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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Configuration and Projected Capabilities of the Common Habitat Medical Care Facility

The Common Habitat is a large, long-duration habitat being explored as part of a conceptual study (not an active NASA program) that uses an SLS core stage Liquid Oxygen (LOX) tank as its primary structure. It is intended for use on the Moon as part of a permanently occupied outpost, on Mars as part of an outpost that will be occupied for hundreds of days at a time, and in deep space as part of the Deep Space Exploration Vehicle where it will support crewed missions up to 1200 days in duration. A study of internal orientation and crew size resulted in a Common Habitat configuration sized for a crew of eight with a three-deck horizontal orientation. Additional work outside the scope of this paper is developing a vertical translation system, a crew mobility aids system based on wearable gecko-derived grippers, and a crew seating/restraint system. These systems are all assumed for use in conjunction with the Medical Care Facility, which is needed to maintain crew well-being during these missions, where distance from Earth precludes the possibility of evacuation to Earth. This paper describes recent improvements in the Common Habitat Medical Care Facility and associated benefits for crew survivability in long duration missions beyond Earth orbit. These improvements were made with the assistance of a NASA Pathways intern whose experience includes a tour of duty in Afghanistan as an Army combat medic with the 691st GHOST-T, attached to the 1st and 7th US Special Forces Groups as part of Operation Freedom’s Sentinel, where he helped provide far-forward surgical capabilities in austere combat environments. The initial baseline Medical Care Facility was developed working in conjunction with University of Houston Space Architecture graduate students. The facility was placed on the upper deck of the Common Habitat in a location that provided privacy, operational volume, and was close to the vertical translation pathway. The notional outfitting repurposed component CAD models from unrelated studies and notionally indicated a level of care roughly equivalent to that aboard the International Space Station. The CAD modeling provided notional stowage volumes, a deployable surface, some fixed equipment, an ultrasound, and a potentially reconfigurable treatment table. While this facility is clearly a competent arrangement, it was desired to leverage available expertise and upgrade the station given the vast distances from Earth to be experienced by the Common Habitat. Key driving requirements applied to the upgrade included to provide NASA’s Medical Level of Care V, offer enhanced telemedicine capabilities, provide patient physical accommodation, provide caregiver access to the patient from all sides, include sliding pocket doors for access to hygiene and to the Vertical Translation System, and to add any additional capability possible for the best achievable medical care. The first step in the facility upgrade was to quantify the current medical inventory on the International Space Station and ensure that sufficient stowage volume was present for this purpose. To that end, the ISS medical kits were reviewed, and eight full size mid deck lockers were placed in the facility. A number of additional devices were also added, based on the co-author’s combat medic experience. Also, two fixed shelves and one horizontal work surface were added to the Medical Care Facility, with the shelves providing storage space for the additional devices and the work surface providing a location for the caregiver to work or stage equipment. Four display monitors were added to the wall above the horizontal work surface, supporting data display, telemedicine, conferencing, or other needs. The existing treatment table was replaced with a mobile surgical stretcher-chair. Two additional doors were added to the Medical Care Facility. One leads directly to the hygiene compartment, allowing it to support medical operations in addition to providing galley/wardroom support. The other door leads directly into the Vertical Translation System. The wall adjacent to the subsystems bay was moved, adding additional volume to the Medical Care Facility. This improved caregiver access to the patient and allowed for a larger number of caregivers to be present. It also provided options for relocation of support equipment relative to the patient as needed. In the upgraded Medical Care Facility, the Surgical Stretcher-Chair and the Vertical Translation System can work together to provide incapacitated crew member transport from a site of injury on any deck of the Common Habitat to the Medical Care Facility. It can also support patient treatment in a variety of positions including a variety of sitting postures and a supine posture at a variety of pitch angles. The facility can also support caregiver office work for review of examination results, private consultation, inventory and maintenance, and a variety of other purposes. A forward activity will be to conduct evaluations of the Medical Care Facility with different medical scenarios. Additionally, ambient and task lighting selections remain as forward work. The eight middeck lockers can be augmented to use as portable equipment carts, similar to a manner in which maintenance facility stowage was used as portable carts during the NASA Desert Research and Technology Studies in the Constellation Program. Trash accommodation will also need forward work to assess, including provision for wet trash, dry trash, and biological waste. It will be important to assess a redesign of the surgical stretcher-chair. The commercial version used in the upgrade can only enable vertical translation in the seated configuration, requiring the patient to bend both hips and knees. A possible redesign of the chair will allow for vertical translation without requiring any bending at the hip or knees. Also, the commercial version is wheeled, making it mobile in gravity but unanchored in microgravity. Work will be needed to adapt the chair for gravity-independent performance. The hygiene compartment can be redesigned to serve both as a medical scrub facility and for galley hand washing. Pending sufficient volume, it may also be possible to place sanitation equipment in this location to clean medical tools. Finally, most space architectures have never allowed for more than one incapacitated crew member, but several scenarios could potentially injure two or more crew in the same incident. This facility could be assessed to determine its present ability to address two or more injured crew in parallel and determine the potential upper limit for number of treatable crew in a multi-crew injury scenario, or to treat polytrauma of a single patient.

