mission and/or life-threatening concern for the National Aeronautics and Space Administration and military and commercial satellite operators. While the frequency of events generally follows the solar cycle, individual event occurrence is sporadic and the prediction of resulting effects prior to the event onset is difficult. In one approach to space weather prediction, the forecaster begins to make predictions after the onset of an event. Previous work proved the efficacy of a forecasting methodology that used Bayesian inference and dose and/or dose rate information obtained early after the onset of an event to make predictions of dose and dose rate time profiles out to 120 h beyond onset. The previous work, however, was restricted to predictions for single-event solar particle events. Some of the largest recorded events, including the October 1989 and August 1972 events, were actually multiple events. In this study, we present an analysis of nine large events, some single and some multiple. This work ties together particle flux and fluence data with dose rate and dose calculations in an effort to develop a criterion for characterising an event as multiple and thus, generalising the Bayesian methodology to allow predictions for all events. Dose time profile predictions are made for the four separate events that made up the October 1989 event.

SPE dose prediction using locally weighted regression.

When astronauts are outside Earth's protective magnetosphere, they are subject to large radiation doses resulting from solar particle events. The total dose received from a major solar particle event in deep space could cause severe radiation poisoning. The dose is usually received over a 20-40 h time interval but the event's effects may be reduced with an early warning system. This paper presents a method to predict the total dose early in the event. It uses a locally weighted regression model, which is easier to train, and provides predictions as accurate as the neural network models that were used previously.

HETC radiation transport code development for cosmic ray shielding applications in space.

In order to facilitate three-dimensional analyses of space radiation shielding scenarios for future space missions, the Monte Carlo radiation transport code HETC is being extended to include transport of energetic heavy ions, such as are found in the galactic cosmic ray spectrum in space. Recently, an event generator capable of providing nuclear interaction data for use in HETC was developed and incorporated into the code. The event generator predicts the interaction product yields and production angles and energies using nuclear models and Monte Carlo techniques. Testing and validation of the extended transport code has begun. In this work, the current status of code modifications, which enable energetic heavy ions and their nuclear reaction products to be transported through thick shielding, are described. Also, initial results of code testing against available laboratory beam data for energetic heavy ions interacting in thick targets are presented.

Overview of secondary neutron production relevant to shielding in space.

An overview of experimental secondary neutron measurements relevant to space-related activities is presented. Stopping target yields and cross section measurements conducted at particle accelerators using heavy ions with energies > 100 MeV per nucleon are discussed.

SPE dose prediction using locally weighted regression.

When astronauts are outside earth's protective magnetosphere, they are subject to large radiation doses resulting from solar particle events (SPEs). The total dose received from a major SPE in deep space could cause severe radiation poisoning. The dose is usually received over a 20-40 h time interval but the event's effects may be mitigated with an early warning system. This paper presents a method to predict the total dose early in the event. It uses a locally weighted regression model, which is easier to train and provides predictions as accurate as neural network models previously used.

Double-differential heavy-ion production cross sections.

Current computational tools used for space or accelerator shielding studies transport energetic heavy ions either using a one-dimensional straight-ahead approximation or by dissociating the nuclei into protons and neutrons and then performing neutron and proton transport using Monte Carlo techniques. Although the heavy secondary particles generally travel close to the beam direction, a proper treatment of the light ions produced in these reactions requires that double-differential cross sections should be utilised. Unfortunately, no fundamental nuclear model capable of serving as an event generator to provide these cross sections for all ions and energies of interest exists currently. Herein, we present a model for producing double-differential heavy-ion production cross sections that uses heavy-ion fragmentation yields produced by the NUCFRG2 fragmentation code coupled with a model of energy degradation in nucleus-nucleus collisions and systematics of momentum distributions to provide energy and angular dependences of the heavy-ion production.

Double-differential light-ion production cross sections.

Codes used for space radiation shielding studies typically transport light-ions from the incident cosmic ray spectrum using either a one-dimensional straight-ahead approximation or in three dimensions, often without accounting for their breakup. Light-ions are also produced by breakup of energetic heavy ions in target materials. Herein, we present cross section models that can be used to predict double-differential light-ion production cross sections. Deuteron breakup is based on a parameterization of the total reaction cross sections. Alpha fragmentation utilizes a parameterization based on an abrasion-ablation model that has been augmented by experimental data. Neutron and proton production is modelled with a quantum mechanical abrasion-ablation-coalescence model. This same model is also used to predict cross sections for triton and 3He breakup. Finally, energies and emission angles for particles other than nucleons are specified using a model of energy degradation in nucleus-nucleus collisions and systematics of momentum distributions.

Electron absorbed fractions based on a new model of the anterior nasal passage.

In a previous work we reported that the fraction of the electron energy absorbed in the basal cell layer of the anterior nasal passages was not very sensitive to changes in the surface area or radius of the cylindrical model adopted in Publication 66 of the International Commission on Radiological Protection. These absorbed fraction data are used in calculation of the dose to a 10-microm-thick basal cell layer located at a depth of 40 microm in the epithelial cell layer of the extrathoracic (ET1) region. However, these data may only be applicable to the assumed cylindrical geometry and may not be valid for more realistic ET1 geometries. The nose differs in size and shape from one person to another, its shape is not cylindrical but closer to a truncated elliptical cone, and in most humans the nostrils are elliptical in shape. We propose herein a more realistic geometry model, the frustum of a cone, for the anterior nose region (ET1) as an alternative to the cylinder model provided in ICRP 66. The results of absorbed fraction calculations using MCNP4B with the new model are reported. These absorbed fractions are compared to the values previously obtained using the MCNP4B code and a cylindrical model (10 cm2 surface area). We also investigate the effects of changing the size of the truncated cone to represent variations due to sex and age.

Interplanetary crew doses and dose equivalents: variations among different bone marrow and skin sites.

Previously, calculations of bone marrow dose from the large solar particle event (SPE) of July 2000 were carried out using the BRYNTRN space radiation transport code and the computerized anatomical man (CAM) model. Results indicated that the dose for a bone marrow site in the mid-thigh might be twice as large as the dose for a site in the pelvis. These large variations may be significant for space radiation protection purposes, which traditionally use an average of many (typically 33) sites throughout the body. Other organs that cover large portions of the body, such as the skin, may also exhibit similar variations with doses differing from site to site. The skin traditionally uses an average of 32 sites throughout the body. Variations also occur from site to site among the dose equivalents, which may be important in determining stochastic effects. In this work, the magnitudes of dose and dose equivalent variations from site to site are investigated. The BRYNTRN and HZETRN transport codes and the CAM model are used to estimate bone marrow and skin doses and dose equivalents as a function of position in the body for several large solar particle events and annual galactic cosmic ray spectra from throughout the space era. These position-specific results are compared with the average values usually used for radiation protection purposes. Various thicknesses of aluminum shielding, representative of nominal spacecraft, are used in the analyses.