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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3

Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials’ cost-effectiveness analyses and key areas for future research.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Utility of Circulating MicroRNA-150 for Rapid Evaluation of Bone Marrow Depletion After Radiation and Efficiency of Bone Marrow Reconstitution

Total body irradiation (TBI) is a common myeloablative preparative regimen used in acute myeloid and lymphoblastic leukemia patients before allogenic hematopoietic stem cell transplantation (HSCT). The inefficient clearance of tumor cells and radiation-induced toxicity to normal tissues is attributed to relapse and morbidity in a significant fraction of patients. Developing biomarkers that indicate an individual's physiological response to radiation will allow personalized treatment and follow-up. We investigated the utility of circulating microRNA150-5p (miR150) for evaluation of radiation dose response.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

MEX3A promotes development and progression of breast cancer through regulation of PIK3CA

Breast cancer has been identified as the most common malignant tumors among women and the morbidity of breast cancer is still increasing rapidly. MEX3A possesses important functions in the regulation of mRNAs and may be involved in a variety of human diseases including cancer, whose relationship with breast cancer is still not clear. In this study, MEX3A was identified as a potential promotor in breast cancer, whose expression was strongly higher in breast cancer tissues than normal tissues. The in vitro experiments showed that MEX3A is capable of promoting the development of breast cancer through stimulating cell proliferation, inhibiting cell apoptosis, arresting cell cycle and promoting cell migration. The functions of MEX3A were also verified in vivo. Furthermore, a combination of genechip analysis and Ingenuity pathway analysis (IPA) identified PIK3CA as a potential downstream target of MEX3A, knockdown of which executes similar inhibitory effects on breast cancer and could alleviate MEX3A-induced progression of breast cancer. In conclusion, our study unveiled, as the first time, MEX3A as a tumor promotor for breast cancer, whose function was carried out probably through the regulation of PIK3CA.

60 APPLIED LIFE SCIENCES↗

Inguinal and Ilio-inguinal Lymphadenectomy in Management of Palpable Melanoma Lymph Node Metastasis: A Long-Term Prospective Evaluation of Morbidity and Quality of Life

Purpose: Prospective data are lacking on long-term morbidity of inguinal lymphadenectomy including the influence of extent of surgery, use of radiotherapy, and patient factors. The aim of this study is to evaluate the effects of these factors on patient outcome, quality of life (QOL), regional symptoms, and limb volumes after inguinal or ilio-inguinal lymphadenectomy for melanoma. Methods: Analysis of the subgroup of patients with inguinal lymph node field relapse of melanoma, treated by inguinal or ilio-inguinal lymphadenectomy in the ANZMTG/TROG randomized trial of adjuvant radiotherapy versus observation. Results: Sixty-nine patients, 46 having undergone inguinal and 23 ilio-inguinal lymphadenectomy, with median follow-up of 73 months were analyzed. Mean limb volume increased rapidly after surgery (7% by 3 months) and continued to increase for at least another 18 months. Patients with body mass index (BMI) ≥ 25 kg/m{sup 2} had greater limb volume increase than normal-weight patients (13.3% versus 6.9%, P = 0.030). QOL improved over the first 18 months, but despite initial improvement, regional symptoms persisted long term. Type of surgery (inguinal or ilio-inguinal lymphadenectomy) had no demonstrably significant effect on limb volume (9.9% versus 13.4%, P = 0.35), QOL (P = 0.68), or regional symptoms (P = 0.65). There was no difference in overall survival between inguinal and ilio-inguinal lymphadenectomy [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.40–1.40, P = 0.43]. Conclusions: Inguinal lymphadenectomy for melanoma is a potentially morbid procedure with significant increases in limb volume. Patients report reasonable QOL but may have ongoing regional symptoms. Overweight/obesity is associated with poorer QOL, increased limb volume, and regional symptoms.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Future Farming: National Predictive Modeling Tool Initiative (NPMTI) [Slides]

The National Predictive Modeling Tool Initiative (NPMTI) is a multi-year program to develop research-based “tools” to forecast incidences of diseases and mycotoxins affecting U.S. crops. The overall goals of NPMTI are to: (1) ensure crop sustainability and crop quality; (2) provide climate change resilience; (3) improve soil health; (4) monitor pathogens and microbial diversity in the environment, but not limited to crop residues, soils, and air; (5) improve disease management thereby reducing yield losses; (6) increase precision of in-season disease management tactics; and (7) increase precision of pesticide use.