Common Habitat↗
DOE OSTI2025

Targeting transcription factors through an IMiD independent zinc finger domain

Abstract Immunomodulatory imide drugs (IMiDs) degrade specific C2H2 zinc finger degrons in transcription factors, making them effective against certain cancers. SALL4, a cancer driver, contains seven C2H2 zinc fingers in three clusters, including an IMiD degron in zinc finger cluster one (ZFC1). Surprisingly, IMiDs do not inhibit the growth of SALL4-expressing cancer cells. To overcome this limit, we focused on a non-IMiD domain, SALL4 zinc finger cluster four (ZFC4). By combining ZFC4-DNA crystal structure and an in silico docking algorithm, in conjunction with cell viability assays, we screened several chemical libraries against a potentially druggable binding pocket, leading to the discovery of SH6, a compound that selectively targets SALL4-expressing cancer cells. Mechanistic studies revealed that SH6 degrades SALL4 protein through the CUL4A/CRBN pathway, while deletion of ZFC4 abolished this activity. Moreover, SH6 treatment led to a significant 87% tumor growth inhibition of SALL4+ patient-derived xenografts and demonstrated good bioavailability in pharmacokinetic studies. In summary, these studies represent a new approach for IMiD independent drug discovery targeting C2H2 transcription factors such as SALL4 in cancer.

Liu, Bee Hui↗
NASA NTRSDate not supplied

Configuration and Projected Capabilities of the Common Habitat Medical Care Facility

The Common Habitat is a large, long-duration habitat being explored as part of a conceptual study (not an active NASA program) that uses an SLS core stage Liquid Oxygen (LOX) tank as its primary structure. It is intended for use on the Moon as part of a permanently occupied outpost, on Mars as part of an outpost that will be occupied for hundreds of days at a time, and in deep space as part of the Deep Space Exploration Vehicle where it will support crewed missions up to 1200 days in duration. A study of internal orientation and crew size resulted in a Common Habitat configuration sized for a crew of eight with a three-deck horizontal orientation. Additional work outside the scope of this paper is developing a vertical translation system, a crew mobility aids system based on wearable gecko-derived grippers, and a crew seating/restraint system. These systems are all assumed for use in conjunction with the Medical Care Facility, which is needed to maintain crew well-being during these missions, where distance from Earth precludes the possibility of evacuation to Earth. This paper describes recent improvements in the Common Habitat Medical Care Facility and associated benefits for crew survivability in long duration missions beyond Earth orbit. These improvements were made with the assistance of a NASA Pathways intern whose experience includes a tour of duty in Afghanistan as an Army combat medic with the 691st GHOST-T, attached to the 1st and 7th US Special Forces Groups as part of Operation Freedom’s Sentinel, where he helped provide far-forward surgical capabilities in austere combat environments. The initial baseline Medical Care Facility was developed working in conjunction with University of Houston Space Architecture graduate students. The facility was placed on the upper deck of the Common Habitat in a location that provided privacy, operational volume, and was close to the vertical translation pathway. The notional outfitting repurposed component CAD models from unrelated studies and notionally indicated a level of care roughly equivalent to that aboard the International Space Station. The CAD modeling provided notional stowage volumes, a deployable surface, some fixed equipment, an ultrasound, and a potentially reconfigurable treatment table. While this facility is clearly a competent arrangement, it was desired to leverage available expertise and upgrade the station given the vast distances from Earth to be experienced by the Common Habitat. Key driving requirements applied to the upgrade included to provide Medical Level of Care V, offer enhanced telemedicine capabilities, provide patient physical accommodation, provide caregiver access to the patient from all sides, include sliding pocket doors for access to hygiene and to the Vertical Translation System, and to add any additional capability possible for the best achievable medical care. The first step in the facility upgrade was to quantify the current medical inventory on the International Space Station and ensure that sufficient stowage volume was present for this purpose. To that end, the ISS medical kits were reviewed, and eight full size mid deck lockers were placed in the facility. A number of additional devices were also added, based on the intern’s combat medic experience. Also, two fixed shelves and one horizontal work surface were added to the Medical Care Facility, with the shelves providing storage space for the additional devices and the work surface providing a location for the caregiver to work or stage equipment. Four display monitors were added to the wall above the horizontal work surface, supporting data display, telemedicine, conferencing, or other needs. The existing treatment table was replaced with a mobile surgical stretcher-chair. Two additional doors were added to the Medical Care Facility. One leads directly to the hygiene compartment, allowing it to support medical operations in addition to providing galley/wardroom support. The other door leads directly into the Vertical Translation System. The wall adjacent to the subsystems bay was moved, adding additional volume to the Medical Care Facility. This improved caregiver access to the patient and allowed for a larger number of caregivers to be present. It also provided options for relocation of support equipment relative to the patient as needed. In the upgraded Medical Care Facility, the Surgical Stretcher-Chair and the Vertical Translation System can work together to provide incapacitated crew member transport from a site of injury on any deck of the Common Habitat to the Medical Care Facility. It can also support patient treatment in a variety of positions including a variety of sitting postures and a supine posture at a variety of pitch angles. The facility can also support caregiver office work for review of examination results, private consultation, inventory and maintenance, and a variety of other purposes. A forward activity will be to conduct evaluations of the Medical Care Facility with different medical scenarios. Additionally, ambient and task lighting selections remain as forward work. The eight mid deck lockers can be augmented to use as portable equipment carts, similar to a manner in which maintenance facility stowage was used as portable carts during the NASA Desert Research and Technology Studies in the Constellation Program. Trash accommodation will also need forward work to assess, including provision for wet trash, dry trash, and biological waste. It will be important to assess a redesign of the surgical stretcher-chair. The commercial version used in the upgrade can only enable vertical translation in the seated configuration, requiring the patient to bend both hips and knees. A possible redesign of the chair will allow for vertical translation without requiring any bending at the hip or knees. Also, the commercial version is wheeled, making it mobile in gravity but unanchored in microgravity. Work will be needed to adapt the chair for gravity-independent performance. The hygiene compartment can be redesigned for dual-use medical scrub and galley handwash facility. Pending sufficient volume, it may also be possible to place sanitation equipment in this location to clean medical tools. Finally, most space architectures have never allowed for more than one incapacitated crew member, but several scenarios could potentially injure two or more crew in the same incident. This facility could be assessed to determine its present ability to address two or more injured crew in parallel and determine the potential upper limit for number of treatable crew in a multi-crew injury scenario, or to treat polytrauma of a single patient.

Habitat↗
DOE OSTI2022

Improving Dose-Optimization Processes Used in Oncology Drug Development to Minimize Toxicity and Maximize Benefit to Patients

This review highlights strategies to integrate dose optimization into premarketing drug development and discusses the underlying statistical principles. Poor dose optimization can have negative consequences for patients, most commonly because of toxicity, including poor quality of life, reduced effectiveness because of inability of patients to stay on current therapy or receive subsequent therapy because of toxicities, and difficulty in developing combination regimens. We reviewed US Food and Drug Administration initial approvals (2019-2021) of small molecules and antibody-drug conjugates for oncologic indications to determine the proportion with a recommended dosage at the maximum tolerated dose or the maximal administered dose, to characterize the use of randomized evaluations of multiple dosages in dose selection, to describe the frequency of dose modifications at the recommended dosage, and to identify case examples that highlight key principles for premarket dose optimization during drug development. Herein, we highlight major principles for dose optimization and review examples of recent US Food and Drug Administration approvals that illustrate how investigation of dose- and exposure-response relationships and use of randomized dose trials can support dose optimization. Although there has been some progress, dose optimization through randomized dose evaluation in oncology trials is not routinely conducted. Dose optimization is essential to ensure that patients receive therapies which maximize efficacy while minimizing toxicity.