59 BASIC BIOLOGICAL SCIENCES↗

Microbial Risk Assessment

Historically, microbiological spaceflight requirements have been established in a subjective manner based upon expert opinion of both environmental and clinical monitoring results and the incidence of disease. The limited amount of data, especially from long-duration missions, has created very conservative requirements based primarily on the concentration of microorganisms. Periodic reevaluations of new data from later missions have allowed some relaxation of these stringent requirements. However, the requirements remain very conservative and subjective in nature, and the risk of crew illness due to infectious microorganisms is not well defined. The use of modeling techniques for microbial risk has been applied in the food and potable water industries and has exceptional potential for spaceflight applications. From a productivity standpoint, this type of modeling can (1) decrease unnecessary costs and resource usage and (2) prevent inadequate or inappropriate data for health assessment. In addition, a quantitative model has several advantages for risk management and communication. By identifying the variable components of the model and the knowledge associated with each component, this type of modeling can: (1) Systematically identify and close knowledge gaps, (2) Systematically identify acceptable and unacceptable risks, (3) Improve communication with stakeholders as to the reasons for resource use, and (4) Facilitate external scientific approval of the NASA requirements. The modeling of microbial risk involves the evaluation of several key factors including hazard identification, crew exposure assessment, dose-response assessment, and risk characterization. Many of these factors are similar to conditions found on Earth; however, the spaceflight environment is very specialized as the inhabitants live in a small, semi-closed environment that is often dependent on regenerative life support systems. To further complicate modeling efforts, microbial dose-response characteristics may be affected by a potentially dysfunctional crew immune system during a mission. In addition, microbial virulence has been shown to change under certain conditions during spaceflight, further complicating dose-response characterization. An initial study of the applicability of microbial risk assessment techniques was performed using Crew Health Care System (CHeCS) operational data from the International Space Station potable water systems. The risk of infection from potable water was selected as the flight systems and microbial ecology are well defined. This initial study confirmed the feasibility of using microbial risk assessment modeling for spaceflight systems. While no immediate threat was detected, the study identified several medically significant microorganisms that could pose a health risk if uncontrolled. The study also identified several specific knowledge gaps in making a risk assessment and noted that filling these knowledge gaps is essential as the risk estimates may change by orders of magnitude depending on the answers. The current phase of the microbial risk assessment studies focuses on the dose-response relationship of specific infectious agents, focusing on Salmonella enterica Typhimurium, Pseudomonas spp., and Escherichia coli, as their evaluation will provide a better baseline for determining the overall hazard characterization. The organisms were chosen as they either have been isolated on spacecraft or have an identified route of infection during a mission. The characterization will utilize dose-response models selected either from the peer-reviewed literature and/or by using statistical approaches. Development of these modeling and risk assessment techniques will help to optimize flight requirements and to protect the safety, health, and performance of the crew.

Ott, C. M.↗

Assessing Land Cover Change Dynamics in the Peruvian Amazon to Map Outbreak Risk and Inform Public Health Interventions for Zoonotic Disease Prevention

Dengue fever and leishmaniasis are two tropical diseases prevalent in Madre de Dios Region of Peru and have been associated with urbanization and road construction. Rapid land use changes such as mining, timber harvesting, and hydroelectric dam development lead to denser human presence in previously sparsely-populated areas which increases the proximity of human settlements to zoonotic disease vectors. In partnership with the Peruvian Ministries of Health (MINSA), the Environment (MINAM), and other in-country collaborators, a NASA DEVELOP team examined Land Use Land Cover (LULC) changes and reported dengue and leishmaniasis incidence in the Madre de Dios region. This sought to help MINSA and MINAM understand the spatial relationship between land use change and zoonotic disease incidence. We created a LULC classification script using Google Earth Engine (GEE) with Landsat 5 Thematic Mapper (TM) and Landsat 8 Operational Land Imager (OLI) imagery to classify land cover in 2010, 2015, and 2020 and evaluate changes over this time period. The team then compared the quantified results of the LULC assessment in conjunction with reported disease cases to evaluate disease incidence and key land cover changes across Madre de Dios’s 11 districts. Follow on work will use these products to develop more detailed outbreak risk maps. These products will allow MINSA, MINAM, and other partners to understand hotspots of land cover change in Peru and the relationship with outbreaks to inform public health decision makers and environmental policy.