Oncology↗
DOE OSTI2024

Identification of integrated proteomics and transcriptomics signature of alcohol-associated liver disease using machine learning

Distinguishing between alcohol-associated hepatitis (AH) and alcohol-associated cirrhosis (AC) remains a diagnostic challenge. In this study, we used machine learning with transcriptomics and proteomics data from liver tissue and peripheral mononuclear blood cells (PBMCs) to classify patients with alcohol-associated liver disease. The conditions in the study were AH, AC, and healthy controls. We processed 98 PBMC RNAseq samples, 55 PBMC proteomic samples, 48 liver RNAseq samples, and 53 liver proteomic samples. First, we built separate classification and feature selection pipelines for transcriptomics and proteomics data. The liver tissue models were validated in independent liver tissue datasets. Next, we built integrated gene and protein expression models that allowed us to identify combined gene-protein biomarker panels. For liver tissue, we attained 90% nested-cross validation accuracy in our dataset and 82% accuracy in the independent validation dataset using transcriptomic data. We attained 100% nested-cross validation accuracy in our dataset and 61% accuracy in the independent validation dataset using proteomic data. For PBMCs, we attained 83% and 89% accuracy with transcriptomic and proteomic data, respectively. The integration of the two data types resulted in improved classification accuracy for PBMCs, but not liver tissue. We also identified the following gene-protein matches within the gene-protein biomarker panels: CLEC4M-CLC4M, GSTA1-GSTA2 for liver tissue and SELENBP1-SBP1 for PBMCs. In this study, machine learning models had high classification accuracy for both transcriptomics and proteomics data, across liver tissue and PBMCs. The integration of transcriptomics and proteomics into a multi-omics model yielded improvement in classification accuracy for the PBMC data. The set of integrated gene-protein biomarkers for PBMCs show promise toward developing a liquid biopsy for alcohol-associated liver disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Optimal vocabulary selection approaches for privacy-preserving deep NLP model training for information extraction and cancer epidemiology

With the use of artificial intelligence and machine learning techniques for biomedical informatics, security and privacy concerns over the data and subject identities have also become an important issue and essential research topic. Without intentional safeguards, machine learning models may find patterns and features to improve task performance that are associated with private personal information. The privacy vulnerability of deep learning models for information extraction from medical textural contents needs to be quantified since the models are exposed to private health information and personally identifiable information. The objective of the study is to quantify the privacy vulnerability of the deep learning models for natural language processing and explore a proper way of securing patients’ information to mitigate confidentiality breaches. The target model is the multitask convolutional neural network for information extraction from cancer pathology reports, where the data for training the model are from multiple state population-based cancer registries. This study proposes the following schemes to collect vocabularies from the cancer pathology reports; (a) words appearing in multiple registries, and (b) words that have higher mutual information. We performed membership inference attacks on the models in high-performance computing environments. The comparison outcomes suggest that the proposed vocabulary selection methods resulted in lower privacy vulnerability while maintaining the same level of clinical task performance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Treatment of antibiotic-manufacturing wastewater enriches for Aeromonas veronii, a zoonotic antibiotic-resistant emerging pathogen

Antibiotic-manufacturing wastewater treatment plants primarily target chemical pollutants, but their processes may select for antibiotic-resistant pathogens and antibiotic resistance genes. Leveraging the combined strengths of deep metagenomic sequencing, 16S rRNA gene sequencing, quantitative polymerase chain reaction, and bacterial culturing, we investigated bacterial communities and antibiotic resistomes across eleven treatment units in a full-scale antibiotic-manufacturing wastewater treatment plant processing wastewater from a β-lactam manufacturing facility. Both bacterial communities and antibiotic resistance gene compositions varied across the treatment units, but were associated. Certain antibiotic resistance gene persisted through treatment, either carried by identical bacterial species, or linked to mobile genetic elements in different species. Despite the satisfactory performance in chemical removal, this plant continuously enriched zoonotic antibiotic-resistant Aeromonas veronii (an emerging pathogen responsible for substantial economic losses in aquaculture and human health) from influent to effluent, probably due to prolonged β-lactam selection pressure and aquatic nature of A. veronii. This enrichment resulted in a significantly higher abundance of A. veronii than other aquatic samples worldwide. Furthermore, the closest evolutionary relative to the retrieved A. veronii was an isolate obtained from the stool of a local diarrhea patient. These findings highlighted a substantial public health risk posed by antibiotic-manufacturing wastewater treatment, underlining its potential role in enriching and disseminating zoonotic antibiotic-resistant pathogens. Beyond chemical monitoring, enhanced surveillance of antibiotic-resistant pathogens and antibiotic resistance genes is needed in effluent discharge standard for antibiotic-manufacturing wastewater treatment plants.

Wang, Xingshuo↗
DOE OSTI2020

Computer-aided classification of suspicious pigmented lesions using wide-field images

Early identification of melanoma is conducted through whole-body visual examinations to detect suspicious pigmented lesions, a situation that fluctuates in accuracy depending on the experience and time of the examiner. Computer-aided diagnosis tools for skin lesions are typically trained using pre-selected single-lesion images, taken under controlled conditions, which limits their use in wide-field scenes. Here, we propose a computer-aided classifier system with such input conditions to aid in the rapid identification of suspicious pigmented lesions at the primary care level. 133 patients with a multitude of skin lesions were recruited for this study. All lesions were examined by a board-certified dermatologist and classified into “suspicious” and “non-suspicious”. A new clinical database was acquired and created by taking Wide-Field images of all major body parts with a consumer-grade camera under natural illumination condition and with a consistent source of image variability. 3–8 images were acquired per patient on different sites of the body, and a total of 1759 pigmented lesions were extracted. A machine learning classifier was optimized and build into a computer aided classification system to binary classify each lesion using a suspiciousness score. In a testing set, our computer-aided classification system achieved a sensitivity of 100% for suspicious pigmented lesions that were later confirmed by dermoscopy examination (“SPL_A”) and 83.2% for suspicious pigmented lesions that were not confirmed after examination (“SPL_B”). Sensitivity for non-suspicious lesions was 72.1%, and accuracy was 75.9%. With these results we defined a suspiciousness score that is aligned with common macro-screening (naked eye) practices. This work demonstrates that wide-field photography combined with computer-aided classification systems can distinguish suspicious from non-suspicious pigmented lesions, and might be effective to assess the severity of a suspicious pigmented lesions. We believe this approach could be useful to support skin screenings at a population-level.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Many-isocenter optimization for robotic radiotherapy

Despite significant dosimetric gains, clinical implementation of the 4π non-coplanar radiotherapy on the widely available C-arm gantry system is hindered by limited clearance, and the need to perform complex coordinated gantry and couch motion. A robotic radiotherapy platform would be conducive to such treatment but a new conflict between field size and MLC modulation resolution needs to be managed for versatile applications. This study investigates the dosimetry and delivery efficiency of purposefully creating many isocenters to achieve simultaneously high MLC modulation resolution and large tumor coverage. An integrated optimization framework was proposed for simultaneous beam orientation optimization (BOO), isocenter selection, and fluence map optimization (FMO). The framework includes a least-square dose fidelity objective, a total variation term for regularizing the fluence smoothness, and a group sparsity term for beam selection. A minimal number of isocenters were identified for efficient target coverage. Colliding beams excluded, high-resolution small-field 4π intensity-modulated radiotherapy (IMRT) treatment plans with 50 cm source-to-isocenter distance (SID-50) on 10 Head and Neck (H&N) cancer patients were compared with low-resolution large-field plans with 100 cm SID (SID-100). With the same or better target coverage, the average reduction of [Dmean, Dmax] of 20-beam SID-50 plans from 20-beam SID-100 plans were [2.09 Gy, 1.19 Gy] for organs at risk (OARs) overall, [3.05 Gy, 0.04 Gy] for parotid gland, [3.62 Gy, 5.19 Gy] for larynx, and [3.27 Gy, 1.10 Gy] for mandible. R50 and integral dose were reduced by 5.3% and 9.6%, respectively. Wilcoxon signed-rank test showed significant difference (p < 0.05) in planning target volume (PTV) homogeneity, PTV Dmax, R50, Integral dose, and OAR Dmean and Dmax. The estimated delivery time of 20-beam [SID-50, SID-100] plans were [19, 18] min and [14, 9] min, assuming 5 fractions and 30 fractions, respectively. Finally, with clinically acceptable delivery efficiency, many-isocenter optimization is dosimetrically desirable for treating large targets with high modulation resolution on the robotic platform.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Treatment of Prostate Cancer with CD46-targeted 225 Ac Alpha Particle Radioimmunotherapy

Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody–drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [ 225 Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. [ 225 Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell-derived (22Rv1, DU145), and patient-derived (LTL-545, LTL484) prostate cancer xenograft models. Biodistribution studies were carried out on 22Rv1 tumor xenograft models to confirm the targeting efficacy. Toxicity analysis of the [ 225 Ac]DOTA-YS5 was carried out on nu/nu mice to study short-term (acute) and long-term (chronic) toxicity. Biodistribution study shows that [ 225 Ac]DOTA-YS5 agent delivers high levels of radiation to the tumor tissue (11.64% ± 1.37%ID/g, 28.58% ± 10.88%ID/g, 29.35% ± 7.76%ID/g, and 31.78% ± 5.89%ID/g at 24, 96, 168, and 408 hours, respectively), compared with the healthy organs. [ 225 Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line–derived and patient-derived xenograft models. Toxicity analysis revealed that the 0.5 μCi activity levels showed toxicity to the kidneys, likely due to redistribution of daughter isotope 213 Bi. [ 225 Ac]DOTA-YS5 suppressed the growth of cell-derived and patient-derived xenografts, including prostate-specific membrane antigen–positive and prostate-specific membrane antigen–deficient models. Overall, this preclinical study confirms that [ 225 Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46-targeted radioligand therapy in prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS1993

Earthbound applications for NASA's physician workstation

The dream of a space probe to Mars or an astronaut colony on the moon persists. Despite years of setbacks and delays, NASA continues to lay the foundation for a new frontier in space. The necessity of a self contained health maintenance facility is an integral part of this stellar venture. As a subsystem of this health maintenance facility, the physician or astronaut workstation was envisioned as the vehicle of interface between the computer resources of the space station and the care provider. Our efforts to define and build this interface have resulted in a series of programs which can now be tested and refined using earth-based applications. The modules which have dual-use application from the NASA workstation include: patient scheduling and master patient index, pharmacy, laboratory, medical library, problem list/progress notes, and digital medical records. Our current plan is to develop these tools as objects that can be assembled in a variety of configurations. This will allow the technology to be used by the private sector where each doctor can select the starting point of his outpatient office system and add modules as he makes progress in system integration and training.

NASA Discipline Number 70-30↗
DOE OSTI2024

Distribution of plutonium and radium in the human heart

Since 1968, the United States Transuranium and Uranium Registries (USTUR) has studied the biokinetics and tissue dosimetry of uranium and transuranium elements in nuclear workers. As part of the USTUR collaboration with the Million Person Study of Low-Dose Health Effects, radiation dose to different parts of the human heart is being estimated for workers with documented intakes of 239 Pu or 226 Ra. The study may be expanded for workers with intakes of 238 U and other radionuclides. The distribution of radionuclides, expressed in terms of concentration (Bq per kg of tissue) serves as an important parameter for estimating radiation dose. Based on available organs from workers who donated their bodies or tissues for research, nine undissected hearts were selected: seven from USTUR registrants with plutonium exposure (males) and two individuals with radium intakes (female and male). For the plutonium workers, estimated 239 Pu systemic deposition ranged from <74 Bq to 1765 Bq. Estimated 226 Ra ‘initial systemic intakes’ were 10.1 MBq and 14.8 kBq for the female patient and male worker, respectively. Organ dissection was based on a heart model published by Borrego et al (2019 J. Radiol. Prot. 39 950–65). This model includes nine cardiac substructures: aorta, left main coronary artery, left atrium, left anterior descending artery, left circumflex artery, left ventricle, right atrium, right coronary artery, and right ventricle. In addition, heart valves, fat attached to epicardium, fluids, and a coronary bypass graft were collected resulting in 111 samples that are currently undergoing radiochemical analyses and mass-spectrometric measurements. The 239 Pu and 226 Ra evaluations are not completed. The results of this study are intended to support radiation worker health studies by improving associated dosimetric and epidemiological models.

USTUR↗
DOE OSTI2022

Case studies in bias reduction and inference for electronic health record data with selection bias and phenotype misclassification

Electronic health records (EHR) are not designed for population‐based research, but they provide easy and quick access to longitudinal health information for a large number of individuals. Many statistical methods have been proposed to account for selection bias, missing data, phenotyping errors, or other problems that arise in EHR data analysis. However, addressing multiple sources of bias simultaneously is challenging. We developed a methodological framework (R package, SAMBA ) for jointly handling both selection bias and phenotype misclassification in the EHR setting that leverages external data sources. These methods assume factors related to selection and misclassification are fully observed, but these factors may be poorly understood and partially observed in practice. As a follow‐up to the methodological work, we demonstrate how to apply these methods for two real‐world case studies, and we evaluate their performance. In both examples, we use individual patient‐level data collected through the University of Michigan Health System and various external population‐based data sources. In case study (a), we explore the impact of these methods on estimated associations between gender and cancer diagnosis. In case study (b), we compare corrected associations between previously identified genetic loci and age‐related macular degeneration with gold standard external summary estimates. These case studies illustrate how to utilize diverse auxiliary information to achieve less biased inference in EHR‐based research.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1992