Nataly Chacon-Buitrago↗

Plant Condition Remote Monitoring Technique

This paper summarizes the results of a radiation transfer study conducted on houseplants using controlled environmental conditions. These conditions included: (1) air and soil temperature; (2) incident and reflected radiation; and (3) soil moisture. The reflectance, transmittance, and emittance measurements were conducted in six spectral bands: microwave, red, yellow, green, violet and infrared, over a period of three years. Measurements were taken on both healthy and diseased plants. The data was collected on plants under various conditions which included: variation in plant bio-mass, diurnal variation, changes in plant pathological conditions (including changes in water content), different plant types, various disease types, and incident light wavelength or color. Analysis of this data was performed to yield an algorithm for plant disease from the remotely sensed data.

Fotedar, L. K.↗

Machine learning mathematical models for incidence estimation during pandemics

Accurate estimates of the incidence of infectious diseases are key for the control of epidemics. However, healthcare systems are often unable to test the population exhaustively, especially when asymptomatic and paucisymptomatic cases are widespread; this leads to significant and systematic under-reporting of the real incidence. Here, we propose a machine learning approach to estimate the incidence of a pandemic in real-time, using reported cases and the overall test rate. In particular, we use Bayesian symbolic regression to automatically learn the closed-form mathematical models that most parsimoniously describe incidence. We develop and validate our models using COVID-19 incidence values for nine different countries, confirming their ability to accurately predict daily incidence. Remarkably, despite the differences in epidemic trajectories and dynamics across countries, we find that a single model for all countries offers a more parsimonious description and is more predictive of actual incidence compared to separate models for each country. Our results show the potential to accurately model incidence in real-time using closed-form mathematical models, providing a valuable tool for public health decision-makers.

Fajardo-Fontiveros, Oscar (ORCID:0000000207058972)↗

Cardiovascular Disease Risk in NASA Astronauts Across the Lifespan: Historical Cohort Studies

Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in space flight activities are potentially associated with cardiovascular disease risk factors (e.g., altered dietary and exercise habits, physical and emotional stress, circadian shifts, radiation). Further, astronauts who travel into space multiple times may be at an increased risk across their lifespan. However, comparing the risk of cardiovascular disease in astronauts to other large cohorts is difficult. For example, comparisons between astronauts and large national cohorts, such as the National Health and Nutrition Examination Survey and the National Health Information Survey, are hampered by significant differences in health status between astronauts and the general population, and most of these national studies fail to provide longitudinal data on population health. To address those limitations, NASA's Longitudinal Study of Astronaut Health previously sought to compare the astronauts to a cohort of civil servants employed at the Johnson Space Center. However, differences between the astronauts and civil servants at the beginning of the study, as well as differential follow up, limited the ability to interpret the results. To resolve some of these limitations, two unique cohorts of healthy workers, U.S. Air Force aviators and Cooper Center Longitudinal Study participants, have been identified as potential comparison populations for the astronaut corps. The Air Force cohort was chosen due to similarities in health at selection, screening, and some occupational exposures that Air Force aviators endure, many of which mirror that of the astronaut corps. The Cooper Clinic cohort, a generally healthy prevention cohort, was chosen for the vast array of clinical cardiovascular measures collected in a longitudinal manner complementary to those collected on astronauts, for a large number of subjects since 1971. The purpose of this study is to understand the incidence of cardiovascular disease outcomes and risk factors in the astronaut corps and determine whether the rates of disease are different than these two cohorts. The research questions are: 1. Are there differences in the incidence of CVD outcomes (MI, revascularization, and stroke) between each cohort and the NASA Astronaut cohort? 2. Are there differences in the incidence of CVD risks (hypertension, hyperlipidemia, arrhythmias, and diabetes) between each cohort and the NASA Astronaut cohort? 3. Are there differences between each cohort and the NASA Astronaut cohort in how CVD risk factors (e.g., lipids, behaviors) change across time? Collectively, results from these studies will enhance our understanding of how cardiovascular disease outcomes and risk factors change across time in astronauts compared to other longitudinally-studied healthy cohorts and determine if there are interactions between or additive effects of the occupational health effects of spaceflight exposure and normal aging.

Charvat, Jacqueline M.↗

Assessment of Knowledge, Attitudes, and Practices Toward Ticks and Tickborne Disease among Healthcare Professionals Working in Schools in New York and Maryland

Healthcare Professionals Working in Schools (HPWS) are responsible for providing health services to students and play a role in providing education to prevent illnesses, including tickborne diseases (TBD). Providing TBD education to children has been shown to increase prevention behaviors and knowledge of TBD symptoms, but little is known regarding the current state of TBD awareness among HPWS. In spring 2019 we conducted a cross-sectional knowledge, attitudes, and practices (KAP) survey of HPWS in two states with a high incidence of Lyme disease (LD) to inform design of TBD prevention programs. The survey queried general knowledge of TBDs, school practices regarding TBDs, and availability of TBD resources. Overall, higher confidence, experience, risk perception, prior training on TBD, and more years employed as a HPWS were independently associated with knowledge of LD transmission, symptoms, and correct tick removal practices. State and local health departments should consider prioritizing engagement with HPWS to provide educational opportunities about tickborne diseases.

Nursing↗

Municipality Level Simulations of Dengue Fever Incidence in Puerto Rico Using Ground Based and Remotely Sensed Climate Data

Dengue fever (DF) is caused by a virus transmitted between humans and Aedes genus mosquitoes through blood feeding. In recent decades incidence of the disease has drastically increased in the tropical Americas, culminating with the Pan American outbreak in 2010 which resulted in 1.7 million reported cases. In Puerto Rico dengue is endemic, however, there is significant inter‐annual, intraannual, and spatial variability in case loads. Variability in climate and the environment, herd immunity and virus genetics, and demographic characteristics may all contribute to differing patterns of transmission both spatially and temporally. Knowledge of climate influences on dengue incidence could facilitate development of early warning systems allowing public health workers to implement appropriate transmission intervention strategies. In this study, we simulate dengue incidence in several municipalities in Puerto Rico using population and meteorological data derived from ground based stations and remote sensing instruments. This data was used to drive a process based model of vector population development and virus transmission. Model parameter values for container composition, vector characteristics, and incubation period were chosen by employing a Monte Carlo approach. Multiple simulations were performed for each municipality and the results were compared with reported dengue cases. The best performing simulations were retained and their parameter values and meteorological input were compared between years and municipalities. Parameter values varied by municipality and year illustrating the complexity and sensitivity of the disease system. Local characteristics including the natural and built environment impact transmission dynamics and produce varying responses to meteorological conditions.

Remote Sensing↗

SPACEFLIGHT-INDUCED CHANGES IN MICROBIAL VIRULENCE AND THE IMPACT TO THE HOST IMMUNE RESPONSE

INTRODUCTION Over the past 50 years, microorganisms have displayed unexpected responses relevant to infectious disease when grown in microgravity and microgravity analogue environments, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, and virulence. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system; consisting of altered leukocyte distribution, reductions in T and NK cell function, altered cytokine profiles, and reactivation of latent herpesviruses. Further, astronauts have some degree of clinical incidence, primarily infectious disease episodes and atopic dermatitis. The impact of the microgravity environment on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized. SPECIFIC AIMS In the Host-Microorganism, Microbial Response aspect of this study, the following Specific Aims are being investigated, using the microbial pathogens, Salmonella enterica Enteritidis, Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, and enterohemorrhagic Escherichia coli. Aim 1: Characterize the effect of spaceflight analogue culture on microbial pathogenesis-related stress responses and in vitro host-pathogen interactions. Analysis will include microbial stress responses as well as colonization and viability following pathogen challenge of three-dimensional (3-D) tissue co-culture models containing immune cells. We specifically selected obligate and opportunistic pathogens that are medically important and have been or are likely to be found aboard spacecraft. Aim 2: Characterize the effect of spaceflight analogue culture on the virulence potential of pathogenic microorganisms. Changes in virulence will be assessed using a mouse model of infection. SIGNIFICANCE The goal of this study is to use spaceflight analogue conditions to gain insight into the breadth of medically-significant International Space Station microorganisms that have altered virulence and the impact of those changes on the immune response of the host, including astronaut immune cells. This information will provide critical understanding into the impact of microgravity on potential alterations in microbial virulence and associated infectious disease risk to crew health during spaceflight missions.