Human low vision image warping - Channel matching considerations

We are investigating the possibility that a video image may productively be warped prior to presentation to a low vision patient. This could form part of a prosthesis for certain field defects. We have done preliminary quantitative studies on some notions that may be valid in calculating the image warpings. We hope the results will help make best use of time to be spent with human subjects, by guiding the selection of parameters and their range to be investigated. We liken a warping optimization to opening the largest number of spatial channels between the pixels of an input imager and resolution cells in the visual system. Some important effects are not quantified that will require human evaluation, such as local 'squashing' of the image, taken as the ratio of eigenvalues of the Jacobian of the transformation. The results indicate that the method shows quantitative promise. These results have identified some geometric transformations to evaluate further with human subjects.

Juday, Richard D.↗
NASA NTRS2000

Evaluation and Treatment of Essential Hypertension During Short Duration Space Flight

During the last four decades of manned space flight, two individuals have successfully flown in space with the preflight diagnosis of essential hypertension (HTN). Treatment of this disease process in the astronaut population warrants special consideration particularly when selecting medication for a mission. A retrospective review of data offers two different clinical scenarios involving the treatment, or lack thereof, for essential hypertension during space flight. Case I; A Caucasian quinquagenerian diagnosed with HTN one year prior to the mission obtained flight certification after a negative diagnostic workup. The patient was placed on a diuretic. Preflight isolated blood pressure (BP) measurements averaged 138/102. Inflight, the patient electively declined medication. A 36-hour BP monitor revealed an average value of 124/87. Postflight, BP measurements returned to preflight BP values. Case II: A Caucasian quatrogenerian diagnosed with HTN 6 months prior to launch completed flight training after a negative diagnostic workup. The patient was placed on an ACE inhibiter. Preflight BP measurements averaged 130/80. Inflight, isolated BP measurements were considerably less. Normotensive values were obtained postflight. In both cases, BP values inflight were lower than pre or postflight values. Yelle et al has confirmed similar findings in the normotensive astronaut population. Spaceflight may result in fluid shifting, mild dehydration, electrolyte imbalance, orthostatic hypotension, and increased heart rates. Based on these factors, certain classes of antihypertensive agents such as vasodilators, beta-blockers, and diuretics are excluded from consideration as a primary therapeutic modality. To date, Ace Inhibitors are viewed as the more acceptable drug of choice during spaceflight. Newer classes of drugs may also provide additional choices. Presently, astronauts developing uncomplicated HTN may continue their careers when treated with the appropriate class of continue their careers when treated with the appropriate class of antihypertensive medication.

Rossum, Alfred C.↗
NASA NTRS1995

The PRP Effect Following Callosotomy: Residual Interference Despite Uncoupling of Lateralized Response Codes

A callosotomy patient was tested in two dual-task experiments requiring successive speeded responses to lateralized stimuli. In accord with the recent findings of Pashler, O'Brien, Luck, Hillyard, Mangun, and Gazzaniga (in press), the patient showed a robust psychological refractory period effect (PRP) responses on Task 2 were inversely related to the stimulus-onset asynchrony (SOA). However, three aspects of our data indicated that the processing limitations for the patient were different than those observed with control subjects. First, the split-brain patient did not show an increase in reaction time when the two tasks required responses from a common output system (i.e., both manual responses) in comparison to when different output systems were used (i.e., manual-vocal). Second, inconsistent stimulus-response mappings for the two tasks greatly inflated response latencies for the control subjects, but had minimal effect on the performance of the split-brain patient. Third, the consistency manipulation was underadditive with SOA for only the patient, suggesting a later bottleneck in processing following callosotomy than was observed for the control subjects. It is proposed that sectioning the corpus callosum eliminates interference resulting from competing stimulus response codes. Nonetheless, dual-task interference persists for the split-brain subject because a subcortical gate constrains when selected responses can be implemented.