C. M. Ott↗

Mapping Incidence and Prevalence Peak Data for SIR Modeling Applications

Infectious disease modeling and forecasting have played a key role in helping assess and respond to epidemics and pandemics. Recent work has leveraged data on disease peak infection and peak hospital incidence to fit compartmental models for the purpose of forecasting and describing the dynamics of a disease outbreak. Incorporating these data can greatly stabilize a compartmental model fit on early observations, where slight perturbations in the data may lead to model fits that forecast wildly unrealistic peak infection. We introduce a new method for incorporating historic data on the value and time of peak incidence of hospitalization into the fit for a Susceptible-Infectious-Recovered (SIR) model by formulating the relationship between an SIR model’s starting parameters and peak incidence as a system of two equations that can be solved computationally. We demonstrate how to calculate SIR parameter estimates – which describe disease dynamics such as transmission and recovery rates – using this method, and determine that there is a noticeable loss in accuracy whenever prevalence data is misspecified as incidence data. To exhibit the modeling potential, we update the Dirichlet-Beta State Space modeling framework to use hospital incidence data, as this framework was previously formulated to incorporate only data on total infections. This approach is assessed for practicality in terms of accuracy and speed of computation via simulation.

97 MATHEMATICS AND COMPUTING↗

Spaceflight-induced Changes in Microbial Virulence and the Impact to the Host Immune Response

INTRODUCTION Over the past 50 years, many microorganisms have displayed unexpected responses relevant to infectious disease when grown in microgravity and microgravity analogue environments, including changes in stress resistance, biofilm production, antibiotic sensitivity, final cell concentration, gene expression, enhanced host-pathogen interaction, and virulence. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system; consisting of altered leukocyte distribution, reductions in T and NK cell function, altered cytokine profiles, and reactivation of latent herpesviruses. Further, astronauts have some degree of clinical incidence, primarily infectious disease episodes and atopic dermatitis. The impact of the microgravity environment on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized. SPECIFIC AIMS In this study, the following Specific Aims are being investigated, using the microbial pathogens, Salmonella enterica Enteritidis, Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, and enterohemorrhagic Escherichia coli (EHEC). Aim 1: Characterize the effect of spaceflight analogue culture on microbial pathogenesis-related stress responses and in vitro host-pathogen interactions. Analyses include microbial stress responses as well as colonization and viability following pathogen challenge of three-dimensional (3-D) tissue co-culture models containing immune cells. We specifically selected obligate and opportunistic pathogens that are medically important and have been or are likely to be found aboard spacecraft. Aim 2: Characterize the effect of spaceflight analogue culture on the virulence potential of pathogenic microorganisms. Virulence will be assessed using a mouse model of infection. SIGNIFICANCE The goal of this study is to use spaceflight analogue conditions to gain insight into the breadth of medically-significant International Space Station microorganisms that have altered virulence and the impact of those changes on the immune response of the host. This information will provide critical understanding into the impact of microgravity on potential alterations in microbial virulence and associated infectious disease risk to crew health during spaceflight missions.

C M Ott↗

Laboratory Aspects of Blood Lipids

Classification of blood hyperlipemias by electrophoresis or ultracentrifugation according to density fraction is described and therapeutic measures for humans with hyperlipoproteinemia are outlined. The statistically significant relationship between high serum cholesterol levels and incidence of coronary disease prescribes restricted caloric intake or physical exercise to burn excess calories as preventive measures.

Townsend, F. M.↗