Ivry, Richard B.↗
NASA NTRS2025

Limitations and Feasibility of Mini X-Ray Devices in Space Environments

LIMITATIONS AND FEASIBILITY OF MINI X-RAY DEVICES IN SPACE ENVIRONMENTS As space exploration advances toward long-duration missions, reliable medical diagnostic tools become increasingly critical. The miniature x-ray (XR) technology demonstrations by the Exploration Medical Capability (ExMC) and the Exploration Medical Integrated Product Team (XMIPT) aim to assess the feasibility and utility of miniature XR devices in spaceflight. This abstract explores the limitations of current miniature XR systems, the challenges of training crew members, the potential role of clinical decision support systems (CDSS), and the feasibility of ground-based image interpretation. We also propose the integration of miniature XR into other ExMC efforts aimed at identifying the capabilities and resources needed for future exploration class missions. One of the primary challenges with miniature XR devices is the ability to achieve specific anatomical views, particularly in the confined and weightless conditions of a spacecraft. Operators may struggle to acquire diagnostic-quality images when space is limited for proper patient positioning and the volume of the imaging device. Since space radiation and detector limitations may further impact image quality, the flexibility of the operating procedures of these devices will be critical for their success in space applications. CHALLENGES IN TRAINING CREW TO OPERATE IMAGING DEVICES Training in the skills necessary to acquire diagnostic-quality scans may be a barrier for non-clinician crewmembers. The curriculum developed for crew medical officers (CMOs) will require simplification and adaptation to fit into the highly truncated pre-flight training period. Therefore, hands-on familiarization and simulation, both pre-flight and just-in-time training during missions, will be crucial to ensuring the crew can operate the devices in real-life situations. The ability to adjust acquisition parameters must be simplified or made automatic through exam selections on equipment user interfaces, and subject and operator positioning should be assisted with laser guidance and pictorial guides. POTENTIAL FOR CDSS OR ARTIFICIAL INTELLIGENCE (AI)-ASSISTED CDSS CDSS and AI-assisted CDSS offer significant promise in assisting crew members with limited medical training. These systems could provide real-time feedback on image quality and interpretation, helping to mitigate the risks of human error during space missions. Integrating procedural guidance tools, such as virtual and augmented reality, will support crewmembers in accurately positioning patients and obtaining high-quality images. However, the success of such systems will depend on the development of robust training datasets, integration with spaceflight-rated hardware, and the medical decision-making capabilities of operators. FEASIBILITY OF GROUND INTERPRETATION AND DATA TRANSMISSION Reliance on ground-based interpretation may prove difficult for acute care during exploration class-missions due to delays in transmission with increasing distance from Earth or complete communication blackout periods. In such instances where immediate interpretation for clinical intervention is required, crew must be able to interpret the images independently or utilize AI-based assistance to do so. File sizes for XR exams can also be large if numerous images are acquired and bandwidth constraints may limit data transmissions for both radiography and ultrasound exams. FUTURE WORK AND INTEGRATION INTO THE EVIDENCE LIBRARY Future work proposes integrating miniature XR devices into NASA’s Evidence Library to address medical conditions identified as significant contributors to crew morbidity and mortality. The possibility of combining miniature XR with other imaging modalities, such as ultrasound devices, is also under investigation. In conclusion, while miniature XR technology holds potential for extraterrestrial medical systems, there are significant challenges to overcome. Training, integration of AI tools, dedicated exam protocols for microgravity, and improved data transmission systems will be key to realizing the full benefits of miniature XR technology in space.

A M Nelson↗
NASA NTRS2009

Microwave Treatment for Cardiac Arrhythmias

NASA seeks to transfer the NASA developed microwave ablation technology, designed for the treatment of ventricular tachycardia (irregular heart beat), to industry. After a heart attack, many cells surrounding the resulting scar continue to live but are abnormal electrically; they may conduct impulses unusually slowly or fire when they would typically be silent. These diseased areas might disturb smooth signaling by forming a reentrant circuit in the muscle. The objective of microwave ablation is to heat and kill these diseased cells to restore appropriate electrical activity in the heart. This technology is a method and apparatus that provides for propagating microwave energy into heart tissues to produce a desired temperature profile therein at tissue depths sufficient for thermally ablating arrhythmogenic cardiac tissue while preventing excessive heating of surrounding tissues, organs, and blood. A wide bandwidth double-disk antenna is effective for this purpose over a bandwidth of about six gigahertz. A computer simulation provides initial screening capabilities for an antenna such as antenna, frequency, power level, and power application duration. The simulation also allows optimization of techniques for specific patients or conditions. In comparison with other methods that involve direct-current pulses or radio frequencies below 1 GHz, this method may prove more effective in treating ventricular tachycardia. This is because the present method provides for greater control of the location, cross-sectional area, and depth of a lesion via selection of the location and design of the antenna and the choice of microwave power and frequency.

Hernandez-Moya, Sonia↗